- Feb 2024
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This potentially useful study reports a new method for restoring sperm motility. Strengths are in the methodology being developed, but the conclusions require additional experimental support. The authors provide inadequate evidence for the success of the method or its mechanism.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Maestri et al report the absence of phylogenetic evidence supporting codiversification of mammalian coronaviruses and their hosts, leading to the important conclusion that the evolutionary history of the virus and its hosts are decoupled through frequent host switches. The evidence for frequent host switching, derived from a probabilistic model of co-evolution, appears convincing, but evidence for quantitative statements about the time of the last common ancestor of extant mammalian coronaviruses remains incomplete. The results would be strengthened by a reconstruction of the evolutionary timescale and further investigation of robustness to sampling biases and unsampled diversity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study links the activity of polymerase III to the regulation of virulence gene expression in the deadliest malaria parasite, Plasmodium falciparum. It identifies Maf1 as a Pol III inhibitor that enables the parasite to respond to external stimuli such as magnesium chloride plasma levels by downregulating Pol III-transcribed ruf6 genes and subsequently regulated var genes. While the evidence presented is generally convincing, some of the results are incomplete, and the mechanistic link between external signals and Maf1 activation remains unknown.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work by Park et al. demonstrates an open-top two-photon light sheet microscopy (OT-TP-LSM) for lesser invasive evaluation of intraoperative 3D pathology. The authors provide convincing evidence for the effectiveness of this technique investigating various human cancer cells. This article will be of broad interest to biologists and, specifically, pathologists utilizing 3D optical microscopy.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides useful initial information on how humans represent two-dimensional abstract spaces in relation to the social traits of warmth and competence. While the study poses an interesting question, the evidence for a grid-like code at present is incomplete. This study will be of interest to researchers working in the field of spatial navigation as well as the navigation of conceptual abstract space.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study presents a series of results to uncover the role of C-terminal half of the Syx1 SNARE domain. The evidence supporting the conclusions is convincing. The paper will be of broad interest to biophysicists and neurobiologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript provides convincing evidence for the involvement of membrane actin, and its regulatory proteins, mDia1/3, RhoA, and Rac1 in the mechanism of synaptic vesicle re-uptake (endocytosis). These important data fill a gap in the understanding of how the regulation of actin dynamics and endocytosis are linked. The manuscript will be of interest to all scientists working on cellular trafficking and membrane remodeling.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study proposes a framework to understand and predict generalization in visual perceptual learning in humans based on form invariants. Using behavioral experiments in humans and by training deep networks, the authors offer evidence that the presence of stable invariants in a task leads to faster learning. However, this interpretation is promising but incomplete. It can be strengthened through clearer theoretical justification, additional experiments, and by rejecting alternate explanations.
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eLife assessment
This paper presents valuable findings that gustation and nutrition might independently influence the preferred environmental temperature in flies. While some of the evidence is solid, support for other claims appears incomplete at this stage but can be addressed with some further experimentation. The finding that flies might thus exhibit a cephalic phase response similar to mammals will be of value for future investigations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The important study established a large-scale objective and integrated multiple optical microscopy systems to demonstrate their potential for long-term imaging of the developmental process. The convincing imaging data cover a wide range of biological applications, such as organoids, mouse brains, and quail embryos, but enhancing image quality can further enhance the method's effectiveness. This work will appeal to biologists and imaging technologists focused on long-term imaging of large fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work contributes to our understanding of the combined effects of metabolic syndrome on fronto-temporal gray matter morphology from two large-scale datasets. The evidence based on state-of-the art multivariate imaging analysis and detailed micro- and macrostructural contextualization analyses is convincing and provides an understanding of the neurological correlates of metabolic syndrome, although the study would have benefitted from the inclusion of longitudinal data.
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www.biorxiv.org www.biorxiv.org
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Editors Assessment:
One limiting factor in the adoption of spatial omics research are workflow systems for data preprocessing, and to address these authors developed the SAW tool to process Stereo-seq data. The analysis steps of spatial transcriptomics involve obtaining gene expression information from space and cells. Existing tools face issues with large data sets, such as intensive spatial localization, RNA alignment, and excessive memory usage. These issues affect the process's applicability and efficiency. To address this, this paper presents a high-performance open-source workflow called SAW for Stereo-Seq. This includes mRNA position reconstruction, genome alignment, matrix generation, clustering, and result file generation for personalized analysis. During review the authors have added examples of MID correction in the article to make the process easier to understand. And In the future, more accurate algorithms or deep learning models may further improve the accuracy of this pipeline.
*This evaluation refers to version 1 of the preprint *
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www.biorxiv.org www.biorxiv.org
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Editors Assessment:
This paper describes a new spatial transcriptomics method that that utilizes cell nuclei staining images and statistical methods to generate high-confidence single-cell spatial gene expression profiles for Stereo-seq data. STCellbin is an update of StereoCell, now using a more advanced cell segmentation technique, so more accurate cell boundaries can be obtained, allowing more reliable single-cell spatial gene expression profiles to be obtained. After peer review more comparisons were added and more description given on what was upgraded in this version to convince the reviewers. Demonstrating it is a more reliable method, particularly for analyzing high-resolution and large-field-of-view spatial transcriptomic data. And extending the capability to automatically process Stereo-seq cell membrane/wall staining images for identifying cell boundaries.
This evaluation refers to version 2 of the preprint
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www.biorxiv.org www.biorxiv.org
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Editors Assessment:
For better data quality assessment of large spatial transcriptomics datasets this new BatchEval software has been developed as a batch effect evaluation tool. This generates a comprehensive report with assessment findings, including basic information of integrated datasets, a batch effect score, and recommended methods for removing batch effects. The report also includes evaluation details for the raw dataset and results from batch effect removal methods. Through peer review and clarification of a number of points it now looks convincing that this tool helps researchers identify and remove batch effects, ensuring reliable and meaningful insights from integrated datasets. Potentially making the tool valuable for researchers who need to analyze large datasets of this type, as it provides an easy and reliable way to assess data quality and ensures that downstream analyses are robust and reliable.
This evaluation refers to version 1 of the preprint
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study advances our understanding of how landscape context affects the relationship between grassland plant diversity and biomass. This study used very well-designed approaches to analyze complex ecological relationships in real-world landscapes and thus provides compelling evidence to support its findings. The work will be of interest to landscape ecologists and community ecologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study could potentially represent a step forward towards personalized medicine by combining cell-based data and a prior-knowledge network to derive Boolean-based predictive logic models to uncover altered protein/signaling networks within cancer cells. The level of evidence supporting the conclusions is solid, as the authors present analyses on independent, real-world data to validate their approach. These findings could be of interest to medical biologists working in the field of cancer, as the work should inform drug development and treatment choices in the field of oncology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important, large experimental study examines the effects of plant species richness, plant genotypic richness, and soil water availability on herbivory patterns for Piper species in several tropical sites. The authors find solid evidence that water availability, as well as intra- and interspecific plant diversity, influence herbivory and herbivore diversity, but that the effects differ geographically.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents important findings on how cells sense and respond to their surroundings, in particular when two environmental signals are presented periodically, in alternation or conjunction. The compelling analyses reveal some unexpected behaviors that could not have been drawn, from simpler experimental designs, related to the dynamic interplay between the starvation and hyper-osmotic stress responses in budding yeast, exemplifying that applying complex signals can unveil new biological insights, even for well-studied systems. The work will be of broad interest to researchers interested in fungal biology, dynamic systems, cell signaling, and cell biology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study of extrachromosomal DNA (ecDNA) identifies genes that distinguish ecDNA+ and ecDNA- tumors. The findings in the manuscript are important and the genomic analyses convincing. However, some of the data remain observational and the inferences would therefore be more robust with experimental validation. This manuscript could well be of relevance to biologists interested in cancer biology and gene regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study extends existing sequentially Markovian coalescent approaches to include the use of hypervariable loci such as epimutations. This is an intriguing addition and the authors provide solid validation of their methods via simulation and analysis of empirical data in Arabidopsis thaliana. Given the increasing availability of such data -- and thus the potential use of this approach -- there would be additional value in more extensive consideration of when and where these methods are best used.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study provides the first assessment of the potentially interactive effects of seasonality and blood source on mosquito fitness, together in one study. However, the experimental approach is incomplete because it is limited without replication of the experiments and because of the small sample sizes for some groups. The work will be of interest to those studying mosquito biology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work presents important insights regarding the mechanism underlying the assembly, maintenance, and disassembly of a very stable microtubule-based structure, termed quiescent-cell nuclear microtubule (Q-nMT) bundle, which is formed in quiescent yeast cells to ensure cell survival and viability. This insight will help to elucidate how very stable microtubules can exist alongside very dynamic microtubules, which is still poorly understood. While the experimental support is overall solid, additional analyses using state-of-the-art methodology would further strengthen some of the claims.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study seeks to disentangle the different selective forces shaping the evolutionary dynamics of transposable elements (TEs) in the wild grass Brachypodium distachyon. Using haplotype-length metrics, and genetic and environmental differentiation tests, the authors present convincing evidence that positive selection on TE polymorphisms is rare and that the distribution of TE ages points to purifying selection being the main force acting on TE evolution in this species. This study will be relevant for anyone interested in the role of TEs in evolution and adaptation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on the impact of metformin-induced shifts in gut microbial community structure and metabolite levels for drug efficacy in a mouse model of liver injury. The current evidence supporting the claims of the authors is solid. This paper will be of broad interest to researchers across multiple disciplines, including the microbiome, liver disease, and pharmacology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study provides new insights into the development and function of medullary thymus epithelial cells (mTEC). The authors provide compelling evidence to support their claims as to the differentiation and lineage outcomes of CCL21+ mTEC progenitors, which further our understanding of how central tolerance of T cells is enforced within the thymus.