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-A glutamine metabolic switch supports erythropoiesis
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+Deficits in or Preservation of Basic Number Processing in Parkinson's Disease? A Registered Report
- Science, Volume 386, Issue 6723, November 2024.+
+Parkinson patients with mild cognitive impairment do not only show established motor (e.g., tremor and rigor) and nonmotor (e.g., depression and global cognitive impairment) symptoms. They also show deficits in some basic numerical functions: (non-) symbolic magnitude comparison and number line estimation In contrast, auditory and written transcoding skills were preserved.
++
ABSTRACT
+Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health care system. Until now, diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests mechanisms of both primary and secondary dyscalculia. The current study systematically investigated basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consisted of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients were stratified into patients with normal cognition (PD-NC) or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing was assessed using transcoding, number line estimation, and (non-) symbolic number magnitude comparison tasks. Discriminant analysis was employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants were subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Results indicate a profile of preserved (verbal representation) and impaired (magnitude representation, place × value activation) function in PD-MCI, hinting at basal ganglia dysfunction affecting numerical cognition in PD. Numerical deficits could not be explained by domain-general cognitive impairments, so that future research needs to incorporate domain-specific tasks of sufficient difficulty.
-in Science on 2024-11-15 08:00:00 UTC. +
in Journal of Neuroscience Research on 2024-11-16 08:04:23 UTC.
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-SPL13 controls a root apical meristem phase change by triggering oriented cell divisions
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+Brain Sciences, Vol. 14, Pages 1148: Visual Cortical Function Changes After Perceptual Learning with Dichoptic Attention Tasks in Adults with Amblyopia: A Case Study Evaluated Using fMRI
- Science, Volume 386, Issue 6723, November 2024.+
Brain Sciences, Vol. 14, Pages 1148: Visual Cortical Function Changes After Perceptual Learning with Dichoptic Attention Tasks in Adults with Amblyopia: A Case Study Evaluated Using fMRI
+Brain Sciences doi: 10.3390/brainsci14111148
+Authors: + Chuan Hou + Zhangziyi Zhou + Ismet Joan Uner + Spero C. Nicholas +
+Background: Amblyopia is a neurodevelopmental disorder of vision, commonly caused by strabismus or anisometropia during early childhood. While studies demonstrated that perceptual learning improves visual acuity and stereopsis in adults with amblyopia, accompanying changes in visual cortical function remain unclear. Methods: We measured functional magnetic resonance imaging (fMRI) responses before and after perceptual learning in seven adults with amblyopia. Our learning tasks involved dichoptic high-attention-demand tasks that avoided V1 function-related tasks and required high-level cortical functions (e.g., intraparietal sulcus) to train the amblyopic eye. Results: Perceptual learning induced low-level visual cortical function changes, which were strongly associated with the etiology of amblyopia and visual function improvements. Anisometropic amblyopes showed functional improvements across all regions of interest (ROIs: V1, V2, V3, V3A, and hV4), along with improvements in visual acuity and stereoacuity. In contrast, strabismic amblyopes showed robust improvements in visual cortical functions only in individuals who experienced significant gains in visual acuity and stereoacuity. Notably, improvements in V1 functions were significantly correlated with the magnitude of visual acuity and stereoacuity improvements when combining both anisometropic and strabismic amblyopes. Conclusions: Our findings provide evidence that learning occurs in both high-level and low-level cortical processes. Our study suggests that early intervention to correct eye alignment (e.g., strabismus surgery) is critical for restoring both visual and cortical functions in strabismic amblyopia.
-in Science on 2024-11-15 08:00:00 UTC. +
in Brain Sciences on 2024-11-16 00:00:00 UTC.
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-Sequence modeling and design from molecular to genome scale with Evo
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+A new look at TFPI inhibition of factor X activation
- Science, Volume 386, Issue 6723, November 2024.+
by Fabian Santiago, Amandeep Kaur, Shannon Bride, Dougald Monroe, Karin Leiderman, Suzanne Sindi
+ +Blood coagulation is a vital physiological process involving a complex network of biochemical reactions, which converge to form a blood clot that repairs vascular injury. This process unfolds in three phases: initiation, amplification, and propagation, ultimately leading to thrombin formation. Coagulation begins when tissue factor (TF) is exposed on an injured vessel’s wall. The first step is when activated factor VII (VIIa) in the plasma binds to TF, forming complex TF:VIIa, which activates factor X. Activated factor X (Xa) is necessary for coagulation, so the regulation of its activation is crucial. Tissue Factor Pathway Inhibitor (TFPI) is a critical regulator of the initiation phase as it inhibits the activation of factor X. While previous studies have proposed two pathways—direct and indirect binding—for TFPI’s inhibitory role, the specific biochemical reactions and their rates remain ambiguous. Many existing mathematical models only assume an indirect pathway, which may be less effective under physiological flow conditions. In this study, we revisit datasets from two experiments focused on activated factor X formation in the presence of TFPI. We employ an adaptive Metropolis method for parameter estimation to reinvestigate a previously proposed biochemical scheme and corresponding rates for both inhibition pathways. Our findings show that both pathways are essential to replicate the static experimental results. Previous studies have suggested that flow itself makes a significant contribution to the inhibition of factor X activation. We added flow to this model with our estimated parameters to determine the contribution of the two inhibition pathways under these conditions. We found that direct binding of TFPI is necessary for inhibition under flow. The indirect pathway has a weaker inhibitory effect due to removal of solution phase inhibitory complexes by flow. -in Science on 2024-11-15 08:00:00 UTC. +
in PLoS Computational Biology on 2024-11-15 14:00:00 UTC.
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-Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1
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+Social learning is triggered by environmental cues in immigrant birds
- Science, Volume 386, Issue 6723, November 2024.+
by Rachel A. Harrison
+ +After dispersal, what cues trigger social learning in immigrants? A new study in wild-caught great tits in PLOS Biology suggests that changes in the physical environment, rather than the social environment, are key in prompting social learning by immigrants. + +After dispersal, what cues trigger social learning in immigrants? This Primer explores a new PLOS Biology study in wild-caught great tits which suggests that changes in the physical environment, rather than the social environment, are key in prompting social learning by immigrants. -in Science on 2024-11-15 08:00:00 UTC. +
in PLoS Biology on 2024-11-15 14:00:00 UTC.
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-Chemical genetic approaches to dissect microbiota mechanisms in health and disease
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+MosAIC: An annotated collection of mosquito-associated bacteria with high-quality genome assemblies
- Science, Volume 386, Issue 6723, November 2024.+
by Aidan Foo, Laura E. Brettell, Holly L. Nichols, 2022 UW-Madison Capstone in Microbiology Students , Miguel Medina Muñoz, Jessica A. Lysne, Vishaal Dhokiya, Ananya F. Hoque, Doug E. Brackney, Eric P. Caragata, Michael L. Hutchinson, Marcelo Jacobs-Lorena, David J. Lampe, Edwige Martin, Claire Valiente Moro, Michael Povelones, Sarah M. Short, Blaire Steven, Jiannong Xu, Timothy D. Paustian, Michelle R. Rondon, Grant L. Hughes, Kerri L. Coon, Eva Heinz
+ +Mosquitoes transmit medically important human pathogens, including viruses like dengue virus and parasites such as Plasmodium spp., the causative agent of malaria. Mosquito microbiomes are critically important for the ability of mosquitoes to transmit disease-causing agents. However, while large collections of bacterial isolates and genomic data exist for vertebrate microbiomes, the vast majority of work in mosquitoes to date is based on 16S rRNA gene amplicon data that provides limited taxonomic resolution and no functional information. To address this gap and facilitate future studies using experimental microbiome manipulations, we generated a bacterial Mosquito-Associated Isolate Collection (MosAIC) consisting of 392 bacterial isolates with extensive metadata and high-quality draft genome assemblies that are publicly available, both isolates and sequence data, for use by the scientific community. MosAIC encompasses 142 species spanning 29 bacterial families, with members of the Enterobacteriaceae comprising 40% of the collection. Phylogenomic analysis of 3 genera, Enterobacter, Serratia, and Elizabethkingia, reveal lineages of mosquito-associated bacteria isolated from different mosquito species in multiple laboratories. Investigation into species’ pangenomes further reveals clusters of genes specific to these lineages, which are of interest for future work to test for functions connected to mosquito host association. Altogether, we describe the generation of a physical collection of mosquito-associated bacterial isolates, their genomic data, and analyses of selected groups in context of genome data from closely related isolates, providing a unique, highly valuable resource for research on bacterial colonisation and adaptation within mosquito hosts. Future efforts will expand the collection to include broader geographic and host species representation, especially from individuals collected from field populations, as well as other mosquito-associated microbes, including fungi, archaea, and protozoa. -in Science on 2024-11-15 08:00:00 UTC. +
in PLoS Biology on 2024-11-15 14:00:00 UTC.
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-Somatosensory and motor contributions to emotion representation
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+The impact of Perspective-Taking on weight stigma among Chinese University students: The mediating role of Common ingroup identity [version 1; peer review: awaiting peer review]
- arXiv:2411.08973v1 Announce Type: new -Abstract: Emotion is often described as something people 'feel' in their bodies. Embodied emotion theorists propose that this connection is not purely linguistic; perceiving an emotion may require somatosensory and motor re-experiencing. However, it remains unclear whether self-reports of emotion-related bodily sensations (i.e., 'lump in my throat') are related to neural simulations of bodily action and sensation or whether they can be explained by cognitive appraisals or the visual features of socioemotional signals. To investigate this, participants (N = 21) were shown arousing emotional images that varied in valence, complexity, and content while undergoing fMRI scans. Participants then rated the images on a set of emotion appraisal scales and indicated where, on a body map, they experienced sensation in response to the image. To derive normative models of responses on these scales, a separate larger online sample online (N = 56 - 128) also rated these images. Representational similarity analysis (RSA) was used to compare the emotional content in the body maps with appraisals and visual features. A pairwise distance matrix between the body maps generated for each stimulus was then used in a whole brain voxel-wise searchlight analysis to identify brain regions which reflect the representational geometry of embodied emotion. This analysis revealed a network including bilateral primary somatosensory and motor cortices, precuneus, insula, and medial prefrontal cortex. The results of this study suggest that the relationship between emotion and the body is not purely conceptual: It is supported by sensorimotor cortical activations. + Background/Objective Weight stigma has significant psychological and social implications, yet studies on perspective-taking as an intervention strategy remain scarce. This study aimed to investigate the effect of perspective-taking on weight stigma among Chinese university students and examine the potential mediating role of common ingroup identity. Methods A randomized controlled experiment with 202 Chinese university students (experimental group, perspective-taking group: n = 102; control group: n = 100) was conducted. Weight stigma was measured pre- and post-intervention using the Anti-Fat Attitudes Test. The study employed a 2 × 2 mixed design with ANCOVA and mediation analysis. Results The experimental group showed significantly lower post-test weight stigma when controlling for pre-test scores (F(1, 199) = 25.69, p < .001). Perspective-taking engagement was significantly higher in the experimental group (t = 3.13, p = .002). Common ingroup identity negatively correlated with post-test weight stigma (r = -.28, p < .001) but did not significantly mediate the perspective-taking and weight stigma reduction relationship. Conclusion Perspective-taking effectively reduces weight stigma among Chinese university students, contributing to stigma reduction strategies in university settings. Further research on underlying mechanisms is warranted. -in arXiv: Quantitative Biology: Neurons and Cognition on 2024-11-15 05:00:00 UTC. +
in F1000Research on 2024-11-15 10:24:37 UTC.
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-Interdependent scaling exponents in the human brain
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+Financial inclusion and stability in Ethiopia using bank-level data: A two-step system GMM estimation [version 1; peer review: awaiting peer review]
- arXiv:2411.09098v1 Announce Type: cross -Abstract: We apply the phenomenological renormalization group to resting-state fMRI time series of brain activity in a large population. By recursively coarse-graining the data, we compute scaling exponents for the series variance, log probability of silence, and largest covariance eigenvalue. The exponents clearly exhibit linear interdependencies, which we derive analytically in a mean-field approach. We find a significant correlation of exponent values with the gray matter volume and cognitive performance. Akin to scaling relations near critical points in thermodynamics, our findings suggest scaling interdependencies are intrinsic to brain organization and may also exist in other complex systems. + Background This paper examines the impact of financial inclusion on bank stability within Ethiopian context, using panel data from 17 commercial banks over the period 2015-2023. Given the scarcity of research focused on the relationship between financial inclusion and bank stability in Ethiopia, this paper seeks to address a crucial gap by analyzing both conventional and digital aspects of financial inclusion in relation with bank stability. Methods A two-stage principal component analysis (PCA) was conducted to construct a composite financial inclusion index, integrating 10 conventional and 5 digital indicators. The study applied a two-step robust system generalized method of moments (GMM) to examine the effects of financial inclusion on bank stability, complemented by Granger causality testing to examine the directionality of this relationship. Results The result reveals a significant positive effect of financial inclusion on bank stability and Granger causality tests confirms a bi-directional relationship between financial inclusion and stability, indicating that improvements in financial inclusion foster greater stability and vice versa. Our results also highlight that while bank efficiency and GDP growth rate positively effect stability, total assets and income diversification exhibit detrimental effects. Conclusions It is essential to capitalize policy synergies to promote bank stability and to enhance financial inclusion through conventional and digital channels, while carefully managing the implications of risks associated with income diversification and asset distribution. Ensuring inclusive financial system is vital for maintaining bank stability, thus positioning it as a key priority for financial institutions. -in arXiv: Quantitative Biology: Neurons and Cognition on 2024-11-15 05:00:00 UTC. +
in F1000Research on 2024-11-15 10:21:26 UTC.
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-The geometry of the deep linear network
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+Performance of Forensic Age Estimation by Aspartic Acid Racemization and DNA Methylation: A Systematic Review [version 1; peer review: awaiting peer review]
- arXiv:2411.09004v1 Announce Type: new -Abstract: This article provides an expository account of training dynamics in the Deep Linear Network (DLN) from the perspective of the geometric theory of dynamical systems. Rigorous results by several authors are unified into a thermodynamic framework for deep learning. - The analysis begins with a characterization of the invariant manifolds and Riemannian geometry in the DLN. This is followed by exact formulas for a Boltzmann entropy, as well as stochastic gradient descent of free energy using a Riemannian Langevin Equation. Several links between the DLN and other areas of mathematics are discussed, along with some open questions. + Background Forensic age estimation is not difficult when the body is found in good condition, but in cases of severe decomposition or damage, such as burnt or separated body parts, then the analysis can only be done with bones and teeth. There has been abundant research and development in the field of related biochemistry over the years. Various molecular changes occur in hard tissues and long-lived proteins, such as those in bones and teeth during the physiological process of aging. Aspartic acid racemization and DNA methylation are still the most frequently used age estimation methods because of their advantages in accuracy. Method This study aimed to compare the accuracy of DNA methylation and aspartic acid racemization methods for age estimation. Journal articles were searched in the electronic databases PubMed, Scopus, and Semantic Scholar of 2017-2022 according to PRISMA guidelines. Result Twelve journal articles were eligible for review. The DNA methylation method is quite simple to use because of commercially available methylation kits. Furthermore, the results can be obtained relatively quickly without requiring many samples, and the method is less sensitive to thermal and other damage than the aspartic acid racemization method. Conclusion The aspartic acid racemization method for age estimation has high accuracy, especially in determining age at death. However, temperature and the condition of the teeth affect the racemization of aspartic acid. Given that DNA methylation is generally stable in a wide range of temperatures, it provides a better approach to determining the chronological age even from charred remains. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-11-15 05:00:00 UTC. +
in F1000Research on 2024-11-15 10:18:56 UTC.
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-Med-Bot: An AI-Powered Assistant to Provide Accurate and Reliable Medical Information
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+“Unmasking the Uncommon”: A case series of multi-drug resistant Elizabethkingia meningoseptica causing late-onset sepsis and meningitis in preterm neonates [version 1; peer review: awaiting peer review]
- arXiv:2411.09648v1 Announce Type: cross -Abstract: This paper introduces Med-Bot, an AI-powered chatbot designed to provide users with accurate and reliable medical information. Utilizing advanced libraries and frameworks such as PyTorch, Chromadb, Langchain and Autogptq, Med-Bot is built to handle the complexities of natural language understanding in a healthcare context. The integration of llamaassisted data processing and AutoGPT-Q provides enhanced performance in processing and responding to queries based on PDFs of medical literature, ensuring that users receive precise and trustworthy information. This research details the methodologies employed in developing Med-Bot and evaluates its effectiveness in disseminating healthcare information. + Elizabethkingia meningoseptica is an uncommon nosocomial pathogen that causes meningitis, pneumonia, and sepsis in neonates and in immunocompromised individuals. It exhibits resistance to many commonly employed first-line antibiotics used to treat gram-negative pathogens. Herein, we present three cases of late-onset sepsis with multi-drug resistant (MDR) Elizabethkingia meningoseptica in high-risk neonates. Case 1 was a one-day-old preterm low-birth-weight infant who presented with respiratory distress syndrome and septic shock. The patient was intubated and administered empirical broad-spectrum antibiotics and antifungal agents. Blood culture grew Candida krusei, hence Amphotericin B was initiated. Repeat blood culture on day 27 showed gram-negative bacilli, identified as Elizabethkingia meningoseptica by MALDI-TOF . Antibiotic susceptibility testing (AST) revealed resistance to Piperacillin/Tazobactam, but sensitivity to Vancomycin, Levofloxacin, and Minocycline. IV Vancomycin was administered, which resulted in clinical improvement and negative blood culture results. Case 2 was an eleven-day-old preterm, low-birth-weight baby who presented with fever. Initial investigations revealed normal complete blood counts (CBC) parameters and elevated CRP levels. Blood and CSF cultures isolated Elizabethkingia meningoseptica with a similar AST pattern. Intravenous Ciprofloxacin was initiated with clinical improvement and negative follow-up blood cultures. Case 3 was a one-day-old preterm baby, appropriate-to-gestational age, presenting with respiratory distress syndrome. The infant was intubated and started on inotropic support and intravenous antibiotics. Blood cultures on day 4 showed Elizabethkingia meningoseptica and Vancomycin was started. Follow-up cultures on days 6 and 14 grew Acinetobacter baumannii. A combination of Levofloxacin and Colistin was added, and blood cultures were negative after seven days, with clinical improvement. Elizabethkingia meningoseptica is a significant cause of hospital-acquired infections, especially in Neonatal Intensive Care Unit (NICU), leading to outbreaks. Clinicians must have a high degree of suspicion of E. meningoseptica for gram-negative bacilli causing sepsis and meningitis in high-risk patients. Recent technological advances have enabled accurate speciation to guide therapy and reduce morbidity and mortality rates. -in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-11-15 05:00:00 UTC. +
in F1000Research on 2024-11-15 10:16:51 UTC.
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-On the Surprising Effectiveness of Attention Transfer for Vision Transformers
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+A glutamine metabolic switch supports erythropoiesis
- arXiv:2411.09702v1 Announce Type: cross -Abstract: Conventional wisdom suggests that pre-training Vision Transformers (ViT) improves downstream performance by learning useful representations. Is this actually true? We investigate this question and find that the features and representations learned during pre-training are not essential. Surprisingly, using only the attention patterns from pre-training (i.e., guiding how information flows between tokens) is sufficient for models to learn high quality features from scratch and achieve comparable downstream performance. We show this by introducing a simple method called attention transfer, where only the attention patterns from a pre-trained teacher ViT are transferred to a student, either by copying or distilling the attention maps. Since attention transfer lets the student learn its own features, ensembling it with a fine-tuned teacher also further improves accuracy on ImageNet. We systematically study various aspects of our findings on the sufficiency of attention maps, including distribution shift settings where they underperform fine-tuning. We hope our exploration provides a better understanding of what pre-training accomplishes and leads to a useful alternative to the standard practice of fine-tuning + Science, Volume 386, Issue 6723, November 2024.-
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-11-15 05:00:00 UTC. +
in Science on 2024-11-15 08:00:00 UTC.
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-Embedding Hardware Approximations in Discrete Genetic-based Training for Printed MLPs
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+SPL13 controls a root apical meristem phase change by triggering oriented cell divisions
- arXiv:2402.02930v2 Announce Type: replace-cross -Abstract: Printed Electronics (PE) stands out as a promisingtechnology for widespread computing due to its distinct attributes, such as low costs and flexible manufacturing. Unlike traditional silicon-based technologies, PE enables stretchable, conformal,and non-toxic hardware. However, PE are constrained by larger feature sizes, making it challenging to implement complex circuits such as machine learning (ML) classifiers. Approximate computing has been proven to reduce the hardware cost of ML circuits such as Multilayer Perceptrons (MLPs). In this paper, we maximize the benefits of approximate computing by integrating hardware approximation into the MLP training process. Due to the discrete nature of hardware approximation, we propose and implement a genetic-based, approximate, hardware-aware training approach specifically designed for printed MLPs. For a 5% accuracy loss, our MLPs achieve over 5x area and power reduction compared to the baseline while outperforming state of-the-art approximate and stochastic printed MLPs. + Science, Volume 386, Issue 6723, November 2024.-
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-11-15 05:00:00 UTC. +
in Science on 2024-11-15 08:00:00 UTC.
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-Reducing ADC Front-end Costs During Training of On-sensor Printed Multilayer Perceptrons
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+Sequence modeling and design from molecular to genome scale with Evo
- arXiv:2411.08674v2 Announce Type: replace-cross -Abstract: Printed electronics technology offers a cost-effectiveand fully-customizable solution to computational needs beyondthe capabilities of traditional silicon technologies, offering ad-vantages such as on-demand manufacturing and conformal, low-cost hardware. However, the low-resolution fabrication of printedelectronics, which results in large feature sizes, poses a challengefor integrating complex designs like those of machine learn-ing (ML) classification systems. Current literature optimizes onlythe Multilayer Perceptron (MLP) circuit within the classificationsystem, while the cost of analog-to-digital converters (ADCs)is overlooked. Printed applications frequently require on-sensorprocessing, yet while the digital classifier has been extensivelyoptimized, the analog-to-digital interfacing, specifically the ADCs,dominates the total area and energy consumption. In this work,we target digital printed MLP classifiers and we propose thedesign of customized ADCs per MLP's input which involvesminimizing the distinct represented numbers for each input,simplifying thus the ADC's circuitry. Incorporating this ADCoptimization in the MLP training, enables eliminating ADC levelsand the respective comparators, while still maintaining highclassification accuracy. Our approach achieves 11.2x lower ADCarea for less than 5% accuracy drop across varying MLPs. + Science, Volume 386, Issue 6723, November 2024.-
in arXiv: Computer Science: Neural and Evolutionary Computing on 2024-11-15 05:00:00 UTC. +
in Science on 2024-11-15 08:00:00 UTC.
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-Brain Sciences, Vol. 14, Pages 1143: Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review
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+Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1
-Brain Sciences, Vol. 14, Pages 1143: Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review
-Brain Sciences doi: 10.3390/brainsci14111143
-Authors: - Francesco Signorelli - Omar Ktari - Ludovico Agostini - Giorgio Ducoli - Fabio Zeoli - Massimiliano Visocchi -
-Background: Spontaneous intracranial hypotension (SIH) is a rare and frequently misdiagnosed disorder characterized by a low volume of cerebrospinal fluid (CSF) caused by the leakage of CSF through the spinal dural membrane. Patients with Marfan Syndrome (MS) and other connective tissue disorders are at an increased risk for dural ectasia, which may predispose them to spontaneous CSF leaks due to the structural weakness of their dural membranes. The management of SIH in MS patients is debated. Conservative measures, an epidural blood patch (EBP), and surgical treatments are the options generally provided. Methods: Herein, we report on the case of a 52-year-old female affected by MS, genetically confirmed, with a two-month history of sudden-onset, &ldquo;thunderclap&rdquo; headache, worsened in an upright position and horizontal diplopia. A Computed Tomography (CT) scan of the brain showed a bilateral chronic subdural hematoma, slit ventricles, and a caudal descent of the brainstem without overt tonsillar herniation. The Magnetic Resonance Imaging (MRI) scan of the whole spine revealed dural ectasia in the lumbosacral area and presacral perineural cyst without extradural CSF collection. The case was successfully managed with bed rest and high-dose corticosteroid therapy. Then, we discuss the pertinent literature, consisting of 25 papers dealing with the treatment of SIH in patients affected by MS. Results: The literature review yielded 25 papers dealing with SIH management in patients with MS, including 28 patients overall; 21 patients underwent EBP, of whom 7 patients had multiple procedures. Overall, in 23 cases (82%), the symptoms improved. In three cases, the patients were managed conservatively with bed rest. In three of these cases, there was an improvement. In one case, the surgical fenestration of two lumbar intradural spinal meningeal cysts was performed and the patient improved after the procedure. Our patient underwent 15 days of steroid therapy (dexamethasone iv 12 mg/day for 7 days, then reduced to 4 mg/day) and intravenous hydration (Ringer lactate 1500 mL/day). In ten days, the symptoms disappeared. At the 6-month follow-up, the patient was in good clinical condition, and a CT scan showed an almost complete regression of the bilateral subdural hematoma. Conclusions: The management of SIH in MS patients is still challenging. Patients with connective tissue disorders such as MS are at an increased risk for SIH. Few studies have assessed the management of these patients and different strategies. Our case and the available literature provide further data for this type of case.
+ Science, Volume 386, Issue 6723, November 2024.-
in Brain Sciences on 2024-11-15 00:00:00 UTC. +
in Science on 2024-11-15 08:00:00 UTC.
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-Assessment of Pelargonium graveolens flower essential oil: Antimicrobial, antioxidant, enzyme inhibition and in vivo topical analgesic and anti-inflammatory efficacy as treatment for atopic dermatitis [version 1; peer review: awaiting peer review]
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+Chemical genetic approaches to dissect microbiota mechanisms in health and disease
- Background Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by pruritus and skin barrier dysfunction. This study aims to evaluate the therapeutic potential of Pelargonium graveolens (Geraniaceae) in managing AD symptoms through its essential oil. Methods The chemical composition of Pelargonium graveolens flower essential oil (PFEO) was analyzed using gas chromatography-mass spectrometry (GC-MS). Its antimicrobial, antioxidant, and anti-inflammatory properties were assessed, along with the inhibitory effects of PFEO on key enzymes involved in skin repair: tyrosinase, elastase, and collagenase. An in vivo evaluation of a gel formulation containing PFEO was also conducted to assess its anti-inflammatory and analgesic efficacy. Results GC-MS analysis identified major compounds in PFEO, including Geraniol (22.83%), beta-citronellol (19.51%), naphthalenemethanol (15.36%), and Geranyl tiglate (9.38%), with minor constituents such as linalool (3.81%) and neryl formate (1.31%). PFEO exhibited bacteriostatic activity against various bacterial and fungal strains, including Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), Bacillus anthracis, Streptococcus pyogenes, Staphylococcus epidermidis, Candida albicans, and Malassezia spp. The essential oil also demonstrated significant antioxidant properties and inhibited key enzymes linked to skin alterations in AD. Conclusions PFEO shows promising therapeutic potential for managing symptoms of atopic dermatitis due to its antimicrobial, antioxidant, and anti-inflammatory properties, as well as its analgesic effects. The findings support further exploration of PFEO as a natural alternative in the treatment of AD. + Science, Volume 386, Issue 6723, November 2024.-
in F1000Research on 2024-11-14 17:57:35 UTC. +
in Science on 2024-11-15 08:00:00 UTC.
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-Clust&See3.0 : clustering, module exploration and annotation [version 2; peer review: 1 approved, 2 approved with reservations]
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+Gibbs states and Brownian models for coexisting haze and cloud droplets
- Background Cytoscape is an open-source software to visualize and analyze networks. However, large networks, such as protein interaction networks, are still difficult to analyze as a whole. Methods Here, we propose Clust&See3.0, a novel version of a Cytoscape app that has been developed to identify, visualize and manipulate network clusters and modules. It is now enriched with functionalities allowing custom annotations of nodes and computation of their statistical enrichments. Results As the wealth of multi-omics data is growing, such functionalities are highly valuable for a better understanding of biological module composition, as illustrated by the presented use case. Conclusions In summary, the originality of Clust&See3.0 lies in providing users with a complete tool for network clusters analyses: from cluster identification, visualization, node and cluster annotations to annotation statistical analyses. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 17:43:17 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Evaluation of the fintech era on the performance of Moroccan banks: analysis through non-performing loans [version 1; peer review: awaiting peer review]
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+Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing
- Background This study aims to contribute to a better understanding of the impact of the financial technologies (fintech) era on the performance in the banking sector, measured through non-performing loans (NPL) and their coverage by provisions for NPL. It is a question of knowing whether banking investment in fintech makes it possible to better evaluate the granting of credits, and therefore makes it possible to reduce overdue credits. Methods To this end, the method used consists of using a regression analysis and a Pearson correlation applied to the financial data of Moroccan banks observed during two distinct periods, namely 2007-2014, considered pre-fintech, and the period 2015-2022, considered as the fintech period. Results With the emergence of the fintech era, the Moroccan banking situation improved slightly compared to the pre-fintech period: bad debts did not increase despite the significant increase in net banking income and the size of banking assets during the fintech era. Conclusions The implementation of fintech has improved customer relationship management, credit risk analysis and loan monitoring services, which ultimately reduces non-performing loans and improves the coverage of non-performing loans by provisions. The main implication of the results allows us to deduce that the implementation of fintech makes it possible to have a positive impact on overdue credits, and they are also likely to serve as a lever for the inclusion of those excluded from banking services. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 17:40:03 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Transcranial Direct Current Stimulation over the Posterior Parietal Cortex Increases Nontarget Retrieval during Visual Working Memory
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+Generative adversarial networks accurately reconstruct pan-cancer histology from pathologic, genomic, and radiographic latent features
-Visual working memory (VWM) requires precise feature binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM; this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 (N = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of nontarget responses (a.k.a. failure of feature binding, pNT). In Experiment 2 (N = 29), combining metacognition estimation, we further investigated whether the effects of PPC stimulation were attributed to misbinding (i.e., participants self-reported "remembered" in nontarget responses) or informed guessing trials (participants self-reported "forgotten" in nontarget responses). We replicated the main findings in Experiment 1 and observed greater tDCS effects of PPC on RT in informed guessing trials while there are comparable effects on pNT in these two types of trials. In Experiment 3 (N = 28), we then examined whether the tDCS effects over PPC specifically influenced the memory retrieval process by using a change detection task. We found that PPC stimulation did not influence the recognition RT or accuracy. Together, this study provided direct causal evidence supporting the specific involvement of PPC in feature binding during VWM retrieval, from both aspects of speed and response preference, expanding our understanding of the neural basis of feature binding in VWM.
+ Science Advances, Volume 10, Issue 46, November 2024.-
in eNeuro on 2024-11-14 17:30:23 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Prenatal Exposure to MAM Impairs mPFC and Hippocampal Inhibitory Function in Mice during Adolescence and Adulthood
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+Decoding the interplay between m6A modification and stress granule stability by live-cell imaging
-Neurodevelopmental abnormalities are considered to be one of the important causes of schizophrenia. The offspring of methylazoxymethanol acetate (MAM)–exposed mice are recognized for the dysregulation of neurodevelopment and are well-characterized with schizophrenia-like phenotypes. However, the inhibition-related properties of the medial prefrontal cortex (mPFC) and hippocampus throughout adolescence and adulthood have not been systematically elucidated. In this study, both 10 and 15 mg/kg MAM-exposed mice exhibited schizophrenia-related phenotypes in both adolescence and adulthood, including spontaneous locomotion hyperactivity and deficits in prepulse inhibition. We observed that there was an obvious parvalbumin (PV) loss in the mPFC and hippocampus of MAM-exposed mice, extending from adolescence to adulthood. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons at mPFC and hippocampus was significantly dampened in the 10 and 15 mg/kg MAM-exposed mice. Furthermore, the firing rate of putative pyramidal neurons in mPFC and hippocampus was increased, while that of putative inhibitory neurons was decreased during both adolescence and adulthood. In conclusion, PV loss in mPFC and hippocampus of MAM-exposed mice may contribute to the impaired inhibitory function leading to the attenuation of inhibition in the brain both in vitro and in vivo.
