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eLife Assessment
This important study explores the interplay between gene dosage and gene mutations in the evolution of antibiotic resistance. The authors provide solid evidence to connect proteostasis with gene duplication during experimental evolution in a model system. If the experiments are found to be rigorous and reproducible, then this paper will be of high interest to other researchers studying antibiotic resistance, proteostasis, and bacterial evolution.
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eLife Assessment
This valuable work explores the timely idea that aperiodic activity in human electrophysiology recordings shows changes in response to task events, which may be relevant for performance, and that these changes could be misinterpreted as oscillatory changes. While it is a timely and interesting topic in principle, in the present form, the analytic approach is incomplete. Further, the data offer inadequate support for the conclusions related to theta without demonstrations that the task evokes theta power. Impressions were split, but there was consensus that the Discussion should be tempered and that revisions would improve the manuscript.
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eLife Assessment
Identifying chromatin interactions with high sensitivity and resolution at the genome-wide scale continues to be technically challenging. This study introduces findings based on the improved MNase-based proximity ligation method, MChIP-C, which enables genome-wide measurement of chromatin interactions at single-nucleosome resolution. The evidence presented in this manuscript is convincing, and the technological advancements will be valuable for the study of 3D genome architecture.
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eLife Assessment
This important study showing that sleep deprivation increases functional synapses while depleting silent synapses supports previous findings that excitatory signaling increases during wakefulness. This manuscript focuses in particular on AMPA/NMDA ratios. An interesting, although speculative, aspect of the manuscript is the inclusion of a model for the accumulation of sleep need that is based upon the MEF2C transcription factor but also links to the sleep-regulating SIK3-HDAC4/5 pathway. The authors have clarified some questions raised in the previous review, but the evidence for major claims was still found to be incomplete, requiring additional experimentation.
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eLife Assessment
This useful study sheds light on the species-specific nature of sperm-oocyte interactions by examining sperm binding and penetration of the zona pellucida across various mammalian species. While the evidence remains incomplete, the authors propose that two distinct mechanisms drive mammalian sperm-oocyte recognition and penetration: a specific, zona pellucida (ZP)-mediated mechanism, and a non-specific, oviductal glycoprotein 1 (OVGP1)-mediated mechanism. Upon revision, this study would offer insights to reproductive biologists, potentially improving porcine in vitro fertilization (IVF) - which is particularly susceptible to polyspermy - and enhancing sperm selection processes in human IVF, ultimately leading to better outcomes in assisted reproduction techniques.
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eLife Assessment
This useful study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the methods used are solid, a limitation of the study, as of any other laboratory-based investigation is the challenge of demonstrating how well measures for fitness related to diapause and its recovery correlates with realities encountered during development in the wild.
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eLife Assessment
This study presents an important finding that ant nest structure and digging behavior depend on ant age demographics for a ground-dwelling ant species (Camponotus fellah). By asking whether ants employ age-polyethism in excavation, the authors address a long-standing question about how individuals in collectives determine the overall state of the task they must perform, and their results may prove to be a key consideration for interpreting results from other studies in the field of social insect behavior. While the experimental evidence that the age of the ants and the group composition affect the digging of tunnels is solid, some of the analyses and modeling are seem superfluous, as they do not further support the results or contribute to a deeper understanding of the system.
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eLife Assessment
This study presents a useful investigation of the use of small, de novo-designed protein binding domains (mini-binders) against the Spike protein of SARS-CoV-2 and EGFR, as ligand binding domains on two classes of synthetic receptors, second-generation synNotch (SNIPR) and CAR. The methods and evidence supporting the focused claims are solid. This work will be of interest to synthetic biologists and cell engineers as a starting point to map out the rules for receptor engineering based on mini-binders and ultimately to advance them in biomedical applications.
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eLife Assessment
The authors developed a method to allow a hypothermic agent, neurotensin, to cross the blood-brain barrier so it could potentially protect the brain from seizures and the adverse effects of seizures. The work is important because it is known that cooling the brain can protect it but developing a therapeutic approach based on that knowledge has not been done. The paper is well presented and the data are convincing.
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eLife Assessment
Fallah et al carefully dissect projections from substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) – two key basal ganglia nuclei – to the pedunculopontine nucleus (PPN), a brainstem nucleus that has a central role in motor control. They consider inputs from these two areas onto 3 types of downstream PPN neurons – GABAergic, glutamatergic, and cholinergic neurons – and carefully map connectivity along the rostrocaudal axis of the PPN. Overall, this valuable study provided convincing data on PPN connectivity with two key input structures that will provide a basis for further understanding PPN function.
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eLife Assessment
This useful manuscript reports on a new mouse model for LAMA2-MD, a rare but very severe congenital muscular dystrophy; the knockout mice were generated by removing exon3 in the Lama2 gene, which results in a frameshift in exon4 and a premature stop codon. These animals lack any laminin-alpha2 protein and confirm results from previous Lama2 knockout models. Additionally, this study includes transcriptomics data that might be a good resource for the field. However, the experimental evidence supporting the main claims of the manuscript is incomplete, citations of previous Lama2 null mice studies are lacking, and both data presentation and interpretation need improvement.
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eLife Assessment
This study makes an important contribution by characterizing the role of the exocyst in secretory granule exocytosis in the Drosophila larval salivary gland. The results are solid and lead to the novel interpretation that the exocyst participates not only in exocytosis, but also in earlier steps of secretory granule biogenesis and maturation. However, the authors are urged to provide additional proof that the exocyst subunit knockdowns were effective and to acknowledge the possibility that inactivation of an essential exocytosis component could indirectly affect other parts of the secretory pathway.
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eLife Assessment
In this important study, the authors use zebrafish to examine protein absorption in the gut. Using a combination of imaging and single-cell RNA-seq, they characterize a population of lysosome-rich enterocytes that are essential for protein uptake. They find that the microbiome impacts the ability of these cells to uptake protein. The RNA-seq provides a rich dataset for future functional experiments, which makes a convincing case for the importance of these cells.
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eLife Assessment
This fundamental study substantially advances our understanding of how habitat fragmentation and climate change jointly influence bird community thermophilization in a fragmented island system. The authors provide convincing evidence using appropriate and validated methodologies to examine how island area and isolation affect the colonization of warm-adapted species and the extinction of cold-adapted species. While minor clarifications regarding the definition of fragmentation could further enhance the presentation, the study is of high interest to ecologists and conservation biologists, as it provides insight into how ecosystems and communities respond to climate change.