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The fMRI study is important because it investigates fundamental questions about the neural basis of multimodal binding using an innovative multi-day learning approach. The results provide solid evidence for learning-related changes in the anterior temporal lobe, however, the interpretation of these changes is not straightforward, and the study does not (yet) provide direct evidence for an integrative code. This paper is of potential interest to a broad audience of neuroscientists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study advances our understanding of how the viral protease in a D-type retrovirus is activated and in particular how the exposure of the myristoyl group is required for processing of the Gag matrix precursor. The supporting evidence is convincing, but the work would benefit from additional data in support of the claims. This manuscript is of interest to retrovirologists and structural biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful assessment of the possible role of type I interferons in inhibiting Adam17 protease/sheddase activity and their correlation with decreased Langerhans Cells signature in lesional and nonlesional CLE and murine models as cause of photosensitive lupus. The data were collected and analyzed using a solid methodology. This work will be of interest to scientists interested in photosensitivity in the setting of lupus.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study used a novel method to relate gastric acidity to subjective ratings of emotions induced by video clips. The findings are solid but could be strengthened by additional analyses and/or visualization. The findings have broad implications for the field of emotion research and opens new avenues of research for understanding psychosomatic disorders.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript presents the lack of effect of closed-loop SWR disruption in guiding behavior and remembering the recent past in short-term memory tasks in rats. These negative results may have important theoretical and practical implications in the field of memory and learning. However, while SWR detection methods are carefully validated, the strength of evidence is incomplete and some additional controls are required.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable findings on the role of the Drosophila ubiquitin-conjugating enzyme UBE2D/eff in maintaining proteostasis during aging. Protein levels of UBE2D decrease with age, and knockdown of UBED2 leads to an accumulation of ubiquitinated proteins, and a shortened lifespan that can be rescued by ectopic expression of the human homologous gene. The work supports a role of this ubiquitin conjugating enzyme in proteostasis, although the evidence is still incomplete. The study will be of broad interest to cell biologists working in aging and age-related diseases.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Pak et al. examined the relationship between the most common spatial patterns of neurodegeneration and transcriptional markers of the density of different cell types in the cerebral cortex. This valuable study uses innovative methods to provide convincing evidence that patterns of grey matter loss in various forms of dementia are correlated with the anatomical distribution of non-neuronal cell types.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work identifies a previously uncharacterized capacity for songbird to recover vocal targets even without sensory experience. The evidence supporting this claim is convincing, with technically difficult and innovative experiments exploring goal-directed vocal plasticity in deafened birds. This work has broad relevance to the fields of vocal and motor learning.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study assesses anatomical, behavioral, physiological, and neurochemical effects of early-life seizures in rats, describing a striking astrogliosis and deficits in cognition and electrophysiological parameters. The solid results come from a wide range of convergent techniques that were used to understand the effects of early-life seizures on behavior as well as hippocampal prefrontal cortical dynamics. This paper will be of interest to neurobiologists, epileptologists, and behavioral scientists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study examining the neural profile of weak and strong fear memories using a variety of imagining and interrogation neural techniques. The data are convincing in detailing the neural profile of neutral, aversive and fear conditioned stimuli in the LC and its input to the dorsal hippocampus and support the conclusion that dopaminergic input from the LC is the key instigator of trace fear conditioning in hippocampus. This paper is of interest to behavioural and neuroscience researchers studying learning, memory and neural networks.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
These important findings stand out from other similar studies via some convincing demonstration of behavioural and neural relationships between two helping tasks - one focusing more on social perception, one more on its influence on social behaviour - that were performed more than 300 days apart. The claims however would be more convincing with a larger sample size.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study addresses the interesting and challenging problem of how neural networks (including possibly the brain) can optimize performance while multi-tasking. The authors address this problem by introducing an information-theoretic framework that balances the costs of control and of automaticity to achieve a desired level of overall performance. They present detailed analyses of this framework, but overall the manuscript is not easily accessible to a broad audience, and the supporting evidence is currently incomplete (but could be greatly improved with substantial revisions). They use information-theoretic terminology in non-standard ways that are not clearly explained, leading to difficulties in interpreting the framework and comparing it to other computational approaches, and the relationship between their findings and empirical data is not always clear.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript describes human intracranial neural recordings in the auditory cortex during speech production, showing that the effects of delayed auditory feedback correlate with the degree of underlying speech-induced suppression. This is an important finding, as previous work has suggested that speech suppression and feedback sensitivity often do not co-localize and may be distinct processes, in contrast with findings in non-human primates where there is a strong correlation. The strength of the evidence is solid, with appropriate experimental methods, data, and analysis, though some additional analysis would strengthen comparisons with past work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study substantially advances our understanding of the role of different-sized soil invertebrates in shaping the rates of leaf litter decomposition, using an experiment across seasons along an aridity gradient. The authors provide compelling evidence that the summed effects of all invertebrates (with large-sized invertebrates being more active in summer and small-sized invertebrates in winter) on decomposition rates result in similar levels of leaf litter decomposition across seasons. The work will be of broad interest to ecosystem ecologists interested in soil food webs, and researchers interested in modeling carbon cycles to understand global warming.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work substantially advances our understanding of episodic memory in individuals with aphantasia, and sheds light on the neural underpinnings of episodic memory and mental imagery. The evidence supporting the conclusions is convincing, including evidence from a well-established interview paradigm complemented with fMRI to assess neural activation during memory recall. The work will be of broad interest to memory researchers and mental imagery researchers alike.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Amacrine cells are a heterogeneous and understudied set of retinal interneurons. This study presents valuable new insights into the structure, function, and circuit connectivity of a particular subset of wide field amacrine cells (WACs). The authors use an impressive set of techniques to study structural and functional properties of these cells and to establish their postsynaptic circuit partners. Evidence for the central conclusions is solid, although some of the most interesting results could be pursued more completely.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study describes patterns of anatomical connectivity between the cortex and the thalamus using magnetic resonance imaging data in humans and non-human primates. The measures are related to numerous other modalities to develop a robust understanding of the organisation of the system. The authors provide solid evidence that there is a difference between sensory and association cortices in terms of their connectivity with the thalamus, which may have downstream effects on brain function. This work will be of interest to neuroscientists interested in the organization and dynamics of cortico-thalamic circuits.
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eLife assessment
This important study introduces a new cortical circuit model for predictive processing. Simulations effectively illustrate that, with appropriate synaptic plasticity, a canonical layer 2/3 cortical circuit - comprising two classes of interneurons providing subtractive and divisive inhibition - can generate uncertainty-modulated prediction errors by pyramidal neurons. The model's effectiveness is supported by solid numerical analysis. Although the model is convincing and offers testable predictions, it currently lacks direct comparison to experimental data, and the presentation clarity could be improved. Nonetheless, the model is expected to be of great interest to those involved in cortical and predictive processing research.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents important findings on the differential activity of noradrenergic and dopaminergic input to dorsal hippocampus CA1 in head-fixed mice traversing a runway in a virtual environment that is familiar or novel. While the data appear to be rigorously analysed, and the observed divergence in the dynamics of activity in the dopaminergic and noradrenergic axons is solid, there are some methodological concerns that mean the strength of evidence is currently incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Alpha-synuclein is a synaptic vesicle associated protein that is linked to a number of neurodegenerative disorders. In this manuscript, the authors provide compelling evidence of alpha-synuclein's interaction with E-domain synapsins as the main culprit mediating the suppression of neurotransmitter release and synaptic vesicle recycling by alpha-synuclein. This important work provides molecular mechanisms underlying alpha-synuclein functions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study proposes a new method for tracking neurons recorded with Neuropixel electrodes across days. The methods and the strength of the evidence are convincing, but the authors do not address whether their approach can be generalized to other brain areas, species, behaviors, or tools. Overall, this method will be potentially of interest to many neuroscientists who want to study long-term activity changes of individual neurons in the brain.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript details a new method and tool for examining TDP-43 loss of nuclear and gain of cytoplasmic function in neurons. This is a valuable resource that does not rely on artificial knockdown or overexpression. While the authors seek to use this new system to induce disease-associated TDP-43 pathology), their overall evaluation is incomplete and requires further characterization to enhance the applicability and utility of this new tool.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Evaluation statement (17 January 2024; revised 31 January 2024)
Feng and colleagues investigate the molecular basis of lipid scrambling in a fungal member of the TMEM16 family of Ca<sup>2+</sup>-dependent lipid scramblases. These proteins possess a groove in their 3D structure that has been implicated in lipid scrambling, which the authors investigate in the absence and presence of Ca<sup>2+</sup> using a combination of cryo-EM structure determination, mutagenesis and functional assays. Their closed-groove structure reveals a continuous file of lipid molecules around the catalytic groove region, providing a structural basis for lipid interaction with the protein. Additionally, the authors capture three novel states of TMEM16, completing the picture of conformational transitions that this protein undergoes. Strikingly, the authors show that both structure and distribution of the protein’s conformations depend on lipid composition and nanodisc scaffold protein.
Biophysics Colab considers this to be exceptional work and recommends it to scientists interested in plasma membrane lipid homeostasis and cryoEM.