+ Science Advances, Volume 10, Issue 46, November 2024.-
in eNeuro on 2024-11-14 17:30:23 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Erratum: White et al., "Learning to Choose: Behavioral Dynamics Underlying the Initial Acquisition of Decision-Making"
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+Landscape burning facilitated Aboriginal migration into Lutruwita/Tasmania 41,600 years ago
- + Science Advances, Volume 10, Issue 46, November 2024.-
in eNeuro on 2024-11-14 17:30:23 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Erratum: Lakhani et al., "Homeostatic Regulation of Spike Rate within Bursts in Two Distinct Preparations"
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+Mechanotransduction governs CD40 function and underlies X-linked hyper-IgM syndrome
- + Science Advances, Volume 10, Issue 46, November 2024.-
in eNeuro on 2024-11-14 17:30:23 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Health care workers hospitalized for COVID-19 in Liberia: who were they, and what were their outcomes? [version 2; peer review: 1 approved, 1 approved with reservations]
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+Gas-phase preparation of silylacetylene (SiH3CCH) through a counterintuitive ethynyl radical (C2H) insertion
- Background Sustaining a ‘fit-for-purpose’ health workforce requires a better understanding of the health care worker cadres that are affected during pandemics and their outcomes. In hospitalized health care workers with confirmed COVID-19 between March 2020 and May 2023 in Liberia, we determined the hospitalization and case fatality rates, type of health care worker cadres affected, their demographic and clinical characteristics and hospital exit outcomes. Methods This was a cohort study using routine data extracted from hospitalization forms for health care workers in 24 designated COVID-19 treatment facilities. Results Of the 424 health care workers with COVID-19, hospitalization rates progressively declined between 2020 and 2023, (P<0.001) with the highest rates in 2020 (24/1,000 health care workers) and 2021 (14/1,000 health care workers). Case fatality was 2% in both 2020 and 2021 with no deaths thereafter. Among those hospitalized, the highest proportions were nursing cadres with 191(45%), physicians with 63 (15%) and laboratory technicians with 42 (10%). The most frequent reported site for COVID-19 infection was the health facility (326, 89%). COVID-19 vaccination coverage in health care workers was 20%. The majority (91%) of hospitalizations were for mild symptomatic infections. Even in referral centres (n-52), 18 (35%) were for mild infections. Of the 424 who were hospitalized, 412 (97%) recovered, 9 (2%) died and 3 (1%) either left against medical advice or absconded. Of the nine deaths, none were vaccinated, seven had moderate-to-severe disease but were not referred to specialized COVID-19 treatment centers. Conclusions The hospitalized health care workers for COVID-19 were predominantly clinical and laboratory personnel who were mostly unvaccinated, and health facilities were hot-spots for contracting infections. The triage and referral system was weak with unnecessary hospitalization of mild infections. This study provides useful insights for outbreak preparedness including priority vaccination and improving health care worker safety in Liberia. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 16:59:59 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-The quality of life in Thai senior table tennis players [version 3; peer review: 1 approved with reservations, 1 not approved]
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+B cell adapter for PI 3-kinase (BCAP) coordinates antigen internalization and trafficking through the B cell receptor
- Background Table tennis presented a unique and accessible sport for people of all ages, particularly seniors compared to other sports. Methods This study utilized a quantitative with 136 Table tennis players those who registered for attending in the Thailand Master Table tennis Championships 2024 which hosted in January 2024 at Chiangmai. The questionnaire based on the measurement quality of life, WHOQOL Thai version, and analyzed using Descriptive statistics, Pearson Correlation. Results Pearson correlation coefficients between the scores of the quality of life in four dimensions and the overall score revealed significant correlations (p < 0.01) with all dimensions, including physical health, psychological health, social relationships, and environmental health. Conclusions Playing Table tennis for senior in the tournament level helped to improve the quality of life in all domains. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 15:21:20 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-The role of therapeutic MicroRNA in arteriogenesis process in limb ischemia: A systematic review [version 2; peer review: 1 approved with reservations]
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+Projected increase in the frequency of extremely active Atlantic hurricane seasons
- Background Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral artery disease (PAD) and has poor clinical outcomes. Recently, stimulating arteriogenesis has been proposed to improve clinical outcomes. Several studies have shown that miRNAs have beneficial effects on limb ischemia related to arteriogenesis. This study aimed to review the roles of therapeutic miRNAs in the arteriogenesis of limb ischemia. Methods A systematic search was conducted through July 2021 using the PubMed, Scopus, and ScienceDirect databases. Two authors independently assessed studies that investigated the role of miRNAs in the arteriogenesis of limb ischemia, both in vivo and in clinical studies. Results All selected studies were in vivo studies, with a total of 36 articles and 28 types of miRNAs. miRNAs potentially regulate arteriogenesis by targeting different targets. The following miRNAs were upregulated to enhance arteriogenesis: miRNA-126-3p, -93, -675, -143-3p, -130a, -210, -146b, -21, -let-7g, -132/212, -150, and 155. Meanwhile, microRNAs needed to be downregulated, namely: miRNA-939-5p, -503, -199a-5p, -146a, -92a, -14q32 microRNA gene cluster, -15a/16, -100, -133a, -139-5p, -223, -352, -615-5p, -15b/5p, -124-3p, and 29a. MiRNA-126 was the most studied miRNA, and SPRED1 was the most common target of microRNA. However, the included studies showed high heterogeneity in terms of inducing hindlimb ischemia, the timing of administration, and the method used for evaluating arteriogenesis. Moreover, most studies presented unclear or high-risk bias. Conclusion MicroRNA application in a preclinical model of hindlimb ischemia has beneficial effects on arteriogenesis. This result indicates that miRNAs might be potentially beneficial in patients with CLTI. Registration The review protocol was registered with PROSPERO under registration number CRD42024484988. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 15:17:25 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Choroidal thickness measurement in central serous chorioretinopathy using swept source optical coherence tomography: an observational study [version 2; peer review: 2 approved with reservations]
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+The HDAC6 inhibitor AVS100 (SS208) induces a pro-inflammatory tumor microenvironment and potentiates immunotherapy
- Background Central serous chorioretinopathy (CSCR) is a common retinal condition with an increased risk of recurrence. Traditional approaches have made choroidal visualization challenging, but recent advances in optical coherence tomography (OCT) innovation have permitted the collection of more accurate choroidal visualizations. This study aimed to measure choroidal thickness in eyes with active CSCR as well as in the unaffected opposite eyes of these same individuals. Methods This research was conducted at the ophthalmology division in Ghazi Al-Hariri Hospital from the 1st of October 2019 until the 31st of March 2020. A total of 49 people, corresponding to 65 eyes, were included in the study. Among these participants, 16 individuals presented with central serous chorioretinopathy (CSCR), affecting a total of 32 eyes. The CSCR individuals were further split into two groups: “Group A” consisted of 20 eyes with active CSCR, and “Group B” encompassed the remaining 12 unaffected opposite eyes. Additionally, the right eyes of 33 individuals who were age and gender-matched served as controls assigned as “Group C”. Results The choroid exhibited a substantial rise in thickness across each of the nine sectors in group A as compared to group C. Similarly, group B showed a significant increase in choroidal thickness in relation to group C. The mean subfoveal choroidal thickness (SFCT) was measured as follows: 474.55μm, 437.5μm, and 292.03μm among groups A, B, and C, correspondingly. These differences were identified as clinically significant for both A vs. C and B vs. C. Conclusions This study’s findings indicate a thickening of the choroid in both eyes exhibiting active CSCR, as well as in the unaffected opposite eyes of those with the disease. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 15:15:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Knowledge and attitudes of health care professionals regarding birth preparedness of women in labour at selected Hospitals in KwaZulu-Natal, South Africa: A qualitative study [version 2; peer review: awaiting peer review]
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+Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria
- Introduction Low and middle-income countries account for the largest proportion of women’s deaths as a result of pregnancy or childbirth-related complications. The sub-Saharan region is the most affected with approximately 70% (202 000) of maternal deaths between 2000 and 2020. These deaths could have been prevented if expectant mothers were prepared for childbirth. Birth preparedness is perceived as a better strategy that helps attain a substantial reduction in maternal mortality. This is achieved by attending early antenatal classes, receiving skilled care during childbirth, and care and support right after birth. The latest survey on antenatal class attendance conducted in South Africa provides an estimated 30.8% of expectant mothers in public healthcare facilities. Methods This study employed a qualitative approach to collect data, as a result, one focus group discussion with five (N=5) participants and two others with six (N=6) participants each (n=6X2=12) and twenty individual interviews were conducted. The study sought to explore and describe the knowledge and attitudes of healthcare professionals regarding the birth preparedness of women in labour at selected hospitals in Durban KwaZulu-Natal. Results Expectant mothers were unprepared for both labour and postnatal care. The unprepared expectant mothers were uncooperative and made the task of midwives difficult to the extent of endangering the life of their expected newborn babies and their own. Factors such as finance, heterogeneity, staff shortage, language barrier, lack of family support, lack of interest, cultural beliefs, and confusion caused by various sources of information were responsible for birth unpreparedness. Conclusion The synergy between expectant mothers and midwives appears to be an important factor in achieving better birth preparedness. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 15:13:17 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Digital and Financial Literacy for Uplifting Women and Achieving Sustainable Development Goals [version 1; peer review: awaiting peer review]
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+Archaeal type six secretion system mediates contact-dependent antagonism
- Digital and financial literacy are changing the landscape of the globe in terms of its approach to development. These two literacies also help to achieve women’s empowerment and, consequently, the sustainable development goals (SDGs) more quickly. This systematic literature review looks at the two literacies and their effects, focusing on women’s participation and showing how digital literacy not only increases women’s access to knowledge and connectivity but is also a door to women’s entrepreneurship and financial independence. Likewise, financial literacy, when coupled with digital skills, can be a breakthrough to the traditional socioeconomic barrier – poverty – by assisting women in making informed economic decisions, increasing their financial independence and resilience in the face of a global crisis. Empirical realities that still hinder women’s education, such as cultural norms, infrastructural deficiencies and educational gaps, still exist. However, the paper points out that to have a more equal world based on the SDGs, the double literacy strategy for women’s empowerment should not be negotiable. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 15:11:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Teaching Self-efficacy and Teaching Methods in the Aquatic Environment [version 1; peer review: awaiting peer review]
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+Mitochondrial pyruvate transport regulates presynaptic metabolism and neurotransmission
- Background Studies have shown that perceived self-efficacy can influence teachers’ emotional state, thoughts and behaviours, and students’ learning. It’s also an important referential of professional satisfaction. In turn, teaching methodologies influence motor learning, as well as psychological, cognitive and social learning, with different impacts on human development and learning retention, levels of intrinsic motivation and continuity of practice in order to support a healthy lifestyle. Research on aquatic educators and teaching methodologies is scarce and at the same time necessary according to the view that aquatic literacy is an integral part of physical literacy and the only possibility of being more able to interact with this environment. Methods In this study we used an online questionnaire, aimed at aquatic professionals, which was answered voluntarily and anonymously to measure the prevalence of the use of different teaching methodologies, the comprehensive aquatic method and the perception of teacher self-efficacy. It has been deposited and can be consulted at https://doi.org/10.6084/m9.figshare.27316242.v1. Results All methods can generate a feeling of self-efficacy in teachers despite having different results, with the methodologies that involve students more actively (cognitivist and constructivist) being those that generate a greater feeling of self-efficacy in teachers. MAC is a method that is more closely related to methodologies focused on active student participation and, consequently, it is a method that generates a high perception of self-efficacy in teachers. Conclusions Levels of self-efficacy influence professional satisfaction, teacher physical, mental and emotional health, as well as student learning. Is recommended that aquatic professionals give prevalence to the cognitivist and constructivist teaching methodologies being MAC a privileged methodological approach for promoting active lifestyle habits throughout life. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 15:09:27 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-GeM-LR: Discovering predictive biomarkers for small datasets in vaccine studies
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+Dynamical control of nanoscale electron density in atomically thin n-type semiconductors via nano-electric pulse generator
-by Lin Lin, Rachel L. Spreng, Kelly E. Seaton, S. Moses Dennison, Lindsay C. Dahora, Daniel J. Schuster, Sheetal Sawant, Peter B. Gilbert, Youyi Fong, Neville Kisalu, Andrew J. Pollard, Georgia D. Tomaras, Jia Li
- -Despite significant progress in vaccine research, the level of protection provided by vaccination can vary significantly across individuals. As a result, understanding immunologic variation across individuals in response to vaccination is important for developing next-generation efficacious vaccines. Accurate outcome prediction and identification of predictive biomarkers would represent a significant step towards this goal. Moreover, in early phase vaccine clinical trials, small datasets are prevalent, raising the need and challenge of building a robust and explainable prediction model that can reveal heterogeneity in small datasets. We propose a new model named Generative Mixture of Logistic Regression (GeM-LR), which combines characteristics of both a generative and a discriminative model. In addition, we propose a set of model selection strategies to enhance the robustness and interpretability of the model. GeM-LR extends a linear classifier to a non-linear classifier without losing interpretability and empowers the notion of predictive clustering for characterizing data heterogeneity in connection with the outcome variable. We demonstrate the strengths and utility of GeM-LR by applying it to data from several studies. GeM-LR achieves better prediction results than other popular methods while providing interpretations at different levels. + Science Advances, Volume 10, Issue 46, November 2024.-
in PLoS Computational Biology on 2024-11-14 14:00:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Human-like dissociations between confidence and accuracy in convolutional neural networks
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+Gene-environment interactions in the influence of maternal education on adolescent neurodevelopment using ABCD study
-by Medha Shekhar, Dobromir Rahnev
- -Prior research has shown that manipulating stimulus energy by changing both stimulus contrast and variability results in confidence-accuracy dissociations in humans. Specifically, even when performance is matched, higher stimulus energy leads to higher confidence. The most common explanation for this effect, derived from cognitive modeling, is the positive evidence heuristic where confidence neglects evidence that disconfirms the choice. However, an alternative explanation is the signal-and-variance-increase hypothesis, according to which these dissociations arise from changes in the separation and variance of perceptual representations. Because artificial neural networks lack built-in confidence heuristics, they can serve as a test for the necessity of confidence heuristics in explaining confidence-accuracy dissociations. Therefore, we tested whether confidence-accuracy dissociations induced by stimulus energy manipulations emerge naturally in convolutional neural networks (CNNs). We found that, across three different energy manipulations, CNNs produced confidence-accuracy dissociations similar to those found in humans. This effect was present for a range of CNN architectures from shallow 4-layer networks to very deep ones, such as VGG-19 and ResNet-50 pretrained on ImageNet. Further, we traced back the reason for the confidence-accuracy dissociations in all CNNs to the same signal-and-variance increase that has been proposed for humans: higher stimulus energy increased the separation and variance of evidence distributions in the CNNs’ output layer leading to higher confidence even for matched accuracy. These findings cast doubt on the necessity of the positive evidence heuristic to explain human confidence and establish CNNs as promising models for testing cognitive theories of human behavior. + Science Advances, Volume 10, Issue 46, November 2024.-
in PLoS Computational Biology on 2024-11-14 14:00:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-AI-powered simulation-based inference of a genuinely spatial-stochastic gene regulation model of early mouse embryogenesis
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+H2S-Prdx4 axis mitigates Golgi stress to bolster tumor-reactive T cell immunotherapeutic response
-by Michael Alexander Ramirez Sierra, Thomas R. Sokolowski
- -Understanding how multicellular organisms reliably orchestrate cell-fate decisions is a central challenge in developmental biology, particularly in early mammalian development, where tissue-level differentiation arises from seemingly cell-autonomous mechanisms. In this study, we present a multi-scale, spatial-stochastic simulation framework for mouse embryogenesis, focusing on inner cell mass (ICM) differentiation into epiblast (EPI) and primitive endoderm (PRE) at the blastocyst stage. Our framework models key regulatory and tissue-scale interactions in a biophysically realistic fashion, capturing the inherent stochasticity of intracellular gene expression and intercellular signaling, while efficiently simulating these processes by advancing event-driven simulation techniques. Leveraging the power of Simulation-Based Inference (SBI) through the AI-driven Sequential Neural Posterior Estimation (SNPE) algorithm, we conduct a large-scale Bayesian inferential analysis to identify parameter sets that faithfully reproduce experimentally observed features of ICM specification. Our results reveal mechanistic insights into how the combined action of autocrine and paracrine FGF4 signaling coordinates stochastic gene expression at the cellular scale to achieve robust and reproducible ICM patterning at the tissue scale. We further demonstrate that the ICM exhibits a specific time window of sensitivity to exogenous FGF4, enabling lineage proportions to be adjusted based on timing and dosage, thereby extending current experimental findings and providing quantitative predictions for both mutant and wild-type ICM systems. Notably, FGF4 signaling not only ensures correct EPI-PRE lineage proportions but also enhances ICM resilience to perturbations, reducing fate-proportioning errors by 10-20% compared to a purely cell-autonomous system. Additionally, we uncover a surprising role for variability in intracellular initial conditions, showing that high gene-expression heterogeneity can improve both the accuracy and precision of cell-fate proportioning, which remains robust when fewer than 25% of the ICM population experiences perturbed initial conditions. Our work offers a comprehensive, spatial-stochastic description of the biochemical processes driving ICM differentiation and identifies the necessary conditions for its robust unfolding. It also provides a framework for future exploration of similar spatial-stochastic systems in developmental biology. + Science Advances, Volume 10, Issue 46, November 2024.-
in PLoS Computational Biology on 2024-11-14 14:00:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Decrease in decision noise from adolescence into adulthood mediates an increase in more sophisticated choice behaviors and performance gain
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+Robust generation of intrinsic C points with magneto-optical bound states in the continuum
-by Vanessa Scholz, Maria Waltmann, Nadine Herzog, Annette Horstmann, Lorenz Deserno
- -Learning and decision-making undergo substantial developmental changes, with adolescence being a particular vulnerable window of opportunity. In adolescents, developmental changes in specific choice behaviors have been observed (e.g., goal-directed behavior, motivational influences over choice). Elevated levels of decision noise, i.e., choosing suboptimal options, were reported consistently in adolescents. However, it remains unknown whether these observations, the development of specific and more sophisticated choice processes and higher decision noise, are independent or related. It is conceivable, but has not yet been investigated, that the development of specific choice processes might be impacted by age-dependent changes in decision noise. To answer this, we examined 93 participants (12 to 42 years) who completed 3 reinforcement learning (RL) tasks: a motivational Go/NoGo task assessing motivational influences over choices, a reversal learning task capturing adaptive decision-making in response to environmental changes, and a sequential choice task measuring goal-directed behavior. This allowed testing of (1) cross-task generalization of computational parameters focusing on decision noise; and (2) assessment of mediation effects of noise on specific choice behaviors. Firstly, we found only noise levels to be strongly correlated across RL tasks. Second, and critically, noise levels mediated age-dependent increases in more sophisticated choice behaviors and performance gain. Our findings provide novel insights into the computational processes underlying developmental changes in decision-making: namely a vital role of seemingly unspecific changes in noise in the specific development of more complex choice components. Studying the neurocomputational mechanisms of how varying levels of noise impact distinct aspects of learning and decision processes may also be key to better understand the developmental onset of psychiatric diseases. + Science Advances, Volume 10, Issue 46, November 2024.-
in PLoS Biology on 2024-11-14 14:00:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Immigrant birds learn from socially observed differences in payoffs when their environment changes
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+Same rule, different genes: Blimp1 is a pair-rule gene in the milkweed bug Oncopeltus fasciatus
-by Michael Chimento, Gustavo Alarcón-Nieto, Lucy M. Aplin
- -Longstanding theory predicts that strategic flexibility in when and how to use social information can help individuals make adaptive decisions, especially when environments are temporally or spatially variable. A short-term increase in reliance on social information under these conditions has been experimentally shown in primates, including humans, but whether this occurs in other taxa is unknown. We asked whether migration between spatially variable environments affected social information use with a large-scale cultural diffusion experiment with wild great tits (Parus major) in captivity, a small passerine bird that can socially learn novel behaviors. We simulated an immigration event where knowledgeable birds were exchanged between groups with opposing preferences for a socially learned foraging puzzle, living in similar or different environments. We found evidence that both immigrants and residents were influenced by social information and attended to the rewards that others received. Our analysis supported the use of a payoff-biased social learning by immigrants when both resources and habitat features were spatially variable. In contrast, immigrants relied more-so on individual learning when payoffs or the environment were unchanged. In summary, our results suggest that great tits assess the payoffs others receive and are more influenced by socially observed differences in payoffs when environmental cues differ in their new environment. Our results provide experimental support for the hypothesis that spatial variability is a strong driver for the evolution of social learning strategies. + Science Advances, Volume 10, Issue 46, November 2024.-
in PLoS Biology on 2024-11-14 14:00:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-The Demographic Profile of Colorectal Cancer Patients in Indonesia: Insights from a Single Center Experience and Exploration of Immune Response and Survival Outcomes [version 1; peer review: awaiting peer review]
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+CO2 capture, geological storage, and mineralization using biobased biodegradable chelating agents and seawater
- Background Understanding the demographics, tumor characteristics, genetic mutations, and immune scores in colorectal cancer (CRC) patients may aid in tailoring treatment and predicting survival. Methods This retrospective cohort study assessed clinical parameters, immune scores, and their relationship with survival in patients with CRC. Results The study included 74 patients, mean age 53.7 years, mostly male (53.3%) and aged 41-70 (77.3%). Common comorbidities included cardiovascular diseases (29.3%) and hypertension (21.3%). Adenocarcinoma (74%) primarily affects the colon (73%). KRAS mutations and Microsatellite instability-High (MSI-H)/deficient mismatch repair (dMMR) were found in 1.3% and 16% of patients, respectively. Stage IV (77.3%) and liver metastases (52.7%) were prevalent. Immune score was influenced by cancer stage (p = 0.04) and metastasis (p=0.05). The immune score was not associated with survival (p = 0.181). Patients with comorbidities had lower one- (p = 0.027) and two-year survival rates (p = 0.037) survival rates. Cardiovascular comorbidities negatively impacted one-year survival (p = 0.047) and two-year survival (p = 0.037). The mean survival time was shorter for males (2.047±0.288 vs. 2.781±0.195 years, p = 0.041), patients with comorbidities (1.772±0.371 vs. 2.702±0.188 years, p = 0.017), and cardiovascular comorbidities (1.558±0.316 vs. 2.685±0.207 years, p = 0.038). Comorbidities (unadjusted hazard ratio [HR] 2.948, p = 0.023) and cardiovascular comorbidities (unadjusted HR 2.695, p = 0.046) were initially associated with survival but lost significance after adjusting for confounding variables. Conclusions This study provides insights into CRC patient demographics and their interplay with the immune score and survival. + Science Advances, Volume 10, Issue 46, November 2024.-
in F1000Research on 2024-11-14 09:48:09 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-The metaphors of artificial intelligence
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+Mechano-gradients drive morphogen-noise correction to ensure robust patterning
- Science, Volume 386, Issue 6723, November 2024.+ Science Advances, Volume 10, Issue 46, November 2024.
-
in Science on 2024-11-14 08:00:00 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-A voyage to victory
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+Tumor-specific delivery of clickable inhibitor for PD-L1 degradation and mitigating resistance of radioimmunotherapy
- Science, Volume 386, Issue 6723, Page 734-734, November 2024.+ Science Advances, Volume 10, Issue 46, November 2024.
-
in Science on 2024-11-14 06:59:04 UTC. +
in Science Advances on 2024-11-15 08:00:00 UTC.
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-Tomorrow’s trees
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+Issue Information
- Science, Volume 386, Issue 6723, Page 733-733, November 2024.+ -
in Science on 2024-11-14 06:59:04 UTC. +
in Journal of Comparative Neurology on 2024-11-15 07:42:57 UTC.
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-Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy
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+Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID‐HS
- Science, Volume 386, Issue 6723, Page 768-776, November 2024.+
Objective
+Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE.
+Methods
+We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls.
+Results
+HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions.
+Interpretation
+Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports. ANN NEUROL 2024
-in Science on 2024-11-14 06:59:04 UTC. +
in Annals of Neurology on 2024-11-15 06:14:52 UTC.
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-High-temperature carbon dioxide capture in a porous material with terminal zinc hydride sites
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+Q&A with Ilaria Elia
- Science, Volume 386, Issue 6723, Page 814-819, November 2024.+ Ilaria Elia, guest editor of the cancer metabolism special issue, spoke with Cell Reports about her scientific interests and her lab’s focus on investigating the metabolic interactions between cancer cells and immune cells within the tumor microenvironment. Ilaria also discussed recent developments and future directions in the field. -
in Science on 2024-11-14 06:59:04 UTC. +
in Cell Reports: Current Issue on 2024-11-15 00:00:00 UTC.
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-Synchronous recognition of amines in oxidative carbonylation toward unsymmetrical ureas
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+Integration of overlapping sequences emerges with consolidation through medial prefrontal cortex neural ensembles and hippocampal–cortical connectivity
- Science, Volume 386, Issue 6723, Page 776-782, November 2024.+ Systems consolidation theories propose two mechanisms that enable the behavioral integration of related memories: coordinated reactivation between hippocampus and cortex, and the emergence of cortical traces that reflect overlap across memories. However, there is limited empirical evidence that links these mechanisms to the emergence of behavioral integration over time. In two experiments, participants implicitly encoded sequences of objects with overlapping structure. Assessment of behavioral integration showed that response times during a recognition task reflected behavioral priming between objects that never occurred together in time but belonged to overlapping sequences. This priming was consolidation-dependent and only emerged for sequences learned 24 hr prior to the test. Critically, behavioral integration was related to changes in neural pattern similarity in the medial prefrontal cortex and increases in post-learning rest connectivity between the posterior hippocampus and lateral occipital cortex. These findings suggest that memories with a shared predictive structure become behaviorally integrated through a consolidation-related restructuring of the learned sequences, providing insight into the relationship between different consolidation mechanisms that support behavioral integration. -
in Science on 2024-11-14 06:59:04 UTC. +
in eLife on 2024-11-15 00:00:00 UTC.
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-Glaciation of liquid clouds, snowfall, and reduced cloud cover at industrial aerosol hot spots
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+Targeting resident astrocytes attenuates neuropathic pain after spinal cord injury
- Science, Volume 386, Issue 6723, Page 756-762, November 2024.+ Astrocytes derive from different lineages and play a critical role in neuropathic pain after spinal cord injury (SCI). Whether selectively eliminating these main origins of astrocytes in lumbar enlargement could attenuate SCI-induced neuropathic pain remains unclear. Through transgenic mice injected with an adeno-associated virus vector and diphtheria toxin, astrocytes in lumbar enlargement were lineage traced, targeted, and selectively eliminated. Pain-related behaviors were measured with an electronic von Frey apparatus and a cold/hot plate after SCI. RNA sequencing, bioinformatics analysis, molecular experiment, and immunohistochemistry were used to explore the potential mechanisms after astrocyte elimination. Lineage tracing revealed that the resident astrocytes but not ependymal cells were the main origins of astrocytes-induced neuropathic pain. SCI-induced mice to obtain significant pain symptoms and astrocyte activation in lumbar enlargement. Selective resident astrocyte elimination in lumbar enlargement could attenuate neuropathic pain and activate microglia. Interestingly, the type I interferons (IFNs) signal was significantly activated after astrocytes elimination, and the most activated Gene Ontology terms and pathways were associated with the type I IFNs signal which was mainly activated in microglia and further verified in vitro and in vivo. Furthermore, different concentrations of interferon and Stimulator of interferon genes (STING) agonist could activate the type I IFNs signal in microglia. These results elucidate that selectively eliminating resident astrocytes attenuated neuropathic pain associated with type I IFNs signal activation in microglia. Targeting type I IFNs signals is proven to be an effective strategy for neuropathic pain treatment after SCI. -
in Science on 2024-11-14 06:59:04 UTC. +
in eLife on 2024-11-15 00:00:00 UTC.
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-Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states
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+Luminal epithelial cells integrate variable responses to aging into stereotypical changes that underlie breast cancer susceptibility
- Science, Volume 386, Issue 6723, Page 802-810, November 2024.+ Effects from aging in single cells are heterogenous, whereas at the organ- and tissue-levels aging phenotypes tend to appear as stereotypical changes. The mammary epithelium is a bilayer of two major phenotypically and functionally distinct cell lineages: luminal epithelial and myoepithelial cells. Mammary luminal epithelia exhibit substantial stereotypical changes with age that merit attention because these cells are the putative cells-of-origin for breast cancers. We hypothesize that effects from aging that impinge upon maintenance of lineage fidelity increase susceptibility to cancer initiation. We generated and analyzed transcriptomes from primary luminal epithelial and myoepithelial cells from younger <30 (y)ears old and older >55y women. In addition to age-dependent directional changes in gene expression, we observed increased transcriptional variance with age that contributed to genome-wide loss of lineage fidelity. Age-dependent variant responses were common to both lineages, whereas directional changes were almost exclusively detected in luminal epithelia and involved altered regulation of chromatin and genome organizers such as SATB1. Epithelial expression of gap junction protein GJB6 increased with age, and modulation of GJB6 expression in heterochronous co-cultures revealed that it provided a communication conduit from myoepithelial cells that drove directional change in luminal cells. Age-dependent luminal transcriptomes comprised a prominent signal that could be detected in bulk tissue during aging and transition into cancers. A machine learning classifier based on luminal-specific aging distinguished normal from cancer tissue and was highly predictive of breast cancer subtype. We speculate that luminal epithelia are the ultimate site of integration of the variant responses to aging in their surrounding tissue, and that their emergent phenotype both endows cells with the ability to become cancer-cells-of-origin and represents a biosensor that presages cancer susceptibility. -
in Science on 2024-11-14 06:59:04 UTC. +
in eLife on 2024-11-15 00:00:00 UTC.
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-Diverse and larger tree islands promote native tree diversity in oil palm landscapes
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+A hierarchical multiscale model of forward and backward alpha-band traveling waves in the visual system
- Science, Volume 386, Issue 6723, Page 795-802, November 2024.+ Recent studies have shown that low-frequency oscillations in the cortex are often organized as traveling waves. The dynamical properties of these waves, that span different scales, have been linked to both sensory processing and cognitive functions. In EEG recordings, alpha-band (~10Hz) traveling waves propagate predominantly in both directions of the occipital-frontal axis, with forward waves being most prominent during visual processing, while backward waves dominate at rest and during sensory suppression. While a previous study has proposed a functional model to explain their generation and propagation, a multi-scale, biologically plausible implementation is still lacking. Here, we present a multi-scale network model with mean-field dynamics that, building on known interlaminar and cortico-cortical projections, reproduces the dynamics of alpha-band traveling waves observed in EEG recordings. We show that scalp-level forward and backward waves can arise from two distinct sub-networks that are connected in infragranular layers at each area. At rest, the network generates spontaneous backward waves and switches to a forward state upon bottom-up sensory stimulation, reproducing the dynamics we observed in EEG recordings in healthy participants. We then expand our model to a cortico-thalamic network with a parallel feedforward pathway through the pulvinar. Our results show that this pathway biases the cortical dynamics to the forward state and that high pulvinar engagement leads to spontaneous forward waves without external input. This result is in line with previous studies suggesting a key role for the pulvinar in directing information flow in the cortex, and provide a computational basis to investigate the role of the pulvinar in cortical dynamics. In summary, our model provides a biologically plausible architecture for modeling the dynamics of macroscale traveling waves. Importantly, our study bridges the gap between distinct scales by connecting laminar mean-field activity to spatial patterns at the scalp level, providing a biologically grounded and comprehensive view of the generation and propagation of alpha-band traveling waves. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-Ribozyme-activated mRNA trans-ligation enables large gene delivery to treat muscular dystrophies
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+High-resolution imaging atlas reveals context-dependent role of pancreatic sympathetic innervation in diabetic mice
- Science, Volume 386, Issue 6723, Page 762-767, November 2024.+ Gaining a better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in islets of adult WT and diabetic mice. Our data shows that more than ~30% alpha/beta-cells are innervated by sympathetic nerves in both WT and diabetic mice. Also, sympathetic innervated alpha/beta-cells are reduced in DIO mice, whereas sympathetic innervated beta-cells are increased in db/db mice. Besides, in situ chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in WT and db/db mice, but decreases in DIO mice. In situ cPSD also enhances insulin sensitivity in diabetic mice without affecting WT mice. Overall, our findings advance our comprehension of diabetes by highlighting the distinctive impact of pancreatic sympathetic innervation on glucose regulation. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-A mechanical qubit
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+Attentional failures after sleep deprivation represent moments of cerebrospinal fluid flow
- Science, Volume 386, Issue 6723, Page 783-788, November 2024.+ Sleep deprivation rapidly disrupts cognitive function, and in the long term contributes to neurological disease. Why sleep deprivation has such profound effects on cognition is not well understood. Here, we use simultaneous fast fMRI-EEG to test how sleep deprivation modulates cognitive, neural, and fluid dynamics in the human brain. We demonstrate that after sleep deprivation, sleep-like pulsatile cerebrospinal fluid (CSF) flow events intrude into the awake state. CSF flow is coupled to attentional function, with high flow during attentional impairment. Furthermore, CSF flow is tightly orchestrated in a series of brain-body changes including broadband neuronal shifts, pupil constriction, and altered systemic physiology, pointing to a coupled system of fluid dynamics and neuromodulatory state. The timing of these dynamics is consistent with a vascular mechanism regulated by neuromodulatory state, in which CSF begins to flow outward when attention fails, and flow reverses when attention recovers. The attentional costs of sleep deprivation may thus reflect an irrepressible need for neuronal rest periods and widespread pulsatile fluid flow. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-Subambient daytime radiative cooling of vertical surfaces
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+Variable Cerebral Blood Flow Responsiveness to Acute Hypoxic Hypoxia
- Science, Volume 386, Issue 6723, Page 788-794, November 2024.+ Cerebrovascular reactivity (CVR) to changes in blood carbon dioxide and oxygen levels is a robust indicator of vascular health. Although CVR is typically assessed with hypercapnia, the interplay between carbon dioxide and oxygen, and their ultimate roles in dictating vascular tone, can vary with pathology. Methods to characterize vasoreactivity to oxygen changes, particularly hypoxia, would provide important complementary information to established hypercapnia techniques. However, existing methods to study hypoxic CVR, typically with arterial spin labeling (ASL) MRI, demonstrate high variability and paradoxical responses. To understand whether these responses are real or due to methodological confounds of ASL, we used phase-contrast MRI to quantify whole-brain blood flow in 21 participants during baseline, hypoxic, and hypercapnic respiratory states in three scan sessions. Hypoxic CVR reliability was poor-to-moderate (ICC=0.42 for CVR relative to PETO2 changes, ICC=0.56 relative to SpO2 changes) and was less reliable than hypercapnic CVR (ICC=0.67). Without the uncertainty from ASL-related confounds, we still observed paradoxical responses at each timepoint. Concurrent changes in blood carbon dioxide levels did not account for paradoxical responses. Hypoxic CVR and hypercapnic CVR shared approximately 40% of variance across the dataset, indicating that the two effects may indeed reflect distinct, complementary elements of vascular regulation. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-Truly listening
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+Single MAPT knock-in mouse models of frontotemporal dementia for sharing with the neurodegenerative research community
- Science, Volume 386, Issue 6723, Page 822-822, November 2024.+ We recently reported development of human MAPT knock-in mice that carry single or double pathogenic mutations of frontotemporal dementia. However, it takes more than 14 months for the line with the most aggressive phenotypes to exhibit tau pathology without forming high-order tau oligomers, along with concomitant abnormal behavior. We thus generated MAPT knock-in mice carrying triple mutations, among which the MAPTP301S;Int10+3;S320F line exhibited robust pathology starting earlier than 6 months. Tau accumulation took place mainly in the thalamus, hypothalamus, amygdala and entorhinal cortex, but less so in the hippocampus, leading to synaptic loss, atrophy and behavioral abnormalities. Crossbreeding MAPTP301S;Int10+3;S320F with App knock-in mice AppNL-G-F resulted in the manifestation of tau pathology in the hippocampus and cortex. These mutant mice will be valuable tools for understanding the mechanisms of frontotemporal dementia, Alzheimer's disease and other tauopathies. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-In Other Journals
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+Regional Brain Entropy, Brain Network and Structural-Functional Coupling in Human Brain
- Science, Volume 386, Issue 6723, Page 741-742, November 2024.+ Brain entropy (BEN) indicates the irregularity, unpredictability and complexity of brain activity. In healthy brains, resting-state fMRI-based regional BEN (rBEN) distribution has been shown to have potential relationships with functional brain networks. However, the relationship between rBEN and structural and functional networks, as well as how rBEN facilitates the coupling between structural and functional networks remains unclear. Additionally, network dimensionality reduction methods, such as the use of connectome gradients, have become popular in recent years for explaining the hierarchical architecture of brain function, and the sensorimotor-association (S-A) axis, as a major axis of hierarchical cortical organization, exerts a widespread influence on both brain structure and function. However, how this functional hierarchy affects the relationship between rBEN and brain networks remains unclear. In this study, we systematically examine the relationship between rBEN and both structural and functional networks, including BOLD-based functional networks and MEG-based functional networks. We also assess the impact of the BEN and network gradients, as well as the influence of the S-A axis, on the relationship between rBEN and brain networks. Our results reveal a negative correlation between BEN and the network efficiency of both structural and BOLD-based functional networks, as assessed by average connection strength, degree centrality, and local efficiency. Additionally, BEN shows a negative correlation with the coupling between structural and BOLD functional networks. In contrast, the relationship between BEN and MEG functional network efficiency varies from negative to positive across different frequency bands, with a shift from negative to positive correlation observed in the coupling between BEN and MEG-functional networks. Moreover, the coupling between BOLD and MEG functional networks is positively correlated with BEN. The relationship between BEN and network gradients is complex, and no consistent patterns were observed. Importantly, the relationship between BEN and brain networks is influenced by the S-A axis, and the connection between BEN and networks is further modulated by changes in cytoarchitectural organization. These results are consistent with the commonly observed relationship between elevated rBEN and impaired networks in psychiatric disorders. The negative correlation between BEN and the efficiency of both structural and BOLD functional networks, as well as their coupling, may suggest that lower rBEN is associated with higher information processing potential. Additionally, the positive correlation between BEN and high-frequency MEG functional networks, as well as the coupling between BOLD and MEG functional networks, may indicate that brain processes related to information acquisition and integration could increase rBEN. In summary, this complex relationship may reflect a dynamic process in which the brain continuously acquires external information for integration (increasing entropy) and internalizes it (decreasing entropy) as part of its information-processing mechanism in different timescales. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-The journey to a mechanical qubit
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+Filling-in of the Blindspot is Multisensory
- Science, Volume 386, Issue 6723, Page 728-729, November 2024.+ The blind spot is an area on the retina that lacks photoreceptors, thus no visual information is encoded. Yet, we can maintain the sense of a seamless visual field owing to perceptual filling-in. Traditionally viewed as a surface interpolation mechanism, filling-in has been studied predominantly under unimodal conditions. However, there are limits to this process; the brain cannot always reconstruct all surfaces. Multisensory processing may bolster the process of perceptual filling-in to occur even with complex and dynamic perceptual stimuli. In this study, we employed the Audiovisual (AV) Rabbit Illusion to investigate how auditory stimuli influence visual filling-in at the blind spot. Our findings confirmed that auditory cues can induce the perception of an illusory flash within the blind spot, indicating that the brain leverages multimodal information to enrich visual scenes. This suggests that perceptual filling-in is not merely unimodal surface interpolation but a cross-modally integrated spatial representation and therefore more similar to other visual field locations than previously hypothesized. Furthermore, for blind spot filling-in to occur, visual stimuli do not need to be spatially contiguous, they simply need to be crossmodally associated (or grouped), which supports a higher-level sensory processing in filling-in than previously understood. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-Learning the language of DNA
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+Regenerative potential of human enteric glia in a preclinical model of acute brain injury
- Science, Volume 386, Issue 6723, Page 729-730, November 2024.+ Acute brain injuries are characterized by extensive tissue damage, resulting in neuronal loss and severe functional deficits in patients. Self-regeneration is insufficient for the repair of damaged tissue. Therapies based on exogenous cells may offer a promising approach. In this study, we evaluated the feasibility of transplanting exogenous human enteric glia (hEG) in a preclinical model of brain injury. hEG were isolated, expanded and administered intranasally in brain-injured immunocompetent rats. hEG satisfied the safety criteria for cell therapy and were well tolerated. Additionally, hEG migrated to the injured area of the brain, where they enhanced endogenous angiogenesis and neurogenesis, contributing to tissue regeneration. Notably, hEG generated neurons that engrafted and integrated into the brain tissue. These neurons were enveloped by host oligodendrocytes and formed synaptic connections within the host tissue. Our findings provide evidence that hEG have regenerative potential and might be safely used for repair strategies in brain injury. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-Heat up to catch carbon
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+On Levodopa interactions with brain disease proteins at the nanoscale
- Science, Volume 386, Issue 6723, Page 727-728, November 2024.+ The cerebral accumulation of alpha-Synuclein (alpha-Syn) and amyloid beta-1-42 (Abeta-42) proteins are known to play a crucial role in the pathology of neurocognitive disorders such as Parkinson's disease (PD). Currently, Levodopa (L-dopa) is the dopamine replacement therapy for treating bradykinetic symptoms visible in PD patients. Here, we use atomic force microscopy to evidence at nanometer length scales the effects of L-dopa on the morphology of alpha-Syn and Abeta-42 protein fibrils. L-dopa treatment reduces the length and diameter of both types of protein fibrils, with a stark reduction observed for Abeta-42 both in physiological buffer and human spinal fluid. The insights gained on Abeta-42 fibril disassembly from the nanoscale imaging experiments are substantiated using atomic-scale molecular dynamics simulations. Our results reveal the mechanism governing L-dopa-driven reversal of protein aggregation, which may be useful in drug design of small molecule drugs for potentially treating neurocognitive disorders and provide leads for designing chemical effector-mediated disassembly of protein architectures. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-The disciplinary matrix of holobiont biology
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+Putative Role of Norrin in Neuroretinal Differentiation Revealed by bulk and scRNA Sequencing of Human Retinal Organoids
- Science, Volume 386, Issue 6723, Page 731-732, November 2024.+ Pathogenic variants in the X-linked gene NDP (Norrie disease protein) have been associated with a variety of non-syndromic and syndromic human retinal diseases, including Norrie disease and familial exudative vitroretinopathy. The gene codes for Norrin, a secreted angiogenic molecule which binds to FZD4 and its co-receptors LRP5/6 and TSPAN12 and activates Wnt-signaling. Additionally, it also potentiates Wnt-signaling by binding to the LGR4 receptor. Norrin was also found to exert a neuroprotective function in the retina, specifically for retinal ganglion cells. Furthermore, it was suggested to be involved in neurodevelopmental processes such as early neuro-ectodermal specification and differentiation, as well as maintenance of cochlear hair cells. To better understand the putative role of Norrin in neuronal cells of the retina we generated NDP mutant and eGFP-expressing NDP reporter human induced pluripotent stem cells, which were differentiated to retinal organoids. Bulk RNA sequencing and fixed single-cell RNA sequencing revealed alterations in gene expression as well as cellular composition, with increased proportions of retinal progenitors as well as Muller glia cells in NDPKO retinal organoids. Differential expression of genes related to glutamate signaling, Wnt and MAPK signaling, as well as neurogenesis was detected. Furthermore, genes associated with functions in the extracellular matrix were also differentially expressed. The considerable decrease in retinal neurons found in our NDPKO organoids suggest that Norrin is also important for retinal neurogenesis, which may precede the vascular manifestations in NDP-associated diseases. -
in Science on 2024-11-14 06:59:04 UTC. +
in bioRxiv: Neuroscience on 2024-11-15 00:00:00 UTC.
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-End illegal sand mining in China
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+Brain Sciences, Vol. 14, Pages 1147: The Impact of Probiotics on Clinical Symptoms and Peripheral Cytokines Levels in Parkinson’s Disease: Preliminary In Vivo Data
- Science, Volume 386, Issue 6723, Page 736-736, November 2024.+
Brain Sciences, Vol. 14, Pages 1147: The Impact of Probiotics on Clinical Symptoms and Peripheral Cytokines Levels in Parkinson’s Disease: Preliminary In Vivo Data
+Brain Sciences doi: 10.3390/brainsci14111147
+Authors: + Luca Magistrelli + Elena Contaldi + Annalisa Visciglia + Giovanni Deusebio + Marco Pane + Angela Amoruso +
+Introduction. Previous studies have shown that probiotics have positive effects on both motor and non-motor symptoms in Parkinson&rsquo;s disease (PD). Additionally, in preclinical settings, probiotics have demonstrated the ability to counteract neuronal loss and alpha-synuclein aggregation, important pathological hallmarks of PD. Notably, preliminary in vitro studies have revealed the immunomodulatory properties of probiotics. This study aims to evaluate the impact of probiotics on symptoms and peripheral cytokines levels in PD patients compared to placebo. Methods. Patients were enrolled and blindly randomized to receive either active probiotics (comprising Bifidobacterium animalis subsp. lactis BS01 LMG P-21384, Bifidobacterium longum BL03 DSM 16603, Bifidobacterium adolescentis BA02 DSM 18351, Fructo-oligosaccharides and Maltodextrin-Group A) or placebo (Maltodextrin-Group B). Clinical evaluations and plasma levels cytokines (TNF-&alpha;, IFN-&gamma;, IL-6, and TGF-&beta;) were also assessed at enrollment and after 12 weeks. Anti-parkinsonian therapy remained stable throughout the study. Results. Forty PD patients were recruited. After 12 weeks, Group A showed significant improvement in motor symptoms (UPDRS III: 13.89 &plusmn; 4.08 vs. 12.74 &plusmn; 4.57, p = 0.028) and non-motor symptoms (NMSS: 34.32 &plusmn; 21.41 vs. 30.11 &plusmn; 19.89, p = 0.041), with notable improvement in the gastrointestinal sub-item (3.79 &plusmn; 4.14 vs. 1.89 &plusmn; 2.54, p = 0.021). A reduction of IFN-&gamma; levels was observed in both groups, but group A also showed a significant decrease in IL-6 and a slight increase in the anti-inflammatory cytokine TGF-&beta;. Conclusions. Our data suggest that probiotics may modulate peripheral cytokines levels and improve clinical symptoms in PD patients. Probiotics may, therefore, represent a valuable adjunctive therapy to conventional anti-parkinsonian drugs.