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eLife assessment
This proof-of-concept study focuses on an A->G DNA base editing strategy that converts CAG repeats to CAA repeats in the human HTT gene, which causes Huntington's disease (HD). These studies are conducted in human HEK293 cells engineered with a 51 CAG canonical repeat and in HD knock-in mice harboring 105+ CAG repeats. The findings of this study are valuable for the HD field, applying state-of-the-art techniques. However, the key experiments have yet to be performed in neuronal systems or brains of these mice: actual disease-rectifying effects relevant to patients have yet to observed, leaving the work incomplete.
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eLife assessment
This study presents a useful examination of the prevalence of interactions between amino acids from different periods of Earth's history and coenzymes. While the premise of this work is well founded, the data lend themselves to alternative interpretations, suggesting that the main conclusions might be incompletely supported by the findings. The work would benefit from the inclusion of additional supplementary data and further analysis. This manuscript would be of interest to evolutionary biologists and biophysicists.
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eLife assessment
This is a valuable study of the mechanisms of microtubule organization in pancreatic islet beta cells that enable optimal insulin secretion. Using a combination of live imaging and photo-kinetic assays in an in vitro culture system, the authors provide solid evidence to demonstrate that kinesin-1-mediated microtubule sliding, which has previously been known from neurons and embryos, is essential for establishing the sub-membranous microtubule band in response to glucose levels in beta cells. The inclusion of an animal model or primary cells, as well as data on the physiological relevance of the finding, would have strengthened the study. The work will be of interest to cell biologists studying cytoskeletal dynamics and organelle trafficking and to translational biologists working on diabetes.
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eLife Assessment
In this valuable paper, the authors created a reporter mouse line in which the Axon Initial Segment (AIS) is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native Ank3 gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordings in vitro, ex vivo, and in vivo, the authors convincingly document that the subcellular scaffold of the AIS and electrophysiological parameters of labeled cells remain unchanged. They further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproducible in vivo labeling of AIS over weeks.
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eLife Assessment
This in several parts valuable study confirms the roles of Dact1 and Dact2, two factors involved in Wnt signaling, during zebrafish gastrulation and demonstrates their genetic interactions with other Wnt components to modulate craniofacial morphologies. Unfortunately, there are several limitations associated with the study, making it challenging to distinguish the primary and secondary effects of each factor, and their roles in craniofacial morphogenesis. The findings of a new potential target of dact1/2-mediated Wnt signaling are potentially of value; however, experimental evidence supporting their functional significance remains incomplete due to inconsistent results and limitations inherent to the overexpression approach.
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eLife Assessment
This important work presents a consolidated overview of the NeuroML2 open community standard and provides convincing evidence for its central role within a broader software ecosystem for the development of neuronal models that are open, shareable, reproducible, and interoperable. A major strength of the work is the continued development over more than two decades to establish, maintain, and adapt this standard to meet the evolving needs of the field. This work is of broad interest to the sub-cellular, cellular, computational, and systems neuroscience communities undertaking studies involving theory, modeling, and simulation.
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eLife Assessment
This useful study uses an intranasal mouse infection model with Streptococcus suis, a gram-positive bacterial pathogen that causes severe losses in pigs around the world. The manuscript provides insights that the capsular polysaccharide, one of the virulence factors of this pathogen, contributes to tissue dissemination and neurotropism in the host. However, the evidence is currently incomplete, and further experiments and careful interpretation of the current results and methods used are necessary to support the conclusions of the manuscript.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
A regression discontinuity analysis finds essentially no effect of 1 additional year of secondary education on brain structure in adulthood. This is a valuable finding that adds to the literature on the impact of education on brain health. The evidence presented is solid, with strengths including methodological novelty as well as principled study design; the impact is, however, limited as the manipulated variable only relates to a single additional year of education (remaining in education to 15 vs 16 years of age). The interpretation is further missing discussion of the healthy volunteer bias of the UK Biobank sample, amplified in the imaging extension.
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eLife Assessment
This is an important study examining the role of conserved PCH-2 protein at different stages of C. elegans meiosis. The authors use elegant molecular genetic approaches to provide convincing evidence to support their claims. The work will be of interest to scientists studying meiosis, DNA recombination, and chromosome segregation.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The manuscript provides important new insights into the mechanisms of statistical learning in early human development, showing that statistical learning in neonates occurs robustly and is not limited to linguistic features but occurs across different domains. The evidence is convincing, although an additional experimental manipulation with conflicting linguistic and non-linguistic information as well as further discussion about the linguistic vs non-linguistic nature of the stimulus materials would have strengthened the manuscript. The findings are highly relevant for researchers working in several domains, including developmental cognitive neuroscience, developmental psychology, linguistics, and speech pathology.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This paper contains valuable ideas for methodology concerned with the identification of genes associated with disease prognosis in a broad range of cancers. However, there are concerns that the statistical properties of MEMORY are incompletely investigated and described. Further, more precise details about the implementation of the method would increase the replicability of the findings by other researchers.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study is important - not only for its comprehensive transcriptomic analysis of the developmental trajectory of syncytiotrophoblasts (STBs), but also for its comparative evaluation of primary human placental tissues and two human trophoblast organoid models. The study highlights the utility of these organoid models in advancing research on human STB biology. The conclusions of this work are supported by compelling analyses and experimental evidence.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study uses robust time-dependent microscopy assays to show that during HIV-1 infection, the viral accessory protein Vif causes cell cycle arrest during metaphase and not G2/M as previously thought. The conclusions are convincing in the context of the immortalized cellular models used, and they serve as a starting point to determine whether Vif-dependent regulation of the cell cycle modulates HIV-1 replication and pathogenesis in more physiologically relevant primary cells or in vivo.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important work investigates the mechanism that underlies the switch between feeding and mating behaviors in the oriental fruit fly, Bactrocera dorsalis. Using a variety of approaches, the authors show that this switch is mediated by the neuropeptide, sulfakinin, acting peripherally through the sulfakinin receptor 1 to regulate the expression of antennal odorant receptors. The evidence is solid in support of the hypothesis that sulfakinin signaling mediates changes in the periphery, although additional experimental details would strengthen these claims.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
Shen et al. present a computational account of individual differences in mouse exploration when faced with a novel object in an open field from a previously published study (Akiti et al.) that relates subject-specific intrinsic exploration and caution about potential hazards to the spectrum of behaviors observed in this setting. Overall, this computational study is an important contribution that leverages a very general modeling framework (a Bayes Adaptive Markov Decision Process) to quantify and interrogate distinct drivers of exploratory behavior under potential threat. Given their assumptions, the modeling results are convincing: the authors are able to describe a substantial amount of the behavioral features and idiosyncracies in this dataset, and their model affords a normative interpretation related to inherent risk aversion and predation hazard "flexibility" of individual animals and should be of broad interest to researchers working to understand open-ended exploratory behaviors.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful study examines the function of the rnc gene, which encodes the RNase III ribonuclease, as it relates to virulence of Salmonella Enteritidis. The authors demonstrate that the rnc gene is markedly upregulated in strains proposed to exhibit high virulence and that the product of the rnc gene promotes the expression of SodA, which contributes to the survival of Salmonella Enteritidis in the face of oxidative stress. The study also suggests that elevated levels of rnc gene expression assist Salmonella Enteritidis in evading immune responses by diminishing the presence of accumulated double-stranded RNA (dsRNA), although the evidence substantiating this and the above assertions remains incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The authors propose that positive biodiversity-ecosystem functioning relationships found in experiments have been exaggerated because commonly used statistical analyses are flawed. To remedy this, a new type of analysis based on a concept of "partial density monoculture yield" is proposed. However, the presented concept and analysis methods are not reproducibly described, do not appear to be complete, and are inadequate for hypothesis testing. The reviewers found that the authors misinterpret current research in the field and made limited efforts to understand or address the reviewer comments on a previous version of the study.