(This evaluation by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study explores numerous lines of evidence for the surprisingly diverse diets of a group of toothed birds that lived over 100 million years ago. The large amount of data the authors collected forms a solid dataset. The methods might in principle be extensible to other limbed vertebrates, although there are concerns regarding some of the details. The article will be of interest to colleagues studying ecological evolution in birds or dinosaurs more generally, as well as to anyone studying the impact of the mass extinction event 66 million years ago.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents an important finding on the splicing regulatory function of RBM7 and its functional impact in breast cancer metastasis. The evidence supporting the claims of the authors is solid, although the inclusion of more delineation of how RBM7 regulates NF-kB and coordinates splicing would have strengthened the study. The work will be of interest to scientists working on breast cancer.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study utilizes proteomics analysis across a large panel of 51 cancer cell lines to elucidate mechanisms underlying the sensitivity of cancer cells to high-dose vitamin C (Ascorbate). While the associations between specific molecular pathways and sensitivity to ascorbate are interesting, a major limitation is that the study is largely descriptive and incomplete, lacking evidence on the molecular underpinnings of cancer cells' sensitivity to high-dose vitamin C.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study proposes a role of lysosomal Ca2+ release in inflammasome signaling and metabolic inflammation. While the proposed model would be of considerable interest to the field of immunology if validated, the experimental approaches to study calcium dynamics are problematic, with one of several concerns being the transfection efficiency. The major claims of the paper are thus only incompletely supported.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study uses a multi-pronged empirical and theoretical approach to advance our understanding of animal cognition. It presents convincing data on how differences in learning relate to differences in the ways that male versus female animals cope with urban environments, and more generally how reversal learning may benefit animals in urban habitats.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study for understanding the pathogenesis of ulcerative colitis. It convincingly demonstrates reduced levels of the vesicular trafficking protein Rab7 in ulcerative colitis and Crohn's disease, leading to altered levels of calcium-activated chloride channel regulator 1 (CLCA1) and subsequent mucin dysregulation, highlighting Rab7's significance in gut homeostasis maintenance. The manuscript advances the field as it provides insights into a novel regulatory pathway implicated in ulcerative colitis, potentially paving the way for the development of targeted therapeutic interventions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Pluripotent stem cells can be obtained from embryos (embryonic stem cells, ESCs) or through induction by transfection (induced pluripotent stem cells, iPSCs). This valuable study uses semi-quantitative proteomics to compare both types of cells, finding interesting differences. The value of the study lies in demonstrating that ESCs and iPSCs cannot be used interchangeably. The conclusions are backed by solid data even if a greater number and diversity in ESC and iPSC clones would help in generalizing the observations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study contributes to the current knowledge in the field of acute and chronic infarction. It is a significant study because the results provide convincing evidence for the need to incorporate additional risk factors for assessing patients after myocardial infarction.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study evaluates the evolutionary significance of variations in the accuracy of the intron-splicing process across vertebrates and insects. Using a powerful combination of comparative and population genomics approaches, the authors present convincing evidence that higher rates of alternative splicing tend to be observed in species with lower effective population size, a key prediction of the drift-barrier hypothesis. The analysis is carefully conducted and has broad implications beyond the studied species. As such, it will strongly appeal to anyone interested in the evolution of genome architecture and the optimisation of genetic systems.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The present study provides valuable evidence on the neurochemical mechanisms underlying working memory in obesity. The authors' approach considering specific working memory operations (maintenance, updating) and putative dopaminergic genes is solid, though the inclusion of a more direct measure of dopamine signaling and further theoretical analysis and interpretation of findings would have strengthened the work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides the fundamental insight that TGN46, a single-pass membrane protein, acts as a cargo receptor for proteins at the Trans-Golgi Network. The authors demonstrate that the luminal domain of TGN46 is crucial for the incorporation of the soluble secretory protein PAUF into CARTS, a class of vesicles mediating TGN to surface traffic. The data presented are compelling, yielding a clear model for the sorting of cargos destined for secretion.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study addresses a central question in systems neuroscience (validation of active inference models of exploration) using a combination of behavior, neuroimaging, and modelling. The data provided are useful but incomplete, missing critical detail. Additionally, some of the conclusions require a comparison model, and proper consideration of alternative explanations.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study reports important findings about new locomotory dynamics of crawling Drosophila larva based on imaging the reaction forces during larval crawling. The evidence with the new high-resolution microscopy method is compelling, as it significantly improves the spatial, temporal, and force resolution compared to previous methods for studying Drosophila larva and could be applied to other crawling organisms. The manuscript explains the new technology, WARP microscopy, and provides analysis of the data to characterize small animal behavior and discover new crawling-associated anatomical features and motor patterns. The work will be of interest to the broad neuroscience community interested in the mechanisms of locomotion in a highly tractable model.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The microRNA lin-4, originally discovered in C. elegans, has a key role in developmental timing across species, but how its expression is developmentally controlled is poorly understood. Here, the authors provide convincing evidence that two MYRF transcription factors are essential positive regulators of lin-4 during early C. elegans larval development. These results provide important insight into the molecular nature of developmental timing that could have significant implications for understanding these processes in more complex systems.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines a range of advanced ultrastructural imaging approaches to define the unusual endosomal system of African trypanosomes. Compelling images reveal that, unlike a conventional set of compartments, the endosome in these protists forms a continuous membrane system with functionally distinct subdomains, as defined by canonical markers for early, late, and recycling endosomes. The findings compellingly support that the endocytic system in bloodstream stages has adapted to support remarkably high rates of membrane turnover necessary for immune complex removal and survival in the blood. This research is particularly relevant to those investigating infectious diseases
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study addresses the earliest events that enable plant roots to reorient growth in response to gravity. Compelling molecular and cell biological data establish that plasma membrane localization of the LAZY or NEGATIVE GRAVITROPIC RESPONSE OF ROOTS (NGR) protein family is required for rapid and polar redirection of D6 protein kinase, an activator of the PIN3 auxin transporter. This work complements and extends recent publications on the NGR family in gravity sensing (PMID: 37741279 and PMID: 37561884). Collectively these papers advance our understanding of rapid plant gravity sensing and response.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study identifies an uncharacterized yeast gene regulating chronological lifespan in a mitochondrial-dependent pathway. The approach to identify and characterise this new gene is appealing, but the evidence in support of some of the major conclusions is incomplete. The paper focuses on chronological lifespan and mitochondrial function, and it will be of interest to yeast biologists working in metabolism and aging.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines experimental and computational data to address crucial aspects of RNA methylation by a vital RNA methyltransferase (MTase). The authors have provided compelling, strong evidence, utilizing well-established techniques, to elucidate aspects of the methyl transfer mechanism of methyltransferase-like protein 3 (METTL3), which is a part of the METTL3-14 complex. This work will be of broad interest to biochemists, biophysicists, and cell biologists alike.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study presents findings regarding the role of Juvenile Hormone in development and cell differentiation in the ametabolous insect Thermobia domestica, providing an in-depth analysis of JH's roles in a member of this basally branching group. The evidence supporting the claims of the authors is convincing, drawing on a broad range of approaches and variety of experimental techniques. While the interpretation of this work in the wider context - its relevance for the evolution of metamorphosis - is in some places somewhat speculative, the work will be of interest to evolutionary developmental biologists studying the evolution of metamorphosis, and the evolution of insects in general.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study reports important findings on identifying sequence motifs that predict substrate specificity in a class of lipid synthesis enzymes. It sheds light on a mechanism used by bacteria to modify the lipids in their membrane to develop antibiotic resistance. The evidence is convincing, with a careful application of machine learning methods, validated by mass spectrometry-based lipid anlaysis experiments. This interdisciplinary study will be of interest to computational biologists and to the community working on lipids and on enzymes involved in lipid synthesis or modification.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study addresses the problem of detecting weak similarity between protein sequences, a procedure commonly used to infer homology or assign putative functions to uncharacterized proteins. The authors present a convincing approach that combines recently developed protein language models with well-established methods. The benchmarks provided show that the proposed tool is fast and accurate for remote homology detection, making this paper of general interest to all researchers working in the fields of protein evolution and genome annotation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The findings in the manuscript are important and the strength of evidences from the genomic analyses is convincing. However, the evidence for the existence of functional MER21B/C remnants in mice, as well as for the imprinting status of Zdbf2 in rabbits and non-human primates was viewed as mainly correlative and incomplete. This manuscript will be of interest to developmental biologists and those working on possible novel mechanisms of gene regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study examines the relationship between positional anchoring of grid cell activity and performance in spatial navigation tasks that requires path integration. The authors demonstrate that grid cells can either fire in relation to the position relative to task-relevant virtual stimuli or independently based on the distance covered. Their findings convincingly reveal that mice exhibited better performance in the path integration task when grid cell activity was anchored to their position on the virtual track rather than the distance traversed, highlighting the contribution of grid firing to spatial navigation behavior. The work will be of interest to experimental and computational neuroscientists interested in spatial navigation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work describes a novel and powerful affinity interactomics approach that allows investigators to identify networks of protein-protein interactions in cells. The important findings presented here describe the application of this technique to the SH3 domain of the membrane remodeling Bridging Integrator 1 (BIN1), the truncation of which leads to centronuclear myopathy. The authors present solid evidence that BIN1 SH3 engages with an unexpectedly high number of cellular proteins, many of which are linked to skeletal muscle disease, and evidence is presented to suggest that BIN1 may play a role in mitosis creating the potential for new avenues in drug development efforts. Some of the findings, however, are rather preliminary, and questions about differences in affinities between whole intact protein and fragment binding partners are not adequately discussed.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This article reports an important fluorescence-based reporter system to evaluate kinase conformations. This assay is applied to four different kinases that have very unique regulatory features, thereby indicating that the assay can be used to provide solid evidence on the conformational state of a large number of kinases. This paper will be of interest to researchers working on kinases and their conformational states.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors identify new mechanisms that link a PIK3R1 mutant to cellular signaling and division in Activated PI3 Kinase Delta Syndrom 1 and 2 (APDS1/2). The conclusion that this mutant serves as a dominant negative form of the protein, impacting PI3K complex assembly and IRS/AKT signaling, is important, and the evidence from constitutive and inducible systems in cultured cells is convincing. Nevertheless, there are several limitations relating to differences between cell lines and expression systems, as well as more global characterization of the protein interaction landscape, which would further enhance the work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study sheds light on the pivotal role of alterations in chondrocyte glycan metabolism in two contexts: The onset of cartilage degeneration and early onset of osteoarthritis (OA). The action is through hypertrophic differentiation of chondrocytes, a finding that provides insights into the identification of nascent markers for early-stage OA. The evidence supporting the claims is solid, with the authors clearly demonstrating the role of articular cartilage corefucosylation in the development of OA. The authors' inferences would be further enhanced through future experiments aimed at analyzing the mechanisms underlying the changes in glycometabolism in cartilage.