-in Science on 2024-11-14 06:59:04 UTC. +
in Brain Sciences on 2024-11-15 00:00:00 UTC.
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-Plastics treaty: Address building materials
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+Brain Sciences, Vol. 14, Pages 1145: New Pharmacological Insight into Etanercept and Pregabalin in Allodynia and Nociception: Behavioral Studies in a Murine Neuropathic Pain Model
- Science, Volume 386, Issue 6723, Page 736-737, November 2024.+
Brain Sciences, Vol. 14, Pages 1145: New Pharmacological Insight into Etanercept and Pregabalin in Allodynia and Nociception: Behavioral Studies in a Murine Neuropathic Pain Model
+Brain Sciences doi: 10.3390/brainsci14111145
+Authors: + Loulwah Alothman + Emad Alhadlaq + Asma Alhussain + Alwaleed Alabdulkarim + Youssef Sari + Shakir D. AlSharari +
+Background/Objectives: Neuropathic pain is challenging to treat, often resistant to current therapies, and associated with significant side effects. Pregabalin, an anticonvulsant that modulates calcium channels, is effective but can impair mental and motor functions, especially in older patients. To improve patient outcomes, reducing the doses of pregabalin and combining it with other drugs targeting different neuropathic pain mechanisms may be beneficial. TNF-&alpha; blockers such as etanercept have shown potential in addressing neuropathic pain by affecting sodium channels, synaptic transmission, and neuroinflammation. This study evaluates the efficacy and safety of combining low doses of etanercept and pregabalin in allodynia and nociceptive tests. Materials and Methods: Male C57/BL6 mice underwent chronic constriction injury (CCI) of the sciatic nerve to induce neuropathic pain. They were divided into seven groups: sham control, CCI control, low and high doses of pregabalin, low and high doses of etanercept, and a combination of low doses of both drugs. Behavioral tests, including von Frey, hot-plate, and rotarod tests, were used to assess pain responses and motor activity. Results: The results indicated that a high dose of pregabalin significantly reduced mechanical allodynia and thermal hyperalgesia but impaired motor function. Conversely, low doses of etanercept alone had no significant effect. However, the combination of low doses of etanercept (20 mg/kg) and pregabalin (5 mg/kg) effectively alleviated pain without compromising locomotor activity. Conclusions: These results suggest a novel therapeutic strategy for neuropathic pain, enhancing analgesic efficacy while minimizing adverse effects.
-in Science on 2024-11-14 06:59:04 UTC. +
in Brain Sciences on 2024-11-15 00:00:00 UTC.
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-Argentina’s unsustainable policies
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+Brain Sciences, Vol. 14, Pages 1146: High Expression of GABAA Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma
- Science, Volume 386, Issue 6723, Page 735-736, November 2024.+
Brain Sciences, Vol. 14, Pages 1146: High Expression of GABAA Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma
+Brain Sciences doi: 10.3390/brainsci14111146
+Authors: + Jander M. Monteiro + Matheus Dalmolin + Marcelo A. C. Fernandes + Jaqueline I. R. Ramos + Carmen A. P. M. Ribas + Fernando I. Tabushi + Rafael Roesler + Gustavo R. Isolan +
+Background/Objectives: Most of the rapid inhibitory neurotransmission in the brain is mediated through activation of the &gamma;-aminobutyric acid (GABA) type A (GABAA) receptor, which is a ligand-gated ion channel. GABAA receptor activation via GABA binding allows for an intracellular influx of Cl&minus; ions, thus inducing cellular hyperpolarization. Each GABAA receptor consists of a combination of five subunits, and several subunits have been proposed as biomarkers and therapeutic targets in cancer. Here, we show the expression of genes encoding &beta; subunits of the GABAA receptor, namely GABRB1, GABRB2, and GABRB3, across the four different molecular subgroups of medulloblastoma (MB), which is the most common malignant pediatric brain tumor. We also show the associations of GABAA receptor &beta; subunits with MB patients&rsquo; overall survival (OS). Methods: The expression of genes encoding GABAA receptor &beta; subunits was analyzed using a previously described dataset comprising 763 MB tumor samples. Patients were classified into high- and low-gene-expression groups, and the Kaplan&ndash;Meier estimate was used to examine the relationship between gene expression levels and patient OS. Results: High GABRB1 expression was associated with better OS within each of the four molecular subgroups. The GABRB2 gene showed higher transcript levels in Group 3 MB compared to all other subgroups, and high expression was associated with better prognosis in Group 3 tumors. GABRB3 expression was significantly higher in Group 3 and Group 4 MB, and high expression of GABRB3 genes was associated with longer OS in the sonic hedgehog (SHH) subgroup. The high expression of GABRB1, GABRB2, and GABRB3 is associated with longer patient OS in a subgroup-specific manner. Conclusions: These results indicate a role for GABAA receptors containing &beta; subunits in influencing MB progression.
-in Science on 2024-11-14 06:59:04 UTC. +
in Brain Sciences on 2024-11-15 00:00:00 UTC.
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-News at a glance
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+Brain Sciences, Vol. 14, Pages 1144: The Role of Cognitive Reserve in Post-Stroke Rehabilitation Outcomes: A Systematic Review
- Science, Volume 386, Issue 6723, Page 710-711, November 2024.+
Brain Sciences, Vol. 14, Pages 1144: The Role of Cognitive Reserve in Post-Stroke Rehabilitation Outcomes: A Systematic Review
+Brain Sciences doi: 10.3390/brainsci14111144
+Authors: + Debora Bertoni + Stefania Bruni + Donatella Saviola + Antonio De Tanti + Cosimo Costantino +
+Background/Objectives: Stroke remains a major cause of disability and death, with survivors facing significant physical, cognitive, and emotional challenges. Rehabilitation is crucial for recovery, but outcomes can vary widely. Cognitive reserve (CR) has emerged as a factor influencing these outcomes. This systematic review evaluates the role of CR in post-stroke rehabilitation, examining whether higher CR is associated with better outcomes. Methods: A systematic search of PubMed, Google Scholar, Scopus, and Cochrane Library databases was conducted for studies published between 2004 and 2024. Studies examining social-behavior CR proxies (e.g., education, bilingualism) and their impact on post-stroke outcomes were included. Data were analyzed using descriptive statistics. The study quality was assessed using the Methodological Index for NOn-Randomized Studies (MINORS) scale. Results: Among 3851 articles screened, 27 met the inclusion criteria. Higher education levels, bilingualism, and engagement in cognitively stimulating activities were associated with better cognitive outcomes and functional recovery. Lower socioeconomic status (SES) correlated with poorer outcomes. Early rehabilitation and dynamic CR proxies showed stronger associations with cognitive recovery than static ones. Conclusions: CR may predict post-stroke rehabilitation outcomes, with education, bilingualism, and active engagement in cognitive activities showing potential benefits. Future research should explore CR&rsquo;s role alongside factors like lesion location and severity in enhancing recovery.
-in Science on 2024-11-14 06:59:04 UTC. +
in Brain Sciences on 2024-11-15 00:00:00 UTC.
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-Research advocates see ‘no good news for science’
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+Brain Sciences, Vol. 14, Pages 1143: Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review
- Science, Volume 386, Issue 6723, Page 712-713, November 2024.+
Brain Sciences, Vol. 14, Pages 1143: Spontaneous Intracranial Hypotension and Dural Ectasia in Marfan Syndrome: An Illustrative Case Successfully Treated with Steroid Therapy and Literature Review
+Brain Sciences doi: 10.3390/brainsci14111143
+Authors: + Francesco Signorelli + Omar Ktari + Ludovico Agostini + Giorgio Ducoli + Fabio Zeoli + Massimiliano Visocchi +
+Background: Spontaneous intracranial hypotension (SIH) is a rare and frequently misdiagnosed disorder characterized by a low volume of cerebrospinal fluid (CSF) caused by the leakage of CSF through the spinal dural membrane. Patients with Marfan Syndrome (MS) and other connective tissue disorders are at an increased risk for dural ectasia, which may predispose them to spontaneous CSF leaks due to the structural weakness of their dural membranes. The management of SIH in MS patients is debated. Conservative measures, an epidural blood patch (EBP), and surgical treatments are the options generally provided. Methods: Herein, we report on the case of a 52-year-old female affected by MS, genetically confirmed, with a two-month history of sudden-onset, &ldquo;thunderclap&rdquo; headache, worsened in an upright position and horizontal diplopia. A Computed Tomography (CT) scan of the brain showed a bilateral chronic subdural hematoma, slit ventricles, and a caudal descent of the brainstem without overt tonsillar herniation. The Magnetic Resonance Imaging (MRI) scan of the whole spine revealed dural ectasia in the lumbosacral area and presacral perineural cyst without extradural CSF collection. The case was successfully managed with bed rest and high-dose corticosteroid therapy. Then, we discuss the pertinent literature, consisting of 25 papers dealing with the treatment of SIH in patients affected by MS. Results: The literature review yielded 25 papers dealing with SIH management in patients with MS, including 28 patients overall; 21 patients underwent EBP, of whom 7 patients had multiple procedures. Overall, in 23 cases (82%), the symptoms improved. In three cases, the patients were managed conservatively with bed rest. In three of these cases, there was an improvement. In one case, the surgical fenestration of two lumbar intradural spinal meningeal cysts was performed and the patient improved after the procedure. Our patient underwent 15 days of steroid therapy (dexamethasone iv 12 mg/day for 7 days, then reduced to 4 mg/day) and intravenous hydration (Ringer lactate 1500 mL/day). In ten days, the symptoms disappeared. At the 6-month follow-up, the patient was in good clinical condition, and a CT scan showed an almost complete regression of the bilateral subdural hematoma. Conclusions: The management of SIH in MS patients is still challenging. Patients with connective tissue disorders such as MS are at an increased risk for SIH. Few studies have assessed the management of these patients and different strategies. Our case and the available literature provide further data for this type of case.
-in Science on 2024-11-14 06:59:04 UTC. +
in Brain Sciences on 2024-11-15 00:00:00 UTC.
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-Trump won. Is NIH in for a major shake-up?
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+Assessment of Pelargonium graveolens flower essential oil: Antimicrobial, antioxidant, enzyme inhibition and in vivo topical analgesic and anti-inflammatory efficacy as treatment for atopic dermatitis [version 1; peer review: awaiting peer review]
- Science, Volume 386, Issue 6723, Page 713-714, November 2024.+ Background Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by pruritus and skin barrier dysfunction. This study aims to evaluate the therapeutic potential of Pelargonium graveolens (Geraniaceae) in managing AD symptoms through its essential oil. Methods The chemical composition of Pelargonium graveolens flower essential oil (PFEO) was analyzed using gas chromatography-mass spectrometry (GC-MS). Its antimicrobial, antioxidant, and anti-inflammatory properties were assessed, along with the inhibitory effects of PFEO on key enzymes involved in skin repair: tyrosinase, elastase, and collagenase. An in vivo evaluation of a gel formulation containing PFEO was also conducted to assess its anti-inflammatory and analgesic efficacy. Results GC-MS analysis identified major compounds in PFEO, including Geraniol (22.83%), beta-citronellol (19.51%), naphthalenemethanol (15.36%), and Geranyl tiglate (9.38%), with minor constituents such as linalool (3.81%) and neryl formate (1.31%). PFEO exhibited bacteriostatic activity against various bacterial and fungal strains, including Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), Bacillus anthracis, Streptococcus pyogenes, Staphylococcus epidermidis, Candida albicans, and Malassezia spp. The essential oil also demonstrated significant antioxidant properties and inhibited key enzymes linked to skin alterations in AD. Conclusions PFEO shows promising therapeutic potential for managing symptoms of atopic dermatitis due to its antimicrobial, antioxidant, and anti-inflammatory properties, as well as its analgesic effects. The findings support further exploration of PFEO as a natural alternative in the treatment of AD. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 17:57:35 UTC.
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-‘America first’ could affect health worldwide
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+Clust&See3.0 : clustering, module exploration and annotation [version 2; peer review: 1 approved, 2 approved with reservations]
- Science, Volume 386, Issue 6723, Page 715-715, November 2024.+ Background Cytoscape is an open-source software to visualize and analyze networks. However, large networks, such as protein interaction networks, are still difficult to analyze as a whole. Methods Here, we propose Clust&See3.0, a novel version of a Cytoscape app that has been developed to identify, visualize and manipulate network clusters and modules. It is now enriched with functionalities allowing custom annotations of nodes and computation of their statistical enrichments. Results As the wealth of multi-omics data is growing, such functionalities are highly valuable for a better understanding of biological module composition, as illustrated by the presented use case. Conclusions In summary, the originality of Clust&See3.0 lies in providing users with a complete tool for network clusters analyses: from cluster identification, visualization, node and cluster annotations to annotation statistical analyses. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 17:43:17 UTC.
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-Famed flipping ship gets second shot at research
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+Evaluation of the fintech era on the performance of Moroccan banks: analysis through non-performing loans [version 1; peer review: awaiting peer review]
- Science, Volume 386, Issue 6723, Page 716-716, November 2024.+ Background This study aims to contribute to a better understanding of the impact of the financial technologies (fintech) era on the performance in the banking sector, measured through non-performing loans (NPL) and their coverage by provisions for NPL. It is a question of knowing whether banking investment in fintech makes it possible to better evaluate the granting of credits, and therefore makes it possible to reduce overdue credits. Methods To this end, the method used consists of using a regression analysis and a Pearson correlation applied to the financial data of Moroccan banks observed during two distinct periods, namely 2007-2014, considered pre-fintech, and the period 2015-2022, considered as the fintech period. Results With the emergence of the fintech era, the Moroccan banking situation improved slightly compared to the pre-fintech period: bad debts did not increase despite the significant increase in net banking income and the size of banking assets during the fintech era. Conclusions The implementation of fintech has improved customer relationship management, credit risk analysis and loan monitoring services, which ultimately reduces non-performing loans and improves the coverage of non-performing loans by provisions. The main implication of the results allows us to deduce that the implementation of fintech makes it possible to have a positive impact on overdue credits, and they are also likely to serve as a lever for the inclusion of those excluded from banking services. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 17:40:03 UTC.
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-Preprint on Alzheimer’s drug deaths ignites author dispute
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+Transcranial Direct Current Stimulation over the Posterior Parietal Cortex Increases Nontarget Retrieval during Visual Working Memory
- Science, Volume 386, Issue 6723, Page 717-718, November 2024.+
Visual working memory (VWM) requires precise feature binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM; this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 (N = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of nontarget responses (a.k.a. failure of feature binding, pNT). In Experiment 2 (N = 29), combining metacognition estimation, we further investigated whether the effects of PPC stimulation were attributed to misbinding (i.e., participants self-reported "remembered" in nontarget responses) or informed guessing trials (participants self-reported "forgotten" in nontarget responses). We replicated the main findings in Experiment 1 and observed greater tDCS effects of PPC on RT in informed guessing trials while there are comparable effects on pNT in these two types of trials. In Experiment 3 (N = 28), we then examined whether the tDCS effects over PPC specifically influenced the memory retrieval process by using a change detection task. We found that PPC stimulation did not influence the recognition RT or accuracy. Together, this study provided direct causal evidence supporting the specific involvement of PPC in feature binding during VWM retrieval, from both aspects of speed and response preference, expanding our understanding of the neural basis of feature binding in VWM.
-in Science on 2024-11-14 06:59:04 UTC. +
in eNeuro on 2024-11-14 17:30:23 UTC.
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-Russia postpones three scientific ‘megaprojects’
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+Prenatal Exposure to MAM Impairs mPFC and Hippocampal Inhibitory Function in Mice during Adolescence and Adulthood
- Science, Volume 386, Issue 6723, Page 718-718, November 2024.+
Neurodevelopmental abnormalities are considered to be one of the important causes of schizophrenia. The offspring of methylazoxymethanol acetate (MAM)–exposed mice are recognized for the dysregulation of neurodevelopment and are well-characterized with schizophrenia-like phenotypes. However, the inhibition-related properties of the medial prefrontal cortex (mPFC) and hippocampus throughout adolescence and adulthood have not been systematically elucidated. In this study, both 10 and 15 mg/kg MAM-exposed mice exhibited schizophrenia-related phenotypes in both adolescence and adulthood, including spontaneous locomotion hyperactivity and deficits in prepulse inhibition. We observed that there was an obvious parvalbumin (PV) loss in the mPFC and hippocampus of MAM-exposed mice, extending from adolescence to adulthood. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons at mPFC and hippocampus was significantly dampened in the 10 and 15 mg/kg MAM-exposed mice. Furthermore, the firing rate of putative pyramidal neurons in mPFC and hippocampus was increased, while that of putative inhibitory neurons was decreased during both adolescence and adulthood. In conclusion, PV loss in mPFC and hippocampus of MAM-exposed mice may contribute to the impaired inhibitory function leading to the attenuation of inhibition in the brain both in vitro and in vivo.
-in Science on 2024-11-14 06:59:04 UTC. +
in eNeuro on 2024-11-14 17:30:23 UTC.
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-The counterattack
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+Erratum: White et al., "Learning to Choose: Behavioral Dynamics Underlying the Initial Acquisition of Decision-Making"
- Science, Volume 386, Issue 6723, Page 719-723, November 2024.+ -
in Science on 2024-11-14 06:59:04 UTC. +
in eNeuro on 2024-11-14 17:30:23 UTC.
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-Science is neither red nor blue
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+Erratum: Lakhani et al., "Homeostatic Regulation of Spike Rate within Bursts in Two Distinct Preparations"
- Science, Volume 386, Issue 6723, Page 707-707, November 2024.+ -
in Science on 2024-11-14 06:59:04 UTC. +
in eNeuro on 2024-11-14 17:30:23 UTC.
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-Advancing alternative methods to reduce animal testing
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+Health care workers hospitalized for COVID-19 in Liberia: who were they, and what were their outcomes? [version 2; peer review: 1 approved, 1 approved with reservations]
- Science, Volume 386, Issue 6723, Page 724-726, November 2024.+ Background Sustaining a ‘fit-for-purpose’ health workforce requires a better understanding of the health care worker cadres that are affected during pandemics and their outcomes. In hospitalized health care workers with confirmed COVID-19 between March 2020 and May 2023 in Liberia, we determined the hospitalization and case fatality rates, type of health care worker cadres affected, their demographic and clinical characteristics and hospital exit outcomes. Methods This was a cohort study using routine data extracted from hospitalization forms for health care workers in 24 designated COVID-19 treatment facilities. Results Of the 424 health care workers with COVID-19, hospitalization rates progressively declined between 2020 and 2023, (P<0.001) with the highest rates in 2020 (24/1,000 health care workers) and 2021 (14/1,000 health care workers). Case fatality was 2% in both 2020 and 2021 with no deaths thereafter. Among those hospitalized, the highest proportions were nursing cadres with 191(45%), physicians with 63 (15%) and laboratory technicians with 42 (10%). The most frequent reported site for COVID-19 infection was the health facility (326, 89%). COVID-19 vaccination coverage in health care workers was 20%. The majority (91%) of hospitalizations were for mild symptomatic infections. Even in referral centres (n-52), 18 (35%) were for mild infections. Of the 424 who were hospitalized, 412 (97%) recovered, 9 (2%) died and 3 (1%) either left against medical advice or absconded. Of the nine deaths, none were vaccinated, seven had moderate-to-severe disease but were not referred to specialized COVID-19 treatment centers. Conclusions The hospitalized health care workers for COVID-19 were predominantly clinical and laboratory personnel who were mostly unvaccinated, and health facilities were hot-spots for contracting infections. The triage and referral system was weak with unnecessary hospitalization of mild infections. This study provides useful insights for outbreak preparedness including priority vaccination and improving health care worker safety in Liberia. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 16:59:59 UTC.
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-Gatekeepers of the brain: Identifying hidden mechanisms of type A GABA receptor signaling and assembly
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+The quality of life in Thai senior table tennis players [version 3; peer review: 1 approved with reservations, 1 not approved]
- Science, Volume 386, Issue 6723, Page 738-739, November 2024.+ Background Table tennis presented a unique and accessible sport for people of all ages, particularly seniors compared to other sports. Methods This study utilized a quantitative with 136 Table tennis players those who registered for attending in the Thailand Master Table tennis Championships 2024 which hosted in January 2024 at Chiangmai. The questionnaire based on the measurement quality of life, WHOQOL Thai version, and analyzed using Descriptive statistics, Pearson Correlation. Results Pearson correlation coefficients between the scores of the quality of life in four dimensions and the overall score revealed significant correlations (p < 0.01) with all dimensions, including physical health, psychological health, social relationships, and environmental health. Conclusions Playing Table tennis for senior in the tournament level helped to improve the quality of life in all domains. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 15:21:20 UTC.
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-Digging below the surface: Hidden risks for ground-nesting bees
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+The role of therapeutic MicroRNA in arteriogenesis process in limb ischemia: A systematic review [version 2; peer review: 1 approved with reservations]
- Science, Volume 386, Issue 6723, Page 739-739, November 2024.+ Background Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral artery disease (PAD) and has poor clinical outcomes. Recently, stimulating arteriogenesis has been proposed to improve clinical outcomes. Several studies have shown that miRNAs have beneficial effects on limb ischemia related to arteriogenesis. This study aimed to review the roles of therapeutic miRNAs in the arteriogenesis of limb ischemia. Methods A systematic search was conducted through July 2021 using the PubMed, Scopus, and ScienceDirect databases. Two authors independently assessed studies that investigated the role of miRNAs in the arteriogenesis of limb ischemia, both in vivo and in clinical studies. Results All selected studies were in vivo studies, with a total of 36 articles and 28 types of miRNAs. miRNAs potentially regulate arteriogenesis by targeting different targets. The following miRNAs were upregulated to enhance arteriogenesis: miRNA-126-3p, -93, -675, -143-3p, -130a, -210, -146b, -21, -let-7g, -132/212, -150, and 155. Meanwhile, microRNAs needed to be downregulated, namely: miRNA-939-5p, -503, -199a-5p, -146a, -92a, -14q32 microRNA gene cluster, -15a/16, -100, -133a, -139-5p, -223, -352, -615-5p, -15b/5p, -124-3p, and 29a. MiRNA-126 was the most studied miRNA, and SPRED1 was the most common target of microRNA. However, the included studies showed high heterogeneity in terms of inducing hindlimb ischemia, the timing of administration, and the method used for evaluating arteriogenesis. Moreover, most studies presented unclear or high-risk bias. Conclusion MicroRNA application in a preclinical model of hindlimb ischemia has beneficial effects on arteriogenesis. This result indicates that miRNAs might be potentially beneficial in patients with CLTI. Registration The review protocol was registered with PROSPERO under registration number CRD42024484988. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 15:17:25 UTC.
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-How to build a human: Piecing together the body’s cellular puzzle
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+Choroidal thickness measurement in central serous chorioretinopathy using swept source optical coherence tomography: an observational study [version 2; peer review: 2 approved with reservations]
- Science, Volume 386, Issue 6723, Page 739-739, November 2024.+ Background Central serous chorioretinopathy (CSCR) is a common retinal condition with an increased risk of recurrence. Traditional approaches have made choroidal visualization challenging, but recent advances in optical coherence tomography (OCT) innovation have permitted the collection of more accurate choroidal visualizations. This study aimed to measure choroidal thickness in eyes with active CSCR as well as in the unaffected opposite eyes of these same individuals. Methods This research was conducted at the ophthalmology division in Ghazi Al-Hariri Hospital from the 1st of October 2019 until the 31st of March 2020. A total of 49 people, corresponding to 65 eyes, were included in the study. Among these participants, 16 individuals presented with central serous chorioretinopathy (CSCR), affecting a total of 32 eyes. The CSCR individuals were further split into two groups: “Group A” consisted of 20 eyes with active CSCR, and “Group B” encompassed the remaining 12 unaffected opposite eyes. Additionally, the right eyes of 33 individuals who were age and gender-matched served as controls assigned as “Group C”. Results The choroid exhibited a substantial rise in thickness across each of the nine sectors in group A as compared to group C. Similarly, group B showed a significant increase in choroidal thickness in relation to group C. The mean subfoveal choroidal thickness (SFCT) was measured as follows: 474.55μm, 437.5μm, and 292.03μm among groups A, B, and C, correspondingly. These differences were identified as clinically significant for both A vs. C and B vs. C. Conclusions This study’s findings indicate a thickening of the choroid in both eyes exhibiting active CSCR, as well as in the unaffected opposite eyes of those with the disease. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 15:15:00 UTC.
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-To target, to escape, perchance to cure: Borrowing a page from cancer’s playbook, scientists learn to evade their own therapies
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+Knowledge and attitudes of health care professionals regarding birth preparedness of women in labour at selected Hospitals in KwaZulu-Natal, South Africa: A qualitative study [version 2; peer review: awaiting peer review]
- Science, Volume 386, Issue 6723, Page 739-739, November 2024.+ Introduction Low and middle-income countries account for the largest proportion of women’s deaths as a result of pregnancy or childbirth-related complications. The sub-Saharan region is the most affected with approximately 70% (202 000) of maternal deaths between 2000 and 2020. These deaths could have been prevented if expectant mothers were prepared for childbirth. Birth preparedness is perceived as a better strategy that helps attain a substantial reduction in maternal mortality. This is achieved by attending early antenatal classes, receiving skilled care during childbirth, and care and support right after birth. The latest survey on antenatal class attendance conducted in South Africa provides an estimated 30.8% of expectant mothers in public healthcare facilities. Methods This study employed a qualitative approach to collect data, as a result, one focus group discussion with five (N=5) participants and two others with six (N=6) participants each (n=6X2=12) and twenty individual interviews were conducted. The study sought to explore and describe the knowledge and attitudes of healthcare professionals regarding the birth preparedness of women in labour at selected hospitals in Durban KwaZulu-Natal. Results Expectant mothers were unprepared for both labour and postnatal care. The unprepared expectant mothers were uncooperative and made the task of midwives difficult to the extent of endangering the life of their expected newborn babies and their own. Factors such as finance, heterogeneity, staff shortage, language barrier, lack of family support, lack of interest, cultural beliefs, and confusion caused by various sources of information were responsible for birth unpreparedness. Conclusion The synergy between expectant mothers and midwives appears to be an important factor in achieving better birth preparedness. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 15:13:17 UTC.
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-In Science Journals
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+Digital and Financial Literacy for Uplifting Women and Achieving Sustainable Development Goals [version 1; peer review: awaiting peer review]
- Science, Volume 386, Issue 6723, Page 740-742, November 2024.+ Digital and financial literacy are changing the landscape of the globe in terms of its approach to development. These two literacies also help to achieve women’s empowerment and, consequently, the sustainable development goals (SDGs) more quickly. This systematic literature review looks at the two literacies and their effects, focusing on women’s participation and showing how digital literacy not only increases women’s access to knowledge and connectivity but is also a door to women’s entrepreneurship and financial independence. Likewise, financial literacy, when coupled with digital skills, can be a breakthrough to the traditional socioeconomic barrier – poverty – by assisting women in making informed economic decisions, increasing their financial independence and resilience in the face of a global crisis. Empirical realities that still hinder women’s education, such as cultural norms, infrastructural deficiencies and educational gaps, still exist. However, the paper points out that to have a more equal world based on the SDGs, the double literacy strategy for women’s empowerment should not be negotiable. -
in Science on 2024-11-14 06:59:04 UTC. +
in F1000Research on 2024-11-14 15:11:00 UTC.
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-Input-specific properties of excitatory synapses on oxytocin receptor-expressing neurons in the lateral septum
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+Teaching Self-efficacy and Teaching Methods in the Aquatic Environment [version 1; peer review: awaiting peer review]
- Journal of Neurophysiology, Ahead of Print.+ Background Studies have shown that perceived self-efficacy can influence teachers’ emotional state, thoughts and behaviours, and students’ learning. It’s also an important referential of professional satisfaction. In turn, teaching methodologies influence motor learning, as well as psychological, cognitive and social learning, with different impacts on human development and learning retention, levels of intrinsic motivation and continuity of practice in order to support a healthy lifestyle. Research on aquatic educators and teaching methodologies is scarce and at the same time necessary according to the view that aquatic literacy is an integral part of physical literacy and the only possibility of being more able to interact with this environment. Methods In this study we used an online questionnaire, aimed at aquatic professionals, which was answered voluntarily and anonymously to measure the prevalence of the use of different teaching methodologies, the comprehensive aquatic method and the perception of teacher self-efficacy. It has been deposited and can be consulted at https://doi.org/10.6084/m9.figshare.27316242.v1. Results All methods can generate a feeling of self-efficacy in teachers despite having different results, with the methodologies that involve students more actively (cognitivist and constructivist) being those that generate a greater feeling of self-efficacy in teachers. MAC is a method that is more closely related to methodologies focused on active student participation and, consequently, it is a method that generates a high perception of self-efficacy in teachers. Conclusions Levels of self-efficacy influence professional satisfaction, teacher physical, mental and emotional health, as well as student learning. Is recommended that aquatic professionals give prevalence to the cognitivist and constructivist teaching methodologies being MAC a privileged methodological approach for promoting active lifestyle habits throughout life. -
in Journal of Neurophysiology on 2024-11-14 05:30:15 UTC. +
in F1000Research on 2024-11-14 15:09:27 UTC.
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-Harvey's Story
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+Annals of Neurology: Volume 96, Number 6, December 2024
-
-Harvey enjoying a good discussion at a lab party in 1996 (photo provided by Harald Luksch). - -
--
ABSTRACT
-Harvey Jules Karten passed away on July 15, 2024. With his passing, the world lost a remarkable and energetic man who had made major contributions to neuroscience, in particular, resetting our understanding of the evolution of the forebrain and the evolution of intelligence. He left behind a legion of loyal colleagues with whom he had collaborated and shared ideas, students he had inspired and trained, and non-neuroscientist friends he had made in the passionate pursuit of his hobbies—sailing, skiing, and hiking.
+ -in Journal of Comparative Neurology on 2024-11-14 04:44:24 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Altered control of breathing in a rat model of allergic lower airway inflammation
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+Issue Information
- Journal of Neurophysiology, Volume 132, Issue 5, Page 1650-1666, November 2024.+ -
in Journal of Neurophysiology on 2024-11-14 03:52:07 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Palytoxin evokes reversible spreading depolarization in the locust CNS
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+Priorities and Recommendations to Make ALS a Livable Disease Emanating from the 2024 National Academies of Sciences, Engineering, and Medicine Report Living with ALS
- Journal of Neurophysiology, Volume 132, Issue 5, Page 1621-1632, November 2024.+
Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report “Living with ALS,” recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024;96:1035–1039
-in Journal of Neurophysiology on 2024-11-14 03:52:06 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Clinical efficacy of low-intensity pulsed ultrasound in Parkinson’s disease with cognitive impairment
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+MEK Pathway Inhibitor‐Mediated Response in BRAF V600‐Mutant Melanoma with Brain Parenchymal and Leptomeningeal Metastases
- Journal of Neurophysiology, Volume 132, Issue 5, Page 1633-1638, November 2024.+ -
in Journal of Neurophysiology on 2024-11-14 03:52:05 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Examining motor evidence for the pause-then-cancel model of action-stopping: insights from motor system physiology
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+Miyazaki Syndrome as a Complication of Shunt Drainage
- Journal of Neurophysiology, Volume 132, Issue 5, Page 1589-1607, November 2024.+ -
in Journal of Neurophysiology on 2024-11-14 03:52:04 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Rat movements reflect internal decision dynamics in an evidence accumulation task
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+Neuro‐Image of a Ring‐Liked Sign in Serpentine Aneurysm
- Journal of Neurophysiology, Volume 132, Issue 5, Page 1608-1620, November 2024.+ -
in Journal of Neurophysiology on 2024-11-14 03:52:04 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Bayesian inference in arm posture perception
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+Syrinx beyond Cord: Syringocephalia Extending to Corona Radiata
- Journal of Neurophysiology, Volume 132, Issue 5, Page 1639-1649, November 2024.+ -
in Journal of Neurophysiology on 2024-11-14 03:52:03 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Impact of sleep deprivation on aperiodic activity: a resting-state EEG study
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+Slowly Expanding Lesions Differentiate Pediatric Multiple Sclerosis from Myelin Oligodendrocyte Glycoprotein Antibody Disease
- Journal of Neurophysiology, Volume 132, Issue 5, Page 1577-1588, November 2024.+
Slowly expanding lesions (SELs) in adults with multiple sclerosis (MS) indicate a progressive pathological process. Whether SELs are present in pediatric-onset MS (POMS) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unknown. We studied 19 children with POMS and 14 with MOGAD (median age 14.3 and 9.4 years, respectively) recruited to the Canadian Pediatric Demyelinating Disease Study with: (1) ≥3 research scans 12 months apart; and (2) ≥1 T2-lesions on the earliest scan. A total of 70 SELs from 16 POMS participants and 1 SEL in the MOGAD group were detected. SELs are an early feature of POMS and essentially not a feature of MOGAD. ANN NEUROL 2024;96:1086–1091
-in Journal of Neurophysiology on 2024-11-14 03:52:02 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Representational spaces in orbitofrontal and ventromedial prefrontal cortex: task states, values, and beyond
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+Polygenic Landscape of Cryptogenic New‐Onset Refractory Status Epilepticus: A Comprehensive Whole‐Genome Sequencing Study
- The orbitofrontal cortex (OFC) and ventromedial-prefrontal cortex (vmPFC) play a key role in decision-making and encode task states in addition to expected value. We review evidence suggesting a connection between value and state representations and argue that OFC / vmPFC integrate stimulus, context, and outcome information. Comparable encoding principles emerge in late layers of deep reinforcement learning (RL) models, where single nodes exhibit similar forms of mixed-selectivity, which enables flexible readout of relevant variables by downstream neurons. Based on these lines of evidence, we suggest that outcome-maximization leads to complex representational spaces that are insufficiently characterized by linear value signals that have been the focus of most prior research on the topic. Major outstanding questions concern the role of OFC/ vmPFC in learning across tasks, in encoding of task-irrelevant aspects, and the role of hippocampus–PFC interactions. +Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition with unclear pathogenesis. Here, we analyzed the genetic underprints of 31 cNORSE patients from an autoimmune encephalitis observational cohort through whole-genome sequencing. Compared to their controls, cNORSE patients exhibited elevated polygenic risk scores (PRS) for traits associated with autoimmune diseases. The individual PRS against these diseases were correlated with specific clinical phenotypes of cNORSE. The variants were enriched in genes expressed in the central nervous system and lymphocytes. These results suggest a shared genetic framework between cNORSE and other autoimmune/autoinflammatory diseases, and its involvement in the disease pathogenesis. ANN NEUROL 2024;96:1201–1208
-in Trends in Neurosciences: In press on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters in collective cell migration of epithelial cells
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+RAN Translation of C9orf72‐Related Dipeptide Repeat Proteins in Zebrafish Recapitulates Hallmarks of Amyotrophic Lateral Sclerosis and Identifies Hypothermia as a Therapeutic Strategy
- Deguchi et al. find that low-affinity EGFR ligands propagate faster and farther than high-affinity ligands in epithelial cells. They demonstrate that EREG, a low-affinity ligand, contributes to skin wound healing. +Objective
+Hexanucleotide repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A large body of evidence implicates dipeptide repeats (DPRs) proteins as one of the main drivers of neuronal injury in cell and animal models.
+Methods
+A pure repeat-associated non-AUG (RAN) translation zebrafish model of C9orf72-ALS/FTD was generated. Embryonic and adult transgenic zebrafish lysates were investigated for the presence of RAN-translated DPR species and adult-onset motor deficits. Using C9orf72 cell models as well as embryonic C9orf72-ALS/FTD zebrafish, hypothermic-therapeutic temperature management (TTM) was explored as a potential therapeutic option for C9orf72-ALS/FTD.
+Results
+Here, we describe a pure RAN translation zebrafish model of C9orf72-ALS/FTD that exhibits significant RAN-translated DPR pathology and progressive motor decline. We further demonstrate that hypothermic-TTM results in a profound reduction in DPR species in C9orf72-ALS/FTD cell models as well as embryonic C9orf72-ALS/FTD zebrafish.
+Interpretation
+The transgenic model detailed in this paper provides a medium throughput in vivo research tool to further investigate the role of RAN-translation in C9orf72-ALS/FTD and further understand the mechanisms that underpin neuroprotective strategies. Hypothermic-TTM presents a viable therapeutic avenue to explore in the context of C9orf72-ALS/FTD. ANN NEUROL 2024;96:1058–1069
-in Cell Reports: Current Issue on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma
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+Population‐Based Evidence for the Use of Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis
- (Cell Reports 43, 114406; July 23, 2024) +Objective
+Neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains (pNfH), established as diagnostic and prognostic biomarkers in hospital-based amyotrophic lateral sclerosis (ALS) cohorts, are now surrogate markers in clinical trials. This study extends their evaluation to a population level, with the aim of advancing their full establishment and assessing the transferability of biomarker findings from controlled cohorts to real-world ALS populations.
+Methods
+We measured serum NfL and pNfH levels in all ALS patients (n = 790) and general population controls (n = 570) with available baseline samples participating in the epidemiological ALS Registry Swabia, providing platform-specific (ELLA™) reference data and Z-scores for controls, as well as reference data, disease-specific Z-scores and longitudinal data in ALS. We evaluated the diagnostic and prognostic utility of neurofilaments and quantified the impact of ALS-related factors and non-ALS confounders.
+Results
+Neurofilaments showed high diagnostic and prognostic utility at the population level, with NfL superior to pNfH. The novel concept of a population-based ALS Z-score significantly improved the prognostic utility compared to absolute raw values. Both biomarkers increased more strongly with age in controls than in ALS, and age adjustment improved diagnostic accuracy. Our data show that disease progression rates, ALS phenotype, body mass index (BMI), and renal function need to be considered when interpreting neurofilament levels; longitudinal neurofilament levels were generally stable in individual patients, especially when adjusted for age and baseline levels.
+Interpretation
+Population-based assessment enhances the utility of particularly serum NfL as a diagnostic and prognostic biomarker in ALS and improves the translation of findings from controlled cohorts to real-world populations. ANN NEUROL 2024;96:1040–1057
-in Cell Reports: Current Issue on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling
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+Laser Ablation of Periventricular Nodular Heterotopia for Medically Refractory Epilepsy
- Alvarez et al. use loss- and gain-of-function approaches in chicken, mouse, and stem cells to show that netrin1 inhibits Bmp activity to confine dorsal neural patterning to the correct compartment in the embryonic spinal cord. Netrin1 regulates mRNA processing to suppress Bmp signaling. +Objective
+Periventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco-resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo-electroencephalography (SEEG) -informed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT).