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eLife Assessment
The authors present an important theoretical framework that describes the interplay between liquid-liquid phase separation and protein aggregation within a mean-field model. This work will be of high interest to the biophysics and molecular biology communities, as it will help understand and analyse assembly within biomolecular condensates in cells or in-vitro. Major strengths of this convincing work are the consideration of aggregates with various dimensionality and the possibility for protein gelation.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study provides an experimental paradigm and state-of-the-art analysis method for studying the existence of call types and transition differences among Mongolian gerbil families in a naturalistic environment. The analyses are convincing, with a thorough treatment of the acoustic data and a demonstration of the robustness of the observed effect across days. The work will likely be of interest to the auditory neuroscience and neuroethology communities.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study investigates evolutionary aspects around a single amino acid polymorphism, known to be under long-term balancing selection, in an immune peptide of Drosophila melanogaster. Using alleles with different substitutions, the investigators demonstrate that while one allele provides better survival after systemic infections by a bacterial pathogen, the alternative allele endows its carriers with a longer lifespan under certain conditions. The authors suggest that these contrasting fitness effects of the two alleles contribute to balancing their long-term evolutionary fate. While the work is very interesting, the strength of the provided evidence is still incomplete, and the study would benefit from more rigorous approaches.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This manuscript addresses infections of the parasite Taenia solium, which causes neurocysticercosis (NCC). NCC is a common parasitic infection that leads to severe neurological problems. It is a major cause of epilepsy, but little is known about how the infection causes epilepsy. The authors used neuronal recordings, imaging of calcium transients in neurons, and glutamate-sensing fluorescent reporters. A strength of the paper is the use of both rodent and human preparations. The results provide convincing evidence that the larvae secrete glutamate and this depolarizes neurons. Although it is still uncertain exactly how epilepsy is triggered, the results suggest that glutamate release contributes. Therefore, the paper is a fundamental step towards understanding how Taenia solium infection leads to epilepsy.
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eLife Assessment
This study presents a valuable new method for probing the DNA and proteins associated with targeted genomic elements in cells. The authors present solid evidence that the method can map DNA-DNA interactions for individual loci and can detect enriched proteins at repetitive DNA loci such as telomeres, but benchmarks of the method's resolution and specificity remain incomplete. The methodological details of this study will be of particular interest and utility to chromatin biologists.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable paper describes the crystal structure of a complex of Sld3-Cdc45-binding domain (CBD) with Cdc45, which is essential for the assembly of an active Cdc45- MCM-GINS (CMG) double hexamers at the replication origin. Although the results shown in the paper are of interest to researchers in DNA replication and genome stability, the biochemical analysis of protein-protein interaction and DNA binding is incomplete, and the paper needs additional data and revised discussion.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The aim of this useful study is to investigate the role of semilunar granule cells on memory engrams in the dentate gyrus. Which cells get recruited during contextual memory processing is a timely and significant question. However, evidence for the study's major conclusions is currently incomplete due to caveats in study design, technical limitations, and missing controls.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study offers a valuable genomic dataset, analyses, and functional studies on gonadal sex determination and development. The work addresses long-standing questions regarding the role of the Drosophila sex determination hierarchy, sex chromosomes, and the interaction between the sex determination hierarchy and sex chromosome composition in gonad development. Although this convincing work has been conducted rigorously, the authors missed some key opportunities in their analysis.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study presents important findings that reveal SEPHS2 and VPS37C as new potential drug targets for dasatinib and hydroxychloroquine respectively in addition to confirming known targets of these drugs. The evidence provided is solid, however, some of the claims are not fully supported by the data. To enhance the conclusions and readability, the writing clarity, data analysis and justification of experimental design rationale need to be worked on to enhance the study's interest among chemical biologists, biochemists, and scientists in drug discovery.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable paper shows image correlation spectroscopy (ICS) as a new tool to analyze the clustering of proteins involved in DNA damage response (DDR). The solid evidence presented demonstrates that this method is more sensitive than traditional focus counting, although some of the claims require further contextualization. This new method provides an alternative tool to analyze immuno-stained focus for researchers in the fields of DDR and cell biology.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study provides a comprehensive analysis of how substitutions within the catalytic domain of the tyrosine kinase Met affect its sensitivity to inhibition by ATP-competitive, small molecule inhibitors and provides a mechanistic framework for understanding drug resistance. The evidence supporting the authors' claims is convincing, the data sets are comprehensive, and the analyses are rigorous. This work will be of broad interest to biochemists, structural biologists, and medicinal chemists.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study leverages an impressive and comprehensive longitudinal 16S microbiome dataset from baboons to provide insights regarding the use of a microbiome-based clock to predict biological age, with solid evidence for age-associated microbiome features and environmental and social variables that impact microbiome aging. This study of microbiomes as markers of host age will be relevant to a broad range of researchers, especially those interested in alternatives to measuring biological aging.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This is a valuable report of tracheal terminal cells (TTCs) in Drosophila being immune privileged. The authors demonstrated that TTCs lack the expression of membrane-associated peptidoglycan recognition receptor PGRP-LC, which protects these cells from activating immune pathway or JNK-mediated cell death to maintain TTC homeostasis. While genetic experiments using RNAi and overexpression are mostly convincing, the data on the expression of PGRP-LCx and cell death phenotypes following immune activation are currently incomplete. The work will be of interest to researchers in innate immunity across various model systems.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