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript describes fundamental single-molecule correlative force and fluorescence microscopy experiments to visualize the 1D diffusion dynamics and long-range nucleosome sliding activity of the yeast chromatin remodelers, RSC and ISW2. Compelling evidence shows that both remodelers exhibit 1D diffusion on bare DNA but utilize different mechanisms, with RSC primarily hopping and ISW2 mainly sliding on DNA. These results will be of interest to researchers working on chromatin remodeling.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study employs multiscale simulations to show that PIP2 lipids bind to DIV S4-S5 linkers within the inactivated state of a voltage-gated sodium channel, affecting the coupling of voltage sensors to the ion-conducting pore. The authors demonstrate that PIP2 prolongs inactivation by binding to the same site that binds the C-terminal during recovery from inactivation, and they suggest that binding to gating charges in the resting state may impede activation, both findings that contribute to our understanding of sodium channel modulation. The coarse-grained and atomistic molecular dynamics simulations are convincing, including state dependence and linker mutants to back up the claims.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This landmark study sheds light on a long-standing puzzle in Protein kinase A activation in Trypanosoma. Extensive experimental work provides exceptional evidence for the conclusions of the work, which represents a significant advancement in our understanding of the molecular mechanism of cyclic nucleotide binding domains. The work is relevant for researchers with interests in kinases and their mechanistic study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports on key characteristics of MYC-driven cancers: dysregulated pre-mRNA splicing and altered metabolism, with the data being overall solid. The manuscript should be of broad interest to cancer biologists due to its therapeutic implications.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This potentially useful study aims to advance our understanding of the structure of the native form of a viral toxin secreted from infected cells. While some of the findings confirm previous reports, the new claims in this study are unfortunately only inadequately supported by the methods and analyses used. More rigorous approaches are needed to justify the main conclusion that the structure of the viral toxin derived from infected cells in this study is distinct from previously reported structures of recombinantly expressed versions of the toxin.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study elucidates the molecular divergence of caspase 3 and 7 in the vertebrate lineage. Convincing biochemical and mutational data provide evidence that in humans, caspase 7 has lost the ability to cleave gasdermin E due to changes in a key residue, S234. The diversification and specialization of gasdermins such as gasdermin E in humans compared to early vertebrates such as teleosts may enable each human gasdermin molecule to have more restricted and tightly regulated physiological functions in different cell death pathways.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work suggests that the observed cosine-like activity in the head direction circuit of insects not only subserves vector addition but also minimizes noise in the representation. The authors provide solid evidence using the locust and fruit fly connectomes. The work raises important theoretical questions about the organization of the navigation system and will be of interest to theoretical and experimental researchers studying navigation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides important new insights into the structural diversity of effectors – proteins secreted by pathogens and symbionts into host cells – from the plant-associated fungus Fusarium oxysporum f. sp. lycopersici. The study provides a convincing approach to elucidate how effectors navigate their host environment by exploiting both computational and experimental approaches to understand how their structure influences binding partners. The work will be of interest to those studying molecular host-microbe interactions and disease protection.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides a fundamental advance in palaeontology by reporting the fossils of a new invertrebrate, Beretella spinosa, and inferring its relationship with already described species. The analysis placed the newly described species in the earliest branch of moulting invertebrates. The study, supported by convincing fossil observation, hypothesizes that early moulting invertebrate animals were not vermiform.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The work by Lewis and co-workers presents important findings on the role of myosin structure/energetics on the molecular mechanisms of hibernation by comparing muscle samples from small and large hibernating mammals. The solid methodological approaches have revealed insights into the mechanisms of non-shivering thermogenesis and energy expenditure.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper presents valuable findings that shed light on the mental organisation of knowledge about real-world objects. It provides diverse, if incomplete and tentative, evidence from behaviour, brain, and large language models that this knowledge is divided categorically between relatively small objects (closer to the relevant scale for direct manipulation) and larger objects (further from the typical scope of human affordances for action).
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study explores the potential influence of physiologically relevant mechanical forces on the extrusion of vesicles from C. elegans neurons. The authors provide compelling evidence to support the idea that uterine distension can induce vesicular extrusion from adjacent neurons. The work would be strengthened by using an additional construct (preferably single-copy) to demonstrate that the observed phenotypes are not unique to a single transgenic reporter. Overall, this work will be of interest to neuroscientists and investigators in the extracellular vesicle and proteostasis fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is a saturation mutagenesis screening of the CDKN2A gene, successfully assessing the functionality of the missense variants. The results seem robust, but currently, the manuscript is incomplete with a number of weaknesses. The work has the potential to serve as a valuable resource for diagnostic labs as well as cancer geneticists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful comparison of the dynamic properties of two RNA-binding domains. The data collection and analysis are solid, making excellent use of a suite of NMR methods. However, evidence to support the proposed model linking dynamic behavior to RNA recognition and binding by the tandem domains remains incomplete. The work will be of interest to biophysicists working on RNA-binding proteins.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study combines multidisciplinary approaches to examine the role of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a potential novel host dependency factor for Zika virus. The main claims are partially supported by the data, but remain incomplete. The evidence would be strengthened by improving the immunofluorescence analyses, addressing the role of IGF2BP2 in "milder" infections, and elucidating the role of IGF2BP2 in the biogenesis of the viral replication organelle. With the experimental evidence strengthened, this work will be of interest to virologists working on flaviviruses.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript explores the ways in which the genetic code evolves, specifically how stop codons are reassigned to become sense codons. The authors present phylogenetic data showing that mutations at position 67 of the termination factor are present in organisms that nevertheless use the UGA codon as a stop codon, thereby questioning the importance of this position in the reassignment of stop codons. Alternative models on the role of eRF1 would reflect a more balanced view of the data. Overall, the data are solid and these findings will be valuable to the genomic/evolution fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on the process of brown to white adipogenic transdifferentiation within the perirenal adipose depot. The evidence supporting the claims is convincing, although limited sequencing depth of single nuclei and lack of regulatory insights somewhat lessens the impact of these findings. The work will be of interested to adipose tissue biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable insights into the evolution of the gasdermin family, making a strong case that a GSDMA-like gasdermin activated by caspase-1 cleavage was already present in early land vertebrates. Convincing biochemical evidence is provided that extant avian, reptilian, and amphibian GSDMA proteins can still be activated by caspase-1 and upon cleavage induce pyroptosis-like cell death -- at least that they do so in the context of human cell lines. The caspase-1 cleavage site has only been lost in mammals, which use the more recently evolved GSDMD as a caspase-1 cleavable pyroptosis inducer. The presented work will be of considerable interest to scientists working on the evolution of cell death pathways, or on cell death regulation in non-mammalian vertebrates.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Bladder dysfunction following spinal cord injury (SCI) represents a severe and disabling complication without effective therapies. Following evidence that AMPA receptors play a key role in bladder function the authors show convincingly that AMPA allosteric activators can ameliorate many of the subacute defects in bladder and sphincter function following SCI, including prolonged voiding intervals and high bladder pressure thresholds for voiding. These valuable results in rodents may help in the development of these agents as therapeutics for humans with SCI-induced bladder dysfunction.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study identifies the TNXB-AKT pathway as a potential mechanism underlying hemophilia-associated cartilage degeneration. The evidence supporting the conclusions is convincing, with murine and human patient evidence as well as genome-wide DNA methylation analysis. This paper would be of interest to cell biologists and biochemists working on musculoskeletal disorders.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study identifies the role of Caveolin1 and Cavin1 as regulators of TransEndothelial Macroaperture (TEM). The methodology used is rigorous and compelling, and further research can point to more mechanistic understanding of the process.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study introduces an innovative method for measuring interocular suppression depth, which implicates mechanisms underlying subconscious visual processing. The evidence is solid in suggesting a limitation of measuring conventional bCFS threshold alone that could be remediated by the new method. It will be of interest not only to cognitive psychologists and neuroscientists who study sensation and perception but also to philosophers who work on theories of consciousness.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript from Richter et al. is a very thorough anatomical description of the external sensory organs in Drosophila larvae. It represents a fundamental step forward for sensory physiology, and provides a tool for investigating the relationship between the structure and function of sensory organs. Using improved electron microscopy analysis and digital modelling, the authors provide compelling evidence that form the basis for further molecular and functional studies to decipher the sensory strategies used by larvae to navigate through their environment.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important paper uses a multifaceted approach to implicate the locus coeruleus-noradrenaline system in the stress-induced transcriptional changes of dorsal and ventral hippocampus. It provides an inventory of dorsal and ventral hippocampal gene expression upregulated by activation of LC-NA system, which can be used as starting point for more functional studies related to the effects of stress-induced physiological and pathological changes. The results convincingly support the conclusions. This paper will be of interest to those interested in stress neurobiology, hippocampal, and/or noradrenaline function.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This valuable manuscript by Lane introduces an exciting way to measure SARS-CoV-2 aerosolized shedding using a disposable exhaled breath condensate collection device (EBCD). The paper draws the conclusion that the contagious shedding of the virus via the aerosol route persists at a high level until 8 days after symptoms. While the methodology is potentially of high importance and the paper is clearly written, the conclusions are incomplete and only partially supported by the data.
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www.biorxiv.org www.biorxiv.org
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Editors Assessment:
The snake pipefish, Entelurus aequoreus, is a species of fish that dwells in open seagrass habitats in the northern Atlantic. As a pipefish, it is a member of the Syngnathidae family of fish which also includes seahorses and seadragons. In recent years it has expanded its population size and range into arctic waters. To better understand these demographic changes genomic data is useful, and to address this a high-quality reference genome has been produced. Building on a previous short-read reference, a near chromosome-scale genome assembly for the snake pipefish was assembled using PacBio CLR and Hi-C reads. After revisions the authors provided more details on the assembly metrics, the final assembly has a length of 1.6 Gbp, with scaffold and contig N50s of 62.3 Mbp and 45.0 Mbp respectively. Demographic inference analysis of the snake pipefish genome using this data enables tracing of population changes over the past 1 million years, and this reference will allow further analyses and studies relating these to changes in climate.
**This evaluation refers to version 1 of the preprint *
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study uses multiple large neuroimaging data sets acquired at different points through the lifespan to provide solid evidence that birthweight (BW) is associated with robust and persistent variations in cortical anatomy, but less-substantial influences on cortical change over time. These findings, supported by robust statistical methods, illustrate the long temporal reach of early developmental influences and carry relevance for how we conceptualize, study, and potentially modify such influences more generally. The paper will be of interest to people interested in brain development and aging.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this valuable study, the authors explore regulatory cascades governing mammalian cochlear hair cell development and survival. They confirm previous studies that the transcription factors Pou4f3 and Gfi1 are necessary for hair cell survival, and use compelling evidence to demonstrate that the RNA binding protein gene RBM24 is regulated by Pou4f3, but not Gfi1. These findings will be of interest to those working on hearing loss, and hold significance for viral gene delivery methods aiming to manipulate gene expression.