+Methods
+A retrospective review of consecutive cases from a single high-volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes.
+Results
+Thirty-nine patients underwent SEEG-guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow-up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (p < 0.001).
+Interpretation
+PVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH-associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further. ANN NEUROL 2024;96:1174–1184
-in Cell Reports: In press on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Structure of scavenger receptor SCARF1 and its interaction with lipoproteins
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+Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B)
- SCARF1 (scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDLs) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here, we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then, we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases. +Objectives
+Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions.
+Methods
+We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B.
+Results
+In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine.
+Interpretation
+Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024;96:1092–1103
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-The epigenetic trajectory of type 1 regulatory T cells
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+Higher Validity, Lower Radiation: A New Ictal Single‐Photon Emission Computed Tomography Framework
- The epigenome of T follicular helper cells prepares them for conversion into type 1 regulatory T cells. +Objective
+To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single-photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted.
+Methods
+We developed 2 pipelines: The first uses ictal and interictal images and compares these to single-photon emission computed tomography and arterial spin labeling of healthy controls. The second pipeline uses only the ictal image and the analogous healthy controls. Both pipelines were compared to the gold standard analysis and evaluated on data of individuals with epilepsy who underwent ictal single-photon emission computed tomography imaging during presurgical evaluation between 2010 and 2022. Fifty healthy controls prospectively underwent arterial spin labeling imaging. The correspondence between the detected hyperperfusion and the postoperative resection cavity or the presumably affected lobe was assessed using Dice score and mean Euclidean distance. Additionally, the outcomes of the pipelines were automatically assigned to 1 of 5 concordance categories.
+Results
+Inclusion criteria were met by 43 individuals who underwent epilepsy surgery and by 73 non-surgical individuals with epilepsy. Compared to the gold standard analysis, both pipelines resulted in significantly higher Dice scores and lower mean distances (p < 0.05). The combination of both provided localizing results in 85/116 cases, compared to 54/116 generated by the current gold standard analysis and the ictal image alone produced localizing results in 60/116 (52%) cases.
+Interpretation
+We propose a new ictal single-photon emission computed tomography protocol; it finds relevantly more ictal hyperperfusion, and halves the radiation dose in about half of the individuals. ANN NEUROL 2024;96:1160–1173
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Proteomic and functional comparison between human induced and embryonic stem cells
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+Single‐Nucleus RNA Sequencing Unravels Early Mechanisms of Human Becker Muscular Dystrophy
- Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives to embryonic stem cells (hESCs) in regenerative medicine and disease modelling. In this study, we characterise the proteomes of multiple hiPSC and hESC lines derived from independent donors and find that while they express a near-identical set of proteins, they show consistent quantitative differences in the abundance of a subset of proteins. hiPSCs have increased total protein content, while maintaining a comparable cell cycle profile to hESCs, with increased abundance of cytoplasmic and mitochondrial proteins required to sustain high growth rates, including nutrient transporters and metabolic proteins. Prominent changes detected in proteins involved in mitochondrial metabolism correlated with enhanced mitochondrial potential, shown using high-resolution respirometry. hiPSCs also produced higher levels of secreted proteins, including growth factors and proteins involved in the inhibition of the immune system. The data indicate that reprogramming of fibroblasts to hiPSCs produces important differences in cytoplasmic and mitochondrial proteins compared to hESCs, with consequences affecting growth and metabolism. This study improves our understanding of the molecular differences between hiPSCs and hESCs, with implications for potential risks and benefits for their use in future disease modelling and therapeutic applications. +Objective
+The transcriptional heterogeneity at a single-nucleus level in human Becker muscular dystrophy (BMD) dystrophic muscle has not been explored. Here, we aimed to understand the transcriptional heterogeneity associated with myonuclei, as well as other mononucleated cell types that underly BMD pathogenesis by performing single-nucleus RNA sequencing.
+Methods
+We profiled single-nucleus transcriptional profiles of skeletal muscle samples from 7 BMD patients and 3 normal controls.
+Results
+A total of 17,216 nuclei (12,879 from BMD patients and 4,337 from controls) were classified into 13 known cell types, including 9 myogenic lineages and 4 non-myogenic lineages, and 1 unclassified nuclear type according to their cell identities. Among them, type IIx myonuclei were the first to degenerate in response to dystrophin reduction. Differential expression analysis revealed that the fibro-adipogenic progenitors (FAPs) population had the largest transcriptional changes among all cell types. Sub-clustering analysis identified a significantly compositional increase in the activated FAPs (aFAPs) subpopulation in BMD muscles. Pseudotime analysis, regulon inference, and deconvolution analysis of bulk RNA-sequencing data derived from 29 BMD patients revealed that the aFAPs subpopulation, a distinctive and previously unrecognized mononuclear subtype, was profibrogenic and expanded in BMD patients. Muscle quantitative real-time polymerase chain reaction and immunofluorescence analysis confirmed that the mRNA and protein levels of the aFAPs markers including LUM, DCN, and COL1A1 in BMD patients were significantly higher than those in controls, respectively.
+Interpretation
+Our results provide insights into the transcriptional diversity of human BMD muscle at a single-nucleus resolution and new potential targets for anti-fibrosis therapies in BMD. ANN NEUROL 2024;96:1070–1085
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Predictive models for secondary epilepsy in patients with acute ischemic stroke within one year
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+Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Mitochondrial DNA Depletion/Deletions Disease
- -/- +
++
++
Objective
+Mitochondrial DNA (mtDNA) depletion/deletions syndrome (MDDS) comprises a group of diseases caused by primary autosomal defects of mtDNA maintenance. Our objective was to study the etiology of MDDS in 4 patients who lack pathogenic variants in known genetic causes.
+Methods
+Whole exome sequencing of the probands was performed to identify pathogenic variants. We validated the mitochondrial defect by analyzing mtDNA, mitochondrial dNTP pools, respiratory chain activities, and GUK1 activity. To confirm pathogenicity of GUK1 deficiency, we expressed 2 GUK1 isoforms in patient cells.
+Results
+We identified biallelic GUK1 pathogenic variants in all 4 probands who presented with ptosis, ophthalmoparesis, and myopathic proximal limb weakness, as well as variable hepatopathy and altered T-lymphocyte profiles. Muscle biopsies from all probands showed mtDNA depletion, deletions, or both, as well as reduced activities of mitochondrial respiratory chain enzymes. GUK1 encodes guanylate kinase, originally identified as a cytosolic enzyme. Long and short isoforms of GUK1 exist. We observed that the long isoform is intramitochondrial and the short is cytosolic. In probands’ fibroblasts, we noted decreased GUK1 activity causing unbalanced mitochondrial dNTP pools and mtDNA depletion in both replicating and quiescent fibroblasts indicating that GUK1 deficiency impairs de novo and salvage nucleotide pathways. Proband fibroblasts treated with deoxyguanosine and/or forodesine, a purine phosphatase inhibitor, ameliorated mtDNA depletion, indicating potential pharmacological therapies.
+Interpretation
+Primary GUK1 deficiency is a new and potentially treatable cause of MDDS. The cytosolic isoform of GUK1 may contribute to the T-lymphocyte abnormality, which has not been observed in other MDDS disorders. ANN NEUROL 2024;96:1209–1224
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Chemokine expression profile of an innate granuloma
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+Fetal Intraparenchymal Hemorrhage Imaging Patterns, Etiology, and Outcomes: A Single Center Cohort Study
- Granulomas are defined by the presence of organized layers of immune cells that include macrophages. Granulomas are often characterized as a way for the immune system to contain an infection and prevent its dissemination. We recently established a mouse infection model where Chromobacterium violaceum induces the innate immune system to form granulomas in the liver. This response successfully eradicates the bacteria and returns the liver to homeostasis. Here, we sought to characterize the chemokines involved in directing immune cells to form the distinct layers of a granuloma. We use spatial transcriptomics to investigate the spatial and temporal expression of all CC and CXC chemokines and their receptors within this granuloma response. The expression profiles change dynamically over space and time as the granuloma matures and then resolves. To investigate the importance of monocyte-derived macrophages in this immune response, we studied the role of CCR2 during C. violaceum infection. Ccr2–/– mice had negligible numbers of macrophages, but large numbers of neutrophils, in the C. violaceum-infected lesions. In addition, lesions had abnormal architecture resulting in loss of bacterial containment. Without CCR2, bacteria disseminated and the mice succumbed to the infection. This indicates that macrophages are critical to form a successful innate granuloma in response to C. violaceum. +Objective
+This study examines associations among fetal brain magnetic resonance imaging (MRI) injury patterns, etiologies, and outcomes in fetal intraparenchymal hemorrhage (IPH).
+Methods
+This is a retrospective, single-center cohort study of IPH diagnosed on fetal MRI (1996–2022). IPH and associated abnormalities were categorized by 2 pediatric neuroradiologists; electronic medical records were reviewed by 2 pediatric neurologists to classify etiology and outcomes including cerebral palsy, epilepsy, developmental delay, and death.
+Results
+Forty-four fetuses with IPH were identified (34 singleton and 10 twin gestations) with MRI at median 24 weeks gestation (interquartile range [IQR] = 22–28 weeks). IPH was commonly supratentorial (84%) and focal (50%) or focal with diffuse injury (43%) and was often associated with germinal matrix hemorrhage (GMH; 75%) and/or intraventricular hemorrhage (IVH; 52%). An etiology was identified in 75%, including twin-twin transfusion syndrome (TTTS, n = 10), COL4A1/2 variants (n = 8), or other fetal/maternal conditions (n = 15). COL4A1/2 variants were associated with focal IPH and the presence of hemorrhagic porencephaly, and intrauterine transfusion was associated with infratentorial hemorrhage. Twenty-two fetuses were liveborn, and 18 pregnancies were terminated. Among those with follow-up ≥ 12 months (median = 7 years), 12 of 13 had cerebral palsy, 6 of 13 had developmental delay, and 5 of 13 had epilepsy.
+Interpretation
+An etiology for fetal IPH with or without GMH-IVH is identified in most cases in our cohort and is commonly TTTS, COL4A1/2 variants, or other maternal/fetal comorbidities. Pattern of fetal IPH on MRI is associated with etiology. Cerebral palsy and neurodevelopmental impairment were common in liveborn infants. Genetic studies should be considered in cases of fetal IPH without an otherwise apparent cause. ANN NEUROL 2024;96:1137–1147
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses
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+Comparison of Perfusion Imaging Definitions of the No‐Reflow Phenomenon after Thrombectomy—What Is the Best Perfusion Imaging Definition?
- The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic and sensory information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells of the DG play a role in memory encoding and information processing and are deeply affected in humans suffering Alzheimer’s disease and temporal lobe epilepsy, contributing to the dysfunctions found in these pathologies. The plasticity of these synapses is not well known yet, as are not known the forms of long-term depression (LTD) existing at those connections. We investigated whether spike timing-dependent long-term depression (t-LTD) exists at these two different EC-DG synaptic connections in mice, and whether they have different action mechanisms. We have found two different forms of t-LTD, at LPP- and MPP-GC synapses and characterised their cellular and intracellular mechanistic requirements. We found that both forms of t-LTD are expressed presynaptically and that whereas t-LTD at LPP-GC synapses does not require NMDAR, t-LTD at MPP-GC synapses requires ionotropic NMDAR containing GluN2A subunits. The two forms of t-LTD require different group I mGluR, mGluR5 LPP-GC synapses and mGluR1 MPP-GC synapses. In addition, both forms of t-LTD require postsynaptic calcium, eCB synthesis, CB1R, astrocyte activity, and glutamate released by astrocytes. Thus, we discovered two novel forms of t-LTD that require astrocytes at EC-GC synapses. +The no-reflow phenomenon is a potential contributor to poor outcome despite successful thrombectomy. There are multiple proposed imaging-based definitions of no-reflow leading to wide variations in reported prevalence. We investigated the agreement between existing imaging definitions and compared the characteristics and outcomes of patients identified as having no-reflow.
+Methods
+We performed an external validation of 4 existing published definitions of no-reflow in thrombectomy patients with extended Thrombolysis in Cerebral Infarction scale 2c to 3 (eTICI2c-3) angiographic reperfusion who underwent 24-hour perfusion imaging from 2 international randomized controlled trials (EXTEND-IA TNK part-1 and 2) and a multicenter prospective observational study. Receiver-operating-characteristic and Bayesian-information-criterion (BIC) analyses were performed with the outcome variable being dependent-or-dead at 90-days (modified Rankin Score [mRS] ≥3).
+Results
+Of 131 patients analyzed, the prevalence of no-reflow significantly varied between definitions (0.8–22.1%; p < 0.001). There was poor agreement between definitions (kappa 5/6 comparisons <0.212). Among patients with no-reflow according to at least 1 definition, there were significant differences between definitions in the intralesional interside differences in cerebral blood flow (CBF) (p = 0.006), cerebral blood volume (CBV) (p < 0.001), and mean-transit-time (MTT) (p = 0.005). No-reflow defined by 3 definitions was associated with mRS ≥3 at 90 days. The definition of >15% CBV or CBF asymmetry was the only definition that improved model fit on BIC analysis (ΔBIC = −8.105) and demonstrated an association between no-reflow and clinical outcome among patients with eTICI3 reperfusion.
+Conclusions
+Existing imaging definitions of no-reflow varied significantly in prevalence and post-treatment perfusion imaging profile, potentially explaining the variable prevalence of no-reflow reported in literature. The definition of >15% CBV or CBF asymmetry best discriminated for functional outcome at 90 days, including patients with eTICI3 reperfusion. ANN NEUROL 2024;96:1104–1114
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Isobaric crosslinking mass spectrometry technology for studying conformational and structural changes in proteins and complexes
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+Interferon Stimulated Gene Expression Is a Biomarker for Primary Mitochondrial Disease
- Dynamic conformational and structural changes in proteins and protein complexes play a central and ubiquitous role in the regulation of protein function, yet it is very challenging to study these changes, especially for large protein complexes, under physiological conditions. Here, we introduce a novel isobaric crosslinker, Qlinker, for studying conformational and structural changes in proteins and protein complexes using quantitative crosslinking mass spectrometry. Qlinkers are small and simple, amine-reactive molecules with an optimal extended distance of ~10 Å, which use MS2 reporter ions for relative quantification of Qlinker-modified peptides derived from different samples. We synthesized the 2-plex Q2linker and showed that the Q2linker can provide quantitative crosslinking data that pinpoints key conformational and structural changes in biosensors, binary and ternary complexes composed of the general transcription factors TBP, TFIIA, and TFIIB, and RNA polymerase II complexes. +Objective
+Mitochondria are implicated in regulation of the innate immune response. We hypothesized that abnormalities in interferon signaling may contribute to pathophysiology in patients with primary mitochondrial disease (PMD).
+Methods
+Expression of interferon stimulated genes (ISGs) was measured by real-time polymerase chain reaction (PCR) in whole blood samples from a cohort of patients with PMD.
+Results
+Upregulated ISG expression was observed in a high proportion (41/55, 75%) of patients with PMD on at least 1 occasion, most frequently IFI27 upregulation, seen in 50% of the samples. Some patients had extremely high IFI27 levels, similar to those seen in patients with primary interferonopathies. A statistically significant correlation was observed between elevated IFI27 gene expression and PMD, but not between IFI27 and secondary mitochondrial dysfunction, suggesting that ISG upregulation is a biomarker of PMD. In some patients with PMD, ISG abnormalities persisted on repeat measurement over several years, indicative of ongoing chronic inflammation. Subgroup analyses suggested common ISG signatures in patients with similar mitochondrial disease mechanisms and positive correlations with disease severity among patients with identical genetic diagnoses.
+Interpretation
+Dysregulated interferon signaling is frequently seen in patients with PMD suggesting that interferon dysregulation is a contributor to pathophysiology. This may indicate a role for repurposing of immunomodulatory therapies for the treatment of PMDs by targeting interferon signaling. ANN NEUROL 2024;96:1185–1200
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-An antimicrobial drug recommender system using MALDI-TOF MS and dual-branch neural networks
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+Prevalence and Distribution of Intracranial Vessel Occlusion on Angiography and Its Association with Functional Outcome in Patients with Atrial Fibrillation Presenting with Ischemic Stroke
- Timely and effective use of antimicrobial drugs can improve patient outcomes, as well as help safeguard against resistance development. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently routinely used in clinical diagnostics for rapid species identification. Mining additional data from said spectra in the form of antimicrobial resistance (AMR) profiles is, therefore, highly promising. Such AMR profiles could serve as a drop-in solution for drastically improving treatment efficiency, effectiveness, and costs. This study endeavors to develop the first machine learning models capable of predicting AMR profiles for the whole repertoire of species and drugs encountered in clinical microbiology. The resulting models can be interpreted as drug recommender systems for infectious diseases. We find that our dual-branch method delivers considerably higher performance compared to previous approaches. In addition, experiments show that the models can be efficiently fine-tuned to data from other clinical laboratories. MALDI-TOF-based AMR recommender systems can, hence, greatly extend the value of MALDI-TOF MS for clinical diagnostics. All code supporting this study is distributed on PyPI and is packaged at https://github.com/gdewael/maldi-nn. +Objectives
+To determine the prevalence and distribution of intracranial vessel occlusion identified on computed tomography (CT) or magnet resonance (MR) angiography and to explore its association with functional outcome in patients with atrial fibrillation (AF) and ischemic stroke.
+Methods
+Multicenter cohort study enrolling consecutive patients with AF with imaging-confirmed ischemic stroke who underwent CT- or MR-angiography on admission (2014–2022). Multivariable regression was used to explore the association between intracranial vessel occlusion and poor functional outcome (modified Rankin Scale score 3–6) at 90 days.
+Results
+The analysis included 10,164 patients (median age 81.5 years, 47.8% female, median National Institutes of Health Stroke Scale score on admission 6; 14.7% on a vitamin K antagonist [VKA], 27.5% on a direct oral anticoagulant [DOAC], 57.8% not receiving oral anticoagulation). Angiography showed intracranial vessel occlusion in 5,190 patients (51.1%), affecting the anterior cerebral circulation in 87.4%. Overall, 29.2% and 29.4% of patients received thrombolysis and mechanical thrombectomy, respectively. The proportion of patients with poor functional outcome at 90 days was 60.6% and 42.7% in those with and without vessel occlusion, respectively. In multivariable analyses, vessel occlusion was associated with poor functional outcome (adjusted odds ratio [aOR]: 1.95, 95% confidence interval [CI]: 1.71–2.22) with consistent results in subgroups according to oral anticoagulation use (VKA, aOR: 1.98, 95% CI: 1.40–2.80; DOAC, aOR: 2.35, 95% CI: 1.83–3.03; none, aOR: 1.76, 95% CI: 1.49–2.09).
+Interpretation
+Intracranial vessel occlusion is common in patients with AF with ischemic stroke, mainly affects the anterior circulation and is associated with poor functional outcome. ANN NEUROL 2024;96:1115–1123
-in eLife on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Feature similarity: a sensitive method to capture the functional interaction of brain regions and networks to support flexible behavior
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+The Relationship between Framingham Stroke Risk Profile on Incident Dementia and Alzheimer's Disease: A 40‐Year Follow‐Up Study Highlighting Female Vulnerability
- The brain is a dynamic system where complex behaviours emerge from interactions across distributed regions. Accurately linking brain function to cognition requires tools that are sensitive to these dynamics. We introduce a novel technique - Feature Similarity (FS) - to capture intricate interaction patterns between brain systems. Our results show that FS can capture functional brain organisation: regions within the same functional network have greater FS compared to those in different networks, and FS also identifies the principal gradient that spans from unimodal to transmodal cortices. FS was found to be more sensitive to task modulation than traditional functional connectivity (FC). Specifically, FS reveals interaction patterns missed by FC, such as a double dissociation in the Dorsal Attention Network (DAN): greater interaction with the Visual network during working memory tasks and greater interaction with the default mode network (DMN) during long-term memory tasks. This study highlights FS as a promising tool for understanding flexibility in brain network dynamics. +Objective
+Sex differences in the association between cardiovascular risk factors and the incident all-cause dementia and the subtype Alzheimer's disease (AD) risk are unclear.
+Methods
+Framingham Heart Study (FHS) participants (n = 4,171, 54% women, aged 55 to 69 years) were included at baseline and followed up to 40 years. The Framingham Stroke Risk Profile (FSRP) was dichotomized into 2 levels (cutoff: 75th percentile of the FSRP z-scores). Cause-specific hazard models, with death as a competing event, and restricted mean survival time (RMST) model were used to analyze the association between FSRP levels and incident all-cause dementia and AD. Interactions between FSRP and sex were estimated, followed by a sex-stratified analysis to examine the sex modification effect.
+Results
+High FSRP was significantly associated with all-cause dementia (hazard ratio [HR] = 1.25, robust 95% confidence interval [CI] = 1.21 to 1.29, p < 0.001) and AD (HR = 1.58, robust 95% CI = 1.57 to 1.59, p < 0.001) in cause-specific hazard models. High FSRP was significantly associated with incident dementia (HR = 2.81, robust 95% CI = 2.75 to 2.87, p < 0.001) and AD (HR = 2.96, robust 95% CI = 2.36 to 3.71, p < 0.001) in women, but not in men. Results were consistent in the RMST models. Current diabetes and high systolic blood pressure as FSRP components were significantly associated with dementia and AD in women but not in men.
+Interpretation
+High FSRP in mid- to early late life is a critical risk factor for all-cause dementia and AD, particularly in women. Sex-specific interventions and further research to elucidate underlying mechanisms are warranted. ANN NEUROL 2024;96:1124–1134
-in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-SEX-RELATED GENE EXPRESSION IN THE POSTERODORSAL MEDIAL AMYGDALA OF CYCLING FEMALE RATS ALONG WITH PROLACTIN MODULATION OF LORDOSIS BEHAVIOR
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+Pro‐Ictal EEG Scheduling Improves the Yield of Epilepsy Monitoring: Validating the Use of Multiday Seizure Cycles to Optimize Video‐EEG Timing
- The rat posterodorsal medial amygdala (MePD) is sexually dimorphic, has a high concentration of receptors for gonadal hormones and prolactin (PRL), and modulates reproduction. To unravel genetic and functional data for this relevant node of the social behavior network, we studied the expression of ERalpha, ERbeta, GPER1, Kiss1, Kiss1R, PRGR, PRL, PRLR, EGR1, JAK2, STAT5A, and STAT5B in the MePD of males and females along the estrous cycle using the RT-qPCR technique. We also investigated whether PRL in the MePD would affect the sexual behavior display of proestrus females by microinjecting saline, the PRL receptor antagonist Del1-9-G129R-hPRL (1 microM and 10 microM), or PRL (1 nM) and Del1-9-G129R-hPRL (10 microM) 3h before the onset of the dark-cycle period. The estrogen-dependent lordosis behavior, indicative of sexual receptivity of proestrus females, was recorded and compared before (control) and after (test) microinjections in these groups. Sex differences were found in the right and left MePD gene expression. ERalpha and Kiss1R, as well as PRL, Short PRLR, and STAT5B expression is higher in cycling females than males. Kiss1 expression is higher in males than females, and GPER1 is higher during diestrus than proestrus. Furthermore, Del1-9-G129R-hPRL in the MePD significantly reduced the full display and quotient of lordosis in proestrus females, an effect restored by the co-microinjection of PRL. In conjunction, the expression of studied genes showed specific sex and estrous cycle phase features while, in proestrus, PRL action in the MePD plays an essential role in the display of lordosis during the ovulatory period. +Objective
+A significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. In this study, we introduce and validate “pro-ictal EEG scheduling”, a method to schedule vEEG monitoring to coincide with periods of increased seizure likelihood as a low-risk approach to enhance the diagnostic yield.
+Methods
+A database of long-term ambulatory vEEG monitoring sessions (n = 5,038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events) to generate cycle-based estimates of seizure risk. In adults, vEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (n = 305) and compared to remaining studies (baseline: n = 3,586). Test of proportions and risk-ratios (RR) were applied to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure, and diary event) during monitoring. The impact of clinical and demographic factors (age, sex, epilepsy-type, and medication) was also explored.
+Results
+During vEEG monitoring, the high-risk group was significantly more likely to have an abnormal vEEG report (190/305:62% vs 1,790/3,586:50% [%change = 12%], RR = 1.25, 95% confidence interval [CI] = [1.137–1.370], p < 0.001), present with a confirmed seizure (56/305:18% vs 424/3,586:11% [%change = 7%], RR = 1.63, 95% CI = [1.265–2.101], p < 0.001) and report an event (153/305:50% vs 1,267/3,586:35% (%change = 15%), RR = 1.420, 95% CI = [1.259:1.602], p < 0.001). Similar effects were observed across clinical and demographic features.
+Interpretation
+This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management. ANN NEUROL 2024;96:1148–1159
-in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 14:07:31 UTC.
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-Multimodal investigation of the neurocognitive deficits underlying dyslexia in adulthood
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+GeM-LR: Discovering predictive biomarkers for small datasets in vaccine studies
- Dyslexia is a neurobiological disorder characterised by reading difficulties, yet its underlying causes remain unclear. Neuroimaging and behavioural studies found anomalous responses in tasks requiring phonological processing, motion perception, and implicit learning, and showed gray and white matter abnormalities in several brain regions of dyslexics compared to controls, indicating that dyslexia is a heterogeneous condition and promoting a multifactorial approach. In order to evaluate whether the combination of behavioural and multimodal MRI can have greater sensitivity in identifying neurocognitive traits of dyslexia compared to monocomponential approaches, in 19 dyslexic and 19 control subjects we acquired behavioural cognitive assessments, multiple (phonological, visual motion, rhythmic) mismatch-response functional MRI tasks, structural diffusion-weighted and T1-weighted images. To examine between-group differences in the multimodal neurocognitive measures, we applied univariate and multivariate approaches. Results showed that dyslexics performed worse than controls in behavioural phonological tasks. Neuroimaging analyses revealed that individuals with dyslexia present reduced cerebellar responses to mismatching rhythmic stimuli, as well as structural disorganization in several white matter tracts and cortical regions previously implicated in dyslexia. Most importantly, in line with the view of dyslexia as a multifactorial phenomenon, a machine learning model trained with features from all three MRI modalities (functional, diffusion, and T1-weighted) discriminated between dyslexics and controls with greater accuracy than models including just one modality. The individual classification scores in the multimodal machine learning model correlated with behavioural reading accuracy. These results confirm that dyslexia should be approached as a composite condition characterised by multiple distinctive cognitive and brain features. +by Lin Lin, Rachel L. Spreng, Kelly E. Seaton, S. Moses Dennison, Lindsay C. Dahora, Daniel J. Schuster, Sheetal Sawant, Peter B. Gilbert, Youyi Fong, Neville Kisalu, Andrew J. Pollard, Georgia D. Tomaras, Jia Li
+ +Despite significant progress in vaccine research, the level of protection provided by vaccination can vary significantly across individuals. As a result, understanding immunologic variation across individuals in response to vaccination is important for developing next-generation efficacious vaccines. Accurate outcome prediction and identification of predictive biomarkers would represent a significant step towards this goal. Moreover, in early phase vaccine clinical trials, small datasets are prevalent, raising the need and challenge of building a robust and explainable prediction model that can reveal heterogeneity in small datasets. We propose a new model named Generative Mixture of Logistic Regression (GeM-LR), which combines characteristics of both a generative and a discriminative model. In addition, we propose a set of model selection strategies to enhance the robustness and interpretability of the model. GeM-LR extends a linear classifier to a non-linear classifier without losing interpretability and empowers the notion of predictive clustering for characterizing data heterogeneity in connection with the outcome variable. We demonstrate the strengths and utility of GeM-LR by applying it to data from several studies. GeM-LR achieves better prediction results than other popular methods while providing interpretations at different levels. -in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in PLoS Computational Biology on 2024-11-14 14:00:00 UTC.
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-Comparative analysis of spike-sorters in large-scale brainstem recordings
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+Human-like dissociations between confidence and accuracy in convolutional neural networks
- Recent technological advancements in high-density multi-channel electrodes have made it possible to record large numbers of neurons from previously inaccessible regions. While the performance of automated spike-sorters has been assessed in recordings from cortex, dentate gyrus, and thalamus, the most effective and efficient approach for spike-sorting can depend on the target region due to differing morphological and physiological characteristics. We therefore assessed the performance of five commonly used sorting packages, Kilosort3, MountainSort5, Tridesclous, SpyKING CIRCUS, and IronClust, in recordings from the rostral ventromedial medulla, a region that has been characterized using single-electrode recordings but that is essentially unexplored at the high-density network level. As demonstrated in other brain regions, each sorter produced unique results. Manual curation preferentially eliminated units detected by only one sorter. Kilosort3 and IronClust required the least curation while maintaining the largest number of units, whereas SpyKING CIRCUS and MountainSort5 required substantial curation. Tridesclous consistently identified the smallest number of units. Nonetheless, all sorters successfully identified classically defined RVM physiological cell types. These findings suggest that while the level of manual curation needed may vary across sorters, each can extract meaningful data from this deep brainstem site. +by Medha Shekhar, Dobromir Rahnev
+ +Prior research has shown that manipulating stimulus energy by changing both stimulus contrast and variability results in confidence-accuracy dissociations in humans. Specifically, even when performance is matched, higher stimulus energy leads to higher confidence. The most common explanation for this effect, derived from cognitive modeling, is the positive evidence heuristic where confidence neglects evidence that disconfirms the choice. However, an alternative explanation is the signal-and-variance-increase hypothesis, according to which these dissociations arise from changes in the separation and variance of perceptual representations. Because artificial neural networks lack built-in confidence heuristics, they can serve as a test for the necessity of confidence heuristics in explaining confidence-accuracy dissociations. Therefore, we tested whether confidence-accuracy dissociations induced by stimulus energy manipulations emerge naturally in convolutional neural networks (CNNs). We found that, across three different energy manipulations, CNNs produced confidence-accuracy dissociations similar to those found in humans. This effect was present for a range of CNN architectures from shallow 4-layer networks to very deep ones, such as VGG-19 and ResNet-50 pretrained on ImageNet. Further, we traced back the reason for the confidence-accuracy dissociations in all CNNs to the same signal-and-variance increase that has been proposed for humans: higher stimulus energy increased the separation and variance of evidence distributions in the CNNs’ output layer leading to higher confidence even for matched accuracy. These findings cast doubt on the necessity of the positive evidence heuristic to explain human confidence and establish CNNs as promising models for testing cognitive theories of human behavior. -in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in PLoS Computational Biology on 2024-11-14 14:00:00 UTC.
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-Brain functional network connectivity interpolation characterizes neuropsychiatric continuum and heterogeneity
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+AI-powered simulation-based inference of a genuinely spatial-stochastic gene regulation model of early mouse embryogenesis
- Psychiatric disorders such as schizophrenia (SZ) and autism spectrum disorder (ASD) are challenging to characterize in part due to their heterogeneous presentation in individuals, with psychotic symptoms now thought to exist on a continuum from the general population to chronic SZ. Conventional diagnostic and neuroimaging analytical approaches rely on subjective assessment or group differences, but typically ignore progression between groups or heterogeneity within a group. Here, we propose a functional network connectivity (FNC) interpolation framework based on an unsupervised generative model, a variational autoencoder (VAE), to estimate the neuropsychiatric continuum and heterogeneity using static FNC (sFNC) and dynamic FNC (dFNC) data from controls and patients with SZ or ASD. We first demonstrate that VAEs significantly outperform a linear baseline and a semi-supervised counterpart in the interpolation task. We next utilize VAEs to perform sFNC and dFNC interpolation separately. For sFNC interpolation, we observe a high degree of correspondence between the generated sFNC and the corresponding original sFNC. We display the sFNC matrices on a two-dimensional grid to examine individual- and group-specific patterns, as well as pattern alterations. Specifically, the interpolated continua from patients to controls in both disorders show increased hyper-connectivity within the auditory, sensorimotor and visual networks, and between the subcortical and cerebellar domains, as well as hypo-connectivity between the subcortical domain and the sensory domains, and between the cerebellar domain and the sensory regions. For dFNC interpolation, we find that the generated dFNC states effectively capture representative and generalizable dynamic properties for each group. Finally, we show examples of how to leverage interpolation in the VAE latent space, following pathological, state-based, or temporal trajectories. The proposed framework offers added advantages over traditional methods, including data-driven discovery of hidden relationships, visualization of individual differences, imputation of missing values along a continuous spectrum, and estimation of the stage where an individual falls within the continuum. Further, it could potentially be applied to identify patient subgroups and predict future disorder progression. +by Michael Alexander Ramirez Sierra, Thomas R. Sokolowski
+ +Understanding how multicellular organisms reliably orchestrate cell-fate decisions is a central challenge in developmental biology, particularly in early mammalian development, where tissue-level differentiation arises from seemingly cell-autonomous mechanisms. In this study, we present a multi-scale, spatial-stochastic simulation framework for mouse embryogenesis, focusing on inner cell mass (ICM) differentiation into epiblast (EPI) and primitive endoderm (PRE) at the blastocyst stage. Our framework models key regulatory and tissue-scale interactions in a biophysically realistic fashion, capturing the inherent stochasticity of intracellular gene expression and intercellular signaling, while efficiently simulating these processes by advancing event-driven simulation techniques. Leveraging the power of Simulation-Based Inference (SBI) through the AI-driven Sequential Neural Posterior Estimation (SNPE) algorithm, we conduct a large-scale Bayesian inferential analysis to identify parameter sets that faithfully reproduce experimentally observed features of ICM specification. Our results reveal mechanistic insights into how the combined action of autocrine and paracrine FGF4 signaling coordinates stochastic gene expression at the cellular scale to achieve robust and reproducible ICM patterning at the tissue scale. We further demonstrate that the ICM exhibits a specific time window of sensitivity to exogenous FGF4, enabling lineage proportions to be adjusted based on timing and dosage, thereby extending current experimental findings and providing quantitative predictions for both mutant and wild-type ICM systems. Notably, FGF4 signaling not only ensures correct EPI-PRE lineage proportions but also enhances ICM resilience to perturbations, reducing fate-proportioning errors by 10-20% compared to a purely cell-autonomous system. Additionally, we uncover a surprising role for variability in intracellular initial conditions, showing that high gene-expression heterogeneity can improve both the accuracy and precision of cell-fate proportioning, which remains robust when fewer than 25% of the ICM population experiences perturbed initial conditions. Our work offers a comprehensive, spatial-stochastic description of the biochemical processes driving ICM differentiation and identifies the necessary conditions for its robust unfolding. It also provides a framework for future exploration of similar spatial-stochastic systems in developmental biology. -in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in PLoS Computational Biology on 2024-11-14 14:00:00 UTC.
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-Older is Order: Entropy reduction in cortical spontaneous activity marks healthy aging
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+Decrease in decision noise from adolescence into adulthood mediates an increase in more sophisticated choice behaviors and performance gain
- Entropy trajectories remain unclear for the aging process of human brain system due to the lacking of longitudinal neuroimaging resource. We used open data from an accelerated longitudinal cohort (PREVENT-AD) that included 24 healthy aging participants followed by 4 years with 5 visits per participant to establish cortical entropy aging curves and distinguish with the effects of age and cohort. This reveals that global cortical entropy decreased with aging, while a significant cohort effect was detectable that people who were born earlier showed higher cortical entropy. Such entropy reductions were also evident for large-scale cortical networks, although with different rates of reduction for different networks. Specifically, the primary and intermediate networks reduce their entropy faster than the higher-order association networks. We conclude two specific characteristics of the entropy of the human cortex with aging: the shift of the complexity hierarchy and the diversity of complexity strengthen. +by Vanessa Scholz, Maria Waltmann, Nadine Herzog, Annette Horstmann, Lorenz Deserno
+ +Learning and decision-making undergo substantial developmental changes, with adolescence being a particular vulnerable window of opportunity. In adolescents, developmental changes in specific choice behaviors have been observed (e.g., goal-directed behavior, motivational influences over choice). Elevated levels of decision noise, i.e., choosing suboptimal options, were reported consistently in adolescents. However, it remains unknown whether these observations, the development of specific and more sophisticated choice processes and higher decision noise, are independent or related. It is conceivable, but has not yet been investigated, that the development of specific choice processes might be impacted by age-dependent changes in decision noise. To answer this, we examined 93 participants (12 to 42 years) who completed 3 reinforcement learning (RL) tasks: a motivational Go/NoGo task assessing motivational influences over choices, a reversal learning task capturing adaptive decision-making in response to environmental changes, and a sequential choice task measuring goal-directed behavior. This allowed testing of (1) cross-task generalization of computational parameters focusing on decision noise; and (2) assessment of mediation effects of noise on specific choice behaviors. Firstly, we found only noise levels to be strongly correlated across RL tasks. Second, and critically, noise levels mediated age-dependent increases in more sophisticated choice behaviors and performance gain. Our findings provide novel insights into the computational processes underlying developmental changes in decision-making: namely a vital role of seemingly unspecific changes in noise in the specific development of more complex choice components. Studying the neurocomputational mechanisms of how varying levels of noise impact distinct aspects of learning and decision processes may also be key to better understand the developmental onset of psychiatric diseases. -in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in PLoS Biology on 2024-11-14 14:00:00 UTC.
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-Modeling Complex Animal Behavior with Latent State Inverse Reinforcement Learning
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+Immigrant birds learn from socially observed differences in payoffs when their environment changes
- Understanding complex animal behavior is crucial for linking brain computation to observed actions. While recent research has shifted towards modeling behavior as a dynamic process, few approaches exist for modeling long-term, naturalistic behaviors such as navigation. We introduce discrete Dynamical Inverse Reinforcement Learning (dDIRL), a latent state-dependent paradigm for modeling complex animal behavior over extended periods. dDIRL models animal behavior as being driven by internal state-specific rewards, with Markovian transitions between the distinct internal states. Using expectation-maximization, we infer reward functions corresponding to each internal states and the transition probabilities between them, from observed behavior. We applied dDIRL to water-starved mice navigating a labyrinth, analyzing each animal individually. Our results reveal three distinct internal states sufficient to describe behavior, including a consistent water-seeking state occupied for less than half the time. We also identified two clusters of animals with different exploration patterns in the labyrinth. dDIRL offers a nuanced understanding of how internal states and their associated rewards shape observed behavior in complex environments, paving the way for deeper insights into the neural basis of naturalistic behavior. +by Michael Chimento, Gustavo Alarcón-Nieto, Lucy M. Aplin
+ +Longstanding theory predicts that strategic flexibility in when and how to use social information can help individuals make adaptive decisions, especially when environments are temporally or spatially variable. A short-term increase in reliance on social information under these conditions has been experimentally shown in primates, including humans, but whether this occurs in other taxa is unknown. We asked whether migration between spatially variable environments affected social information use with a large-scale cultural diffusion experiment with wild great tits (Parus major) in captivity, a small passerine bird that can socially learn novel behaviors. We simulated an immigration event where knowledgeable birds were exchanged between groups with opposing preferences for a socially learned foraging puzzle, living in similar or different environments. We found evidence that both immigrants and residents were influenced by social information and attended to the rewards that others received. Our analysis supported the use of a payoff-biased social learning by immigrants when both resources and habitat features were spatially variable. In contrast, immigrants relied more-so on individual learning when payoffs or the environment were unchanged. In summary, our results suggest that great tits assess the payoffs others receive and are more influenced by socially observed differences in payoffs when environmental cues differ in their new environment. Our results provide experimental support for the hypothesis that spatial variability is a strong driver for the evolution of social learning strategies. -in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in PLoS Biology on 2024-11-14 14:00:00 UTC.