Ulcerative colitis (UC) is a chronic gut inflammatory condition affecting the colon in humans. This study uses human samples as well as a mouse model of colitis induced by a chemical, DSS, to investigate the role of an immune marker, CD131, in UC pathogenesis. The study, as presented, is incomplete, as experimental details are lacking, the statistical analyses are deficient, and there is not yet direct evidence for a CD131-mediated mechanism of gut inflammation.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful study presents the first detailed and comprehensive description of brain sulcus anatomy of a range of carnivoran species based on a robust manual labeling model allowing species comparisons. Although the database is recognized and the method for reconstructing cortical surfaces is convincing, the evidence supporting the conclusions is incomplete due to the lack of appropriate quantitative measurements and analyses. Considering additional specimens to assess intraspecies variations, as well as exploring the functional correlates of interspecies differences would increase the scope of the study. Setting an instructive foundation for comparative anatomy, this study will be of interest to neuroscientists and neuroimaging researchers interested in that field, as well as in brain morphology and sulcal patterns, their phylogeny, and ontogeny in relation to functional development and behaviour.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important paper by Lechler and colleagues describes the transcriptomic signature and fate of intermediate cells (ICs), a transient and poorly defined embryonic cell type in the skin. The paper convincingly shows through lineage tracing that ICs are granular and not spinous cell precursors, and through ectopic expression in vivo, that cell contractility, a mechanical feature of ICs, lies upstream of differentiation.
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- Oct 2024
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study shows that eliminating a large portion of the principal neurons in the mammalian olfactory bulb does not affect the initial establishment of the circuit but has an impact on its maintenance. The strength of the paper is that the anatomical changes induced by genetic ablation of neurons are clear-cut. There is solid support for the findings, with a description of the structural and behavioral effects of ablating the majority of M/T neurons.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents a valuable finding on a potential signaling pathway responsible for the direct effects of nicotine on intestinal stem cell growth and tumorigenesis. The evidence supporting the claims of the authors is solid. This research will be of interest to medical biologists specializing in intestinal tumors.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study provides an important re-evaluation of modality-specific information processing in the thalamus of trained mice. Using an elegant task design that probes competing tactile and visual stimuli, the authors present compelling evidence that behavioral training reshapes the sensitivity of higher-order thalamic nuclei. Despite the powerful task design and the significance of the main findings, the origin of the cross-modal responses remains an open question and requires future investigation.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This paper addresses an important topic (normative trajectory modelling), seeking to provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on a pre-trained population normative model. The evidence provided for the new methods is, however, incomplete, with the simulations validating the method needing to be extended.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This article presents valuable findings on the impact of climate change on odonates, integrating phenological and range shifts to broaden our understanding of biodiversity change. The study leverages extensive natural history data, offering a combined analysis of temporal trends in phenology and distribution and their potential drivers. The support for the findings is solid, though additional clarification regarding the methods and alternative sensitivity analyses could make the conclusions stronger.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study poses an important step forward in understanding the brain-network embedding of beta oscillations. The study advances our circuit-level understanding of the pathophysiology associated with dopaminergic alterations in psychiatric or neurological disorders. The study provides compelling evidence that beta oscillations across the neocortex and basal ganglia map onto shared functional and structural networks that show significant positive correlations with dopamine receptors.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study substantially advances our understanding of nocturnal animal navigation and the ways that animals use polarized light. The evidence supporting the conclusions is convincing, with elegant behavioural experiments in actively navigating ants. The work will be of interest to biologists working on animal navigation or sensory ecology.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study presents a statistical framework for the analysis of photometry signals and provides an open-source implementation. The evidence supporting the benefits of the presented functional mixed-effect modeling analysis as opposed to 1) summary statistics and 2) other pointwise regression models is convincing with a thorough comparison with other methods and datasets. This work will be of great interest to researchers using not only fiber photometry, but other time-series data such as calcium imaging or electrophysiology data, and wanting to implement trial-by-trial temporal analysis, taking also into account variability within the dataset.
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eLife Assessment
This valuable study is a companion to a paper introducing a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs). The evidence that recurrent SNVs or CDNs are common in true cancer driver genes is convincing, with more limited evidence that many more undiscovered cancer driver mutations will have CDNs, and that this approach could identify these undiscovered driver genes with about 100,000 samples.
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eLife Assessment
This important paper introduces a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs), primarily based on single nucleotide variant (SNV) frequencies. A variety of solid approaches indicate that a mutation recurring three or more times is more likely to reflect selection rather than being the consequence of a mutation hotspot. The method is rigorously quantitative, though the requirement for larger datasets to fully identify all CDNs remains a noted limitation. The work will be of broad interest to cancer geneticists and evolutionary biologists.