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www.biorxiv.org www.biorxiv.org
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Editors Assessment: Understanding the distribution of Anopheles mosquito species is essential for planning and implementing malaria control programmes, a task undertaken in this study that assesses the composition and distribution of the Anopheles in different districts of Kinshasa in the Democratic Republic of Congo. Mosquitoes were collected using CDC light traps, and then identified by morphological and molecular means. In total 3,839 Anopheles were collected, and data was digitised, validated and shared via the GBIF database under a CC0 waiver. The project monitoring the monthly dynamics of four species of Anopheles, showing a fluctuation in their respective frequencies during the study period. Review improved the metadata by adding more accurate date information, and this data can provide important information for further basic and advanced studies on the ecology and phenology of these vectors in West Africa.
*This evaluation refers to version 1 of the preprint
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable set of calcium imaging data to analyze the dynamics of excitatory and inhibitory responses in the projection neurons of the honeybees during and after odor presentations. The neural circuit model fed with the imaging data recapitulated odor-specific activity in the Kenyon cells in the post-odor period and the timing shift of behavioral response in associative learning. This solid work will be of interest to researchers working on associative learning.
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eLife assessment
This important study develops a machine learning method to reveal hidden unknown functions and behavior in gene regulatory networks by searching parameter space in an efficient way. The evidence for some parts of the paper is still incomplete and needs systematic comparison to other methods and to the ground truth, but the work will be of broad interest to anyone working in biology of all stripes since the ideas reach beyond gene regulatory networks to revealing hidden functions in any complex system with many interacting parts.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides important insights into the role of neurexins as regulators of synaptic strength and timing at the glycinergic synapse between neurons of the medial nucleus of the trapezoid body and the lateral superior olive, key components of the auditory brainstem circuit involved in computing sound source location from differences in the intensity of sounds arriving at the two ears. Through an elegant combination of genetic manipulation, fluorescence in-situ hybridization, ex vivo slice electrophysiology, pharmacology, and optogenetics, the authors provide convincing evidence to support their claims. While further work is needed to reveal the mechanistic basis by which neurexins influence glycinergic neurotransmission, this work will be of interest to both auditory and synaptic neuroscientists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides important evidence supporting the ability of a new type of neuroimaging, OPM-MEG system, to measure beta-band oscillation in sensorimotor tasks on 2-14 years old children and to demonstrate the corresponding development changes, since neuroimaging methods with high spatiotemporal resolution that could be used on small children are quite limited. The evidence supporting the conclusion is solid but lacks clarifications about the much-discussed advantages of OPM-MEG system (e.g., motion tolerance), control analyses (e.g., trial number), and rationale for using sensorimotor tasks. This work will be of interest to the neuroimaging and developmental science communities.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study seeks to address the importance of physical interaction between proteins in higher-order complexes for covariation of evolutionary rates at different sites in these interacting proteins. Following up on a previous analysis with a smaller dataset, the authors provide compelling evidence that the exact contribution of physical interactions, if any, remains difficult to quantify. The work will be of relevance to anyone interested in protein evolution.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper investigates the impact of intranasal instillation of SARS CoV2 spike protein in mouse models of lung inflammation. The authors conclude that the spike protein can interact with macrophages through carbohydrate recognition and can induce recruitment and NETosis of neutrophils, contributing to lung inflammation. They also use the cremaster muscle model to investigate effect of the spike proteins on neutrophil dynamics and death using intravital microscopy. Given that mucosal vaccines using SARS CoV2 spike variants could be envisioned as desirable, the observation that spike can induce lung/mucosal inflammation even without an adjuvant is important. Despite limitations of some loose terminology and some weak controls, the key observations are solid and demand further attention given the importance of the antigen.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study provides insight into the fascinating process of self- and non-self-recognition in the protist Tetrahymena thermophila, a species with seven distinct mating types. Using an elegant combination of phenotypic assays, protein studies, and imaging, the authors present convincing evidence that a large multifunctional protein complex at the cell surface mediates both self- and non-self mating-type recognition. This study extends our understanding of how more than two mating types/sexes may be specified in a species, and it will be relevant for anyone interested in sexual systems and cell-cell communication.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study advances our understanding of the potential therapeutic strategies for the treatment of pheochromocytomas using single-cell transcriptomics. The authors propose a new molecular classification criterion based on the characterization of tumor microenvironmental features, based on solid evidence. The work, which could be improved further through delineating the choice of the PASS scoring system, will be of broad interest to clinicians, medical researchers, and scientists working in the field of pheochromocytoma.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important paper provides solid evidence that the angular gyrus plays a role in insight-based memory updating. The study is well conducted, timely, and presents clear-cut behavioral results. While the study provides robust evidence that transcranial magnetic stimulation to the angular gyrus impacts memory, evidence for the strong claim of a causal contribution of the angular gyrus in particular – apart from other connected regions, including the hippocampus – is not conclusive.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study identifies novel small molecule antagonists of CXCR4 that disrupt nanocluster formation and chemotactic function without blocking CXCL12 binding and downstream signals. The conclusions are based on solid evidence, but the work could be improved by including kinetic and dose information on the most active inhibitors. We also note that modeling and mutagenesis implicate helix V and VI in an allosteric mechanism, but that the description of the modeling is not sufficiently detailed such that others could replicate it.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors report the cryo-EM structure of human vesicular monoamine transporter 2 (VMAT2) bound to the noncompetitive inhibitor tetrabenazine (in an occluded state). This important achievement captures the structure of a major facilitator superfamily (MFS) transporter critical for human neurotransmission. The evidence for the structure is solid, but the molecular dynamics aspect of the study is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors have made important contributions to our understanding of the pathogenesis of erectile dysfunction (ED) in diabetic patients. They have identified the gene Lbh, expressed in pericytes of the penis and decreased in diabetic animals. Overexpression of Lbh appears to counteract ED in these animals. The authors also confirm Lbh as a potential marker in cavernous tissues in both humans and mice. While solid evidence supports Lbh's functional role as a marker gene, further research is needed to elucidate the specific mechanisms by which it exerts its effects. This work is of interest to those working in the fields of ED and angiogenesis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study examines how deletion of a major DNA repair gene in bacteria may facilitate the rise of mutations that confer resistance against a range of different antibiotics. Although the phenotypic evidence is intriguing, the interpretation of the phenotypic data presented and the proposed mechanism by which these mutations are generated are incomplete, relying on untested assumptions and suboptimal methodology. If substantially improved, this work could be of interest to microbiologists studying antibiotic resistance, genome integrity, and evolution, but as yet is of unclear significance.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study advances our understanding of early Cambrian cnidarian paleoecology and suggests that the reconstructed ancestral feeding and respiration mechanisms predate jet-propelled swimming utilized by modern jellyfish. The work combines solid evidence of fluid and structural mechanics modeling, simulating for the first time the feeding and respiratory capacities in a microfossil (Quadrapyrgites), which in turn opens new possibilities using this approach for paleontological research. Assuming that the prior interpretations and assumptions concerning the modeled organism's soft part and skeletal anatomy are correct, the hypotheses that (1) the organism could alternately contract and expand the oral region and (2) such movement increased feeding efficiency seem plausible.
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arxiv.org arxiv.org
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eLife assessment
By assessing what it means to replicate a null finding, and by proposing two methods that can be used to evaluate whether null findings have been replicated (frequentist equivalence testing, and Bayes factors), this article represents an important contribution to work on reproducibility. Through a compelling re-analysis of results from the Reproducibility Project: Cancer Biology, the authors demonstrate that even when 'replication success' is reduced to a single criterion, different methods to assess replication of a null finding can lead to different conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important study by Theriot et al., the authors utilize an impressive set of innovative approaches to conduct a CRISPRi pooled screen in human cells using large-scale microscopy screen data. They leverage an improved barcoding approach to identify genes targeted in specific cells and examine the effects on cell morphology using high-dimensional phenotypic analysis. The method and data presented are compelling.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The findings of this study are valuable as they challenge the dogma regarding the link between lowered bacterial metabolism and tolerance to aminoglycosides. The authors propose that the well-known tolerance to AG of mutants such as those of complexes I and II is not due to a decrease in the proton motive force and thus antibiotic uptake. The results presented here are solid but incomplete and the conclusions require additional experimental support.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on the possible use of vilazodone in the management of thrombocytopenia through regulating 5-HT1A receptor signaling. The evidence supporting the claims of the authors is solid, with the combined use of computational methods and biochemical assays. The work will be of broad interest to scientists working in the field of thrombocytopenia.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript is a valuable contribution to our understanding of foraging behaviors in marine bacteria. The authors present a conceptual model for how a marine bacterial species consumes an abundant polysaccharide. Using experiments in microfluidic devices and through measurements of motility and gene expression, the authors offer solid evidence that the degradation products of polysaccharide digestion can stimulate motility.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors of this study implemented an important toolset for 3D reconstruction and segmentation of dissection photographs, which could serve as an alternative for cadaveric and ex vivo MRIs. The tools were tested on synthetic and real data with compelling performance. This toolset could further contribute to the study of neuroimaging-neuropathological correlations.