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-Interactions established by isoform-specific TrkB-T1 sequences govern inflammatory response and neurotoxicity in stroke
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+Sex‐Specific Vulnerabilities to Subclinical Vascular Brain Injury in Early Late‐Life: The Framingham Heart Study
- Glia reactivity, neuroinflammation and excitotoxic neuronal death are central processes to ischemic stroke and neurodegenerative diseases, altogether a leading cause of death, disability, and dementia. Due to the high incidence of these pathologies and the lack of efficient treatments, it is a priority developing brain protective therapies impacting both neurons and glial cells. Truncated neurotrophin receptor TrkB-T1, a protein produced by all these cells, plays relevant roles in excitotoxicity and ischemia. We have hypothesized that interactions established by isoform-specific TrkB-T1 sequences might be relevant to neurotoxicity and/or reactive gliosis and, therefore, constitute a therapeutic target. We identify here the TrkB-T1-specific interactome, poorly described to date, and demonstrate that interference of these protein-protein interactions using brain-accessible TrkB-T1-derived peptides can prevent reactive gliosis and decrease excitotoxicity-induced damage in cellular and mouse models of stroke. The pivotal role played by TrkB-T1 on microglia and astrocyte reactivity suggests that isoform-derived peptides could become important in development of therapies for human stroke and other excitotoxicity-associated pathologies. +Objective
+Subclinical vascular brain injury is an increasingly recognized risk factor for stroke and dementia. Despite well-established sex differences in vascular risk and disease prevalence, the impact of sex on drivers of subclinical vascular brain injury remains unclear, presenting a barrier to developing sex-specific prevention guidelines. We aimed to establish the extent to which sex moderates associations between vascular risk factors and magnetic resonance imaging (MRI) measures of subclinical brain injury in stroke-free older adults.
+Methods
+We leveraged cross-sectional data from 1,579 stroke- and dementia-free Framingham Heart Study Offspring participants at exam 8 (age 65.7 ± 8.8 years, 53% women). Vascular risks were assessed using components of the Framingham Stroke Risk Profile (FSRP) and diastolic blood pressure (DBP). White matter hyperintensity volume (WMH), total cerebral brain volume (TBV), and covert brain infarcts were quantified using MRI. We examined whether vascular risk factors were associated with MRI measures across the combined cohort, and then determined whether sex modified these associations.
+Results
+Higher FSRP and specifically systolic blood pressure (SBP) were associated with greater WMH. These associations were stronger in women and remained after adjusting for menopause age and hormone therapy use. By contrast, diabetes and lower DBP were associated with smaller TBV primarily in men. The DBP-atrophy relationship was only observed in men with declining DBP or prior hypertension.
+Interpretation
+Our findings highlight differential vulnerability to the impact of vascular risk factors on white matter health in women and global atrophy in men, supporting the development of sex-specific guidelines to better preserve vascular brain health in aging. ANN NEUROL 2024
-in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 10:14:09 UTC.
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-A Unified Approach for Identifying PET-based Neuronal Activation and Molecular Connectivity with the functional PET toolbox
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+Distinct Constructs Underlie Patient‐Reported and Performance‐Rated Outcomes after Stroke
- Purpose: Functional PET (fPET) enables the identification of stimulation-specific changes of various physiological processes (e.g., glucose metabolism, neurotransmitter synthesis) as well as computation of individual molecular connectivity and group-level molecular covariance. However, currently no consistent analysis approach is available for these techniques. We present a versatile, freely available toolbox designed for the analysis of fPET data, thereby filling a gap in the assessment of neuroimaging data. Methods: The fPET toolbox supports analyses for a variety of radiotracers, scanners, experimental protocols, cognitive tasks and species. It includes general linear model (GLM)-based assessment of task-specific effects, percent signal change and absolute quantification, as well as independent component analysis (ICA) for data-driven analyses. Furthermore, it allows computation of molecular connectivity via temporal correlations of PET signals between regions and molecular covariance as between-subject covariance using static images. Results: Toolbox performance was validated by analysis protocols established in previous work. Stimulation-induced changes in [18F]FDG metabolic demands and neurotransmitter dynamics obtained with 6-[18F]FDOPA and [11C]AMT were robustly detected across different cognitive tasks. Molecular connectivity analysis demonstrated metabolic interactions between different networks, whereas group-level covariance analysis highlighted interhemispheric relationships. These results underscore the flexibility of fPET in capturing dynamic molecular processes. Conclusions: The toolbox offers a comprehensive, unified and user-friendly platform for analyzing fPET data across a variety of experimental settings. It provides a reproducible analysis approach, which in turn facilitates sharing of analyses pipelines and comparison across centers to advance the study of brain metabolism and neurotransmitter dynamics in health and disease. +Objective
+Patient-reported outcome measures (PROMs), which capture patients' perspectives on the consequences of health and disease, are widely used in neurological care and research. However, it is unclear how PROMs relate to performance-rated impairments. Sociodemographic factors are known to affect PROMs. Direct damage to brain regions critical for self-awareness (i.e., parietal regions and the salience/ventral-attention network) may also impair self-report outcomes. This study examined the relationship between PROMs and performance-based measures in stroke survivors with arm motor impairments. We hypothesized that PROMs would be distinct from performance-based outcomes, influenced by sociodemographic factors, and linked to damage in brain circuits involved in self-perception.
+Methods
+We longitudinally assessed 54 stroke survivors using patient-reported and performance-rated measures at 4 timepoints. We used factor analysis to reveal the outcome battery's factorial structure. Linear regression examined the association between classes of measures and sociodemographics. Voxel-lesion-symptom-mapping, region-of-interest-based analysis, and voxel-lesion-network-mapping investigated the relationship between classes of outcomes and stroke-related injury.
+Results
+Performance-based and patient-reported measures formed distinct factors, consistent across recovery phases. Higher education (β1 = 0.36, p = 0.02) and income adequacy (β2 = 0.48, p = 0.05) were associated with patient-reported, but not performance-rated outcomes. Greater parietal lobe injury, irrespective of hemisphere, was associated with worse patient-reported outcomes; greater corticospinal tract injury related to worse performance-rated outcomes. Lesions with greater functional connectivity to the salience/ventral-attention network were associated with worse patient-reported outcomes (r = −0.35, p = 0.009).
+Interpretation
+Our findings reveal important differences between performance-rated and patient-reported outcomes, each with specific associated factors and anatomy post-stroke. Incorporating sociodemographic and neuroanatomic characteristics into neurorehabilitation strategies may inform and optimize patient outcomes. ANN NEUROL 2024
-in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Annals of Neurology on 2024-11-14 09:56:32 UTC.
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-Bidirectional Impact of miR-29a modulation on Memory Stability in the Adult Brain
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+The Demographic Profile of Colorectal Cancer Patients in Indonesia: Insights from a Single Center Experience and Exploration of Immune Response and Survival Outcomes [version 1; peer review: awaiting peer review]
- MicroRNAs are key regulators of brain gene expression, with miR-29a notably upregulated from development to adulthood and in aging, and showing links to cognitive decline. However, the extent to which miR-29 levels influence learning and memory processes, and its molecular mediators, remains to be determined. Here, we down- and up-regulated miR-29a levels in the dorsal hippocampus of adult mice to reveal miR-29 role in memory. Inhibiting miR-29a enhanced trace fear memory stability, increased Dnmt3a levels, and affected CpG methylation in gene regulation regions. In contrast, increasing miR-29a impaired memory performances and decreased Dnmt3a levels, suggesting a destabilization of memory processes. Proteomic and transcriptomic analysis demonstrated that miR-29a antagonism upregulated RNA-binding and synaptic proteins and downregulated inflammation and myelin associated proteins. These results underscore miR-29a pivotal role in memory persistence, plasticity, and cognitive aging, suggesting that miR-29a modulation could offer potential strategies for cognitive enhancement and age-related memory decline. + Background Understanding the demographics, tumor characteristics, genetic mutations, and immune scores in colorectal cancer (CRC) patients may aid in tailoring treatment and predicting survival. Methods This retrospective cohort study assessed clinical parameters, immune scores, and their relationship with survival in patients with CRC. Results The study included 74 patients, mean age 53.7 years, mostly male (53.3%) and aged 41-70 (77.3%). Common comorbidities included cardiovascular diseases (29.3%) and hypertension (21.3%). Adenocarcinoma (74%) primarily affects the colon (73%). KRAS mutations and Microsatellite instability-High (MSI-H)/deficient mismatch repair (dMMR) were found in 1.3% and 16% of patients, respectively. Stage IV (77.3%) and liver metastases (52.7%) were prevalent. Immune score was influenced by cancer stage (p = 0.04) and metastasis (p=0.05). The immune score was not associated with survival (p = 0.181). Patients with comorbidities had lower one- (p = 0.027) and two-year survival rates (p = 0.037) survival rates. Cardiovascular comorbidities negatively impacted one-year survival (p = 0.047) and two-year survival (p = 0.037). The mean survival time was shorter for males (2.047±0.288 vs. 2.781±0.195 years, p = 0.041), patients with comorbidities (1.772±0.371 vs. 2.702±0.188 years, p = 0.017), and cardiovascular comorbidities (1.558±0.316 vs. 2.685±0.207 years, p = 0.038). Comorbidities (unadjusted hazard ratio [HR] 2.948, p = 0.023) and cardiovascular comorbidities (unadjusted HR 2.695, p = 0.046) were initially associated with survival but lost significance after adjusting for confounding variables. Conclusions This study provides insights into CRC patient demographics and their interplay with the immune score and survival. -in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in F1000Research on 2024-11-14 09:48:09 UTC.
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-Sulfatide deficiency-induced astrogliosis and myelin lipid dyshomeostasis are independent of Trem2-mediated microglial activation
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+The metaphors of artificial intelligence
- Disrupted lipid homeostasis and neuroinflammation often co-exist in neurodegenerative disorders including Alzheimer's disease (AD). However, the intrinsic connection and causal relationship between these deficits remain elusive. Our previous studies show that the loss of sulfatide (ST), a class of myelin-enriched lipids, causes AD-like neuroinflammatory responses, cognitive impairment, bladder enlargement, as well as lipid dyshomeostasis. To better understand the relationship between neuroinflammation and lipid disruption induced by ST deficiency, we established a ST-deficient mouse model with constitutive Trem2 knockout and studied the impact of Trem2 in regulating ST deficiency-induced microglia-mediated neuroinflammation, astrocyte activation and lipid disruption. Our study demonstrates that Trem2 regulates ST deficiency-induced microglia-mediated neuroinflammatory pathways and astrogliosis at the transcriptomic level, but not astrocyte activation at the protein level, suggesting that Trem2 is indispensable for ST deficiency-induced microglia-mediated neuroinflammation but not astrogliosis. Meanwhile, ST loss-induced lipidome disruption and free water retention were consistently observed in the absence of Trem2. Collectively, these results emphasize the essential role of Trem2 in mediating lipid loss-associated microglia-mediated neuroinflammation, but not both astrogliosis and myelin lipid disruption. Moreover, we demonstrated that attenuating neuroinflammation has a limited impact on brain ST loss-induced lipidome alteration or AD-like peripheral disorders. Our findings suggest that preserving lipidome and astrocyte balance may be crucial in decelerating the progression of AD. + Science, Volume 386, Issue 6723, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 08:00:00 UTC.
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-Spatial Transcriptomic Analysis Identifies a SERPINA3-Expressing Astrocytic State Associated with the Human Neuritic Plaque Microenvironment
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+A voyage to victory
- Single-nucleus transcriptomic studies have revealed glial cell states associated with Alzheimer's disease; however, these nuclei are dissociated from the complex architecture of the human neocortex. Here, we successfully performed an unbiased distance-based analytic strategy on spatially-registered transcriptomic data. Leveraging immunohistochemistry in the same tissue section, our analyses prioritized SERPINA3 and other genes, such as metallothioneins, as altered in the vicinity of neuritic amyloid plaques. Results were validated at the protein level by immunofluorescence, highlighting that a reactive SERPINA3+ astrocyte subtype, Ast.5, plays a role in the plaque microenvironment. + Science, Volume 386, Issue 6723, Page 734-734, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Modeling of blood flow dynamics in the rat somatosensory cortex
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+Tomorrow’s trees
- The cerebral microvasculature forms a dense network of interconnected blood vessels where flow is modulated partly by astrocytes. Increased neuronal activity stimulates astrocytes to release vasoactive substances at the endfeet, altering the diameters of connected vessels. Our study simulated the coupling between blood flow variations and vessel diameter changes driven by astrocytic activity in the rat somatosensory cortex. We developed a framework with three key components: coupling between vasculature and synthesized astrocytic morphologies, a fluid dynamics model to compute flow in each vascular segment, and a stochastic process replicating the effect of astrocytic endfeet on vessel radii. The model was validated against experimental flow values from literature across cortical depths. We found that local vasodilation from astrocyte activity increased blood flow, especially in capillaries, exhibiting a layer-specific response in deeper cortical layers. Additionally, the highest blood flow variability occurred in capillaries, emphasizing their role in cerebral perfusion regulation. We discovered that astrocytic activity impacts blood flow dynamics in a localized, clustered manner, with most vascular segments influenced by two to three neighboring endfeet. These insights enhance our understanding of neurovascular coupling and guide future research on blood flow-related diseases. + Science, Volume 386, Issue 6723, Page 733-733, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Restoring Synaptic Balance in Schizophrenia: Insights from a thalamo-cortical conductance-based model.
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+Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states
- The dysconnectivity hypothesis of schizophrenia suggests that atypical, aberrant neural communication underlies the disorder's diverse symptoms. Building on this framework, our study introduces a novel approach to understanding schizophrenia and exploring potential ways to adjust neural activity through synaptic restoration. Using a combination of magnetoencephalography data and dynamic causal modeling, we identified specific synaptic disturbances in schizophrenia patients, including increased NMDA receptor-mediated excitation in superficial pyramidal neurons and reduced GABA-B receptor-mediated inhibition between interneurons and pyramidal cells. These findings reveal a critical imbalance in excitation and inhibition within thalamo-cortical circuits, manifesting as altered gamma and alpha oscillations. The cornerstone of our research is an in silico synaptic restoration analysis, which demonstrates that targeted modifications to AMPA, NMDA, GABA-A, and GABA-B receptor-mediated connections can recalibrate altered neural activity in schizophrenia, aligning it with healthy control patterns. This restoration approach not only highlights the complex nature of synaptic dysfunction in the disorder but also identifies specific pathways as potential therapeutic targets, offering new avenues for investigating schizophrenia's diverse symptomatology. + Science, Volume 386, Issue 6723, Page 802-810, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Astrocytic connexin43 phosphorylation contributes to seizure susceptibility after mild Traumatic Brain Injury
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+Pathogenic proteotoxicity of cryptic splicing is alleviated by ubiquitination and ER-phagy
- Astrocytes play a crucial role in maintaining brain homeostasis through functional gap junctions (GJs) primarily formed by connexin43 (Cx43). These GJs facilitate electrical and metabolic coupling between astrocytes, allowing the passage of ions, glucose, and metabolites. Dysregulation of Cx43 has been implicated in various pathologies, including traumatic brain injury (TBI) and acquired epilepsy. We previously identified a subset of atypical astrocytes after mild TBI that exhibit reduced Cx43 expression and coupling and are correlated with the development of spontaneous seizures. Given that mild TBI affects millions globally and can lead to long-term complications, including post-traumatic epilepsy, understanding the molecular events post-TBI is critical for developing therapeutic strategies. In the present study, we assessed the heterogeneity of Cx43 protein expression after mild TBI. In accordance with our previous findings, a subset of astrocytes lost Cx43 expression. As previously reported after TBI, we also found a significant increase in total Cx43 protein expression after mild TBI, predominantly in the soluble form, suggesting that while junctional Cx43 protein levels remained stable, hemichannels and cytoplasmic Cx43 were increased. We then investigated the phosphorylation of Cx43 at serine 368 after TBI, which is known to influence GJ assembly and function. Phosphorylation of Cx43 at serine 368 is elevated following TBI and Cx43S368A mutant mice, lacking this phosphorylation, exhibited reduced susceptibility to seizures induced by pentylenetetrazol (PTZ). These findings suggest that TBI-induced Cx43 phosphorylation enhances seizure susceptibility, while inhibiting this modification presents a potential therapeutic avenue for mitigating neuronal hyperexcitability and seizure development. + Science, Volume 386, Issue 6723, Page 768-776, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Dynamic prioritisation of sensory and motor contents in working memory
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+High-temperature carbon dioxide capture in a porous material with terminal zinc hydride sites
- Internal selective attention prioritises both sensory and motor contents in working memory to guide prospective behaviour. Prior research has shown how attention modulation of sensory contents is flexible and temporally tuned depending on access requirements, but whether the prioritisation of motor contents follows similar flexible dynamics remains elusive. Also uncharted is the degree of co-dependence of sensory and motor modulation, which gets at the nature of both working-memory representations and internal attention functions. To address these questions, we independently tracked the prioritisation of sensory and motor working-memory contents as a function of dynamically evolving temporal expectations. The design orthogonally manipulated when an item location (left vs right side) and associated prospective action (left vs right hand) would be relevant. Contralateral modulation of posterior alpha (8-12 Hz) activity in electroencephalography (EEG) tracked prioritisation of the item location, while contralateral modulation of central mu/beta (8-30 Hz) activity tracked response prioritisation. Proactive and dynamic alpha and mu/beta modulation confirmed the flexible and temporally structured prioritisation of sensory and motor contents alike. Intriguingly, the prioritisation of sensory and motor contents was temporally uncoupled, showing dissociable patterns of modulation. The findings reveal multiple modulatory functions of internal attention operating in tandem to prepare relevant aspects of internal representations for adaptive behaviour. + Science, Volume 386, Issue 6723, Page 814-819, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Pathological microcircuits initiate epileptiform events in patient hippocampal slices
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+Synchronous recognition of amines in oxidative carbonylation toward unsymmetrical ureas
- How seizures begin at the level of microscopic neural circuits remains unknown. High-density CMOS microelectrode arrays provide a new avenue for investigating neuronal network activity, with unprecedented spatial and temporal resolution. We use high-density CMOS-based microelectrode arrays to probe the network activity of human hippocampal brain slices from six patients with mesial temporal lobe epilepsy in the presence of hyperactivity promoting media. Two slices from the dentate gyrus exhibited epileptiform activity in the presence of low magnesium media with kainic acid. Both slices displayed an electrophysiological phenotype consistent with a reciprocally connected circuit, suggesting a recurrent feedback loop is a key driver of epileptiform onset. Larger prospective studies are needed, but these findings have the potential to elucidate the network signals underlying the initiation of seizure behavior. + Science, Volume 386, Issue 6723, Page 776-782, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-No Effect of Value on the Task Irrelevant Auditory Mismatch Negativity
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+Glaciation of liquid clouds, snowfall, and reduced cloud cover at industrial aerosol hot spots
- Behavioural and neuroscientific evidence suggests visual stimuli that signal value involuntarily capture attention and are preferentially processed, even when unattended. We examined whether learned value associations for task-irrelevant auditory stimuli modulate pre-attentive processing and involuntarily capture attention. Across two experiments, the effect of learned value on the visual- and auditory-evoked mismatch negativity (MMN) and P3a event-related potential (ERP) components was measured. Participants performed a primary visual detection task while an irrelevant, unattended oddball stimulus stream was concurrently presented. Deviants within this oddball stream had been previously learned to signal one of several value outcomes: monetary reward, loss or no change. Neither the auditory nor the visual MMN was influenced by these value associations. However, stimulus value affected performance on the primary task and the magnitude of the P3a in those who could identify the stimulus-value pairings at test. Supplementary mass univariate analyses and time frequency decomposition (theta phase-locking) confirmed the presence of the MMN and the absence of any influence of stimulus value on the MMN response. Findings suggest that learned value associations do not meaningfully influence the MMN prediction signaling mechanism for task-irrelevant auditory stimuli. + Science, Volume 386, Issue 6723, Page 756-762, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation
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+Diverse and larger tree islands promote native tree diversity in oil palm landscapes
- It is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC[->]SDH-NA neurons), that is activated by acute exposure to restraint stress and is required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, the primary target of spinal NA released from descending LC[->]SDH-NAergic terminals causing the stress-induced pain hypersensitivity was 1A-adrenaline receptors (1ARs) in Hes5-positive (Hes5+) astrocytes located in the SDH, an astrocyte subset that has an ability to induce pain sensitization. Furthermore, activation of Hes5+ astrocytes reduced activity of SDH-inhibitory neurons (SDH-INs) that have an inhibitory role in pain processing. This astrocytic reduction of IN activity was canceled by an A1-adenosine receptor (A1R)-knockdown in SDH-INs, and the A1R-knockdown suppressed pain hypersensitivity caused by acute restraint stress. Therefore, our findings suggest that LC[->]SDH-NA neuronal signaling to Hes5+ SDH astrocytes and subsequent astrocytic reduction of SDH-IN activity are essential for pain facilitation caused by stress. + Science, Volume 386, Issue 6723, Page 795-802, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Humans anticipate the consequences of motor control demands when making perceptual decisions between actions
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+Ribozyme-activated mRNA trans-ligation enables large gene delivery to treat muscular dystrophies
- Animals, including humans, are often faced with situations where they must decide between potential actions to perform based on various sources of information, including movement parameters that incur time and energy costs. Consistent with this fact, many behavioral studies indicate that decisions and actions show a high level of integration during goal-directed behavior. In particular, motor costs very often bias the choice process of human and non-human subjects facing successive decisions between actions. However, it appears as well that depending on the design in which the experiment occurs, the effect of motor costs on decisions can vary or even vanish. This suggests a contextual dependence of the influence of motor costs on decision-making. Moreover, it is not currently known whether or not the impact of motor costs on perceptual decisions depend on the difficulty of the decision. We addressed these two important issues by studying the behavior of healthy human subjects engaged in a new perceptual decision-making paradigm in which the constraint level associated with the movement executed to report a choice was volitionally chosen by the participants, and in which the difficulty of the perceptual decision to make continuously evolved depending on their motor performance. The results indicate that the level of constraint associated with a movement executed to express a perceptual decision strongly impacts the duration of these decisions, with a shortening of decisions when these are expressed by demanding movements. This influence appears most important when the decisions are difficult, but it is also present for easy decisions. We interpret this strategy as an adaptive way to optimize the participants' overall rate of success at the session level. + Science, Volume 386, Issue 6723, Page 762-767, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Impaired online and enhanced offline motor sequence learning in individuals with Parkinson's disease
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+A mechanical qubit
- Whereas memory consolidation research has traditionally focused on longer temporal windows (i.e., hours to days) following an initial learning episode, recent research has also examined the functional significance of the shorter rest epochs commonly interspersed with blocks of task practice (i.e., "micro-offline" intervals on the timescale of seconds to minutes). In the motor sequence learning domain, evidence from young, healthy individuals suggests that micro-offline epochs afford a rapid consolidation process that is supported by the hippocampus. Consistent with these findings, amnesic patients with hippocampal damage were recently found to exhibit degraded micro-offline performance improvements. Interestingly, these offline losses were compensated for by larger performance gains during online practice. Given the known role of the striatum in online motor sequence learning, we hypothesized that individuals with dysfunction of the striatal system would exhibit impaired online, yet enhanced micro-offline, learning (i.e., a pattern of results opposite to those observed in patients with hippocampal lesions). We tested this hypothesis using Parkinson's disease (PD) as a model of striatal dysfunction. Forty-two de novo, drug-naive individuals (men and women) with a clinical diagnosis of unilateral PD and 29 healthy control subjects completed a motor sequence learning paradigm. Individuals with PD exhibited deficits during online task practice that were paralleled by greater improvements over micro-offline intervals. This pattern of results could not be explained by disease-related deficits in movement execution. These data suggest that striatal dysfunction disrupts online learning, yet total learning remains unchanged because of greater micro-offline performance improvements that potentially reflect hippocampal-mediated compensatory processes. + Science, Volume 386, Issue 6723, Page 783-788, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord
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+Subambient daytime radiative cooling of vertical surfaces
- Development of therapeutic approaches that target specific microglia responses in amyotrophic lateral sclerosis (ALS) is crucial due to the involvement of microglia in ALS progression. Our study identifies the predominant microglia subset in human ALS primary motor cortex and spinal cord as an undifferentiated phenotype with dysregulated respiratory electron transport. Moreover, we find that the interferon response microglia subset is enriched in donors with aggressive disease progression, while a previously described potentially protective microglia phenotype is depleted in ALS. Additionally, we observe an enrichment of non-microglial immune cell, mainly NK/T cells, in ALS central nervous system, primarily in the spinal cord. These findings pave the way for the development of microglia subset-specific therapeutic interventions to slow or even stop ALS progression. + Science, Volume 386, Issue 6723, Page 788-794, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Deep Neural Networks Explain Spiking Activity in Auditory Cortex
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+Truly listening
- For static stimuli or at gross (~1-s) time scales, artificial neural networks (ANNs) that have been trained on challenging engineering tasks, like image classification and automatic speech recognition, are now the best predictors of neural responses in primate visual and auditory cortex. It is, however, unknown whether this success can be extended to spiking activity at fine time scales, which are particularly relevant to audition. Here we address this question with ANNs trained on speech audio, and acute multi-electrode recordings from the auditory cortex of squirrel monkeys. We show that layers of trained ANNs can predict the spike counts of neurons responding to speech audio and to monkey vocalizations at bin widths of 50 ms and below. For some neurons, the ANNs explain close to all of the explainable variance---much more than traditional spectrotemporal--receptive-field models, and more than untrained networks. Non-primary neurons tend to be more predictable by deeper layers of the ANNs, but there is much variation by neuron, which would be invisible to coarser recording modalities. + Science, Volume 386, Issue 6723, Page 822-822, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Spontaneous Brain Dynamics Associated With Acceleration Of Longterm Functional Connectome In Postnatal Development
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+In Other Journals
- The first six postnatal months are a critical period for brain development, marked by rapid changes in functional neural circuits. However, long-term changes in neonatal functional connectome lacks an interpretive imaging indicator for the future development due to the non-linearity characteristics. In this study, we introduce an approach to extract intrinsic brain states from short-term brain dynamics to study the long-term (longitudinal) development. We found a high association (r=0.460) between the co-activated pattern of specific brain state and the acceleration pattern of non-linear development of static functional connectome. The fractional occupancy, self-sustaining probability of this short-term state share the similar age tendency with the long-term change rate within the majority of the function connectome. These findings suggest that short-term brain dynamics could serve as potential biomarkers for predicting the long-term development of functional connectome. + Science, Volume 386, Issue 6723, Page 741-742, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Single-cell transcriptomic analysis of macaque LGN neurons reveals novel subpopulations
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+The journey to a mechanical qubit
- Neurons in the lateral geniculate nucleus (LGN) provide a pivotal role in the visual system by modulating and relaying signals from the retina to the visual cortex. Although the primate LGN, with its distinct divisions (magnocellular, M; parvocellular, P; and koniocellular, K), has been extensively characterized, the intrinsic heterogeneity of LGN neurons has remained unexplained. With the development of high-throughput single-cell transcriptomics, researchers can rapidly isolate and profile large sets of neuronal nuclei, revealing a surprising diversity of genetic expression within the nervous systems. Here, we analyzed the transcriptomes of individual cells belonging to macaque LGN using raw data from a public database to explore the heterogeneity of LGN neurons. Using statistical analyses, we found additional subpopulations within the LGN transcriptomic population, whose gene expressions imply functional differences. Our results suggest the existence of a more nuanced complexity in LGN processing beyond the classic view of the three cell types and highlight a need to combine transcriptomic and functional assessments. A complete account of the cell type diversity of the primate LGN is critical to understanding how vision works. + Science, Volume 386, Issue 6723, Page 728-729, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Unique Asymmetric Branching of Drosophila Neurons Optimizes Temporal Dendritic Computation
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+Learning the language of DNA
- Neurons execute a versatile array of computations through a complex interplay of factors, including their morphology and synaptic architecture. Dendritic branching encodes upstream inputs into diverse spike patterns transmitted via downstream axons. While earlier studies highlighted the distinct morphologies and functions of a few representative neurons, the availability of large-scale electron microscopy and fluorescent imaging now enables comprehensive data analysis and further simulations to explore structure-function relationships more broadly. This study investigates the general morphological characteristics of diverse neuron types in the fly model. By employing the Strahler Order (SO) metric, we identified a specific bias towards asymmetry in neuronal branching and further investigated the effect of the asymmetry on computational capabilities. Specifically, symmetric branching enhances coincidence detection capability, whereas asymmetric branching increases input order-selectivity. While certain neurons exhibit extreme symmetry or asymmetry optimized for specific tasks, most neurons strike a balance between these computational strategies. This balance underscores the intricate relationship between neuronal structure and function. In contrast to the wide range of branching symmetries found in random bifurcation models, neurons across different species exhibit species-specific asymmetry, suggesting shared underlying branching mechanisms. Our findings provide a fresh perspective on the exploration of neuronal morphologies and their computational roles. + Science, Volume 386, Issue 6723, Page 729-730, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases
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+Heat up to catch carbon
- TAR DNA-binding protein 43 (TDP-43) proteinopathy plays a critical role in neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia (FTD). In our recent discovery, we identified that TDP-43 plays a critical role in DNA double-strand break (DSB) repair via the non-homologous end joining (NHEJ) pathway. Here, we found persistent DNA damage in brains of ALS/FTD patients, primarily in the transcribed regions of the genome. We further investigated the underlying mechanism and found that the activity of polynucleotide kinase 3' phosphatase (PNKP) was severely impaired in the nuclear extracts of both the patient brains and TDP-43-depleted cells. PNKP is a key player in DSB repair within the transcribed genome, where its 3'-P termini processing activity is crucial for preventing persistent DNA damage and neuronal death. The inactivation of PNKP in ALS/FTD was due to reduced levels of its interacting partner, phosphofructo-2-kinase fructose 2,6 bisphosphatase (PFKFB3), and its biosynthetic product, fructose-2,6 bisphosphate (F2,6BP), an allosteric modulator of glycolysis. Recent work from our group has shown that F2,6BP acts as a positive modulator of PNKP activity in vivo. Notably, exogenous supplementation with F2,6BP restored PNKP activity in both nuclear extracts from ALS/FTD brain samples and in patient-derived induced pluripotent stem (iPS) cells harboring pathological mutations. Our findings underscore the possibility of exploring the therapeutic potential of F2,6BP or its analogs in TDP-43 pathology-associated motor neuron diseases. + Science, Volume 386, Issue 6723, Page 727-728, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Calcium-based input timing learning
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+The disciplinary matrix of holobiont biology
- Stimulus-triggered synaptic long-term plasticity is the foundation of learning and other cognitive abilities of the brain. In general, long-term synaptic plasticity is subdivided into two different forms: homosynaptic plasticity describes synaptic changes at stimulated synapses, while heterosynaptic plasticity summarizes synaptic changes at non-stimulated synapses. For homosynaptic plasticity, the Ca2+-hypothesis pinpoints the calcium concentration within a stimulated dendritic spine as key mediator or controller of underlying biochemical and -physical processes. On the other hand, for heterosynaptic plasticity, although theoretical studies attribute important functional roles to it, such as synaptic competition and cooperation, experimental results remain ambiguous regarding its manifestation and biological basis. By integrating insights from Ca2+-dependent homosynaptic plasticity with experimental data of dendritic Ca2+-dynamics, we developed a mathematical model that describes the complex temporal and spatial dynamics of calcium in the dendritic shaft and respective dendritic spines. We show that the increased influx of calcium into a stimulated spine can lead to its diffusion through the shaft to neighboring spines, triggering heterosynaptic effects such as synaptic competition or cooperation. By considering different input strengths, our model explains the ambiguity of reported experimental results of heterosynaptic plasticity, suggesting that the Ca2+ hypothesis of homosynaptic plasticity can be extended to also model heterosynaptic plasticity. Furthermore, our model predicts that, via diffusion of calcium, a synapse can modulate the expression of homosynaptic plasticity at a neighboring synapse in an input-timing-dependent manner, without the need of postsynaptic spiking. The resulting sensitivity of synaptic plasticity on input-spike-timing can be influenced by the distance between involved spines as well as the local diffusion properties of the connecting dendritic shaft, providing a new way of dendritic computation. + Science, Volume 386, Issue 6723, Page 731-732, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Subcortical nuclei of the human ascending arousal system encode anticipated reward but do not predict subsequent memory
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+End illegal sand mining in China
- Subcortical nuclei of the ascending arousal system play an important role in regulating brain and cognition. However, functional MRI of these nuclei in humans involves unique challenges due to their size and location deep within the brain. Here, we used ultra-high-field MRI and other methodological advances to investigate the activity of six subcortical nuclei during reward anticipation and memory encoding: the locus coeruleus, basal forebrain, median and dorsal raphe nuclei, substantia nigra and ventral tegmental area. Participants performed a monetary incentive delay task, which successfully induced a state of reward anticipation, and a 24-hour delayed surprise memory test. Region-of-interest analyses revealed that activity in all subcortical nuclei increased in anticipation of potential rewards as opposed to neutral outcomes. In contrast, activity in none of the nuclei predicted memory performance 24 hours later. These findings provide new insights into the cognitive functions that are supported by the human ascending arousal system. + Science, Volume 386, Issue 6723, Page 736-736, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-An integrative layer-resolved atlas of the adult human meninges
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+Plastics treaty: Address building materials
- The human meninges are a dynamic tri-layered brain border that plays a key role in brain development, CSF homeostasis, immune regulation, and higher-level brain function. The meninges have also been implicated in central nervous system (CNS) pathologies such as infection, autoimmunity, and brain trauma. To understand how the meningeal microenvironment is altered under pathological conditions it is necessary to have a complete understanding of its normotypic cellular architecture and function. To date, there is no complete atlas of the normotypic adult human meninges. By surgically extracting each human meningeal layer during surgery, we generated the first layer-resolved map of all meningeal cell types via an integration of whole cell single cell RNA sequencing, multiplexed error-robust fluorescence in situ hybridization (MERFISH), and protein immunolabelling. Since fibroblasts play key roles in meningeal homeostasis yet remain less well-characterised than other meningeal cell types, we deeply phenotyped these cells in all layers. We identified 10 fibroblast subpopulations with unique predicted functions that localise to distinct neuroanatomical niches. Fibroblast interaction analysis in the dura and subarachnoid space (SAS) uncovered novel interactions with vascular cell populations mediated by insulin growth factor signaling. Together, these data serve as a comprehensive resource for future investigations of meningeal function in the healthy and diseased brain. + Science, Volume 386, Issue 6723, Page 736-737, November 2024.-
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Brain Sciences, Vol. 14, Pages 1142: Examining the Neural Markers of Speech Rhythm in Silent Reading Using Mass Univariate Statistics of EEG Single Trials
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+Argentina’s unsustainable policies
-Brain Sciences, Vol. 14, Pages 1142: Examining the Neural Markers of Speech Rhythm in Silent Reading Using Mass Univariate Statistics of EEG Single Trials
-Brain Sciences doi: 10.3390/brainsci14111142
-Authors: - Stephanie J. Powell - Srishti Nayak - Cyrille L. Magne -
-Background/Objectives: The Implicit Prosody Hypothesis (IPH) posits that individuals generate internal prosodic representations during silent reading, mirroring those produced in spoken language. While converging behavioral evidence supports the IPH, the underlying neurocognitive mechanisms remain largely unknown. Therefore, this study investigated the neurophysiological markers of sensitivity to speech rhythm cues during silent word reading. Methods: EEGs were recorded while participants silently read four-word sequences, each composed of either trochaic words (stressed on the first syllable) or iambic words (stressed on the second syllable). Each sequence was followed by a target word that was either metrically congruent or incongruent with the preceding rhythmic pattern. To investigate the effects of metrical expectancy and lexical stress type, we examined single-trial event-related potentials (ERPs) and time&ndash;frequency representations (TFRs) time-locked to target words. Results: The results showed significant differences based on the stress pattern expectancy and type. Specifically, words that carried unexpected stress elicited larger ERP negativities between 240 and 628 ms after the word onset. Furthermore, different frequency bands were sensitive to distinct aspects of the rhythmic structure in language. Alpha activity tracked the rhythmic expectations, and theta and beta activities were sensitive to both the expected rhythms and specific locations of the stressed syllables. Conclusions: The findings clarify neurocognitive mechanisms of phonological and lexical mental representations during silent reading using a conservative data-driven approach. Similarity with neural response patterns previously reported for spoken language contexts suggests shared neural networks for implicit and explicit speech rhythm processing, further supporting the IPH and emphasizing the centrality of prosody in reading.
+ Science, Volume 386, Issue 6723, Page 735-736, November 2024.-
in Brain Sciences on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Brain Sciences, Vol. 14, Pages 1141: Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis
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+News at a glance
-Brain Sciences, Vol. 14, Pages 1141: Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis
-Brain Sciences doi: 10.3390/brainsci14111141
-Authors: - Alin Ciubotaru - Daniel Alexa - Cristina Grosu - Lilia Böckels - Ioana Păvăleanu - Alexandra Maștaleru - Maria Magdalena Leon - Roxana Covali - Emanuel Matei Roman - Cătălina Elena Bistriceanu - Cristina Mihaela Ghiciuc - Doina Azoicăi - Emilian Bogdan Ignat -
-Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by progressive impairment of neuronal transmission due to focal demyelination. The most common form is RRMS (relapsing-remitting multiple sclerosis), which, under the influence of certain factors, can progress to SPMS (secondary progressive multiple sclerosis). Our study aimed to validate the criteria proposed by a working group of the Romanian Society of Neurology versus the criteria proposed by a group of experts from Spain, Karolinska, and Croatia concerning the progression from RRMS to SPMS. Methods: This was done by gathering epidemiological data (age, gender) and by applying clinical tests such as the 9HPT (9-hole peg test), 25FWT (25-foot walk test), and EDSS (expanded disability status scale) tests and the SDMT test (symbol digit modalities test). The present research is a cohort study that included a number of 120 patients diagnosed with MS according to the McDonald Diagnostic Criteria 2017. The study was carried out between January 2023 and April 2024, including patients hospitalized in the Neurology Clinic of the Clinical Rehabilitation Hospital from Iasi, Romania. The data were collected at baseline (T0) and at a 12-month interval (T1). Results: The statistical analysis was conducted using Kaiser&ndash;Meyer&ndash;Olkin analysis, which indicated a value of 0.683, thus validating the clinical tests used. The correlation matrix and the linear regression for all the tests showed highly significant statistical results. Furthermore, the ROC curve analysis of the criteria suggested by the working group of the Romanian Society of Neurology demonstrated that the EDSS, 9HPT, and 25FWT are highly sensitive in diagnosing SPMS, an opinion that is shared with the Spanish experts, but not with the Karolinska expert panel. Using the criteria given by the Croatian expert group in the ROC curve analysis showed that only the EDSS was strongly significant for the progression to the SPMS phase. Conclusions: In conclusion, all clinical methods used demonstrated that they are valid and can contribute to identifying patients with an increased risk of progression. The model proposed by the Romanian Society of Neurology working group is similar to other countries&rsquo; expert opinions and can be used to detect the risk of disease progression and establish a more tailored therapeutic management of SPMS.