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arxiv.org arxiv.org
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eLife Assessment
The authors proposed an important novel deep-learning framework to estimate posterior distributions of tissue microstructure parameters. The method shows superior performance to conventional Bayesian approaches and there is convincing evidence for generalizing the method to use data from different protocol acquisitions and work with models of varying complexity.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The manuscript reports a valuable finding on dopamine receptor-mediated regulation, the firing of striatal cholinergic interneurons in both healthy and dyskinesia states, identifying that Kv1 channels play a key role in the burst-dependent pause. The study presents solid experimental data, and provides additional mechanistic insights into how burst activity in SCINs leads to a subsequent pause, highlighting the involvement of D1/D5 receptors. This work will be of interest to researchers studying the pathological mechanisms of Parkinson's disease.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study introduces a novel method for estimating spatial spectra from irregularly sampled intracranial EEG data, revealing cortical activity across all spatial frequencies, which supports the global and integrated nature of cortical dynamics. The study showcases important technical innovations and rigorous analyses, including tests to rule out potential confounds; however, the lack of comprehensive theoretical justification and assumptions about phase consistency across time points renders the strength of evidence incomplete. The dominance of low spatial frequencies in cortical phase dynamics continues to be of importance, and further elaboration on the interpretation and justification of the results would strengthen the link between evidence and conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The authors show MRI relaxation time changes that are claimed to originate from cell membrane potential changes. This would be very important if true because it may provide a mechanism whereby membrane potential changes could be inferred noninvasively. However, the membrane potential manipulations applied here will induce cell swelling, and cell swelling has been previously shown to affect relaxation time. Therefore, the claim that the relaxation time changes observed in this manuscript are due to cell membrane potential changes is inadequately supported.
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eLife Assessment
The authors have provided a valuable addition to the literature on large-scale electrophysiological experiments across many labs. The evidence that the authors provided was incomplete - while some comparisons with analyses outside of the manuscript's approaches were provided, a more complete manuscript would have compared with alternative standardized analyses. In particular, alternative spike sorting metrics and the alternative of GLM-based analysis of data would have made the interpretation of the results clearer.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
In this paper, Seon and Chung investigate changes in own risk-taking behavior, when they are being observed by a "risky" or "safe" player. Using computational modeling and model-informed fMRI, the authors present solid evidence that participants adjust their choice congruent with the other player's type (either risky or safe). The conclusions of the paper are an important contribution to the field of social decision-making as they show a differentiated adjustment of choices and not just a universally riskier choice behavior when being observed as has been claimed in previous studies.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
In this useful study, the authors tested a novel approach to eradicating HIV reservoirs by constructing a herpes simplex virus (HSV)-based therapeutic vaccine and evaluating efficacy in experimental infections of chronically SIV-infected, antiretroviral therapy (ART)-treated macaques. While mean viremia at rebound was lower in the HSV vaccine-treated group, the evidence presented appears to be incomplete, as the group size was small and the viral load at rebound was highly variable. This is a revised paper, but the support for the conclusions, particularly the effect of the HSV-vectored therapeutic vaccine on the SIV reservoir in the SIV-infected macaques, remains limited.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful study reports on the impact of antibiotic pressure on the genomic stability of the mc2155 strain of Mycobacterium smegmatis, a model for Mycobacterium tuberculosis. The findings of the study indicate that exposure to antibiotics did not lead to the development of new adaptive mutations in controlled laboratory environments, challenging the notion that antibiotic resistance arises from drug-induced microevolution. The genomic analysis provides detailed insights into the stability of M. smegmatis following exposure to standard TB treatment antibiotics, and the evidence suggesting that antibiotic pressure does not contribute to the emergence of new adaptive mutations is solid.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
Yamamoto and Matano provide convincing evidence that a G63E CD8+ T-cell escape mutation in the accessory viral protein Nef facilitates the induction of neutralizing antibody (nAb) responses in rhesus macaques infected with SIVmac239. Functional analyses support that this mutation specifically impairs Nef`s ability to stimulate PI3K/Akt/mTORC2 signalling. This important study suggests that the accessory viral Nef protein impairs B cell function and effective humoral immune responses and is of interest for researchers and physicians interested in HIV/AIDS and vaccine development.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study presents a significant methodological advance by leveraging previously discarded, unmapped DNA sequence reads to estimate pest infestation loads across plant accessions, and map variation in these apparent pest loads to defense genes. The bioinformatics approach is compelling, and the results should bear broad implications for phenotype-genotype prediction, especially regarding the use of unmapped reads for GWAS.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study examines the effects of NFKB2 mutations on pituitary gland development through hypothalamic-pituitary organoids. The evidence supporting the main conclusions is solid, although analysis of additional clones to exclude inter-clone variability would strengthen the conclusions. This is a revised study, but insight into the mechanism of action of NFKB2 during pituitary development is incomplete. This work will be of interest to endocrinologists and biologists working on pituitary gland development and disease.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This work identifies the molecular function of an orphan human transporter, SLC35G1, providing convincing evidence that this protein is involved in intestinal citrate absorption. This work provides important insight into transporter function and human physiology.
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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 compelling, with a careful application of machine learning methods, validated by mass spectrometry-based lipid analysis 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 provides convincing evidence that developing neurons in the neocortex regulate glial cell development. The data demonstrates that the transcription factor FOXG1 negatively regulates gliogenesis by controlling the expression of a member of the FGF ligand family and by suppressing the receptor for this ligand in developing neurons. This study leads to a new understanding of the cascade of events regulating the timing of glial development in the neocortex.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This manuscript establishes a mathematical model to estimate the key parameters that control the repopulation of planarian stem cells after sublethal irradiation as they undergo fate-switching as part of their differentiation and self-renewal process. The findings are valuable for future investigation of stem cell division in planarians. The methods are solid, integrating modeling with perturbations of key transcription factors known to be critical for cell fate decisions, but the authors have only shown that this is the case for a small number of stem cell types.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important work attempts to establish a causal link between neurotrophin signaling and experience-induced structural plasticity in dopaminergic circuits in the adult fly brain, a topic of broad interest to the neuroscience community. While the authors provide solid evidence for the role of this signaling in regulating the structure and synapses of dopaminergic circuits, the evidence for a direct link between neurotrophin signaling and experience-induced structural plasticity remains incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents important findings that will allow for a better understanding of the role of mitochondria in behaviours of C. elegans. There is convincing evidence that mutants in a subunit of the mitochondrial calcium uniporter (MCU-1) show defects in olfactory adaptation and this gene regulates neuropeptide secretion and allows for behavioural modulation in C. elegans. However, the evidence that mitochondrial calcium modulates odour-based behaviour in C. elegans is incomplete. This claim would require support from calcium imaging in conditioned WT and mcu-1 animals. This work would be of interest to labs working on behaviours across phyla.