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eLife assessment
This study presents a valuable investigation of how people approach and avoid uncertainty, with a particular focus on the effects of overall uncertainty. They find that individuals approach uncertainty to a point, but when uncertainty is particularly high, they avoid it. The results are interpreted under a cognitive cost-resource rational framework. The methods are convincing, using appropriate and current methodologies, but more details on analyses and placing the work more fully in the context of the existing literature would make the contribution more significant.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The work by Hornberger and team presents a novel workflow for the visualisation of myofibrils with high resolution and contrast that will be highly valued by the scientific community. The novel methods include solid validation of both sample preparation and analysis, and have been used to make the fundamental discovery of myofibrillogenesis as the mechanism of mechanical loading-induced growth. However, whether this mechanism is present in other settings of muscle growth (i.e non-loading), other striated tissue (e.g myocardium), or is sex-dependent requires future experiments.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The work by Hornberger and team presents a novel workflow for the visualisation of myofibrils with high resolution and contrast that will be highly valued by the scientific community. The methods include solid validation of both sample preparation and analysis, and have been used to make the fundamental discovery of myofibrillogenesis as the mechanism of mechanical loading-induced growth. Whether this mechanism is present in other settings of muscle growth (i.e., non-loading), other striated tissue (e.g myocardium), or is sex-dependent, will require future experiments.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work performed fMRI experiments in a rodent model of absence seizures. The results provide new information regarding the brain's responsiveness to environmental stimuli during absence seizures. The authors suggest reduced responsiveness occurs during this type of seizure, and the evidence leading to the conclusion is solid, although reviewers had divergent opinions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study demonstrates that the cells in the behavior of the presomitic mesoderm in zebrafish embryos depends on both an intrinsic program and external information, which provides new insight into the biology underlying embryo axis segmentation. The findings are supported convincingly by a thorough and quantitative single-cell real-time imaging approach, both in vitro and in vivo, which the authors developed.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable prospective study develops a new tool to accelerate pharmacological studies by using neural networks to emulate the human ventricular cardiomyocyte action potential. The evidence supporting the conclusions is convincing, based on using a large and high-quality dataset to train the neural network emulator. There are nevertheless a few areas in which the article may be improved through validating the neural network emulators against extensive experimental data. In addition, the article may be improved through delineating the exact speed-up achieved and the scope for acceleration. The work will be of broad interest to scientists working in cardiac simulation and quantitative system pharmacology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines experimental infections with laboratory and field Plasmodium falciparum isolates to quantify the force of human malaria parasite transmission. By using compelling methodological approaches, the authors establish clear positive correlations between mosquito infection levels (as determined by oocyst numbers), sporozoite loads in salivary glands, and sporozoites expelled during feeding. The link between heterogenous infection levels in the mosquitoes and malaria transmission would be of interest to vector biologists, parasitologists, immunologists, and mathematical modellers.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study advances our understanding of the biological significance of the DNA sequence adjacent to telomeres. The data presented convincingly demonstrates that subtelomeric repeats are non-essential and have a minimal, if any, role in maintaining telomere integrity of budding yeast. The work will be of interest to telomere community specifically and the genome integrity community more broadly.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work presents an example of how genomic data can be used to improve understanding of an ongoing, long-term bacterial outbreak in a hospital with an application to multi-drug resistant Pseudomonas aeruginosa, and will be of interest to researchers concerned with the spread of drug-resistant bacteria in hospital settings. The convincing genomic analyses highlight the value of routine surveillance of patients and environmental sampling and show how such data can help in dating the origin of the outbreak and in characterising the epidemic lineages. These findings highlight the importance of understanding environmental factors contributing to the transmission of P. aeruginosa for guiding and tailoring infection control efforts; however, epidemiological information was limited and the sampling methodology was inconsistent, complicating interpretation of inferences about exact transmission routes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable findings on the role of the sirtuins SIRT1 and SIRT3 during Salmonella Typhimurium infection. Although the work increases our understanding of the mechanisms used by this pathogen to interact with its host and may have implications for other intracellular pathogens, the reviewers found that the evidence to support the claims is incomplete. In particular, the discrepancy between results obtained using cultured cell lines and the animal model of infection stands out.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript examines shared and divergent mechanisms of disruptions of five different mTOR pathway genes on embryonic mouse brain neuronal development. The significance of the manuscript is important, because it bridges several different genetic causes of focal malformations of cortical development. The strength of evidence is compelling, relying on both gain and loss of function, demonstrating differential impact on excitatory synaptic activity, conferring gene-specific mechanisms of hyperexcitability. The results have both theoretical and practical implications for the field of developmental neurobiology and clinical epilepsy.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
Little is known about the role of the microbiome alterations in epithelial ovarian cancer. This important and rigorous study carefully examined the microbiome composition of 1001 samples from close to 200 ovarian cancer cases and controls, and presents compelling evidence that the fallopian tube microbiota are perturbed in ovarian cancer patients. These insights are expected to fuel further exploration into translational opportunities stemming from these findings.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding for the immunotherapy of cancer. The data support the role of PDLIM2 as a tumor suppressor, and more immediately, its relevance for strategies to improve the efficacy of immunotherapy. The evidence supporting the conclusions is compelling and the work will be of interest to biomedical scientists working on cancer immunology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful resource for the gene expression profiles of different cell types in the parietal lobe of the cerebral cortex of prenatal macaques. The evidence supporting the claims of the authors is solid, and revision has clarified some of the cell isolation and cell classification issues flagged by reviewers. This dataset will be of interest to developmental neurobiologists and could potentially be used for future comparative studies on early brain development.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents two useful new mouse models that individually tag proteins from the SMAD family to identify distinct roles during early pregnancy. Solid evidence is provided that SMAD1 and SMAD5 target many of the same genomic regions as each other and the progesterone receptor. Given the broad effect of these signaling pathways in multiple systems, these new tools will most likely interest readers across biological disciplines.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
The authors conduct a valuable GWAS meta-analysis for COVID-19 hospitalization in admixed American populations and prioritized risk variants and genes. The evidence supporting the claims of the authors is incomplete. The work will be of interest to scientists studying the genetic basis of COVID pathogenesis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study on DNA gyrase that provides further evidence for its mode of action via a double-stranded DNA break and against a recently-proposed alternative mechanism. The evidence presented is solid and is derived from state-of-the-art techniques. The work casts new light on the interactions that occur between gyrase molecules and will be of interest to biochemists and cell biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The important work by Aballay et al. significantly advances our understanding of how G protein-coupled receptors (GPCRs) regulate immunity and pathogen avoidance. The authors provide convincing evidence for the GPCR NPR-15 to mediate immunity by altering the activity of several key transcription factors. This work will be of broad interest to immunologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study characterized the activity of optogenetically identified dopaminergic and GABAergic neurons in the ventral tegmental area in mice performing a memory-guided T-maze task, and shows that subpopulations of dopaminergic and GABAergic neurons exhibited choice-related activity during the delay period, consistent with some previous studies (e.g. Morris et al., 2006, Parker et al., 2016). The authors demonstrate that these delay-period activities were enhanced when the task requires short-term memory. The results are convincing and this study provides important results regarding the nature of delay-period activity in the task.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study used prolonged stimulation of a limb to examine possible plasticity in somatosensory evoked potentials and the role of the blood brain barrier (BBB). The significance is important because thus far BBB modulation of plasticity is mostly in the context of pathology. The revisions greatly improved the paper and the strength of evidence is convincing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study by Yogesh and Keller provides a set of results describing the response properties of cholinergic input and its functional impacts in the mouse visual cortex. They found that cholinergic inputs are elevated by locomotion in a binary manner regardless of locomotor speeds, and activation of cholinergic input differently modulated the activity of Later 2/3 and Layer 5 visual cortex neurons induced by bottom-up (visual stimuli) and top-down (visuomotor mismatch) inputs. The reviewers found that the experiments are cutting-edge and well executed, and the results to be mostly convincing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study examined the mechanisms underlying reduced excitability of ventral tegmental area dopamine neurons in mice that underwent a chronic mild unpredictable stress treatment. The authors identify NALCN and TRPC6 channels as key mechanisms that regulate spontaneous firing of ventral tegmental area dopamine neurons and examined their roles in reduced firing in mice that underwent a chronic mild unpredictable stress treatment. The authors' conclusions on neurophysiological data are supported by multiple approaches and convincing, although the relevance of the behavioral results to human depression remains unclear.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Using state-of-the-art single-nucleus RNA sequencing, Yao et al. investigate the transcriptomic features of neural stem cells (NSCs) in the human hippocampus to address how they vary across different age groups and stroke conditions. The authors report alterations in NSC subtype proportions and gene expression profiles after stroke and an exemplary gene elevated in NSCs and reactive astrocytes in stroke patients. Although the study is valuable, the significance is restricted by technical limitations and the incomplete evidence supporting the main conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important multicenter study provides convincing evidence that the auditory noise emitted during online transcranial ultrasound stimulation (TUS) protocols can pose a considerable confound and is able to explain corticospinal excitability changes as measured with Motor Evoked Potentials (MEP). The findings lay the ground for future studies optimising protocols and control conditions to leverage TUS as a meaningful experimental and clinical tool. A clear strength of the study is the multitude of control conditions (i.e., control sites, acoustic masking, acoustic stimulation). These findings will be of interest to neuroscience researchers using brain stimulation approaches.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study utilizes a virus-mediated short hairpin RNA (shRNA) approach to investigate in a novel way the role of the wild-type PHOX2B transcription factor in critical chemosensory neurons in the brainstem retrotrapezoid nucleus (RTN) region for maintaining normal CO2 chemoreflex control of breathing in adult rats. The solid results presented show blunted ventilation during elevated inhaled CO2 (hypercapnia) with knockdown of PHOX2B, accompanied by a reduction in expression of Gpr4 and Task2 mRNA for the proposed RTN neuron proton sensor proteins GPR4 and TASK2. These results suggest that maintained expression of wild-type PHOX2B affects respiratory control in adult animals, which complements previous studies showing that PHOX2B-expressing RTN neurons may be critical for chemosensory control throughout the lifespan and with implications for neurological disorders involving the RTN. When some methodological, data interpretation, and prior literature reference issues further highlighting novelty are adequately addressed, this study will be of interest to neuroscientists studying respiratory neurobiology as well as the neurodevelopmental control of motor behavior.