+ Science, Volume 386, Issue 6723, Page 710-711, November 2024.-
in Brain Sciences on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Brain Sciences, Vol. 14, Pages 1140: Temperament and the Experience of Tension and Self-Injurious Behaviour in Adolescents—The Mediating Role of Maladaptive Perfectionism
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+Research advocates see ‘no good news for science’
-Brain Sciences, Vol. 14, Pages 1140: Temperament and the Experience of Tension and Self-Injurious Behaviour in Adolescents—The Mediating Role of Maladaptive Perfectionism
-Brain Sciences doi: 10.3390/brainsci14111140
-Authors: - Magdalena Chęć - Sylwia Michałowska - Alicja Gnych-Pietrzak - Albina Rybarska - Klaudia Strochalska -
-Background: Adolescence is an important point in the emotional development of young people. It is a time when young people are characterised by a high degree of emotional instability and seek effective ways to regulate their emotions. One of the frequent methods they use to cope with emotional tension is self-injurious behaviour. Methods: In the context of the rising incidence of self-harm among adolescents, this study aims to understand the association of temperament with the experience of tension and self-injurious behaviour along with the mediating role of perfectionism among 366 adolescents aged 15 to 20 years (Mage = 17.98, SD = 1.302, 52.7% female). Participants completed questionnaires on temperament traits, level of perfectionism, and experience of tension and self-injurious behaviour. Results: The results show that traits such as perfectionism, sensory sensitivity and emotional reactivity increase the risk of self-injurious behaviour. Maladaptive perfectionism partially mediates the relationship between these traits and the tendency to experience emotional tension. A temperament profile with a protective role was also identified. Conclusions: The results of the study highlight the importance of innate traits as well as environmental and cognitive influences, and may contribute to a better understanding of the mechanisms leading to self-injurious behaviour and strategies aimed at its prevention.
+ Science, Volume 386, Issue 6723, Page 712-713, November 2024.-
in Brain Sciences on 2024-11-14 00:00:00 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Analysis of Circulating Plasma MicroRNA Profile in Low-Grade and High-Grade Glioma – A Cross-Sectional Study [version 1; peer review: awaiting peer review]
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+Trump won. Is NIH in for a major shake-up?
- Background Glioma is the second most common type of brain tumor, accounting for 24% of all brain tumor cases. The current diagnostic procedure is through an invasive tissue sampling to obtain histopathological analysis, however, not all patients are able to undergo a high-risk procedure. Circulating microRNAs (miRNAs) are considered as promising biomarkers for glioma due to their sensitivity, specificity, and non-invasive properties. There is currently no defined miRNA profile that contributes to determining the grade of glioma. This study aims to find the answer for “Is there any significant miRNA that able to distinguish different grades of glioma?”. Methods This study was conducted to compare the expression of miRNAs between low-grade glioma (LGG) and high-grade glioma (HGG). Eighteen blood plasma samples from glioma patients and 6 healthy controls were analyzed for 798 human miRNA profiles using NanoString nCounter Human v3 miRNA Expression Assay. The differential expressions of miRNAs were then analyzed to identify the differences in miRNA expression between LGG and HGG. Results Analyses showed significant expressions in 12 miRNAs between LGG and HGG, where all of them were downregulated. Out of these significant miRNAs, miR-518b, miR-1271-3p, and miR-598-3p showed the highest potential for distinguishing HGG from LGG, with area under curve (AUC) values of 0.912, 0.889, and 0.991, respectively. Conclusion miR-518b, miR-1271-3p, and miR-598-3p demonstrate significant potentials in distinguishing LGG and HGG. + Science, Volume 386, Issue 6723, Page 713-714, November 2024.-
in F1000Research on 2024-11-13 18:17:12 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Climate Change and Veterinary Medicine: A Call to Action for a Healthier Planet [version 1; peer review: awaiting peer review]
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+‘America first’ could affect health worldwide
- Abstract Climate change is rapidly transforming ecosystems and reshaping the landscapes of animal health, with profound consequences for public health, food security, and biodiversity. Rising temperatures, shifting weather patterns, and increased frequency of natural disasters are driving the emergence and spread of infectious diseases, particularly zoonotic and vector-borne diseases. These environmental shifts endanger the health and welfare of animals and the delicate balance between human populations, livestock, and wildlife. As the stewards of animal health, veterinarians are uniquely positioned to lead the change in addressing these complex challenges at the nexus of human, animal, and environmental health and well-being. This article calls for urgent actions to integrate climate adaptation and mitigation strategies into veterinary practice and education. It underscores the critical need for veterinarians to embrace the One Health approach to tackle climate-driven disease outbreaks and the growing threat of antimicrobial resistance to safeguard human and animal populations while protecting natural ecosystems. The article further explores the role of veterinarians in fostering sustainable agricultural practices, reducing the environmental impact of livestock production, conserving biodiversity and advocating for policy reforms that protect both animal and planetary health. As we face an era of unprecedented climate disruption, this call to action aims to inspire the global veterinary community to actively get involved in combating climate change and its worst impacts. By building climate-resilient practices, enhancing disease surveillance, and championing environmental stewardship, veterinarians can contribute significantly to a healthier, more sustainable future for all species on Earth. + Science, Volume 386, Issue 6723, Page 715-715, November 2024.-
in F1000Research on 2024-11-13 18:10:34 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-De-ethnicizing Ethiopian higher education leadership: the quest for merit-based governance [version 1; peer review: awaiting peer review]
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+Famed flipping ship gets second shot at research
- Background This study examines the growing trend of ethnicized leadership in Ethiopian higher education institutions and advocates for a shift toward merit-based governance to improve institutional integrity and performance. Since 1991, with the introduction of ethnic federalism, leadership appointments in Ethiopian universities have increasingly been based on ethnic identity rather than qualifications. This has led to governance challenges, weakened academic standards, and reduced institutional efficiency. The study highlights the need for governance reforms prioritizing meritocracy to enhance the quality and sustainability of Ethiopia’s ethnically diverse higher education system. Methods The study utilizes a qualitative research approach, combining both primary and secondary data. Primary data were collected through semi-structured interviews with university administrators, faculty, and governance experts, while secondary data were gathered from institutional reports, government policies, and academic literature. Institutional theory, principal-agent theory, and meritocratic theory frame the analysis, providing insights into how ethnic-based leadership appointments affect university governance and performance. Results The findings reveal that ethnicized leadership has eroded governance structures, lowered academic quality, and compromised institutional efficiency. Leadership appointments based on ethnicity rather than merit have led to poor decision-making, weakened accountability, and reduced transparency. In contrast, merit-based governance improves accountability, decision-making, and institutional performance. The study emphasizes that transitioning to a meritocratic leadership model is vital for restoring institutional integrity and academic excellence in Ethiopian universities. Conclusions Ethnic federalism, while initially designed to empower regions, has politicized federal institutions, including universities, reducing them to regional entities rather than national institutions. This system of ethnicized leadership has fostered a culture of favoritism, rampant corruption, and ineffective governance, ultimately weakening Ethiopia’s higher education system. Recommendations Governance reforms that prioritize merit-based appointments are urgently needed. Legal reforms, transparent leadership selection processes, depoliticization efforts, and capacity-building initiatives are recommended to foster a meritocratic culture and improve institutional performance in Ethiopian universities. + Science, Volume 386, Issue 6723, Page 716-716, November 2024.-
in F1000Research on 2024-11-13 18:05:17 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Identifying and Assessing Physiological Biomarkers for Food and Energy Intake: A Systematic Review with Meta-Analysis Protocol [version 1; peer review: awaiting peer review]
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+Preprint on Alzheimer’s drug deaths ignites author dispute
- Background Traditional dietary assessments are often inaccurate and prone to self-reporting biases. Tracking the physiological responses associated with eating and digestion events via wearable technologies may provide an effective approach for continuously monitoring food intake and estimating energy consumption. Eating and digestion are accompanied by a series of changes in the heart rate, skin temperature, blood oxygen saturation, and blood pressure. These changes can be tracked by wearable devices, such as smartwatches, which have been widely accepted in the market. This systematic review is the first to evaluate the effectiveness of tracking such physiological biomarkers in differentiating between high- and low-calorie meals, potentially paving the way for more accurate dietary monitoring. Methods Following the PRISMA-P guidelines, we will conduct a systematic literature search through MEDLINE, EMBASE, and PubMed for clinical trials that investigated physiological responses following meal intake in healthy subjects. Two independent reviewers will screen and select articles based on pre-defined eligibility criteria, with a third review to resolve any discrepancies. This will be followed by data extraction and quality assessment of the included studies. Statistical analyses, including meta-analyses, will be performed using R Studio software. Our primary outcome will be the comparison of physiological biomarkers before and after meal intake, while secondary outcomes will include comparisons of physiological biomarkers between high- and low-calorie meal consumption and the correlation between the caloric content of consumed meals and postprandial physiological changes. Discussion This systematic review and meta-analysis will identify physiological indicators for eating events and inform the design of wearable sensors that estimate food intake in healthy subjects. Systematic Review Registration PROSPERO Registration ID: CRD42024544353 + Science, Volume 386, Issue 6723, Page 717-718, November 2024.-
in F1000Research on 2024-11-13 17:39:17 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Molecular docking and dynamics studies to identify novel active compounds targeting potential breast cancer receptor proteins from an indigenous herb Euphorbia thymifolia Linn [version 2; peer review: 1 approved with reservations]
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+Russia postpones three scientific ‘megaprojects’
- Background Breast cancer has become the most prevalent disease and its incidence has almost doubled in the Indian population. This increased burden demands new targeted therapies with novel compounds either synthetically produced or derived from indigenous plants, which could be a promising approach for the development of drugs. Euphorbia thymifolia L is a widely growing tropical herb that has been reported to have various ethnopharmacological properties. Although Euphorbia genus is reported to have anticancer properties, E. thymifolia is not reported to have anticancer properties to date. Therefore, the aim of the present study was to screen the phytoconstituents and identify the active compounds present in the methanolic extract of E. thymifolia (ME.ET) as ligands to inhibit human cancer cell lines with special reference to potential protein targets implicated in breast cancer using an In-silico approach. Methods ME.ET was subjected to GC-MS analysis to screen the phytoconstituents, and the identified compounds were docked with protein targets such as extracellular signal-regulated kinases (ERK1), a serine/threonine kinase-1(AKT1), human epidermal growth factor 2 (HER2), estrogen receptor (ER), maternal embryonic leucine zipper kinase (MELK), polo-like kinase-1(PLK1), and protein tyrosine kinase (PTK6). Compounds with good docking scores were further subjected to dynamic studies to understand the protein ligand binding stability, ligand pathway calculation, and molecular mechanics energies combined with Poisson-Boltzmann (MM/PBSA) calculations using the Schrodinger suite. Results GC-MS analysis revealed the presence of 245 phytoconstituents, 219 of which were unique. When subjected to docking, these phytocompounds, namely 3,6,9,12-tetraoxatetradecane-1,14-diyl dibenzoate (TTDB) and succinic acid, 2-(dimethylamino) ethyl 4-isopropylphenyl ester (SADPE), showed good docking scores. Molecular dynamics studies showed a high affinity and low binding energy for TTDB with HER2, ERK1, and SADPE with ER. Conclusions Hence, in this study, we identified two lead compounds in E.thymifolia linn. Further invitro and invivo anticancer studies can be performed to confirm these results and to understand the molecular mechanism by which they exhibit anticancer activity against breast cancer. + Science, Volume 386, Issue 6723, Page 718-718, November 2024.-
in F1000Research on 2024-11-13 17:31:58 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Orbitofrontal Cortex Mediates Sustained Basolateral Amygdala Encoding of Cued Reward-Seeking States
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+The counterattack
-Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS– cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of the orbitofrontal cortex (OFC), a major reciprocal partner to the BLA. Inactivation of the OFC while simultaneously recording in the BLA revealed a blunting of sustained cue-evoked activity in the BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in the BLA also reduced reward seeking. Our data indicate that the BLA represents reward-seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward-seeking behavior.
+ Science, Volume 386, Issue 6723, Page 719-723, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-This Week in The Journal
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+Science is neither red nor blue
- + Science, Volume 386, Issue 6723, Page 707-707, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Neural Predictors of Fear Depend on the Situation
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+Advancing alternative methods to reduce animal testing
-The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n = 21; 10 females and 11 males) viewed ~20 s clips depicting spiders, heights, or social encounters and rated fear after each video. Searchlight multivoxel pattern analysis was used to identify whether and which brain regions carry information that predicts fear experience and the degree to which the fear-predictive neural codes in these areas depend on or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation-dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern but rather a collection of multiple heterogeneous brain states.
+ Science, Volume 386, Issue 6723, Page 724-726, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-The Role of the Rat Prefrontal Cortex and Sex Differences in Decision-Making
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+Gatekeepers of the brain: Identifying hidden mechanisms of type A GABA receptor signaling and assembly
-The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift diffusion models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. μ-Opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process toward high-value stimuli. These effects were observed without any impact on the rats’ choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls "when," but not "how," to act.
+ Science, Volume 386, Issue 6723, Page 738-739, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Deciphering Peripheral Taste Neuron Diversity: Using Genetic Identity to Bridge Taste Bud Innervation Patterns and Functional Responses
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+Digging below the surface: Hidden risks for ground-nesting bees
-Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the taste bud) stemming from Penk+ neurons displayed diverse branching patterns and lacked stereotypical endings. The range in complexity observed for individual taste arbors from Penk+ neurons mirrored the entire population, suggesting that taste arbor morphologies are not primarily regulated by the neuron type. Notably, the distinguishing feature of arbors from Penk+ neurons was their propensity to come within 110 nm (in apposition with) different types of taste-transducing cells within the taste bud. This finding is contrary to the expectation of genetically defined taste neuron types that functionally represent a single stimulus. Consistently, further investigation of Penk+ neuron function revealed that they are more likely to respond to innately aversive stimuli—sour, bitter, and high salt concentrations—as compared with the full taste population. Penk+ neurons are less likely to respond to nonaversive stimuli—sucrose, umami, and low salt—compared with the full population. Our data support the presence of a genetically defined neuron type in the geniculate ganglion that is responsive to innately aversive stimuli. This implies that genetic expression might categorize peripheral taste neurons into hedonic groups, rather than simply identifying neurons that respond to a single stimulus.
+ Science, Volume 386, Issue 6723, Page 739-739, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Dynamics of Saccade Trajectory Modulation by Distractors: Neural Activity Patterns in the Frontal Eye Field
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+How to build a human: Piecing together the body’s cellular puzzle
-The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field of two male rhesus monkeys shifting gaze to a target while a distractor with the same eccentricity appeared either left or right of the target at various delays after target presentation. We found that the population level of presaccadic activity of neurons representing the distractor location encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature toward the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved toward distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push–pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets.
+ Science, Volume 386, Issue 6723, Page 739-739, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-A Prefrontal->Periaqueductal Gray Pathway Differentially Engages Autonomic, Hormonal, and Behavioral Features of the Stress-Coping Response
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+To target, to escape, perchance to cure: Borrowing a page from cancer’s playbook, scientists learn to evade their own therapies
-The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats’ active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC->vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal->midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences.
+ Science, Volume 386, Issue 6723, Page 739-739, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Monocyte Invasion into the Retina Restricts the Regeneration of Neurons from Müller Glia
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+In Science Journals
-Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to reprogram a subset of Müller glia into neurons. We have reported that neuroinflammation from microglia inhibits neurogenesis from Müller glia. Here we found that the peripheral immune response is a barrier to CNS regeneration. We show that monocytes from the peripheral immune system infiltrate the injured retina and negatively influence neurogenesis from Müller glia. Using CCR2 knock-out mice of both sexes, we found that preventing monocyte infiltration improves the neurogenic and proliferative capacity of Müller glia stimulated by Ascl1. Using scRNA-seq analysis, we identified a signaling axis wherein Osteopontin, a cytokine highly expressed by infiltrating immune cells is sufficient to suppress mammalian neurogenesis. This work implicates the response of the peripheral immune system as a barrier to regenerative strategies of the retina.
+ Science, Volume 386, Issue 6723, Page 740-742, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Science on 2024-11-14 06:59:04 UTC.
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-Encoding of Vibrotactile Stimuli by Mechanoreceptors in Rodent Glabrous Skin
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+Input-specific properties of excitatory synapses on oxytocin receptor-expressing neurons in the lateral septum
-Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in the rodent glabrous skin has received scant attention, unlike in primates where the glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability), whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Using in vivo extracellular recordings in male rats and mice of either sex, we measured the reliability and precision of LTMR responses to tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RA1 and RA2/Pacinian afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that coactivation patterns play a greater role in population coding than for dichotomously tuned primate RAs.
+ Journal of Neurophysiology, Ahead of Print.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Journal of Neurophysiology on 2024-11-14 05:30:15 UTC.
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-Behavioral and Neural Mechanisms of Face-Specific Attention during Goal-Directed Visual Search
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+Harvey's Story
-Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Compared with distractors, fixations on targets reduced spike–LFP coherence within the temporal cortex. Importantly, target-induced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks.
+
+Harvey enjoying a good discussion at a lab party in 1996 (photo provided by Harald Luksch). + +
++
ABSTRACT
+Harvey Jules Karten passed away on July 15, 2024. With his passing, the world lost a remarkable and energetic man who had made major contributions to neuroscience, in particular, resetting our understanding of the evolution of the forebrain and the evolution of intelligence. He left behind a legion of loyal colleagues with whom he had collaborated and shared ideas, students he had inspired and trained, and non-neuroscientist friends he had made in the passionate pursuit of his hobbies—sailing, skiing, and hiking.
-in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Journal of Comparative Neurology on 2024-11-14 04:44:24 UTC.
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-Monosynaptic Inputs to Ventral Tegmental Area Glutamate and GABA Co-transmitting Neurons
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+Altered control of breathing in a rat model of allergic lower airway inflammation
-A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus (SC), lateral hypothalamus (LH), midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from the dorsal raphe nucleus, lateral habenula, and VTA. Based on these and prior data, we hypothesized that LH and SC inputs were from glutamatergic neurons. Optical activation of glutamatergic LH neurons activated VTA VGluT2+VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic SC neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic LH neurons, but not glutamatergic SC neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity and inhibition of LH glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally salient outcomes.
+ Journal of Neurophysiology, Volume 132, Issue 5, Page 1650-1666, November 2024.-
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC. +
in Journal of Neurophysiology on 2024-11-14 03:52:07 UTC.
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-Distinct Modulation of Ih by Synaptic Potentiation in Excitatory and Inhibitory Neurons
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+Palytoxin evokes reversible spreading depolarization in the locust CNS
-Selective modifications in the expression or function of dendritic ion channels regulate the propagation of synaptic inputs and determine the intrinsic excitability of a neuron. Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels open upon membrane hyperpolarization and conduct a depolarizing inward current (Ih). HCN channels are enriched in the dendrites of hippocampal pyramidal neurons where they regulate the integration of synaptic inputs. Synaptic plasticity can bidirectionally modify dendritic HCN channels in excitatory neurons depending on the strength of synaptic potentiation. In inhibitory neurons, however, the dendritic expression and modulation of HCN channels are largely unknown. In this study, we systematically compared the modulation of Ih by synaptic potentiation in hippocampal CA1 pyramidal neurons and stratum radiatum (sRad) interneurons in mouse organotypic cultures. Ih properties were similar in inhibitory and excitatory neurons and contributed to resting membrane potential and action potential firing. We found that in sRad interneurons, HCN channels were downregulated after synaptic plasticity, irrespective of the strength of synaptic potentiation. This suggests differential regulation of Ih in excitatory and inhibitory neurons, possibly signifying their distinct role in network activity.
+ Journal of Neurophysiology, Volume 132, Issue 5, Page 1621-1632, November 2024.-
in eNeuro on 2024-11-13 17:30:17 UTC. +
in Journal of Neurophysiology on 2024-11-14 03:52:06 UTC.
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-Visual Processing by Hierarchical and Dynamic Multiplexing
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+Clinical efficacy of low-intensity pulsed ultrasound in Parkinson’s disease with cognitive impairment
-The complexity of natural environments requires highly flexible mechanisms for adaptive processing of single and multiple stimuli. Neuronal oscillations could be an ideal candidate for implementing such flexibility in neural systems. Here, we present a framework for structuring attention-guided processing of complex visual scenes in humans, based on multiplexing and phase coding schemes. Importantly, we suggest that the dynamic fluctuations of excitability vary rapidly in terms of magnitude, frequency and wave-form over time, i.e., they are not necessarily sinusoidal or sustained oscillations. Different elements of single objects would be processed within a single cycle (burst) of alpha activity (7–14 Hz), allowing for the formation of coherent object representations while separating multiple objects across multiple cycles. Each element of an object would be processed separately in time—expressed as different gamma band bursts (>30 Hz)—along the alpha phase. Since the processing capacity per alpha cycle is limited, an inverse relationship between object resolution and size of attentional spotlight ensures independence of the proposed mechanism from absolute object complexity. Frequency and wave-shape of those fluctuations would depend on the nature of the object that is processed and on cognitive demands. Multiple objects would further be organized along the phase of slower fluctuations (e.g., theta), potentially driven by saccades. Complex scene processing, involving covert attention and eye movements, would therefore be associated with multiple frequency changes in the alpha and lower frequency range. This framework embraces the idea of a hierarchical organization of visual processing, independent of environmental temporal dynamics.
+ Journal of Neurophysiology, Volume 132, Issue 5, Page 1633-1638, November 2024.-
in eNeuro on 2024-11-13 17:30:17 UTC. +
in Journal of Neurophysiology on 2024-11-14 03:52:05 UTC.
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-Distinct Strategies Regulate Correlated Ion Channel mRNAs and Ionic Currents in Continually versus Episodically Active Neurons
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Examining motor evidence for the pause-then-cancel model of action-stopping: insights from motor system physiology
-Relationships among membrane currents allow central pattern generator (CPG) neurons to reliably drive motor programs. We hypothesize that continually active CPG neurons utilize activity-dependent feedback to correlate expression of ion channel genes to balance essential membrane currents. However, episodically activated neurons experience absences of activity-dependent feedback and, thus, presumably employ other strategies to coregulate the balance of ionic currents necessary to generate appropriate output after periods of quiescence. To investigate this, we compared continually active pyloric dilator (PD) neurons with episodically active lateral gastric (LG) CPG neurons of the stomatogastric ganglion (STG) in male Cancer borealis crabs. After experimentally activating LG for 8 h, we measured three potassium currents and abundances of their corresponding channel mRNAs. We found that ionic current relationships were correlated in LG's silent state, but ion channel mRNA relationships were correlated in the active state. In continuously active PD neurons, ion channel mRNAs and ionic currents are simultaneously correlated. Therefore, two distinct relationships exist between channel mRNA abundance and the ionic current encoded in these cells: in PD, a direct correlation exists between Shal channel mRNA levels and the A-type potassium current it carries. Conversely, such channel mRNA–current relationships are not detected and appear to be temporally uncoupled in LG neurons. Our results suggest that ongoing feedback maintains membrane current and channel mRNA relationships in continually active PD neurons, while in LG neurons, episodic activity serves to establish channel mRNA relationships necessary to produce the ionic current profile necessary for the next bout of activity.
+ Journal of Neurophysiology, Volume 132, Issue 5, Page 1589-1607, November 2024.-
in eNeuro on 2024-11-13 17:30:17 UTC. +
in Journal of Neurophysiology on 2024-11-14 03:52:04 UTC.
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-Post-pubertal management of undescended testes from the malignancy risk point of view: a systematic review [version 3; peer review: 2 approved, 1 approved with reservations]
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+Rat movements reflect internal decision dynamics in an evidence accumulation task
- Background Undescended testes (UDT) is a condition where one or both testes is absent in the scrotum. The general age recommendation in which the treatment should be performed is before 18 months old due to the infertility risk and malignancy in later life. In post-pubertal UDT, the current guideline recommends orchiectomy; however, the strength rating of this recommendation is weak. Therefore, this study aimed to provide a systematic review of post-pubertal UDT treatment, focusing on the malignancy risk point of view. Methods A systematic search was performed using PubMed, Wiley Online Library and the Cochrane Library up to 5 March 2023. Any study with either post-pubertal orchiectomy or orchidopexy in patients with UDT and reporting the testicular malignancy was included. The exclusion criteria were studies with lack of information of UDT correction time, no history of correction and the full text wasn’t available. The data collected were the occurrence of testicular malignancy in post-pubertal UDT patients corrected with any method. Quality and bias assessment was assessed with Newcastle-Ottawa scale and Joanna Briggs Institute tools. Results Seven articles (three case reports and four observational studies) were reviewed with a total of 42 patients who underwent post-pubertal correction of either unilateral or bilateral UDT. The correction age ranged from 13 to 34 years old, with follow-up of 48.7–252 months. Among those who developed malignancies, the most common were seminoma, teratoma and carcinoma in situ of the testes. In addition, this study was able to propose an algorithm for post-pubertal UDT treatment strategy. Conclusions The scarce resource was the main limitation of this study. Nevertheless, this review showed that post-pubertal UDT management should be tailored individually. Several factors that should be considered include the condition of the contralateral descended testis, UDT location, serum testosterone level, patient’s age, comorbidities, and interest in fertility. + Journal of Neurophysiology, Volume 132, Issue 5, Page 1608-1620, November 2024.-
in F1000Research on 2024-11-13 17:20:00 UTC. +
in Journal of Neurophysiology on 2024-11-14 03:52:04 UTC.
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-Linear-regression-based algorithms can succeed at identifying microbial functional groups despite the nonlinearity of ecological function
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+Bayesian inference in arm posture perception
-by Yuanchen Zhao, Otto X. Cordero, Mikhail Tikhonov
- -Microbial communities play key roles across diverse environments. Predicting their function and dynamics is a key goal of microbial ecology, but detailed microscopic descriptions of these systems can be prohibitively complex. One approach to deal with this complexity is to resort to coarser representations. Several approaches have sought to identify useful groupings of microbial species in a data-driven way. Of these, recent work has claimed some empirical success at de novo discovery of coarse representations predictive of a given function using methods as simple as a linear regression, against multiple groups of species or even a single such group (the ensemble quotient optimization (EQO) approach). Modeling community function as a linear combination of individual species’ contributions appears simplistic. However, the task of identifying a predictive coarsening of an ecosystem is distinct from the task of predicting the function well, and it is conceivable that the former could be accomplished by a simpler methodology than the latter. Here, we use the resource competition framework to design a model where the “correct” grouping to be discovered is well-defined, and use synthetic data to evaluate and compare three regression-based methods, namely, two proposed previously and one we introduce. We find that regression-based methods can recover the groupings even when the function is manifestly nonlinear; that multi-group methods offer an advantage over a single-group EQO; and crucially, that simpler (linear) methods can outperform more complex ones. + Journal of Neurophysiology, Volume 132, Issue 5, Page 1639-1649, November 2024.-
in PLoS Computational Biology on 2024-11-13 14:00:00 UTC. +
in Journal of Neurophysiology on 2024-11-14 03:52:03 UTC.
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-Mechanical stress and anionic lipids synergistically stabilize an atypical structure of the angiotensin II type 1 receptor (AT1)
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Impact of sleep deprivation on aperiodic activity: a resting-state EEG study
-by Rym Ben Boubaker, Daniel Henrion, Marie Chabbert
- -Environmental factors, including mechanical stress and surrounding lipids, can influence the response of GPCRs, such as the mechanosensitive angiotensin II type 1 receptor (AT1). To investigate the impact of these factors on AT1 activation, we developed a steered molecular dynamics simulations protocol based on quaternion formalism. In this protocol, a pulling force was applied to the N-terminus of transmembrane helix 6 (TM6) to induce the TM6 opening characteristic of activation. Subsequently, the simulations were continued without constraints to allow the receptor to relax around the novel TM6 conformation under different conditions. We analyzed the responses of AT1 to membrane stretching, modeled by applying surface tension, in different bilayers. In phosphocholine bilayers without surface tension, we could observe a transient atypical structure of AT1, with an outward TM7 conformation, at the beginning of the activation process. This atypical structure then evolved toward a pre-active structure with outward TM6 and inward TM7. Strikingly, the presence of anionic phosphoglycerol lipids and application of surface tension synergistically favored the atypical structure, which led to an increase in the cross-section area of the receptor intracellular domain. Lipid internalization and H-bonds between lipid heads and the receptor C-terminus increased in phosphoglycerol vs phosphocholine bilayers, but did not depend on surface tension. The difference in the cross-section area of the atypical and pre-active conformations makes the conformational transition sensitive to lateral pressure, and favors the atypical conformation upon surface tension. Anionic lipids act as allosteric modulators of the conformational transition, by stabilizing the atypical conformation. These findings contribute to decipher the mechanisms underlying AT1 activation, highlighting the influence of environmental factors on GPCR responses. Moreover, our results reveal the existence of intermediary conformations that depend on receptor environment and could be targeted in drug design efforts. + Journal of Neurophysiology, Volume 132, Issue 5, Page 1577-1588, November 2024.-
in PLoS Computational Biology on 2024-11-13 14:00:00 UTC. +
in Journal of Neurophysiology on 2024-11-14 03:52:02 UTC.
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-Spatiotemporal integration of contextual and sensory information within the cortical hierarchy in human pain experience
+- Wallabag.it! - Save to Instapaper - Save to Pocket -
+Representational spaces in orbitofrontal and ventromedial prefrontal cortex: task states, values, and beyond
-by Suhwan Gim, Seok-Jun Hong, Elizabeth A. Reynolds Losin, Choong-Wan Woo
- -Pain is not a mere reflection of noxious input. Rather, it is constructed through the dynamic integration of current predictions with incoming sensory input. However, the temporal dynamics of the behavioral and neural processes underpinning this integration remain elusive. In the current study involving 59 human participants, we identified a series of brain mediators that integrated cue-induced expectations with noxious inputs into ongoing pain predictions using a semicircular scale designed to capture rating trajectories. Temporal mediation analysis revealed that during the early-to-mid stages of integration, the frontoparietal and dorsal attention network regions, such as the lateral prefrontal, premotor, and parietal cortex, mediated the cue effects. Conversely, during the mid-to-late stages of integration, the somatomotor network regions mediated the effects of stimulus intensity, suggesting that the integration occurs along the cortical hierarchy from the association to sensorimotor brain systems. Our findings advance the understanding of how the brain integrates contextual and sensory information into pain experience over time. + The orbitofrontal cortex (OFC) and ventromedial-prefrontal cortex (vmPFC) play a key role in decision-making and encode task states in addition to expected value. We review evidence suggesting a connection between value and state representations and argue that OFC / vmPFC integrate stimulus, context, and outcome information. Comparable encoding principles emerge in late layers of deep reinforcement learning (RL) models, where single nodes exhibit similar forms of mixed-selectivity, which enables flexible readout of relevant variables by downstream neurons. Based on these lines of evidence, we suggest that outcome-maximization leads to complex representational spaces that are insufficiently characterized by linear value signals that have been the focus of most prior research on the topic. Major outstanding questions concern the role of OFC/ vmPFC in learning across tasks, in encoding of task-irrelevant aspects, and the role of hippocampus–PFC interactions. -in PLoS Biology on 2024-11-13 14:00:00 UTC. +
in Trends in Neurosciences: In press on 2024-11-14 00:00:00 UTC.
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-Youthful insight: Nitrogen sequestration in larvae provides clues to coral bleaching
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+Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters in collective cell migration of epithelial cells
-by Christian R. Voolstra
- -Impaired nutrient cycling under thermal stress foregoes coral bleaching, the loss of symbiotic algae. A new study in PLOS Biology sheds light on how coral larvae avoid bleaching through nitrogen sequestration to uphold glucose translocation from their algal symbionts. - -Impaired nutrient cycling under thermal stress foregoes coral bleaching, the loss of symbiotic algae. This Primer explores a new study in PLOS Biology which sheds light on how coral larvae avoid bleaching through nitrogen sequestration to uphold glucose translocation from their algal symbionts. + Deguchi et al. find that low-affinity EGFR ligands propagate faster and farther than high-affinity ligands in epithelial cells. They demonstrate that EREG, a low-affinity ligand, contributes to skin wound healing. -in PLoS Biology on 2024-11-13 14:00:00 UTC. +
in Cell Reports: Current Issue on 2024-11-14 00:00:00 UTC.
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-Computational microscopy beyond perfect lenses
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+ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma
-Author(s): Xingyuan Lu, Minh Pham, Elisa Negrini, Damek Davis, Stanley J. Osher, and Jianwei Miao
We demonstrate that in situ coherent diffractive imaging (CDI), which leverages the coherent interference between strong and weak beams to illuminate static and dynamic structures, can serve as a highly dose-efficient imaging method. At low doses, in situ CDI can achieve higher resolution than perfe…
[Phys. Rev. E 110, 054407] Published Wed Nov 13, 2024
+ (Cell Reports 43, 114406; July 23, 2024) -in Physical Review E: Biological physics on 2024-11-13 10:00:00 UTC. +
in Cell Reports: Current Issue on 2024-11-14 00:00:00 UTC.
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-Active curling of epithelial monolayers dominated by actin cytoskeleton mechanics
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+Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling
-Author(s): Huan Wang, Jiu-Tao Hang, and Guang-Kui Xu
Active curling of epithelial tissues, as an indispensable component of developmental morphogenesis, occurs frequently both in vivo and in vitro microenvironments. Deciphering the mechanisms underlying the active curling of epithelial monolayers is crucial for understanding many physiological and pat…
[Phys. Rev. E 110, 054410] Published Wed Nov 13, 2024
+ Alvarez et al. use loss- and gain-of-function approaches in chicken, mouse, and stem cells to show that netrin1 inhibits Bmp activity to confine dorsal neural patterning to the correct compartment in the embryonic spinal cord. Netrin1 regulates mRNA processing to suppress Bmp signaling. -in Physical Review E: Biological physics on 2024-11-13 10:00:00 UTC. +
in Cell Reports: In press on 2024-11-14 00:00:00 UTC.
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-The vacuolar K+/H+ exchangers and calmodulin-like CML18 constitute a pH-sensing module that regulates K+ status in Arabidopsis
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+Structure of scavenger receptor SCARF1 and its interaction with lipoproteins
- Science Advances, Volume 10, Issue 46, November 2024.+ SCARF1 (scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDLs) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here, we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then, we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-Extreme wind events responsible for an outsized role in shelf-basin exchange around the southern tip of Greenland
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+An antimicrobial drug recommender system using MALDI-TOF MS and dual-branch neural networks
- Science Advances, Volume 10, Issue 46, November 2024.+ Timely and effective use of antimicrobial drugs can improve patient outcomes, as well as help safeguard against resistance development. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently routinely used in clinical diagnostics for rapid species identification. Mining additional data from said spectra in the form of antimicrobial resistance (AMR) profiles is, therefore, highly promising. Such AMR profiles could serve as a drop-in solution for drastically improving treatment efficiency, effectiveness, and costs. This study endeavors to develop the first machine learning models capable of predicting AMR profiles for the whole repertoire of species and drugs encountered in clinical microbiology. The resulting models can be interpreted as drug recommender systems for infectious diseases. We find that our dual-branch method delivers considerably higher performance compared to previous approaches. In addition, experiments show that the models can be efficiently fine-tuned to data from other clinical laboratories. MALDI-TOF-based AMR recommender systems can, hence, greatly extend the value of MALDI-TOF MS for clinical diagnostics. All code supporting this study is distributed on PyPI and is packaged at https://github.com/gdewael/maldi-nn. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-TET2 regulates early and late transitions in exhausted CD8+ T cell differentiation and limits CAR T cell function
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+The epigenetic trajectory of type 1 regulatory T cells
- Science Advances, Volume 10, Issue 46, November 2024.+ The epigenome of T follicular helper cells prepares them for conversion into type 1 regulatory T cells. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-A nearly terrestrial D/H for comet 67P/Churyumov-Gerasimenko
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+Isobaric crosslinking mass spectrometry technology for studying conformational and structural changes in proteins and complexes
- Science Advances, Volume 10, Issue 46, November 2024.+ Dynamic conformational and structural changes in proteins and protein complexes play a central and ubiquitous role in the regulation of protein function, yet it is very challenging to study these changes, especially for large protein complexes, under physiological conditions. Here, we introduce a novel isobaric crosslinker, Qlinker, for studying conformational and structural changes in proteins and protein complexes using quantitative crosslinking mass spectrometry. Qlinkers are small and simple, amine-reactive molecules with an optimal extended distance of ~10 Å, which use MS2 reporter ions for relative quantification of Qlinker-modified peptides derived from different samples. We synthesized the 2-plex Q2linker and showed that the Q2linker can provide quantitative crosslinking data that pinpoints key conformational and structural changes in biosensors, binary and ternary complexes composed of the general transcription factors TBP, TFIIA, and TFIIB, and RNA polymerase II complexes. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-INF2 mutations cause kidney disease through a gain-of-function mechanism
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+Proteomic and functional comparison between human induced and embryonic stem cells
- Science Advances, Volume 10, Issue 46, November 2024.+ Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives to embryonic stem cells (hESCs) in regenerative medicine and disease modelling. In this study, we characterise the proteomes of multiple hiPSC and hESC lines derived from independent donors and find that while they express a near-identical set of proteins, they show consistent quantitative differences in the abundance of a subset of proteins. hiPSCs have increased total protein content, while maintaining a comparable cell cycle profile to hESCs, with increased abundance of cytoplasmic and mitochondrial proteins required to sustain high growth rates, including nutrient transporters and metabolic proteins. Prominent changes detected in proteins involved in mitochondrial metabolism correlated with enhanced mitochondrial potential, shown using high-resolution respirometry. hiPSCs also produced higher levels of secreted proteins, including growth factors and proteins involved in the inhibition of the immune system. The data indicate that reprogramming of fibroblasts to hiPSCs produces important differences in cytoplasmic and mitochondrial proteins compared to hESCs, with consequences affecting growth and metabolism. This study improves our understanding of the molecular differences between hiPSCs and hESCs, with implications for potential risks and benefits for their use in future disease modelling and therapeutic applications. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-Achieving strong optical nonlinearity and wide bandgap of pnictides via ionic motif–driven directed assembly of covalent groups
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+Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses
- Science Advances, Volume 10, Issue 46, November 2024.+ The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic and sensory information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells of the DG play a role in memory encoding and information processing and are deeply affected in humans suffering Alzheimer’s disease and temporal lobe epilepsy, contributing to the dysfunctions found in these pathologies. The plasticity of these synapses is not well known yet, as are not known the forms of long-term depression (LTD) existing at those connections. We investigated whether spike timing-dependent long-term depression (t-LTD) exists at these two different EC-DG synaptic connections in mice, and whether they have different action mechanisms. We have found two different forms of t-LTD, at LPP- and MPP-GC synapses and characterised their cellular and intracellular mechanistic requirements. We found that both forms of t-LTD are expressed presynaptically and that whereas t-LTD at LPP-GC synapses does not require NMDAR, t-LTD at MPP-GC synapses requires ionotropic NMDAR containing GluN2A subunits. The two forms of t-LTD require different group I mGluR, mGluR5 LPP-GC synapses and mGluR1 MPP-GC synapses. In addition, both forms of t-LTD require postsynaptic calcium, eCB synthesis, CB1R, astrocyte activity, and glutamate released by astrocytes. Thus, we discovered two novel forms of t-LTD that require astrocytes at EC-GC synapses. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-Unambiguous discrimination of general quantum operations
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+Chemokine expression profile of an innate granuloma
- Science Advances, Volume 10, Issue 46, November 2024.+ Granulomas are defined by the presence of organized layers of immune cells that include macrophages. Granulomas are often characterized as a way for the immune system to contain an infection and prevent its dissemination. We recently established a mouse infection model where Chromobacterium violaceum induces the innate immune system to form granulomas in the liver. This response successfully eradicates the bacteria and returns the liver to homeostasis. Here, we sought to characterize the chemokines involved in directing immune cells to form the distinct layers of a granuloma. We use spatial transcriptomics to investigate the spatial and temporal expression of all CC and CXC chemokines and their receptors within this granuloma response. The expression profiles change dynamically over space and time as the granuloma matures and then resolves. To investigate the importance of monocyte-derived macrophages in this immune response, we studied the role of CCR2 during C. violaceum infection. Ccr2–/– mice had negligible numbers of macrophages, but large numbers of neutrophils, in the C. violaceum-infected lesions. In addition, lesions had abnormal architecture resulting in loss of bacterial containment. Without CCR2, bacteria disseminated and the mice succumbed to the infection. This indicates that macrophages are critical to form a successful innate granuloma in response to C. violaceum. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-Experience-dependent, sexually dimorphic synaptic connectivity defined by sex-specific cadherin expression
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+Predictive models for secondary epilepsy in patients with acute ischemic stroke within one year
- Science Advances, Volume 10, Issue 46, November 2024.+ -/- -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in eLife on 2024-11-14 00:00:00 UTC.