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eLife Assessment
This manuscript presents a valuable minimal model of habituation which is quantified by information theoretic measures. The results here could be of use in interpreting habituation behavior in a range of biological systems. However, the evidence presented is incomplete and would benefit from more rigorous approaches and a fuller accounting of the hallmarks of habituation.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The paper describes a novel approach for inferring features of synaptic networks from recordings of individual cells within the network. The paper will be a valuable contribution to those studying central pattern generators, including those involved in respiration. However, the theoretical approach to drawing inferences regarding the underlying synaptic currents is incomplete as it relies on unsupported simplifying assumptions.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study by Power and colleagues is important as elucidating the dynamic immune responses to photoreceptor damage in vivo potentiates future work in the field to better understand the disease process. However the evidence supporting the authors' claims is incomplete. The current manuscript would further benefit from validating their conclusion with additional supporting data from earlier time points (6 to 12 hours), additional markers to characterize neutrophils, more n numbers to strengthen the analysis, and evaluation of immune responses in mice with a stronger laser ablation, as well as further evidence to distinguish resident microglia vs. infiltrating macrophages due to the BRB breakdown. The authors should reorganize the article to make it easier and more straightforward to follow.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful study combines multiplexed RNA-FISH with downstream analyses and modelling to describe novel dendritic mRNA distribution and behavioural features. Although the downstream analysis pipeline is novel, the results from this study are as of yet incomplete. Further inclusion of key missing controls, further work to better assess the physiological relevance, or additional modelling to expand their conclusions would make this work of greater interest to RNA biologists.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
Abdelmageed et al. demonstrate POLK expression in neurons and report an important observation that POLK exhibits an age-dependent change in subcellular localization, from the nucleus in young tissue to the cytoplasm in old tissue. Despite potentially exciting and novel findings, many of the authors' claims are provided with incomplete support (e.g. lack of validation of the POLK antibody, characterization of the subcellular compartment, etc).
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study is useful for advancing understanding of spinal cord injuries, but it presents inadequate evidence due to the use of multiple datasets. Data were collected from different models of spinal cord injury, various regions of the spinal cord, and an iPSC model, with the differences between these models making it difficult to draw reliable conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
Barzó et al. assessed the electrophysiological and anatomical properties of a large number of layer 2/3 pyramidal neurons in brain slices of human neocortex across a wide range of ages, from infancy to elderly individuals, using whole-cell patch clamp recordings and anatomical reconstructions. This large data set represents a valuable contribution to our understanding of how these properties change across the human lifespan, and although the results presented are convincing, analyzing the data by absolute age rather than age ranges as well as clarifying the methods used and some of the statistical approaches applied would strengthen the conclusions. The analysis of spine density requires additional biological replicates to support the conclusions stated. These data strengthen our understanding of how these properties change with age and will contribute to building more realistic models of human cortical function.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
Oor and colleagues report the potentially independent effects of the spatial and feature-based selection history on visuomotor choices. They outline compelling evidence, tracking the dynamic history effects based on their extremely clever experimental design (urgent version of the search task). Their finding is of fundamental significance, broadening the framework to identify variables contributing to choice behavior and their neural correlates in future studies.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The manuscript explores how bacterial evolution in the presence of lytic phages modulates b-lactams resistance and virulence properties in methicillin-resistant Staphylococcus aureus (MRSA). The work is useful as it identifies underlying mutations that may confer sensitivity to b-lactams and alter virulence properties. While the findings are generally convincing, additional experiments linking how particular mutations regulate phenotypic changes are required to improve the work mechanistically.
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www.medrxiv.org www.medrxiv.org
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eLife Assessment
This study investigates a dietary intervention that employs a smartphone app to promote meal regularity, which may be useful. Despite no self-reported changes in caloric intake, the authors report significant weight loss for the relatively short duration of only 6 weeks. While the concept is very interesting and deserves to be studied due to its potential clinical relevance, the study's rigor needs to be improved upon and is currently considered incomplete, notably the reliance on self-reported food intake, a highly unreliable way to assess food intake. Additionally, the study theorizes that the intervention resets the circadian clock, but the study needs more reliable methods for assessing circadian rhythms, such as actigraphy. Further, if this restrictive dietary intervention has any more promise in achieving long-term weight loss than the myriad other restrictive diets, it remains to be tested.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important revised report describes the control of the activity of the RNA-activated protein kinase, PKR, by the Vaccinia virus K3 protein. A strength of the manuscript is the powerful combination of a classic yeast-based assay with high-throughput sequencing and its convincing experimental use to characterize large numbers of PKR variants, now with improved controls for potential biases. A minor current limitation that the authors may address in the future is the scope of the screen in terms of the segments of PKR included.
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www.medrxiv.org www.medrxiv.org
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eLife Assessment
This study retrospectively analyzed clinical data to develop a risk prediction model for pulmonary hypertension in high-altitude populations. The evidence is solid, and the findings are useful and hold clinical significance as the model can be used for intuitive and individualized prediction of pulmonary hypertension risk in these populations.