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study on the effects of fasting on safety learning rests on basic premises and concepts that both reviewers found difficult to follow. If these can be clarified, the findings may well be useful and of some utility for the field of emotional learning as well as experimental clinical psychology. However, the main claims of the study are only partially supported and are therefore incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This potentially valuable study uses classic neuroanatomical techniques and synchrotron X-ray tomography to investigate the mapping of the trunk within the brainstem nuclei of the elephant brain. Given its unique specializations, understanding the somatosensory projections from the elephant trunk would be of general interest to evolutionary neurobiologists, comparative neuroscientists, and animal behavior scientists. However, the anatomical analysis is inadequate to support the authors' conclusion that they have identified the elephant trigeminal sensory nuclei rather than a different brain region, specifically the inferior olive.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study investigated the role of specific proteins in a mouse model of developmental epilepsy. The significance of the work is important because a new mouse model was used to simulate a type of developmental epilepsy. The work is also significant because the deletion of two proteins together, but not separately, improved the symptoms, and data were convincing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors used an innovative modified 10X genomic sequencing method to detect cPCDHg is-forms in pyramidal neurons. With solid electrophysiological recordings, they showed that neurons expressing the same sets of cPCDHg isoforms are less likely to form synapses with each other. These valuable findings confirms previous results and extend our understanding of cPCDHg diversity and neuronal connectivity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study tests the hypothesis that a high autism quotient in neurotypical adults is strongly associated with suboptimal motor planning and visual updating after eye movements, which in turn, is related to a disrupted efference copy mechanism. The implication is that such abnormal behavior would be exaggerated in those with ASD and may contribute to sensory overload - a key symptom in this condition. The evidence presented is convincing, with significant effects in both visual and motor domains, adequate sample sizes, and consideration of alternatives. However, the study would be strengthened with minor but necessary corrections to methods and statistics, as well as a moderation of claims regarding direct application to ASD in the absence of testing such patients.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides a valuable contribution to understanding the neural mechanisms underlying age-related changes in attention and speech understanding. The large dataset (N=105) provides convincing evidence for how speech recognition behaviour and neural tracking of speech separately evolve in about 2 years. The work would be of interest to psychologists, neuroscientists, and audiologists.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This paper explores the relationships among evolutionary and epidemiological quantities in influenza, and presents fundamental findings that substantially advance our understanding of the drivers of influenza epidemics. The authors use a rich set of data sources to gather and analyze compelling evidence on the roles of genetic distance, other influenza dynamics and epidemiological indicators in predicting influenza epidemics. The central findings highlight the significant influence of genetic distance on A(H3N2) virus epidemiology and emphasize the role of A(H1N1) virus incidence in shaping A(H3N2) epidemics, suggesting subtype interference as a key factor. This paper also makes relevant data available to the research community.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important study, the authors develop a promising experimental approach to a central question in ecology: What are the contributions of resource use and interactions in the shaping of an ecosystem? For this, they develop a synthetic ecosystem set-up, a variant of SELEX that allows very detailed control over ecological variables. The evidence is convincing, and the work should be of broad interest to the ecology community, leading to further quantitative studies.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study describes mice with a knock out of the IQ motif-containing H (IQCH) gene, to model a human loss-of-function mutation in IQCH associated with male sterility. The infertility is reproduced in the mouse, making it a compelling model, but some of the mechanistic experiments provide only indirect and thus incomplete evidence for interaction between IQCH and potential RNA binding proteins. With more rigorous approaches, the paper should be of interest to cell biologists and male reproductive biologists working on the sperm flagellar cytoskeleton and mitochondrial structure.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable examination into the role Notch-RBP-J signalling in regulating monocyte subset homeostasis. The data were collected and analysed using solid and validated methodology and can be used as a starting point for exploring the mechanisms involved in RBP-J signalling in non-classical monocytes. The data presented strongly confirm the authors conclusions. However, this paper primarily focuses on providing a description, and additional studies are necessary to fully elucidate the mechanisms through which RBP-J deficiency contributes to the specific increase in Ly6Clo monocyte numbers in both the blood and lungs.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides an important finding that the local abundance of metabolites impacts the biology of the tumor microenvironment by utilizing kidney tumors from patients and adjacent normal tissues. The evidence supporting the claims of the authors is convincing although certain caveats need to be taken into consideration as the authors acknowledged in the paper. The work will be of interest to the research community working on metabolism and on kidney cancer especially.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study is useful as it provides further analysis of previously published data to address which specific genes are part of the masculinizing actions of E2 on female zebra finches, and where these key genes are expressed in the brain. However the data supporting the conclusion of masculinizing the song system are incomplete as the current manuscript is a re-analysis of differential gene expression modulated by E2 treatment between male/female zebra finches without manipulation of gene expression. The conclusions (and title) regarding song learning are not completely supported, with no gene manipulation or song analysis. The use of WGCNA for a question of sex-chromosome expression in species without dosage compensation is considered inadequate. As the experimental design did not include groups to directly test for song learning, and there was also no analysis of song performance, these data were also considered inadequate in that regard.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This landmark study presents MetaPathPredict, a method that uses a stacked ensemble of neural networks to predict the presence or absence of KEGG modules based on annotated features in the genome. The evidence supporting the conclusions is compelling, with a tool that allows for prediction of KEGG modules in sparse gene sequence datasets.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important study, the authors explore the importance of developmental changes in cortico-DRN innervation in the balance of behavioral control in a foraging task. The authors report somewhat convincing evidence that while juvenile mice and adult mice both perform the task, juveniles exhibit more impulsive behavior due to reduced efficacy of cortico-DRN projections. The authors conclude that the development of cortico-DRN (esp mPFC) projections allows 5HT input to promote perseveration (or exploitation) in the balance of behavioral control. However, reviewers raised issues regarding the strength of the evidence without further experiments.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Using single-cell sequencing, high-resolution imaging, and inducible genetic deletion of yolk-sac (YS) derived macrophages, the authors present a useful map of fetal liver macrophage subpopulations and provide important data demonstrating that heterogeneous fetal liver macrophages regulate erythrocyte enucleation, interact physically with fetal HSCs, and may regulate neutrophil accumulation in the fetal liver. These novel findings, although yet incomplete, might provide a solid foundation for further investigating the effects of macrophages on HSC function during fetal hematopoiesis and into adulthood and will be useful for the field of macrophage biology and developmental hematopoiesis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript addresses a non-canonical function of the Class 2 ribonuclease III Drosha in the regulation of adult neural stem cell fate, important for understanding how these cells generate neurons or oligodendrocytic cells.<br /> Overall, this manuscript has many strengths. The authors identify 165 proteins, several of them enriched in neural stem cells, and potentially specific for miRNA dependent or independent Drosha macromolecular complexes.<br /> While the authors provide systematic and convincing evidence on the biochemical interactions among the key players in this cascade, the significance of these interactions for neural stem cell fate determination in vivo remains unclear, as the in vitro cellular systems used to document most of the data reported in the paper may not (fully) represent resident neural stem cells in the adult hippocampus. The in vivo function mediated by Drosha/ Safb1 needs to be substantiated by more evidence and/or complementary approaches.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
The authors observed a positive correlation between FSH and fat mass, as well as a negative association with the appendicular lean mass/fat mass ratio. These valuable findings in male subjects within a hypogonadal setting following Degarelix treatment imply that FSH might function as a predictor, similar to observations in women. However, it's important to note that the analysis is incomplete, as other major confounding factors such as testosterone were not included.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The findings are important and would potentially have theoretical and practical implications outside the field. However the strength of evidence presented was assessed as being incomplete in several respects. Major strengths are (1) genetic factors in facial appearance are of broad interest, and the potential influence of possibly identical factors in a serious congenital disorder (cleft lip/palate) heightens that interest further; (2) proving which single nucleotide variants influence phenotypes, and by what mechanisms, is a major challenge for the field as a whole. The weakness, as assessed, was that in its present form the experimental approach was not sufficiently rigorous to support the conclusions unambiguously.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study presents data suggesting that HFD-induced histone epimutations in sperm may impact the transcriptome of the placenta, thereby contributing to the paternal transmission of paternal metabolic disorders to offspring. Although the hypothesis is interesting and the evidence presented is compelling, more careful statistical analyses and functional validation experiments are needed to further strengthen the conclusion.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In their short technical report, Verma et al. describe how endogenously-tagged dynein and dynactin molecules localize to growing microtubule plus-ends and move processively along microtubules in cells. The authors present solid evidence that cytoplasmic dynein is a processive motor that takes long excursions prior to dissociating from microtubules. However, there are concerns about the robustness of the imaging and analysis protocols, which should be more clearly defined. This is a useful study that will be of interest to cell biologists and biochemists in the motor protein field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The important study uses a new experimental method to provide compelling evidence on how sense- and anti-sense transcription is differentially regulated. The method described here can generally be used to study the alterations in transcription. This paper will be of interest to scientists working in the gene regulation community.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Benner et al. identify OVO as a transcriptional factor instrumental in promoting the expression of hundreds of genes essential for female germline identity and early embryo development. While they provide the dataset that supports their model, the major evidence for the model proposed in this manuscript comes from a separate manuscript by the same group, making the contribution of this manuscript somewhat unclear - that is, the evidence provided in this paper is incomplete to support the proposal of this paper. Overall, the study provides useful information that will help understand the function of ovo during oogenesis and early embryonic development.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study combines molecular genetics and target validation to discover genes involved in obesity and determine their role. It was unanimously agreed that the work is important in terms of significance as it has conceptual and practical implications beyond metabolism, including embryonic and placental development. The strength of evidence is convincing from the use of their forward genetic screen in mice.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors report a previously published method ReplicaDock to improve predictions from AlphaFold-multimer (AFm) for protein docking studies. The level of improvement is modest for cases where AFm is successful; for cases where AFm is not as successful, the improvement is more significant, although the accuracy of prediction is also notably lower. Therefore, the evidence for the ReplicaDock approach being more predictive than AFm is solid for some cases (e.g., the antibody-antigen test case) but incomplete for the more extensive test sets (e.g., those presented in Figure 6). Overall, the study makes a valuable contribution by combining data- and physics-driven approaches.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study provides compelling evidence that the low-cost and open-hardware UC2 microscopy framework can be expanded to enable single-molecule localization microscopy. The authors managed to fit the instrumentation and control thereof in a unit that can be placed in a small stage-top-incubator. Together with providing adapted software for data acquisition and data analysis, the UC.STORM setup can rival the capabilities of comparable commercial instruments at a fraction of the costs.