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-Channel width modulates the permeability of DNA origami–based nuclear pore mimics
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+Feature similarity: a sensitive method to capture the functional interaction of brain regions and networks to support flexible behavior
- Science Advances, Volume 10, Issue 46, November 2024.+ The brain is a dynamic system where complex behaviours emerge from interactions across distributed regions. Accurately linking brain function to cognition requires tools that are sensitive to these dynamics. We introduce a novel technique - Feature Similarity (FS) - to capture intricate interaction patterns between brain systems. Our results show that FS can capture functional brain organisation: regions within the same functional network have greater FS compared to those in different networks, and FS also identifies the principal gradient that spans from unimodal to transmodal cortices. FS was found to be more sensitive to task modulation than traditional functional connectivity (FC). Specifically, FS reveals interaction patterns missed by FC, such as a double dissociation in the Dorsal Attention Network (DAN): greater interaction with the Visual network during working memory tasks and greater interaction with the default mode network (DMN) during long-term memory tasks. This study highlights FS as a promising tool for understanding flexibility in brain network dynamics. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Breaking Abbe’s diffraction limit with harmonic deactivation microscopy
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+SEX-RELATED GENE EXPRESSION IN THE POSTERODORSAL MEDIAL AMYGDALA OF CYCLING FEMALE RATS ALONG WITH PROLACTIN MODULATION OF LORDOSIS BEHAVIOR
- Science Advances, Volume 10, Issue 46, November 2024.+ The rat posterodorsal medial amygdala (MePD) is sexually dimorphic, has a high concentration of receptors for gonadal hormones and prolactin (PRL), and modulates reproduction. To unravel genetic and functional data for this relevant node of the social behavior network, we studied the expression of ERalpha, ERbeta, GPER1, Kiss1, Kiss1R, PRGR, PRL, PRLR, EGR1, JAK2, STAT5A, and STAT5B in the MePD of males and females along the estrous cycle using the RT-qPCR technique. We also investigated whether PRL in the MePD would affect the sexual behavior display of proestrus females by microinjecting saline, the PRL receptor antagonist Del1-9-G129R-hPRL (1 microM and 10 microM), or PRL (1 nM) and Del1-9-G129R-hPRL (10 microM) 3h before the onset of the dark-cycle period. The estrogen-dependent lordosis behavior, indicative of sexual receptivity of proestrus females, was recorded and compared before (control) and after (test) microinjections in these groups. Sex differences were found in the right and left MePD gene expression. ERalpha and Kiss1R, as well as PRL, Short PRLR, and STAT5B expression is higher in cycling females than males. Kiss1 expression is higher in males than females, and GPER1 is higher during diestrus than proestrus. Furthermore, Del1-9-G129R-hPRL in the MePD significantly reduced the full display and quotient of lordosis in proestrus females, an effect restored by the co-microinjection of PRL. In conjunction, the expression of studied genes showed specific sex and estrous cycle phase features while, in proestrus, PRL action in the MePD plays an essential role in the display of lordosis during the ovulatory period. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Fractional change of scattering and absorbing aerosols contributes to Northern Hemisphere Hadley circulation expansion
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+Multimodal investigation of the neurocognitive deficits underlying dyslexia in adulthood
- Science Advances, Volume 10, Issue 46, November 2024.+ Dyslexia is a neurobiological disorder characterised by reading difficulties, yet its underlying causes remain unclear. Neuroimaging and behavioural studies found anomalous responses in tasks requiring phonological processing, motion perception, and implicit learning, and showed gray and white matter abnormalities in several brain regions of dyslexics compared to controls, indicating that dyslexia is a heterogeneous condition and promoting a multifactorial approach. In order to evaluate whether the combination of behavioural and multimodal MRI can have greater sensitivity in identifying neurocognitive traits of dyslexia compared to monocomponential approaches, in 19 dyslexic and 19 control subjects we acquired behavioural cognitive assessments, multiple (phonological, visual motion, rhythmic) mismatch-response functional MRI tasks, structural diffusion-weighted and T1-weighted images. To examine between-group differences in the multimodal neurocognitive measures, we applied univariate and multivariate approaches. Results showed that dyslexics performed worse than controls in behavioural phonological tasks. Neuroimaging analyses revealed that individuals with dyslexia present reduced cerebellar responses to mismatching rhythmic stimuli, as well as structural disorganization in several white matter tracts and cortical regions previously implicated in dyslexia. Most importantly, in line with the view of dyslexia as a multifactorial phenomenon, a machine learning model trained with features from all three MRI modalities (functional, diffusion, and T1-weighted) discriminated between dyslexics and controls with greater accuracy than models including just one modality. The individual classification scores in the multimodal machine learning model correlated with behavioural reading accuracy. These results confirm that dyslexia should be approached as a composite condition characterised by multiple distinctive cognitive and brain features. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Ediacaran origin and Ediacaran-Cambrian diversification of Metazoa
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+Comparative analysis of spike-sorters in large-scale brainstem recordings
- Science Advances, Volume 10, Issue 46, November 2024.+ Recent technological advancements in high-density multi-channel electrodes have made it possible to record large numbers of neurons from previously inaccessible regions. While the performance of automated spike-sorters has been assessed in recordings from cortex, dentate gyrus, and thalamus, the most effective and efficient approach for spike-sorting can depend on the target region due to differing morphological and physiological characteristics. We therefore assessed the performance of five commonly used sorting packages, Kilosort3, MountainSort5, Tridesclous, SpyKING CIRCUS, and IronClust, in recordings from the rostral ventromedial medulla, a region that has been characterized using single-electrode recordings but that is essentially unexplored at the high-density network level. As demonstrated in other brain regions, each sorter produced unique results. Manual curation preferentially eliminated units detected by only one sorter. Kilosort3 and IronClust required the least curation while maintaining the largest number of units, whereas SpyKING CIRCUS and MountainSort5 required substantial curation. Tridesclous consistently identified the smallest number of units. Nonetheless, all sorters successfully identified classically defined RVM physiological cell types. These findings suggest that while the level of manual curation needed may vary across sorters, each can extract meaningful data from this deep brainstem site. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Forecast skill assessment of an operational continental heat-cold-health forecasting system: New avenues for health early warning systems
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+Brain functional network connectivity interpolation characterizes neuropsychiatric continuum and heterogeneity
- Science Advances, Volume 10, Issue 46, November 2024.+ Psychiatric disorders such as schizophrenia (SZ) and autism spectrum disorder (ASD) are challenging to characterize in part due to their heterogeneous presentation in individuals, with psychotic symptoms now thought to exist on a continuum from the general population to chronic SZ. Conventional diagnostic and neuroimaging analytical approaches rely on subjective assessment or group differences, but typically ignore progression between groups or heterogeneity within a group. Here, we propose a functional network connectivity (FNC) interpolation framework based on an unsupervised generative model, a variational autoencoder (VAE), to estimate the neuropsychiatric continuum and heterogeneity using static FNC (sFNC) and dynamic FNC (dFNC) data from controls and patients with SZ or ASD. We first demonstrate that VAEs significantly outperform a linear baseline and a semi-supervised counterpart in the interpolation task. We next utilize VAEs to perform sFNC and dFNC interpolation separately. For sFNC interpolation, we observe a high degree of correspondence between the generated sFNC and the corresponding original sFNC. We display the sFNC matrices on a two-dimensional grid to examine individual- and group-specific patterns, as well as pattern alterations. Specifically, the interpolated continua from patients to controls in both disorders show increased hyper-connectivity within the auditory, sensorimotor and visual networks, and between the subcortical and cerebellar domains, as well as hypo-connectivity between the subcortical domain and the sensory domains, and between the cerebellar domain and the sensory regions. For dFNC interpolation, we find that the generated dFNC states effectively capture representative and generalizable dynamic properties for each group. Finally, we show examples of how to leverage interpolation in the VAE latent space, following pathological, state-based, or temporal trajectories. The proposed framework offers added advantages over traditional methods, including data-driven discovery of hidden relationships, visualization of individual differences, imputation of missing values along a continuous spectrum, and estimation of the stage where an individual falls within the continuum. Further, it could potentially be applied to identify patient subgroups and predict future disorder progression. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Toxic small alarmone synthetase FaRel2 inhibits translation by pyrophosphorylating tRNAGly and tRNAThr
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+Older is Order: Entropy reduction in cortical spontaneous activity marks healthy aging
- Science Advances, Volume 10, Issue 46, November 2024.+ Entropy trajectories remain unclear for the aging process of human brain system due to the lacking of longitudinal neuroimaging resource. We used open data from an accelerated longitudinal cohort (PREVENT-AD) that included 24 healthy aging participants followed by 4 years with 5 visits per participant to establish cortical entropy aging curves and distinguish with the effects of age and cohort. This reveals that global cortical entropy decreased with aging, while a significant cohort effect was detectable that people who were born earlier showed higher cortical entropy. Such entropy reductions were also evident for large-scale cortical networks, although with different rates of reduction for different networks. Specifically, the primary and intermediate networks reduce their entropy faster than the higher-order association networks. We conclude two specific characteristics of the entropy of the human cortex with aging: the shift of the complexity hierarchy and the diversity of complexity strengthen. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Rubbery organic frameworks (ROFs) toward ultrapermeable CO2-selective membranes
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+Modeling Complex Animal Behavior with Latent State Inverse Reinforcement Learning
- Science Advances, Volume 10, Issue 46, November 2024.+ Understanding complex animal behavior is crucial for linking brain computation to observed actions. While recent research has shifted towards modeling behavior as a dynamic process, few approaches exist for modeling long-term, naturalistic behaviors such as navigation. We introduce discrete Dynamical Inverse Reinforcement Learning (dDIRL), a latent state-dependent paradigm for modeling complex animal behavior over extended periods. dDIRL models animal behavior as being driven by internal state-specific rewards, with Markovian transitions between the distinct internal states. Using expectation-maximization, we infer reward functions corresponding to each internal states and the transition probabilities between them, from observed behavior. We applied dDIRL to water-starved mice navigating a labyrinth, analyzing each animal individually. Our results reveal three distinct internal states sufficient to describe behavior, including a consistent water-seeking state occupied for less than half the time. We also identified two clusters of animals with different exploration patterns in the labyrinth. dDIRL offers a nuanced understanding of how internal states and their associated rewards shape observed behavior in complex environments, paving the way for deeper insights into the neural basis of naturalistic behavior. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Ekman revisited: Surface currents to the left of the winds in the Northern Hemisphere
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+Interactions established by isoform-specific TrkB-T1 sequences govern inflammatory response and neurotoxicity in stroke
- Science Advances, Volume 10, Issue 46, November 2024.+ Glia reactivity, neuroinflammation and excitotoxic neuronal death are central processes to ischemic stroke and neurodegenerative diseases, altogether a leading cause of death, disability, and dementia. Due to the high incidence of these pathologies and the lack of efficient treatments, it is a priority developing brain protective therapies impacting both neurons and glial cells. Truncated neurotrophin receptor TrkB-T1, a protein produced by all these cells, plays relevant roles in excitotoxicity and ischemia. We have hypothesized that interactions established by isoform-specific TrkB-T1 sequences might be relevant to neurotoxicity and/or reactive gliosis and, therefore, constitute a therapeutic target. We identify here the TrkB-T1-specific interactome, poorly described to date, and demonstrate that interference of these protein-protein interactions using brain-accessible TrkB-T1-derived peptides can prevent reactive gliosis and decrease excitotoxicity-induced damage in cellular and mouse models of stroke. The pivotal role played by TrkB-T1 on microglia and astrocyte reactivity suggests that isoform-derived peptides could become important in development of therapies for human stroke and other excitotoxicity-associated pathologies. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Acoustofluidic tweezers via ring resonance
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+A Unified Approach for Identifying PET-based Neuronal Activation and Molecular Connectivity with the functional PET toolbox
- Science Advances, Volume 10, Issue 46, November 2024.+ Purpose: Functional PET (fPET) enables the identification of stimulation-specific changes of various physiological processes (e.g., glucose metabolism, neurotransmitter synthesis) as well as computation of individual molecular connectivity and group-level molecular covariance. However, currently no consistent analysis approach is available for these techniques. We present a versatile, freely available toolbox designed for the analysis of fPET data, thereby filling a gap in the assessment of neuroimaging data. Methods: The fPET toolbox supports analyses for a variety of radiotracers, scanners, experimental protocols, cognitive tasks and species. It includes general linear model (GLM)-based assessment of task-specific effects, percent signal change and absolute quantification, as well as independent component analysis (ICA) for data-driven analyses. Furthermore, it allows computation of molecular connectivity via temporal correlations of PET signals between regions and molecular covariance as between-subject covariance using static images. Results: Toolbox performance was validated by analysis protocols established in previous work. Stimulation-induced changes in [18F]FDG metabolic demands and neurotransmitter dynamics obtained with 6-[18F]FDOPA and [11C]AMT were robustly detected across different cognitive tasks. Molecular connectivity analysis demonstrated metabolic interactions between different networks, whereas group-level covariance analysis highlighted interhemispheric relationships. These results underscore the flexibility of fPET in capturing dynamic molecular processes. Conclusions: The toolbox offers a comprehensive, unified and user-friendly platform for analyzing fPET data across a variety of experimental settings. It provides a reproducible analysis approach, which in turn facilitates sharing of analyses pipelines and comparison across centers to advance the study of brain metabolism and neurotransmitter dynamics in health and disease. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Near-infrared spectroscopy–enabled electromechanical systems for fast mapping of biomechanics and subcutaneous diagnosis
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+Bidirectional Impact of miR-29a modulation on Memory Stability in the Adult Brain
- Science Advances, Volume 10, Issue 46, November 2024.+ MicroRNAs are key regulators of brain gene expression, with miR-29a notably upregulated from development to adulthood and in aging, and showing links to cognitive decline. However, the extent to which miR-29 levels influence learning and memory processes, and its molecular mediators, remains to be determined. Here, we down- and up-regulated miR-29a levels in the dorsal hippocampus of adult mice to reveal miR-29 role in memory. Inhibiting miR-29a enhanced trace fear memory stability, increased Dnmt3a levels, and affected CpG methylation in gene regulation regions. In contrast, increasing miR-29a impaired memory performances and decreased Dnmt3a levels, suggesting a destabilization of memory processes. Proteomic and transcriptomic analysis demonstrated that miR-29a antagonism upregulated RNA-binding and synaptic proteins and downregulated inflammation and myelin associated proteins. These results underscore miR-29a pivotal role in memory persistence, plasticity, and cognitive aging, suggesting that miR-29a modulation could offer potential strategies for cognitive enhancement and age-related memory decline. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Compact highly sensitive photothermal RT-LAMP chip for simultaneous multidisease detection
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+Sulfatide deficiency-induced astrogliosis and myelin lipid dyshomeostasis are independent of Trem2-mediated microglial activation
- Science Advances, Volume 10, Issue 46, November 2024.+ Disrupted lipid homeostasis and neuroinflammation often co-exist in neurodegenerative disorders including Alzheimer's disease (AD). However, the intrinsic connection and causal relationship between these deficits remain elusive. Our previous studies show that the loss of sulfatide (ST), a class of myelin-enriched lipids, causes AD-like neuroinflammatory responses, cognitive impairment, bladder enlargement, as well as lipid dyshomeostasis. To better understand the relationship between neuroinflammation and lipid disruption induced by ST deficiency, we established a ST-deficient mouse model with constitutive Trem2 knockout and studied the impact of Trem2 in regulating ST deficiency-induced microglia-mediated neuroinflammation, astrocyte activation and lipid disruption. Our study demonstrates that Trem2 regulates ST deficiency-induced microglia-mediated neuroinflammatory pathways and astrogliosis at the transcriptomic level, but not astrocyte activation at the protein level, suggesting that Trem2 is indispensable for ST deficiency-induced microglia-mediated neuroinflammation but not astrogliosis. Meanwhile, ST loss-induced lipidome disruption and free water retention were consistently observed in the absence of Trem2. Collectively, these results emphasize the essential role of Trem2 in mediating lipid loss-associated microglia-mediated neuroinflammation, but not both astrogliosis and myelin lipid disruption. Moreover, we demonstrated that attenuating neuroinflammation has a limited impact on brain ST loss-induced lipidome alteration or AD-like peripheral disorders. Our findings suggest that preserving lipidome and astrocyte balance may be crucial in decelerating the progression of AD. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Three modes of viral adaption by the heart
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+Spatial Transcriptomic Analysis Identifies a SERPINA3-Expressing Astrocytic State Associated with the Human Neuritic Plaque Microenvironment
- Science Advances, Volume 10, Issue 46, November 2024.+ Single-nucleus transcriptomic studies have revealed glial cell states associated with Alzheimer's disease; however, these nuclei are dissociated from the complex architecture of the human neocortex. Here, we successfully performed an unbiased distance-based analytic strategy on spatially-registered transcriptomic data. Leveraging immunohistochemistry in the same tissue section, our analyses prioritized SERPINA3 and other genes, such as metallothioneins, as altered in the vicinity of neuritic amyloid plaques. Results were validated at the protein level by immunofluorescence, highlighting that a reactive SERPINA3+ astrocyte subtype, Ast.5, plays a role in the plaque microenvironment. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Frailty or resilience? Hazard-based and cumulative phenotype approaches to discerning signals of health inequality in medieval London
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+Modeling of blood flow dynamics in the rat somatosensory cortex
- Science Advances, Volume 10, Issue 46, November 2024.+ The cerebral microvasculature forms a dense network of interconnected blood vessels where flow is modulated partly by astrocytes. Increased neuronal activity stimulates astrocytes to release vasoactive substances at the endfeet, altering the diameters of connected vessels. Our study simulated the coupling between blood flow variations and vessel diameter changes driven by astrocytic activity in the rat somatosensory cortex. We developed a framework with three key components: coupling between vasculature and synthesized astrocytic morphologies, a fluid dynamics model to compute flow in each vascular segment, and a stochastic process replicating the effect of astrocytic endfeet on vessel radii. The model was validated against experimental flow values from literature across cortical depths. We found that local vasodilation from astrocyte activity increased blood flow, especially in capillaries, exhibiting a layer-specific response in deeper cortical layers. Additionally, the highest blood flow variability occurred in capillaries, emphasizing their role in cerebral perfusion regulation. We discovered that astrocytic activity impacts blood flow dynamics in a localized, clustered manner, with most vascular segments influenced by two to three neighboring endfeet. These insights enhance our understanding of neurovascular coupling and guide future research on blood flow-related diseases. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Electrically switchable chiral nonlinear optics in an achiral ferroelectric 2D van der Waals halide perovskite
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+Restoring Synaptic Balance in Schizophrenia: Insights from a thalamo-cortical conductance-based model.
- Science Advances, Volume 10, Issue 46, November 2024.+ The dysconnectivity hypothesis of schizophrenia suggests that atypical, aberrant neural communication underlies the disorder's diverse symptoms. Building on this framework, our study introduces a novel approach to understanding schizophrenia and exploring potential ways to adjust neural activity through synaptic restoration. Using a combination of magnetoencephalography data and dynamic causal modeling, we identified specific synaptic disturbances in schizophrenia patients, including increased NMDA receptor-mediated excitation in superficial pyramidal neurons and reduced GABA-B receptor-mediated inhibition between interneurons and pyramidal cells. These findings reveal a critical imbalance in excitation and inhibition within thalamo-cortical circuits, manifesting as altered gamma and alpha oscillations. The cornerstone of our research is an in silico synaptic restoration analysis, which demonstrates that targeted modifications to AMPA, NMDA, GABA-A, and GABA-B receptor-mediated connections can recalibrate altered neural activity in schizophrenia, aligning it with healthy control patterns. This restoration approach not only highlights the complex nature of synaptic dysfunction in the disorder but also identifies specific pathways as potential therapeutic targets, offering new avenues for investigating schizophrenia's diverse symptomatology. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity
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+Astrocytic connexin43 phosphorylation contributes to seizure susceptibility after mild Traumatic Brain Injury
- Science Advances, Volume 10, Issue 46, November 2024.+ Astrocytes play a crucial role in maintaining brain homeostasis through functional gap junctions (GJs) primarily formed by connexin43 (Cx43). These GJs facilitate electrical and metabolic coupling between astrocytes, allowing the passage of ions, glucose, and metabolites. Dysregulation of Cx43 has been implicated in various pathologies, including traumatic brain injury (TBI) and acquired epilepsy. We previously identified a subset of atypical astrocytes after mild TBI that exhibit reduced Cx43 expression and coupling and are correlated with the development of spontaneous seizures. Given that mild TBI affects millions globally and can lead to long-term complications, including post-traumatic epilepsy, understanding the molecular events post-TBI is critical for developing therapeutic strategies. In the present study, we assessed the heterogeneity of Cx43 protein expression after mild TBI. In accordance with our previous findings, a subset of astrocytes lost Cx43 expression. As previously reported after TBI, we also found a significant increase in total Cx43 protein expression after mild TBI, predominantly in the soluble form, suggesting that while junctional Cx43 protein levels remained stable, hemichannels and cytoplasmic Cx43 were increased. We then investigated the phosphorylation of Cx43 at serine 368 after TBI, which is known to influence GJ assembly and function. Phosphorylation of Cx43 at serine 368 is elevated following TBI and Cx43S368A mutant mice, lacking this phosphorylation, exhibited reduced susceptibility to seizures induced by pentylenetetrazol (PTZ). These findings suggest that TBI-induced Cx43 phosphorylation enhances seizure susceptibility, while inhibiting this modification presents a potential therapeutic avenue for mitigating neuronal hyperexcitability and seizure development. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-The Summer North Atlantic Oscillation, Arctic sea ice, and Arctic jet Rossby wave forcing
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+Dynamic prioritisation of sensory and motor contents in working memory
- Science Advances, Volume 10, Issue 46, November 2024.+ Internal selective attention prioritises both sensory and motor contents in working memory to guide prospective behaviour. Prior research has shown how attention modulation of sensory contents is flexible and temporally tuned depending on access requirements, but whether the prioritisation of motor contents follows similar flexible dynamics remains elusive. Also uncharted is the degree of co-dependence of sensory and motor modulation, which gets at the nature of both working-memory representations and internal attention functions. To address these questions, we independently tracked the prioritisation of sensory and motor working-memory contents as a function of dynamically evolving temporal expectations. The design orthogonally manipulated when an item location (left vs right side) and associated prospective action (left vs right hand) would be relevant. Contralateral modulation of posterior alpha (8-12 Hz) activity in electroencephalography (EEG) tracked prioritisation of the item location, while contralateral modulation of central mu/beta (8-30 Hz) activity tracked response prioritisation. Proactive and dynamic alpha and mu/beta modulation confirmed the flexible and temporally structured prioritisation of sensory and motor contents alike. Intriguingly, the prioritisation of sensory and motor contents was temporally uncoupled, showing dissociable patterns of modulation. The findings reveal multiple modulatory functions of internal attention operating in tandem to prepare relevant aspects of internal representations for adaptive behaviour. -
in Science Advances on 2024-11-13 08:00:00 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Forthcoming Articles
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+Pathological microcircuits initiate epileptiform events in patient hippocampal slices
- The Neuroscientist, Volume 30, Issue 6, Page 640-640, December 2024.+ How seizures begin at the level of microscopic neural circuits remains unknown. High-density CMOS microelectrode arrays provide a new avenue for investigating neuronal network activity, with unprecedented spatial and temporal resolution. We use high-density CMOS-based microelectrode arrays to probe the network activity of human hippocampal brain slices from six patients with mesial temporal lobe epilepsy in the presence of hyperactivity promoting media. Two slices from the dentate gyrus exhibited epileptiform activity in the presence of low magnesium media with kainic acid. Both slices displayed an electrophysiological phenotype consistent with a reciprocally connected circuit, suggesting a recurrent feedback loop is a key driver of epileptiform onset. Larger prospective studies are needed, but these findings have the potential to elucidate the network signals underlying the initiation of seizure behavior. -
in The Neuroscientist on 2024-11-13 06:22:22 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-The Day After
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+No Effect of Value on the Task Irrelevant Auditory Mismatch Negativity
- The Neuroscientist, Volume 30, Issue 6, Page 641-642, December 2024.+ Behavioural and neuroscientific evidence suggests visual stimuli that signal value involuntarily capture attention and are preferentially processed, even when unattended. We examined whether learned value associations for task-irrelevant auditory stimuli modulate pre-attentive processing and involuntarily capture attention. Across two experiments, the effect of learned value on the visual- and auditory-evoked mismatch negativity (MMN) and P3a event-related potential (ERP) components was measured. Participants performed a primary visual detection task while an irrelevant, unattended oddball stimulus stream was concurrently presented. Deviants within this oddball stream had been previously learned to signal one of several value outcomes: monetary reward, loss or no change. Neither the auditory nor the visual MMN was influenced by these value associations. However, stimulus value affected performance on the primary task and the magnitude of the P3a in those who could identify the stimulus-value pairings at test. Supplementary mass univariate analyses and time frequency decomposition (theta phase-locking) confirmed the presence of the MMN and the absence of any influence of stimulus value on the MMN response. Findings suggest that learned value associations do not meaningfully influence the MMN prediction signaling mechanism for task-irrelevant auditory stimuli. -
in The Neuroscientist on 2024-11-13 06:22:19 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Single-Nuclei Multiomics of the Prefrontal Cortex: 388 Brains Tell a Powerful Story
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+Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation
- The Neuroscientist, Volume 30, Issue 6, Page 642-642, December 2024.+ It is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC[->]SDH-NA neurons), that is activated by acute exposure to restraint stress and is required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, the primary target of spinal NA released from descending LC[->]SDH-NAergic terminals causing the stress-induced pain hypersensitivity was 1A-adrenaline receptors (1ARs) in Hes5-positive (Hes5+) astrocytes located in the SDH, an astrocyte subset that has an ability to induce pain sensitization. Furthermore, activation of Hes5+ astrocytes reduced activity of SDH-inhibitory neurons (SDH-INs) that have an inhibitory role in pain processing. This astrocytic reduction of IN activity was canceled by an A1-adenosine receptor (A1R)-knockdown in SDH-INs, and the A1R-knockdown suppressed pain hypersensitivity caused by acute restraint stress. Therefore, our findings suggest that LC[->]SDH-NA neuronal signaling to Hes5+ SDH astrocytes and subsequent astrocytic reduction of SDH-IN activity are essential for pain facilitation caused by stress. -
in The Neuroscientist on 2024-11-13 06:22:19 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-A new frontier in the treatment of schizophrenia
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+Humans anticipate the consequences of motor control demands when making perceptual decisions between actions
- The Neuroscientist, Volume 30, Issue 6, Page 643-643, December 2024.+ Animals, including humans, are often faced with situations where they must decide between potential actions to perform based on various sources of information, including movement parameters that incur time and energy costs. Consistent with this fact, many behavioral studies indicate that decisions and actions show a high level of integration during goal-directed behavior. In particular, motor costs very often bias the choice process of human and non-human subjects facing successive decisions between actions. However, it appears as well that depending on the design in which the experiment occurs, the effect of motor costs on decisions can vary or even vanish. This suggests a contextual dependence of the influence of motor costs on decision-making. Moreover, it is not currently known whether or not the impact of motor costs on perceptual decisions depend on the difficulty of the decision. We addressed these two important issues by studying the behavior of healthy human subjects engaged in a new perceptual decision-making paradigm in which the constraint level associated with the movement executed to report a choice was volitionally chosen by the participants, and in which the difficulty of the perceptual decision to make continuously evolved depending on their motor performance. The results indicate that the level of constraint associated with a movement executed to express a perceptual decision strongly impacts the duration of these decisions, with a shortening of decisions when these are expressed by demanding movements. This influence appears most important when the decisions are difficult, but it is also present for easy decisions. We interpret this strategy as an adaptive way to optimize the participants' overall rate of success at the session level. -
in The Neuroscientist on 2024-11-13 06:22:19 UTC. +
in bioRxiv: Neuroscience on 2024-11-14 00:00:00 UTC.
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-Velocity coding in the central brain of bumblebees
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+Brain Sciences, Vol. 14, Pages 1142: Examining the Neural Markers of Speech Rhythm in Silent Reading Using Mass Univariate Statistics of EEG Single Trials
- Journal of Neurophysiology, Ahead of Print.+
Brain Sciences, Vol. 14, Pages 1142: Examining the Neural Markers of Speech Rhythm in Silent Reading Using Mass Univariate Statistics of EEG Single Trials
+Brain Sciences doi: 10.3390/brainsci14111142
+Authors: + Stephanie J. Powell + Srishti Nayak + Cyrille L. Magne +
+Background/Objectives: The Implicit Prosody Hypothesis (IPH) posits that individuals generate internal prosodic representations during silent reading, mirroring those produced in spoken language. While converging behavioral evidence supports the IPH, the underlying neurocognitive mechanisms remain largely unknown. Therefore, this study investigated the neurophysiological markers of sensitivity to speech rhythm cues during silent word reading. Methods: EEGs were recorded while participants silently read four-word sequences, each composed of either trochaic words (stressed on the first syllable) or iambic words (stressed on the second syllable). Each sequence was followed by a target word that was either metrically congruent or incongruent with the preceding rhythmic pattern. To investigate the effects of metrical expectancy and lexical stress type, we examined single-trial event-related potentials (ERPs) and time&ndash;frequency representations (TFRs) time-locked to target words. Results: The results showed significant differences based on the stress pattern expectancy and type. Specifically, words that carried unexpected stress elicited larger ERP negativities between 240 and 628 ms after the word onset. Furthermore, different frequency bands were sensitive to distinct aspects of the rhythmic structure in language. Alpha activity tracked the rhythmic expectations, and theta and beta activities were sensitive to both the expected rhythms and specific locations of the stressed syllables. Conclusions: The findings clarify neurocognitive mechanisms of phonological and lexical mental representations during silent reading using a conservative data-driven approach. Similarity with neural response patterns previously reported for spoken language contexts suggests shared neural networks for implicit and explicit speech rhythm processing, further supporting the IPH and emphasizing the centrality of prosody in reading.
-in Journal of Neurophysiology on 2024-11-13 03:05:41 UTC. +
in Brain Sciences on 2024-11-14 00:00:00 UTC.
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-White matter aging and its impact on brain function
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+Brain Sciences, Vol. 14, Pages 1141: Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis
- Aging leads to a decrease in white matter volume and damage to myelinated axons, contributing to neurodegeneration. Myelin breakdown can trigger inflammation, creating a vicious cycle that causes further damage. Understanding these changes is key to preventing age-related neurodegenerative disease. +Brain Sciences, Vol. 14, Pages 1141: Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis
+Brain Sciences doi: 10.3390/brainsci14111141
+Authors: + Alin Ciubotaru + Daniel Alexa + Cristina Grosu + Lilia Böckels + Ioana Păvăleanu + Alexandra Maștaleru + Maria Magdalena Leon + Roxana Covali + Emanuel Matei Roman + Cătălina Elena Bistriceanu + Cristina Mihaela Ghiciuc + Doina Azoicăi + Emilian Bogdan Ignat +
+Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by progressive impairment of neuronal transmission due to focal demyelination. The most common form is RRMS (relapsing-remitting multiple sclerosis), which, under the influence of certain factors, can progress to SPMS (secondary progressive multiple sclerosis). Our study aimed to validate the criteria proposed by a working group of the Romanian Society of Neurology versus the criteria proposed by a group of experts from Spain, Karolinska, and Croatia concerning the progression from RRMS to SPMS. Methods: This was done by gathering epidemiological data (age, gender) and by applying clinical tests such as the 9HPT (9-hole peg test), 25FWT (25-foot walk test), and EDSS (expanded disability status scale) tests and the SDMT test (symbol digit modalities test). The present research is a cohort study that included a number of 120 patients diagnosed with MS according to the McDonald Diagnostic Criteria 2017. The study was carried out between January 2023 and April 2024, including patients hospitalized in the Neurology Clinic of the Clinical Rehabilitation Hospital from Iasi, Romania. The data were collected at baseline (T0) and at a 12-month interval (T1). Results: The statistical analysis was conducted using Kaiser&ndash;Meyer&ndash;Olkin analysis, which indicated a value of 0.683, thus validating the clinical tests used. The correlation matrix and the linear regression for all the tests showed highly significant statistical results. Furthermore, the ROC curve analysis of the criteria suggested by the working group of the Romanian Society of Neurology demonstrated that the EDSS, 9HPT, and 25FWT are highly sensitive in diagnosing SPMS, an opinion that is shared with the Spanish experts, but not with the Karolinska expert panel. Using the criteria given by the Croatian expert group in the ROC curve analysis showed that only the EDSS was strongly significant for the progression to the SPMS phase. Conclusions: In conclusion, all clinical methods used demonstrated that they are valid and can contribute to identifying patients with an increased risk of progression. The model proposed by the Romanian Society of Neurology working group is similar to other countries&rsquo; expert opinions and can be used to detect the risk of disease progression and establish a more tailored therapeutic management of SPMS.
-in Neuron: In press on 2024-11-13 00:00:00 UTC. +
in Brain Sciences on 2024-11-14 00:00:00 UTC.
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-Leader cells promote immunosuppression to drive ovarian cancer progression in vivo
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+Brain Sciences, Vol. 14, Pages 1140: Temperament and the Experience of Tension and Self-Injurious Behaviour in Adolescents—The Mediating Role of Maladaptive Perfectionism
- Wilson et al. demonstrate that KRT14+ leader cells drive ovarian cancer metastasis by promoting immunosuppression. Loss of KRT14+ leader cells impairs tumor progression, while their overexpression accelerates metastasis through chemokine-mediated immune evasion. These findings reveal KRT14+ leader cells as a potential therapeutic target to hinder metastasis and enhance anti-tumor immunity. +Brain Sciences, Vol. 14, Pages 1140: Temperament and the Experience of Tension and Self-Injurious Behaviour in Adolescents—The Mediating Role of Maladaptive Perfectionism
+Brain Sciences doi: 10.3390/brainsci14111140
+Authors: + Magdalena Chęć + Sylwia Michałowska + Alicja Gnych-Pietrzak + Albina Rybarska + Klaudia Strochalska +
+Background: Adolescence is an important point in the emotional development of young people. It is a time when young people are characterised by a high degree of emotional instability and seek effective ways to regulate their emotions. One of the frequent methods they use to cope with emotional tension is self-injurious behaviour. Methods: In the context of the rising incidence of self-harm among adolescents, this study aims to understand the association of temperament with the experience of tension and self-injurious behaviour along with the mediating role of perfectionism among 366 adolescents aged 15 to 20 years (Mage = 17.98, SD = 1.302, 52.7% female). Participants completed questionnaires on temperament traits, level of perfectionism, and experience of tension and self-injurious behaviour. Results: The results show that traits such as perfectionism, sensory sensitivity and emotional reactivity increase the risk of self-injurious behaviour. Maladaptive perfectionism partially mediates the relationship between these traits and the tendency to experience emotional tension. A temperament profile with a protective role was also identified. Conclusions: The results of the study highlight the importance of innate traits as well as environmental and cognitive influences, and may contribute to a better understanding of the mechanisms leading to self-injurious behaviour and strategies aimed at its prevention.
-in Cell Reports: Current Issue on 2024-11-13 00:00:00 UTC. +
in Brain Sciences on 2024-11-14 00:00:00 UTC.
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-Tissue-colonizing disseminated tumor cells secrete prostaglandin E2 to promote NK cell dysfunction and evade anti-metastatic immunity
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+Analysis of Circulating Plasma MicroRNA Profile in Low-Grade and High-Grade Glioma – A Cross-Sectional Study [version 1; peer review: awaiting peer review]
- NK cells are critical for immunosurveillance of metastases. Pedde et al. reveal that tissue-seeding DTCs utilize the PGE2-EP2/EP4 signaling axis to induce NK cell dysfunction and immune escape following organ colonization, and show that preventing PGE2-induced NK cell dysfunction results in effective immune control of metastatic disease. + Background Glioma is the second most common type of brain tumor, accounting for 24% of all brain tumor cases. The current diagnostic procedure is through an invasive tissue sampling to obtain histopathological analysis, however, not all patients are able to undergo a high-risk procedure. Circulating microRNAs (miRNAs) are considered as promising biomarkers for glioma due to their sensitivity, specificity, and non-invasive properties. There is currently no defined miRNA profile that contributes to determining the grade of glioma. This study aims to find the answer for “Is there any significant miRNA that able to distinguish different grades of glioma?”. Methods This study was conducted to compare the expression of miRNAs between low-grade glioma (LGG) and high-grade glioma (HGG). Eighteen blood plasma samples from glioma patients and 6 healthy controls were analyzed for 798 human miRNA profiles using NanoString nCounter Human v3 miRNA Expression Assay. The differential expressions of miRNAs were then analyzed to identify the differences in miRNA expression between LGG and HGG. Results Analyses showed significant expressions in 12 miRNAs between LGG and HGG, where all of them were downregulated. Out of these significant miRNAs, miR-518b, miR-1271-3p, and miR-598-3p showed the highest potential for distinguishing HGG from LGG, with area under curve (AUC) values of 0.912, 0.889, and 0.991, respectively. Conclusion miR-518b, miR-1271-3p, and miR-598-3p demonstrate significant potentials in distinguishing LGG and HGG. -in Cell Reports: Current Issue on 2024-11-13 00:00:00 UTC. +
in F1000Research on 2024-11-13 18:17:12 UTC.