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www.medrxiv.org www.medrxiv.org
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eLife Assessment
The authors analyze a comprehensive cohort of human plasma samples to identify an extracellular vesicles protein signature for early diagnosis of pancreatic cancer. The application of liquid biopsies is valuable, and the work addresses a key clinical problem as pancreas cancer is often diagnosed in late stages. The strength of evidence is solid. Altogether, this work supports the potential use of extracellular vesicles in clinical settings, with promising value to scientists and clinicians.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This fundamental work by Mäkelä et al. presents compelling experimental evidence supported by a theoretical model that the amount of chromosomal DNA can become limiting for the total rate of mRNA transcription and consequently protein production in the model bacterium Escherichia coli. The work is based on a mutant that allows inhibition of DNA replication while following growth at the single-cell level due to cell filamentation. The work significantly advances our understanding of growth and of the central dogma, and will be of considerable interest within both systems biology and microbial physiology.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study uses dynamic metabolic models to compare perturbation responses in a bacterial system, analyzing whether they return to their steady state or amplify beyond the initial perturbation. The evidence supporting the emergent properties of perturbed metabolic systems to network topology and sensitivity to specific metabolites is solid, although the authors do not explain the origin of some significant inconsistencies between models.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This fundamental study generated a single cell atlas of mouse periosteal cells under both steady-state and fracture healing conditions to address the knowledge gap regarding cellular composition of the periosteum and their responses to injury. Based on convincing transcriptome analyses and experimental validation, the authors identified the injury induced fibrogenic cell (IIFC) as a characteristic cell type appearing in the bone regeneration process and proposed that the IIFC is a progenitor undergoing osteochondrogenic differentiation. This study will provide a significant publicly accessible dataset to reexamine the expression of the reported periosteal stem and progenitor cell markers.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This manuscript describes an important study of a new lipid-mediated regulation mechanism of adenylyl cyclases. The biochemical evidence provided is convincing and will trigger more research in this mechanism. This manuscript will be of interest to all scientists working on lipid regulation and adenylyl cyclases.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The neurotrophic factor Neuritin can moderate T-cell tolerance and immunity through both regulatory T (Treg) and effector T cells, promoting Treg cell expansion and suppression while dampening effector T cells to mediate the inflammatory response. Neuritin expression influences the membrane potential, ion channels, and nutrient transporter expression patterns of CD4+ T cells, contributing to differential metabolic states in Treg and effector T cells. These findings are solid and important for understanding immune regulation involving Treg cells and effector T cells.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
In this valuable study, Li and others identified cell membrane receptors for juvenile hormone (JH), a terpenoid hormone in insects that regulates their development and reproduction. While intracellular receptors for JH have been well characterized, membrane receptors for JH remained elusive for many years. Although the authors provide solid evidence to indicate that the receptor tyrosine kinases they identified bind to JH in vitro and induce non-genomic responses in cultured cells, their loss-of-function phenotypes are not consistent with known JH functions, so additional work is required to define physiological roles of these receptors.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important work presents data showing that all non-proneural phenotypes of the Inhibitor of DNA binding (Id) protein Emc are mediated through inappropriate nonapoptotic caspase activity. Using the developing Drosophila retina as a model the authors show that Emc acts by transcriptionally regulating the Death-Associated Inhibitor of Apoptosis 1 (diap1) gene, which impacts on Notch signaling by caspase-dependent increase of Delta protein. These are compelling findings, interesting for the caspase/apoptosis field as they add more non-apoptotic functions of caspases to the list, as well as for the Id field, which examines how Id proteins inhibit cell differentiation.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study, which will be of interest to those studying the evolution and maintenance of antibiotic resistance, addresses the hypothesis that antibiotic resistance arising de novo during treatment will carry a higher fitness cost and will revert to susceptibility more readily than resistance that has been transmitted between hosts. There are, however, concerns that the 'putatively transmitted isolates' in this study do not necessarily represent resistant isolates that have been transmitted between hosts. The support for the central claim of different patterns of reversion between isolates with de novo resistance and putatively transmitted resistant isolates is currently incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents valuable data on the increase in individual differences in functional connectivity with the auditory cortex in individuals with congenital/early-onset hearing loss compared to individuals with normal hearing. The evidence supporting the study's claims is convincing, although additional work using resting-state functional connectivity and further links to how the results align with the underlying biology could have further strengthened the study. The work will be of interest to neuroscientists working on brain plasticity and may have implications for the design of interventions and compensatory strategies.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study describes the application of machine learning and Markov state models to characterize the binding mechanism of alpha-Synuclein to the small molecule Fasudil. The results suggest that entropic expansion can explain such binding. However, the simulations and analyses in their present form are inadequate.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
So et al. present an optimized protocol for single-nuclei RNA sequencing of adipose tissue in mice, ensuring better RNA quality and nuclei integrity. The authors use this protocol to explore the cellular landscape in both lean and diet-induced obese mice, identifying a dysfunctional hypertrophic adipocyte subpopulation linked to obesity. The data analyses are solid, and the findings are supported by the evidence presented. This study provides valuable information for the field of adipose tissue biology and will be particularly helpful for researchers using single-nuclei transcriptomics in various tissues.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The specific questions taken up for study by the authors-in mice of HDAC and Polycomb function in the context of vascular endothelial cell (EC) gene expression relevant to the blood-brain barrier, (BBB)-are potentially useful in the context of vascular diversification in understanding and remedying situations where BBB function is compromised. The strength of the evidence presented is incomplete, and to elaborate, it is known that the culturing of endothelial cells can have a strong effect on gene expression.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study investigates the role of the Cadherin Flamingo (Fmi) in cell competition in developing tissues in Drosophila melanogaster. The findings are valuable in that they show that Fmi is required in winning cells in several competitive contexts. The evidence supporting the conclusions is solid, as the authors identify Fmi as a potential new regulator of cell competition, however, they don't delve into a mechanistic understanding of how this occurs.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The authors have reported an important study in which they use a double-blind design to explore pharmacological manipulations in the context of a behavioral task. While the sample size is small, the use of varied methodology, including electrophysiology, behavior, and pharmacology, makes this manuscript particularly notable. Overall, the findings are solid and motivate future explanations into the relationships between acetylcholine and motivation.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The paper reports the important discovery that the mouse dorsal inferior colliculus, an auditory midbrain area, encodes sound location. The evidence supporting the claims is solid, being supported by both optical and electrophysiological recordings. The observations described should be of interest to auditory researchers studying the neural mechanisms of sound localization and the role of noise correlations in population coding.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful work reveals differential activity to food and shock outcomes in central amygdala GABAergic neurons. Solid evidence supports claims of unconditioned stimulus activity that changes with learning. However, the evidence regarding claims related to valence or salience signaling in these neurons is inadequate. This work will be of interest to neuroscientists studying sensory processing and learning in the amygdala.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study reveals that Excitatory Amino Acid Transporters play a role in chromatic information processing in the retina. The combination of (double) mutants, behavioral assays, immunohistochemistry, and electroretinograms provides solid evidence supporting the appropriately conservative conclusions. The work will be of interest to neurobiologists working on color vision or retinal processing.