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important collection of over 800 new cell type-specific driver lines will be an invaluable resource for researchers studying associative learning in Drosophila. Thoroughly characterized and well documented, this collection will permit researchers to selectively target neurons that deliver information to, or receive it from, the memory center of the fly brain called the Mushroom Body. Given the wealth of new drivers and the genetic access they provide to over 300 cell types, this compelling work will be of interest not only to researchers studying the mechanisms of associative learning but more generally to those dissecting sensorimotor circuits in the fly nervous system.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable intracranial findings on how two types of natural auditory stimuli – speech and music – are processed in the human brain, and demonstrates that speech and music largely share network-level brain activities, thus challenging the domain-specific processing view. The evidence supporting the claims of the authors is solid but somewhat incomplete: although the data analysis is thorough, the results are robust and the stimuli have ecological validity, considerations such as low-level acoustics control, limitations of experimental design, and in-depth analysis, are lacking. The work will be of broad interest to speech and music researchers as well as cognitive scientists in general.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this study, the authors provide compelling evidence for dysgranular insular involvement in top-down and bottom-up interoceptive processing. Its translational application in ADE patients corroborates the assumption that the mid-insula may indeed be a locus of 'interoceptive disruption' in psychiatric disorders, which underscores the study's high relevance for both body-brain as well as clinical research. The authors' findings are fundamental and substantially advance our understanding of the neural basis of interoception and its putative disruption in psychiatric disorders.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study investigates the environmental drivers behind termite construction, focusing, in particular, on pellet deposition behavior, with the conclusion that termites likely sense curvature indirectly through substrate evaporation. The findings reconcile discrepancies between previous studies through experimental and computational approaches. While the strength of the evidence supporting these claims is compelling, the authors do not discuss how their results affect our understanding of insect nest construction or animal-built structures more broadly.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study substantially advances our understanding of molecular mechanisms driving the phase separation behavior of HP1 paralogs. The evidence supporting the conclusions is convincing, with rigorous and well-designed computational simulations. The work will be of broad interest to biophysicists and biochemists.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
In this valuable study, the authors aimed to identify and characterize intrinsic factors that govern the aging process of bone marrow mesenchymal stromal cells (BMSCs), which are believed to be related to osteoporosis. The authors conclude that PCBP2 is an intrinsic aging factor, the decrease of its expression during aging results in cell proliferation activity decrease and cell senescence. The study provides convincing evidence in support of its conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study describes an investigation of the properties of two heterologously-expressed Nav1.4 channels, with mutations close to the selectivity filter found in tetrodotoxin(TTX)-resistant snakes. The authors studied these mutants by electrophysiological methods, assessed the muscle properties of two types of snakes bearing these mutations, and built homology models of the channels to hypothesize a molecular explanation of the altered channel properties. The methods employed and the results are generally solid, although some aspects would benefit from additional experiments and a more nuanced discussion.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors provide solid data on a functional investigation of potential nucleoid-associated proteins and the modulation of chromosomal conformation in a model cyanobacterium. While the experiments presented are convincing, the manuscript could benefit from restructuring towards the precise findings; alternatively, additional data buttressing the claims made would significantly enhance the study. These valuable findings will be of interest to the chromosome and microbiology fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript describes a valuable method to boost WNT signaling in a tissue-specific manner. The work extends previous data from the authors based on fusing an RSPO2 mutant protein to an antibody that binds ASGR1/2. In the current manuscript, two new antibodies with similar effects are described, that expand this solid approach and provide alternatives for potential future clinical applications. This manuscript will be of interest to all scientists studying protein engineering and cellular targeting.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors examined in detail the epigenetic changes and alterations in the subnuclear arrangement of a unique var gene associated with Plasmodium falciparum placental malaria. Although the observations are mainly confirmatory, the findings are valuable for theoretical considerations and practical applications. Applying the latest methods for the analysis of histone marks, transcriptomics, DNA methylation, and chromosome conformation, the authors provide observations that are convincing, thus making their claims appropriate.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work significantly advances the field of computational modelling of genome organisation through the development of OpenNucleome. The evidence supporting the tool's effectiveness is compelling, as the authors compare their predictions with experimental data. It is anticipated that OpenNucleome will attract significant interest from the biophysics and genomics communities. Providing comprehensive tutorials and documentation is highly encouraged.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors identify a new role for C1ql2 at moss fiber synapses in the hippocampus and find that C1ql2, whose expression is controlled by Bcl11b, controls the recruitment of synaptic vesicles to active zones and is necessary for synaptic plasticity. The data implicating C1ql2 involvement, using numerous viral/genetic rescue approaches, are largely convincing, while the experimental evidence supporting the role of the specific Nrxn3 splice variant is less complete. These data are valuable, building on prior discoveries of how Bcl11b, a disease-relevant molecule, contributes to our understanding of mossy-fiber synaptic development.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors identify a new role for C1ql2 at mossy fiber synapses in the hippocampus and convincingly find that C1ql2, whose expression is controlled by Bcl11b, controls the recruitment of synaptic vesicles to active zones and is necessary for synaptic plasticity. These important results build upon prior discoveries of how Bcl11b, a disease-relevant molecule, contributes to our understanding of mossy-fiber synaptic development.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful strategy in which the authors devised a simple method to attenuate Candida albicans and deliver a live whole-cell vaccine in a mouse model of systemic candidiasis. While a robust candidiasis vaccine will be critical for the field, the study in its current form is incomplete. The strength of the evidence could be augmented with additional experiments to more fully characterize vaccine efficacy and host immune responses.
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arxiv.org arxiv.org
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eLife assessment
This useful study tackles the well-established overflow metabolism issue by applying a coarse-grained metabolic flux model to predict how individual cells execute various energy strategies, such as respiration versus fermentation. While the model's population average is convincing enough to align with experimental observations on overflow metabolism, the overall assertions to enhance our comprehension of this biological phenomenon are incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on the relationship between neuronal dynamics in the thalamus and brain state modulation. The evidence supporting the claims of the authors is incomplete, as additional analyses and better presentation of the data are needed to support the specific role of the mediodorsal nucleus in this phenomenon. The work will be of interest to systems neuroscientists interested in brain dynamics and behavioural states.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript by Agha et al. provides a fundamental understanding regarding the participation of V2a interneurons in generating and patterning the locomotor rhythm. The authors provide convincing and solid evidence regarding the heterogeneity of V2a neurons in their intrinsic and synaptic properties and how these shape their outputs. The manuscript could be much improved by the inclusion of statistical analysis of some of the key data currently presented qualitatively.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents an important set of results illuminating how movement sequences are planned. Using several different behavioural manipulations and analysis methods, the authors present compelling evidence that multiple future movements are planned simultaneously with execution, and that these future movement plans influence each other. The work will be of great interest to those studying motor control.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study, of interest for students of the biology of genomes, uses simulations in combination with published data to examine how many TADs remain after cohesin depletion. The authors suggest that a significant subset of chromosome conformations do not require cohesin, and that knowledge of specific epigenetic states can be used to identify regions of the genome that still interact in the absence of cohesin. The theoretical approaches and quantitative analysis are state-of-the-art, and the data quality and strength of the conclusions are convincing, but it is unfortunately still unclear whether physical boundaries (of domains?) in the model appear to be a consequence of preserved TADs, or whether preserved TADs are caused by the physical boundaries.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study uses a microfluidic method to evaluate the ability of single human white blood cells to produce combinations of cytokines and the evidence that this takes place is solid. The paper highlights polyfunctionality using data that are similar to a prior dataset from the same group. The authors comment that, in analysis of larger panels, single cells rarely make more than 2 or 3 cytokines so that investigation of 3 cytokines at a time is sufficient to investigate this phenomenon. Coupling this approach to other modes of single cell analysis may provide greater insight into what limits simultaneous production of multiple cytokines.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study indicates a significant role for individual let-7 miRNA clusters in regulating generation of Tc17 CD8 cells and emphysema severity in a mouse model. The authors provide convincing evidence for let-7-mediated repression of the transcription factor RORgt and consequent modulation of IL-17-producing CD8 T cells, with correlated data from human emphysema material, though the most effective let-7 cluster/s is/are yet to be tested for its/their ability to modulate disease. The findings, which substantially advance the understanding of roles that let-7 miRNA clusters play in modulating both T cell responses and emphysematous lung disease, will be of interest to T cell and lung disease researchers.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this useful study, the authors analyze droplet size distributions of multiple protein condensates and their fit to a scaling ansatz, highlighting that they exhibit features of first- and second-order phase transitions. The experimental evidence is still incomplete as the measurements were apparently done only at one time point, neglecting the possibility that droplet size distribution can evolve with time. The text would benefit from a connection to and contextualization with the well-understood expectations from the coupling of percolation and phase separation in protein condensates - a phenomenon that is increasingly gaining consensus amongst the community and that emphasizes "liquid-gas" criticality.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study explores the relationship between guanine-quadruplex structures and pathogenicity islands in 89 bacterial strains representing a range of pathogens. Guanine-quadruplex structures were found to be non-randomly distributed within pathogenicity islands and conserved within the same strains. These compelling findings shed light on the molecular mechanisms of Guanine-quadruplex structure-pathogenicity island interactions and will be of interest to all microbiologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study advances our understanding of spatial-temporal cell dynamics both in vivo and in vitro. The authors provide solid evidence for their innovative deep learning-based apoptosis detection system, ADeS, which utilizes the principle of activity recognition. This work will be of broad interest to cell biologists and neuroscientists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript provides a useful reconstruction of the structure of the sirtuin-class histone deacetylase Sirt6 bound to a nucleosome based on cryo-EM observations, and additional characterization of the flexibility of the histone tails in the complex based on molecular dynamics simulations. While similar structures have recently been published elsewhere, this solid study supports the conclusions of those papers and also includes new insights into the potential dynamics of Sirt6 bound to a nucleosome, insights that help explain its substrate specificity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript presents potentially valuable results indicating a plastic enhancement in the vasomotion response of pial cortical arterioles to external stimulation in awake mice using a wide range of external visual stimulation paradigms. The evidence for this interesting effect, with broad potential applications, is, however, incomplete because it is unclear whether the effect is a modulation of vasomotion rather than stimulus-driven hyperaemia and whether it is reversible. These results are relevant for scientists and clinicians interested in the regulation of blood flow in the brain.
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