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-The immune landscape of murine skeletal muscle regeneration and aging
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+Climate Change and Veterinary Medicine: A Call to Action for a Healthier Planet [version 1; peer review: awaiting peer review]
- Sousa et al. characterized, with time and single-cell resolution, the immune environment of the regenerating skeletal muscle, revealing a profound remodeling of myeloid and lymphoid compartments in aging. This knowledge anticipates the potential of immune cells as targets to improve regenerative capacity in aging. + Abstract Climate change is rapidly transforming ecosystems and reshaping the landscapes of animal health, with profound consequences for public health, food security, and biodiversity. Rising temperatures, shifting weather patterns, and increased frequency of natural disasters are driving the emergence and spread of infectious diseases, particularly zoonotic and vector-borne diseases. These environmental shifts endanger the health and welfare of animals and the delicate balance between human populations, livestock, and wildlife. As the stewards of animal health, veterinarians are uniquely positioned to lead the change in addressing these complex challenges at the nexus of human, animal, and environmental health and well-being. This article calls for urgent actions to integrate climate adaptation and mitigation strategies into veterinary practice and education. It underscores the critical need for veterinarians to embrace the One Health approach to tackle climate-driven disease outbreaks and the growing threat of antimicrobial resistance to safeguard human and animal populations while protecting natural ecosystems. The article further explores the role of veterinarians in fostering sustainable agricultural practices, reducing the environmental impact of livestock production, conserving biodiversity and advocating for policy reforms that protect both animal and planetary health. As we face an era of unprecedented climate disruption, this call to action aims to inspire the global veterinary community to actively get involved in combating climate change and its worst impacts. By building climate-resilient practices, enhancing disease surveillance, and championing environmental stewardship, veterinarians can contribute significantly to a healthier, more sustainable future for all species on Earth. -in Cell Reports: Current Issue on 2024-11-13 00:00:00 UTC. +
in F1000Research on 2024-11-13 18:10:34 UTC.
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-Rationally designed pooled CRISPRi-seq uncovers an inhibitor of bacterial peptidyl-tRNA hydrolase
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+De-ethnicizing Ethiopian higher education leadership: the quest for merit-based governance [version 1; peer review: awaiting peer review]
- Bacterial knockdown libraries allow chemical-genetic profiling of antimicrobials, useful in antibiotic drug discovery. Rahman A.S.M.Z. et al. created CIMPLE, a rationally designed pooled CRISPRi library with essential genome coverage. CRISPRi-seq with CIMPLE showed that the target of PHAR(A), a growth inhibitor of a new class, is the bacterial peptidyl-tRNA hydrolase. + Background This study examines the growing trend of ethnicized leadership in Ethiopian higher education institutions and advocates for a shift toward merit-based governance to improve institutional integrity and performance. Since 1991, with the introduction of ethnic federalism, leadership appointments in Ethiopian universities have increasingly been based on ethnic identity rather than qualifications. This has led to governance challenges, weakened academic standards, and reduced institutional efficiency. The study highlights the need for governance reforms prioritizing meritocracy to enhance the quality and sustainability of Ethiopia’s ethnically diverse higher education system. Methods The study utilizes a qualitative research approach, combining both primary and secondary data. Primary data were collected through semi-structured interviews with university administrators, faculty, and governance experts, while secondary data were gathered from institutional reports, government policies, and academic literature. Institutional theory, principal-agent theory, and meritocratic theory frame the analysis, providing insights into how ethnic-based leadership appointments affect university governance and performance. Results The findings reveal that ethnicized leadership has eroded governance structures, lowered academic quality, and compromised institutional efficiency. Leadership appointments based on ethnicity rather than merit have led to poor decision-making, weakened accountability, and reduced transparency. In contrast, merit-based governance improves accountability, decision-making, and institutional performance. The study emphasizes that transitioning to a meritocratic leadership model is vital for restoring institutional integrity and academic excellence in Ethiopian universities. Conclusions Ethnic federalism, while initially designed to empower regions, has politicized federal institutions, including universities, reducing them to regional entities rather than national institutions. This system of ethnicized leadership has fostered a culture of favoritism, rampant corruption, and ineffective governance, ultimately weakening Ethiopia’s higher education system. Recommendations Governance reforms that prioritize merit-based appointments are urgently needed. Legal reforms, transparent leadership selection processes, depoliticization efforts, and capacity-building initiatives are recommended to foster a meritocratic culture and improve institutional performance in Ethiopian universities. -in Cell Reports: Current Issue on 2024-11-13 00:00:00 UTC. +
in F1000Research on 2024-11-13 18:05:17 UTC.
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-Histone H1 kills MRSA
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+Identifying and Assessing Physiological Biomarkers for Food and Energy Intake: A Systematic Review with Meta-Analysis Protocol [version 1; peer review: awaiting peer review]
- Marsman et al. detect histone H1 in MRSA in human abscesses and demonstrate that it kills MRSA under physiological conditions. They identify through selective evolution and a genome-wide screen that histone H1 targets wall teichoic acids and permeabilizes potentiated membranes of metabolically active and dividing cells, providing molecular insight into host-mediated clearance of MRSA. + Background Traditional dietary assessments are often inaccurate and prone to self-reporting biases. Tracking the physiological responses associated with eating and digestion events via wearable technologies may provide an effective approach for continuously monitoring food intake and estimating energy consumption. Eating and digestion are accompanied by a series of changes in the heart rate, skin temperature, blood oxygen saturation, and blood pressure. These changes can be tracked by wearable devices, such as smartwatches, which have been widely accepted in the market. This systematic review is the first to evaluate the effectiveness of tracking such physiological biomarkers in differentiating between high- and low-calorie meals, potentially paving the way for more accurate dietary monitoring. Methods Following the PRISMA-P guidelines, we will conduct a systematic literature search through MEDLINE, EMBASE, and PubMed for clinical trials that investigated physiological responses following meal intake in healthy subjects. Two independent reviewers will screen and select articles based on pre-defined eligibility criteria, with a third review to resolve any discrepancies. This will be followed by data extraction and quality assessment of the included studies. Statistical analyses, including meta-analyses, will be performed using R Studio software. Our primary outcome will be the comparison of physiological biomarkers before and after meal intake, while secondary outcomes will include comparisons of physiological biomarkers between high- and low-calorie meal consumption and the correlation between the caloric content of consumed meals and postprandial physiological changes. Discussion This systematic review and meta-analysis will identify physiological indicators for eating events and inform the design of wearable sensors that estimate food intake in healthy subjects. Systematic Review Registration PROSPERO Registration ID: CRD42024544353 -in Cell Reports: Current Issue on 2024-11-13 00:00:00 UTC. +
in F1000Research on 2024-11-13 17:39:17 UTC.
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-Engineered IscB-ωRNA system with improved base editing efficiency for disease correction via single AAV delivery in mice
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+Molecular docking and dynamics studies to identify novel active compounds targeting potential breast cancer receptor proteins from an indigenous herb Euphorbia thymifolia Linn [version 2; peer review: 1 approved with reservations]
- Guo et al. engineered an IscB-associated ωRNA variant, ωRNA∗-v2, of the transposon-encoded OMEGA system to enhance gene knockout and cytosine and adenine base editing activity in human cells and to correct disease-causing mutations in a disease mouse model via single AAV in vivo delivery. + Background Breast cancer has become the most prevalent disease and its incidence has almost doubled in the Indian population. This increased burden demands new targeted therapies with novel compounds either synthetically produced or derived from indigenous plants, which could be a promising approach for the development of drugs. Euphorbia thymifolia L is a widely growing tropical herb that has been reported to have various ethnopharmacological properties. Although Euphorbia genus is reported to have anticancer properties, E. thymifolia is not reported to have anticancer properties to date. Therefore, the aim of the present study was to screen the phytoconstituents and identify the active compounds present in the methanolic extract of E. thymifolia (ME.ET) as ligands to inhibit human cancer cell lines with special reference to potential protein targets implicated in breast cancer using an In-silico approach. Methods ME.ET was subjected to GC-MS analysis to screen the phytoconstituents, and the identified compounds were docked with protein targets such as extracellular signal-regulated kinases (ERK1), a serine/threonine kinase-1(AKT1), human epidermal growth factor 2 (HER2), estrogen receptor (ER), maternal embryonic leucine zipper kinase (MELK), polo-like kinase-1(PLK1), and protein tyrosine kinase (PTK6). Compounds with good docking scores were further subjected to dynamic studies to understand the protein ligand binding stability, ligand pathway calculation, and molecular mechanics energies combined with Poisson-Boltzmann (MM/PBSA) calculations using the Schrodinger suite. Results GC-MS analysis revealed the presence of 245 phytoconstituents, 219 of which were unique. When subjected to docking, these phytocompounds, namely 3,6,9,12-tetraoxatetradecane-1,14-diyl dibenzoate (TTDB) and succinic acid, 2-(dimethylamino) ethyl 4-isopropylphenyl ester (SADPE), showed good docking scores. Molecular dynamics studies showed a high affinity and low binding energy for TTDB with HER2, ERK1, and SADPE with ER. Conclusions Hence, in this study, we identified two lead compounds in E.thymifolia linn. Further invitro and invivo anticancer studies can be performed to confirm these results and to understand the molecular mechanism by which they exhibit anticancer activity against breast cancer. -in Cell Reports: Current Issue on 2024-11-13 00:00:00 UTC. +
in F1000Research on 2024-11-13 17:31:58 UTC.
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-Sleep deprivation leads to non-adaptive alterations in sleep microarchitecture and amyloid-β accumulation in a murine Alzheimer model
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+Orbitofrontal Cortex Mediates Sustained Basolateral Amygdala Encoding of Cued Reward-Seeking States
- Cankar et al. report that sleep loss suppresses NREM norepinephrine oscillations in a murine model of Alzheimer’s disease along with a parallel buildup of amyloid-β. Thus, overexpression of amyloid-β inhibits recovery sleep and thereby slows glymphatic clearance after sleep deprivation. Norepinephrine oscillations persisted in wild-type mice after sleep deprivation. +Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS– cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of the orbitofrontal cortex (OFC), a major reciprocal partner to the BLA. Inactivation of the OFC while simultaneously recording in the BLA revealed a blunting of sustained cue-evoked activity in the BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in the BLA also reduced reward seeking. Our data indicate that the BLA represents reward-seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward-seeking behavior.
-in Cell Reports: Current Issue on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Hemispheric divergence of interoceptive processing across psychiatric disorders
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+This Week in The Journal
- Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered functional neuroimaging study of 46 individuals with anxiety, depression, and/or eating disorders (ADE) and 46 propensity-matched healthy comparisons (HC), comparing their neural activity across two interoceptive tasks differentially recruiting top-down or bottom-up processing within the same scan session. During an interoceptive attention task, top-down attention was voluntarily directed towards cardiorespiratory or visual signals. In contrast, during an interoceptive perturbation task, intravenous infusions of isoproterenol (a peripherally-acting beta-adrenergic receptor agonist) were administered in a double-blinded and placebo-controlled fashion to drive bottom-up cardiorespiratory sensations. Across both tasks, neural activation converged upon the insular cortex, localizing within the granular and ventral dysgranular subregions bilaterally. However, contrasting hemispheric differences emerged, with the ADE group exhibiting (relative to HCs) an asymmetric pattern of overlap in the left insula, with increased or decreased proportions of co-activated voxels within the left or right dysgranular insula, respectively. The ADE group also showed less agranular anterior insula activation during periods of bodily uncertainty (i.e. when anticipating possible isoproterenol-induced changes that never arrived). Finally, post-task changes in insula functional connectivity were associated with anxiety and depression severity. These findings confirm the dysgranular mid-insula as a key cortical interface where attention and prediction meet real-time bodily inputs, especially during heightened awareness of interoceptive states. Furthermore, the dysgranular mid-insula may indeed be a ‘locus of disruption’ for psychiatric disorders. + -in eLife on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Reorganization of the flagellum scaffolding induces a sperm standstill during fertilization
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+Neural Predictors of Fear Depend on the Situation
- Mammalian sperm delve into the female reproductive tract to fertilize the female gamete. The available information about how sperm regulate their motility during the final journey to the fertilization site is extremely limited. In this work, we investigated the structural and functional changes in the sperm flagellum after acrosomal exocytosis (AE) and during the interaction with the eggs. The evidence demonstrates that the double helix actin network surrounding the mitochondrial sheath of the midpiece undergoes structural changes prior to the motility cessation. This structural modification is accompanied by a decrease in diameter of the midpiece and is driven by intracellular calcium changes that occur concomitant with a reorganization of the actin helicoidal cortex. Midpiece contraction occurs in a subset of cells that undergo AE, and live-cell imaging during in vitro fertilization showed that the midpiece contraction is required for motility cessation after fusion is initiated. These findings provide the first evidence of the F-actin network’s role in regulating sperm motility, adapting its function to meet specific cellular requirements during fertilization, and highlighting the broader significance of understanding sperm motility. +The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n = 21; 10 females and 11 males) viewed ~20 s clips depicting spiders, heights, or social encounters and rated fear after each video. Searchlight multivoxel pattern analysis was used to identify whether and which brain regions carry information that predicts fear experience and the degree to which the fear-predictive neural codes in these areas depend on or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation-dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern but rather a collection of multiple heterogeneous brain states.
-in eLife on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties
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+The Role of the Rat Prefrontal Cortex and Sex Differences in Decision-Making
- Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here, we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection of Dkk2 knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single-cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested hepatocyte nuclear factor 4 alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region of Sox9, a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers. +The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift diffusion models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. μ-Opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process toward high-value stimuli. These effects were observed without any impact on the rats’ choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls "when," but not "how," to act.
-in eLife on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-CXCR3-expressing myeloid cells recruited to the hypothalamus protect against diet-induced body mass gain and metabolic dysfunction
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+Deciphering Peripheral Taste Neuron Diversity: Using Genetic Identity to Bridge Taste Bud Innervation Patterns and Functional Responses
- Microgliosis plays a critical role in diet-induced hypothalamic inflammation. A few hours after a high-fat diet (HFD), hypothalamic microglia shift to an inflammatory phenotype, and prolonged fat consumption leads to the recruitment of bone marrow-derived cells to the hypothalamus. However, the transcriptional signatures and functions of these cells remain unclear. Using dual-reporter mice, this study reveals that CX3CR1-positive microglia exhibit minimal changes in response to a HFD, while significant transcriptional differences emerge between microglia and CCR2-positive recruited myeloid cells, particularly affecting chemotaxis. These recruited cells also show sex-specific transcriptional differences impacting neurodegeneration and thermogenesis. The chemokine receptor CXCR3 is emphasized for its role in chemotaxis, displaying notable differences between recruited cells and resident microglia, requiring further investigation. Central immunoneutralization of CXCL10, a ligand for CXCR3, resulted in increased body mass and decreased energy expenditure, especially in females. Systemic chemical inhibition of CXCR3 led to significant metabolic changes, including increased body mass, reduced energy expenditure, elevated blood leptin, glucose intolerance, and decreased insulin levels. This study elucidates the transcriptional differences between hypothalamic microglia and CCR2-positive recruited myeloid cells in diet-induced inflammation and identifies CXCR3-expressing recruited immune cells as protective in metabolic outcomes linked to HFD consumption, establishing a new concept in obesity-related hypothalamic inflammation. +Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the taste bud) stemming from Penk+ neurons displayed diverse branching patterns and lacked stereotypical endings. The range in complexity observed for individual taste arbors from Penk+ neurons mirrored the entire population, suggesting that taste arbor morphologies are not primarily regulated by the neuron type. Notably, the distinguishing feature of arbors from Penk+ neurons was their propensity to come within 110 nm (in apposition with) different types of taste-transducing cells within the taste bud. This finding is contrary to the expectation of genetically defined taste neuron types that functionally represent a single stimulus. Consistently, further investigation of Penk+ neuron function revealed that they are more likely to respond to innately aversive stimuli—sour, bitter, and high salt concentrations—as compared with the full taste population. Penk+ neurons are less likely to respond to nonaversive stimuli—sucrose, umami, and low salt—compared with the full population. Our data support the presence of a genetically defined neuron type in the geniculate ganglion that is responsive to innately aversive stimuli. This implies that genetic expression might categorize peripheral taste neurons into hedonic groups, rather than simply identifying neurons that respond to a single stimulus.
-in eLife on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Rescuable sleep and synaptogenesis phenotypes in a Drosophila model of O-GlcNAc transferase intellectual disability
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+Dynamics of Saccade Trajectory Modulation by Distractors: Neural Activity Patterns in the Frontal Eye Field
- O-GlcNAcylation is an essential intracellular protein modification mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations in OGT have been linked to intellectual disability, indicating that this modification is important for the development and functioning of the nervous system. However, the processes that are most sensitive to perturbations in O-GlcNAcylation remain to be identified. Here, we uncover quantifiable phenotypes in the fruit fly Drosophila melanogaster carrying a patient-derived OGT mutation in the catalytic domain. Hypo-O-GlcNAcylation leads to defects in synaptogenesis and reduced sleep stability. Both these phenotypes can be partially rescued by genetically or chemically targeting OGA, suggesting that a balance of OGT/OGA activity is required for normal neuronal development and function. +The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field of two male rhesus monkeys shifting gaze to a target while a distractor with the same eccentricity appeared either left or right of the target at various delays after target presentation. We found that the population level of presaccadic activity of neurons representing the distractor location encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature toward the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved toward distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push–pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets.
-in eLife on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Rethinking sensorimotor circuits
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+A Prefrontal->Periaqueductal Gray Pathway Differentially Engages Autonomic, Hormonal, and Behavioral Features of the Stress-Coping Response
- New research shows that the neural circuit responsible for stabilising gaze can develop in the absence of motor neurons, contrary to a long-standing model in the field. +The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats’ active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC->vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal->midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences.
-in eLife on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Functional characteristics and computational model of abundant hyperactive loci in the human genome
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+Monocyte Invasion into the Retina Restricts the Regeneration of Neurons from Müller Glia
- Enhancers and promoters are classically considered to be bound by a small set of transcription factors (TFs) in a sequence-specific manner. This assumption has come under increasing skepticism as the datasets of ChIP-seq assays of TFs have expanded. In particular, high-occupancy target (HOT) loci attract hundreds of TFs with often no detectable correlation between ChIP-seq peaks and DNA-binding motif presence. Here, we used a set of 1003 TF ChIP-seq datasets (HepG2, K562, H1) to analyze the patterns of ChIP-seq peak co-occurrence in combination with functional genomics datasets. We identified 43,891 HOT loci forming at the promoter (53%) and enhancer (47%) regions. HOT promoters regulate housekeeping genes, whereas HOT enhancers are involved in tissue-specific process regulation. HOT loci form the foundation of human super-enhancers and evolve under strong negative selection, with some of these loci being located in ultraconserved regions. Sequence-based classification analysis of HOT loci suggested that their formation is driven by the sequence features, and the density of mapped ChIP-seq peaks across TF-bound loci correlates with sequence features and the expression level of flanking genes. Based on the affinities to bind to promoters and enhancers we detected five distinct clusters of TFs that form the core of the HOT loci. We report an abundance of HOT loci in the human genome and a commitment of 51% of all TF ChIP-seq binding events to HOT locus formation thus challenging the classical model of enhancer activity and propose a model of HOT locus formation based on the existence of large transcriptional condensates. +Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to reprogram a subset of Müller glia into neurons. We have reported that neuroinflammation from microglia inhibits neurogenesis from Müller glia. Here we found that the peripheral immune response is a barrier to CNS regeneration. We show that monocytes from the peripheral immune system infiltrate the injured retina and negatively influence neurogenesis from Müller glia. Using CCR2 knock-out mice of both sexes, we found that preventing monocyte infiltration improves the neurogenic and proliferative capacity of Müller glia stimulated by Ascl1. Using scRNA-seq analysis, we identified a signaling axis wherein Osteopontin, a cytokine highly expressed by infiltrating immune cells is sufficient to suppress mammalian neurogenesis. This work implicates the response of the peripheral immune system as a barrier to regenerative strategies of the retina.
-in eLife on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Brain Sciences, Vol. 14, Pages 1139: Efficacy and Safety of Lithium for Suicide and Suicide-Related Behaviors in Youth: A Review of the Literature
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+Encoding of Vibrotactile Stimuli by Mechanoreceptors in Rodent Glabrous Skin
-Brain Sciences, Vol. 14, Pages 1139: Efficacy and Safety of Lithium for Suicide and Suicide-Related Behaviors in Youth: A Review of the Literature
-Brain Sciences doi: 10.3390/brainsci14111139
-Authors: - Gianluca Sesso - Francesca Bargnesi - Francesca Olzi - Giulia Mutti - Stefano Berloffa - Valentina Viglione - Pamela Fantozzi - Greta Tolomei - Fulvio Guccione - Annarita Milone - Gabriele Masi -
-Objectives: This systematic review evaluates the anti-suicidal properties of Lithium in children and adolescents with Bipolar Disorder (BD), addressing gaps in evidence regarding its efficacy and safety in reducing suicidality and self-harming behaviors. Methods: A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus up to February 2024. Eligible studies were those focusing on patients aged 25 years or younger, examining Lithium therapy and its impact on suicidal ideation and behaviors. The review included randomized controlled trials, longitudinal prospective and retrospective studies, and cross-sectional studies, while excluding expert opinions and case reports. Results: Evidence generally supports the efficacy of Lithium in reducing suicidal ideation and self-harming behaviors in youth with BD, though results are mixed. Randomized controlled trials demonstrated its effectiveness in mitigating suicidal thoughts during acute manic episodes, with effects persisting post-treatment. Longitudinal studies suggested that Lithium might offer superior outcomes compared to other mood stabilizers, although its specific impact on suicidality remains inconclusive. Cross-sectional studies and retrospective analyses reveal associations between Lithium use and reduced self-harming behaviors, but causality remains uncertain. While mood-stabilizing effects of Lithium offer potential benefits for reducing suicidality in youth, evidence on its direct impact on emotional dysregulation (ED) and long-term efficacy is limited. Variability in individual responses and adherence issues underscore the need for further research. Future studies should include larger, diverse samples, focus on ED symptoms, and explore Lithium mechanisms in suicidality prevention. Conclusions: Lithium remains a promising treatment for mood stabilization and reduction in suicidality in youth with BD.
+Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in the rodent glabrous skin has received scant attention, unlike in primates where the glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability), whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Using in vivo extracellular recordings in male rats and mice of either sex, we measured the reliability and precision of LTMR responses to tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RA1 and RA2/Pacinian afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that coactivation patterns play a greater role in population coding than for dichotomously tuned primate RAs.
-in Brain Sciences on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Brain Sciences, Vol. 14, Pages 1138: Closed-Loop Auditory Stimulation (CLAS) During Sleep Augments Language and Discovery Learning
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+Behavioral and Neural Mechanisms of Face-Specific Attention during Goal-Directed Visual Search
-Brain Sciences, Vol. 14, Pages 1138: Closed-Loop Auditory Stimulation (CLAS) During Sleep Augments Language and Discovery Learning
-Brain Sciences doi: 10.3390/brainsci14111138
-Authors: - Vincent P. Clark - Hector P. Valverde - Mason S. Briggs - Teagan Mullins - Jacqueline Ortiz - Christopher J. H. Pirrung - Olivia S. O’Keeffe - Madeline Hwang - Sidney Crowley - Marko Šarlija - Panagiotis Matsangas -
-Background/Objectives: Slow oscillation (SO) brainwaves observed during sleep have been shown to reflect the process of memory consolidation, that underlies the critical role of sleep in learning, memory, and other cognitive functions. Closed-loop auditory stimulation (CLAS) uses tones presented in phase with SOs to increase their amplitude and number, along with other brainwave signatures related to memory consolidation. Prior studies have found that CLAS maximizes the ability to perform rote memorization tasks, although this remains controversial. The present study examined whether CLAS affects a broader range of learning tasks than has been tested previously, including a rote language learning task requiring basic memorization and also two discovery learning tasks requiring insight, hypothesis testing, and integration of experience, all processes that benefit from memory consolidation. Methods: Twenty-eight healthy participants performed language and discovery learning tasks before sleeping in our laboratory for three continuous nights per week over two weeks, with verum or control CLAS using a prototype NeuroGevity system (NeuroGeneces, Inc., Santa Fe, NM, USA) in a crossed, randomized, double-blind manner. Results: Language learning showed a 35% better word recall (p = 0.048), and discovery learning showed a 26% better performance (p &lt; 0.001) after three continuous nights of CLAS vs. control. EEG measures showed increased SO amplitude and entrainment, SO-spindle coupling, and other features that may underlie the learning benefits of CLAS. Conclusions: Taken together, the present results show that CLAS can alter brain dynamics and enhance learning, especially in complex discovery learning tasks that may benefit more from memory consolidation compared with rote word pair or language learning.
+Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Compared with distractors, fixations on targets reduced spike–LFP coherence within the temporal cortex. Importantly, target-induced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks.
-in Brain Sciences on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-Brain Sciences, Vol. 14, Pages 1137: Association Between the Enriched Environment Level and Serum Brain-Derived Neurotrophic Factor (BDNF) in Patients with Major Depressive Disorder
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+Monosynaptic Inputs to Ventral Tegmental Area Glutamate and GABA Co-transmitting Neurons
-Brain Sciences, Vol. 14, Pages 1137: Association Between the Enriched Environment Level and Serum Brain-Derived Neurotrophic Factor (BDNF) in Patients with Major Depressive Disorder
-Brain Sciences doi: 10.3390/brainsci14111137
-Authors: - Andrés Vega-Rosas - Mónica Flores-Ramos - Gerardo Bernabé Ramírez-Rodríguez -
-Major Depressive Disorder (MDD) is a neuropsychiatric condition whose neurobiological characteristics include alterations in brain plasticity, modulated by Brain-Derived Neurotrophic Factor (BDNF). In animal models, environmental enrichment promotes neuroplasticity and reduces depressive-like behaviors. In humans, we proposed to assess the level of Enriched Environment (EE) using a questionnaire that includes different domains of the EE (cognitive, social, and physical), which we named the EE Indicator (EEI). Objective: To determine the relationship between the level of EE and serum BDNF in participants with MDD and healthy controls. Materials: Participants with MDD without antidepressant treatment and healthy controls were recruited, and their EE level and serum BDNF concentration were determined looking for correlations between their clinical characteristics and the cognitive, social, and physical activities according to the EEI. Results: A total of 25 participants were recruited, of which 6 participants with MDD and the same number of controls were selected in a paired manner. Although no differences were found in the concentration of BDNF between the groups, positive correlations were observed between cognitive EE and BDNF (r = 0.62, p = 0.035), as well as negative social EE and the Hamilton Depression Rating Scale (HDRS) (r = &minus;0.86, p = 0.001). The sum between cognitive and social EE showed a positive correlation with the serum concentration of BDNF (r = 0.34, p = 0.0451). Conclusions: The level of EE is potentially modulating the presence and severity of MDD at a clinical level, but it can also influence at a neuroplastic level through promoting or limiting the concentration of BDNF.
+A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus (SC), lateral hypothalamus (LH), midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from the dorsal raphe nucleus, lateral habenula, and VTA. Based on these and prior data, we hypothesized that LH and SC inputs were from glutamatergic neurons. Optical activation of glutamatergic LH neurons activated VTA VGluT2+VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic SC neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic LH neurons, but not glutamatergic SC neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity and inhibition of LH glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally salient outcomes.
-in Brain Sciences on 2024-11-13 00:00:00 UTC. +
in Journal of Neuroscience on 2024-11-13 17:30:19 UTC.
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-The complete mitogenome of an unidentified Oikopleura species [version 1; peer review: awaiting peer review]
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+Distinct Modulation of Ih by Synaptic Potentiation in Excitatory and Inhibitory Neurons
- Appendicularians are planktonic tunicates abundant all over the world. Currently, only two complete annotated mitochondrial genome assemblies are available for appendicularians, both for cryptic species of Oikopleura dioica. This underrepresentation of available appendicularian mitochondrial genomes limits environmental DNA sequencing (eDNA) studies that rely on mitochondrial markers as a taxonomic barcode. We report the complete mitochondrial genome assembly and annotation of an unknown appendicularian species isolated from the Amami Oshima island, Kagoshima prefecture, Japan, that has significant sequence difference with other currently available assemblies and will serve as a useful resource for ecological studies and further mitochondrial studies of appendicularians. +Selective modifications in the expression or function of dendritic ion channels regulate the propagation of synaptic inputs and determine the intrinsic excitability of a neuron. Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels open upon membrane hyperpolarization and conduct a depolarizing inward current (Ih). HCN channels are enriched in the dendrites of hippocampal pyramidal neurons where they regulate the integration of synaptic inputs. Synaptic plasticity can bidirectionally modify dendritic HCN channels in excitatory neurons depending on the strength of synaptic potentiation. In inhibitory neurons, however, the dendritic expression and modulation of HCN channels are largely unknown. In this study, we systematically compared the modulation of Ih by synaptic potentiation in hippocampal CA1 pyramidal neurons and stratum radiatum (sRad) interneurons in mouse organotypic cultures. Ih properties were similar in inhibitory and excitatory neurons and contributed to resting membrane potential and action potential firing. We found that in sRad interneurons, HCN channels were downregulated after synaptic plasticity, irrespective of the strength of synaptic potentiation. This suggests differential regulation of Ih in excitatory and inhibitory neurons, possibly signifying their distinct role in network activity.
-in F1000Research on 2024-11-12 16:13:27 UTC. +
in eNeuro on 2024-11-13 17:30:17 UTC.
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-Protocol for a co-design study for the development of a chronotherapeutic mobile health behaviour change intervention targeting light exposure among older adults [version 1; peer review: awaiting peer review]
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+Visual Processing by Hierarchical and Dynamic Multiplexing
- Through its wide-ranging effects on human physiology and behaviour, daily light exposure is an important environmental modulator of healthy ageing. Integrating mobile health (mHealth) technology with behaviour change strategies offers a promising approach to optimise light exposure and positively impact sleep, rest-wake cycles, cognitive function, and mood at scale. This study aims to develop the LightSPAN mHealth behaviour change intervention to optimise light exposure across the lifespan. Employing a co-design methodology, the study comprises two distinct workstreams. The first focuses on conceptualising the theoretical framework and implementation strategies through a comprehensive review of light exposure interventions, behaviour change theories, mHealth user personas, and recommendations for designing mHealth interventions for older adults. The second workstream centres on co-designing the intervention, involving consultation with community service providers and engagement with older adults at ageing community centres (≥60 years of age). Community service providers will be consulted through open-ended discussions (target n=5). Older adult participants (n=20) will engage in telephone interviews, focus group discussions and prototyping workshops to explore older adult participants’ characteristics, needs, preferences, and mHealth intervention design elements and co-design the LightSPAN mHealth behaviour change intervention. The insights generated in these co-design components will ensure that the intervention addresses the needs of its future users. +The complexity of natural environments requires highly flexible mechanisms for adaptive processing of single and multiple stimuli. Neuronal oscillations could be an ideal candidate for implementing such flexibility in neural systems. Here, we present a framework for structuring attention-guided processing of complex visual scenes in humans, based on multiplexing and phase coding schemes. Importantly, we suggest that the dynamic fluctuations of excitability vary rapidly in terms of magnitude, frequency and wave-form over time, i.e., they are not necessarily sinusoidal or sustained oscillations. Different elements of single objects would be processed within a single cycle (burst) of alpha activity (7–14 Hz), allowing for the formation of coherent object representations while separating multiple objects across multiple cycles. Each element of an object would be processed separately in time—expressed as different gamma band bursts (>30 Hz)—along the alpha phase. Since the processing capacity per alpha cycle is limited, an inverse relationship between object resolution and size of attentional spotlight ensures independence of the proposed mechanism from absolute object complexity. Frequency and wave-shape of those fluctuations would depend on the nature of the object that is processed and on cognitive demands. Multiple objects would further be organized along the phase of slower fluctuations (e.g., theta), potentially driven by saccades. Complex scene processing, involving covert attention and eye movements, would therefore be associated with multiple frequency changes in the alpha and lower frequency range. This framework embraces the idea of a hierarchical organization of visual processing, independent of environmental temporal dynamics.
-in F1000Research on 2024-11-12 15:54:07 UTC. +
in eNeuro on 2024-11-13 17:30:17 UTC.
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-Assessment of potential drug-drug interactions in hospitalized patients with infectious diseases: an experience from a secondary care hospital [version 3; peer review: 1 approved, 2 not approved]
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+Distinct Strategies Regulate Correlated Ion Channel mRNAs and Ionic Currents in Continually versus Episodically Active Neurons
- Background Polypharmacy is common among hospitalized patients with infectious infections owing to comorbidities or concomitant illnesses. This raises the likelihood of drug-drug interactions and creates uncertainty for healthcare providers. This study aimed to assess the potential drug-drug interactions (pDDIs) among hospitalized patients with infectious diseases in a secondary care hospital. Methods A prospective observational study was conducted in the internal medicine ward for six months after the ethics committee’s approval. Data were collected from patient case records, and prescriptions were screened for pDDIs from a portable electronic physician information database (PEPID) resource analyzed using SPSS, version 27.0. Results In total, 148 patient case records were analyzed, and 549 pDDIs were identified, with 66.8% having at least one or more DDIs. The mean number of drug interactions was 3.70 ± 4.58 per prescription. The most frequently encountered drug interactions were drug combinations such as bisoprolol with atorvastatin and aspirin with tazobactam/piperacillin. Bivariate analysis showed that age, comorbidities, length of hospital stay, and the number of drugs prescribed were risk factors associated with DDIs (p<0.05). In the multiple binary logistic regression analysis, DDIs were significantly associated with comorbidities and the number of prescribed medications (p<0.0001). Conclusions This study observed the prevalence of DDIs in hospitalized patients with infectious diseases of ‘moderate’ severity. Prescription screening using a drug information database assists in early identification and prevention of DDIs, enhancing drug safety and quality of patient-centered care. +Relationships among membrane currents allow central pattern generator (CPG) neurons to reliably drive motor programs. We hypothesize that continually active CPG neurons utilize activity-dependent feedback to correlate expression of ion channel genes to balance essential membrane currents. However, episodically activated neurons experience absences of activity-dependent feedback and, thus, presumably employ other strategies to coregulate the balance of ionic currents necessary to generate appropriate output after periods of quiescence. To investigate this, we compared continually active pyloric dilator (PD) neurons with episodically active lateral gastric (LG) CPG neurons of the stomatogastric ganglion (STG) in male Cancer borealis crabs. After experimentally activating LG for 8 h, we measured three potassium currents and abundances of their corresponding channel mRNAs. We found that ionic current relationships were correlated in LG's silent state, but ion channel mRNA relationships were correlated in the active state. In continuously active PD neurons, ion channel mRNAs and ionic currents are simultaneously correlated. Therefore, two distinct relationships exist between channel mRNA abundance and the ionic current encoded in these cells: in PD, a direct correlation exists between Shal channel mRNA levels and the A-type potassium current it carries. Conversely, such channel mRNA–current relationships are not detected and appear to be temporally uncoupled in LG neurons. Our results suggest that ongoing feedback maintains membrane current and channel mRNA relationships in continually active PD neurons, while in LG neurons, episodic activity serves to establish channel mRNA relationships necessary to produce the ionic current profile necessary for the next bout of activity.
-in F1000Research on 2024-11-12 14:18:12 UTC. +
in eNeuro on 2024-11-13 17:30:17 UTC.
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-Evolutionary history of calcium-sensing receptors unveils hyper/hypocalcemia-causing mutations
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+Post-pubertal management of undescended testes from the malignancy risk point of view: a systematic review [version 3; peer review: 2 approved, 1 approved with reservations]
-by Aylin Bircan, Nurdan Kuru, Onur Dereli, Berkay Selçuk, Ogün Adebali
- -Despite advancements in understanding the structure and functions of the Calcium Sensing Receptor (CaSR), gaps persist in our knowledge of the specific functions of its residues. In this study, we used phylogeny-based techniques to identify functionally equivalent orthologs of CaSR, predict residue significance, and compute specificity-determining position (SDP) scores to understand its evolutionary basis. The analysis revealed exceptional conservation of the CaSR subfamily, emphasizing the critical role of residues with high SDP scores in receptor activation and pathogenicity. To further enhance the findings, gradient-boosting trees were applied to differentiate between gain- and loss-of-function mutations responsible for hypocalcemia and hypercalcemia. Lastly, we investigated the importance of these mutations in the context of receptor activation dynamics. In summary, through comprehensive exploration of the evolutionary history of the CaSR subfamily, coupled with innovative phylogenetic methodologies, we identified activating and inactivating residues, providing valuable insights into the regulation of calcium homeostasis and its connections to associated disorders. + Background Undescended testes (UDT) is a condition where one or both testes is absent in the scrotum. The general age recommendation in which the treatment should be performed is before 18 months old due to the infertility risk and malignancy in later life. In post-pubertal UDT, the current guideline recommends orchiectomy; however, the strength rating of this recommendation is weak. Therefore, this study aimed to provide a systematic review of post-pubertal UDT treatment, focusing on the malignancy risk point of view. Methods A systematic search was performed using PubMed, Wiley Online Library and the Cochrane Library up to 5 March 2023. Any study with either post-pubertal orchiectomy or orchidopexy in patients with UDT and reporting the testicular malignancy was included. The exclusion criteria were studies with lack of information of UDT correction time, no history of correction and the full text wasn’t available. The data collected were the occurrence of testicular malignancy in post-pubertal UDT patients corrected with any method. Quality and bias assessment was assessed with Newcastle-Ottawa scale and Joanna Briggs Institute tools. Results Seven articles (three case reports and four observational studies) were reviewed with a total of 42 patients who underwent post-pubertal correction of either unilateral or bilateral UDT. The correction age ranged from 13 to 34 years old, with follow-up of 48.7–252 months. Among those who developed malignancies, the most common were seminoma, teratoma and carcinoma in situ of the testes. In addition, this study was able to propose an algorithm for post-pubertal UDT treatment strategy. Conclusions The scarce resource was the main limitation of this study. Nevertheless, this review showed that post-pubertal UDT management should be tailored individually. Several factors that should be considered include the condition of the contralateral descended testis, UDT location, serum testosterone level, patient’s age, comorbidities, and interest in fertility. -in PLoS Computational Biology on 2024-11-12 14:00:00 UTC. +
in F1000Research on 2024-11-13 17:20:00 UTC.