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study explores the neural basis for a well known auditory illusion, often utilized in movie soundtracks, in which a sequence of two complex tones can be perceived as either rising or falling in pitch depending on the context in which they are presented. Convincing single-neuron data and analyses are presented to show that correlates of these pitch-direction changes are found in the ferret primary auditory cortex. While these findings provide an interesting link between cortical activity and perception, the manuscript could be clearer on the wider implications of the failure of traditional decoding models to account for these results.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This revised version of the study is important, showing that age-related gut microbiota modulate uric acid metabolism through the NLRP3 inflammasome pathway and thereby regulate susceptibility to age-related gout. Several experimental approaches (mechanistic insights) and methods (data quality) are still incomplete. If strengthened, this paper would be of broad interest to researchers working on gout and the microbiota.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This article describes a novel mechanism allows Drosophila to combat enteric pathogens while also preserving the beneficial indigenous microbiota. The authors provide compelling evidence that oral infection of Drosophila larvae by pathogenic bacteria activate a valve that traps the intruders in the anterior midgut, allowing them to be killed by antimicrobial peptides. This is an important finding revealing a new mechanism of host defense in the gut of insects.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
These authors present findings on the role of the sirtuins SIRT1 and SIRT3 during Salmonella Typhimurium infection. This valuable study 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 disagreed on the strength of the evidence to support the claims. Although one reviewer found the strength of the evidence convincing, the other found that it was incomplete, and that the main claims are only partially supported, as can be seen from the public reviews.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study proposes that protein secreted by colon cancer cells induces cells with Paneth-like properties that favor colon cancer metastasis. The evidence supporting the conclusions is solid but the study would benefit from more direct experiments to test the functional role of Paneth-like cells and to monitor metastasis from colon tumors. The work will be of interest to researchers studying colon cancer metastasis.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful study presents a novel microscopy technique called "Expansion Tiling Light Sheet Microscopy" and an accompanying computational pipeline for the faster collection and analysis of 3D volumetric images in animals like planarians. This approach produces beautiful 3D microscropy images and is solid on a technical level. However, due to the use of antibody reagents that visualize many – but not all – neurons and muscle subtypes, the evidence for the biological conclusions in this study remains incomplete. With the claims appropriately contextualized, this paper will be of interest to cell biologists working on imaging and analyzing whole animals.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study provides a valuable perspective on visual cortex architecture by identifying two cortical gradients that change across the lifespan and have distinct functional and structural features. The first gradient captures well-mapped variations in cortical thickness and myelination markers from early sensory to higher-order cortex, while the second gradient shows divergence in these measures with a more localized structure, notably predicting a previously unknown cluster of visual field maps in the anterior temporal lobe. The large-scale lifespan data are compelling, but the evidence overall is incomplete with key questions around methodical checks and implementation, the standard of evidence for the new visual maps, and how the gradient model relates to sharp tissue boundaries parcellating the cortex.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The authors present three valuable transgenic models carrying three representative exon deletions of the dystrophin gene. The findings are supported by rigorous biochemical assays and state-of-the-art microscopy methods, although the evidence, while overall solid, is only partially developed, and some points could be improved.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study analyzes a cohort of small intestine neuroendocrine tumors, and the description of tumor-intrinsic programs that govern such rare cancers is felt to be valuable. The methods are for the most part felt to be solid, however, some broad concerns were raised that the possible separation of samples by a program may be impacted by fresh versus frozen sequencing. Similarly, the heterogeneity of the SiNET tumor microenvironment is unclear given a mixing of subtypes and the proliferation of NE and immune cells in SiNET could be influenced by technical factors. Recommendations were made to extend these data with other published datasets of SiNET tumors, expanding technical clarity and details, and validating findings using cell lines/PDX if available.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study by Chen and Phillips provides evidence for a dynamic switch in the small RNA repertoire of the Argonaute protein NRDE-3 during embryogenesis in C. elegans. The work is supported by solid experimental data, although some conclusions regarding the functional role of specific RNA granules remain uncertain. Nevertheless, this study offers valuable insights into RNA regulation and developmental biology, with broader implications for understanding small RNA pathways in other systems.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents valuable findings on changes in neuronal alpha activity elicited by prolonged pain in healthy human participants. The evidence supporting the claims of the authors, however, is incomplete and would benefit from clarifications of analytical strategies, additional statistical analyses, and shaping of the interpretations. With the methodological and interpretative parts strengthened, the work will be of interest to neuroscientists investigating the brain mechanisms of pain to identify new approaches to pain treatment
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eLife Assessment
The study is a valuable addition to the field, showing how particulate matter may be acting via nociceptor neurons towards neutrophilic asthma exacerbations. The solid evidence for the role of a nociceptive pathway in model systems is relevant to human asthma in its current form but would be further strengthened by mechanistic insights. This would be particularly relevant to further translational research towards blocking the exacerbating effect of air pollution on asthma.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study presents the first identification of the odorant receptor for the trail pheromone in termites. The evidence supporting the conclusions is compelling, with state-of-the-art neurophysiological and genetic methods. The work will be of broad interest in multiple disciplines, such as entomology, chemical ecology, and sensory physiology.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study builds on previous work by the authors by presenting a potentially key method for correcting optical aberrations in GRIN lens-based micro endoscopes used for imaging deep brain regions. By combining simulations and experiments, the authors show that the obtained field of view is significantly increased with corrected, versus uncorrected microendoscopes. The evidence supporting the claims of the authors is solid, although some aspects of the manuscript should be clarified and missing information provided. Because the approach described in this paper does not require any microscope or software modifications, it can be readily adopted by neuroscientists who wish to image neuronal activity deep in the brain.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study provides valuable insight into the biological significance of SARS-CoV-2 by using a series of computational analyses of viral proteins. While evidence is solid, it is obscured by a lack of clarity about the objectives of the analyses and in the overall writing of the article. The study will be impactful to the researchers in the field but will benefit from improved presentation.
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eLife Assessment
This important paper employs multiple experimental approaches and presents evidence that changes in membrane voltage directly affect ERK signaling to regulate cell division. This result is relevant because it supports an ion channel-independent pathway by which changes in membrane voltage can affect cell growth. The reviewers point out that some experimental results and interpretations are compelling, but the strength of evidence is incomplete and additional experiments are needed to rule out other possible interpretations of the data.
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Editors Assessment:
This paper reports the establishment of the International Cannabis Genomics Research Consortium (ICGRC) web portal leveraging the open source Tripal platform to enhance data accessibility and integration for Cannabis sativa (Cannabis) multi-omics research. With the aim of bringing together the wealth of publicly available genomic, transcriptomic, proteomic, and metabolomic data sets to improve cannabis for food, fiber and medicinal traits. Tripal is a content management system for genomics data, presenting a ready-to-use specialized ‘omics modules for loading, visualization, and analysis, and is GMOD (Generic Model Organism Database) standards-compliant. The paper explaining how this was put together, what data and features are available, and providing a case study for other communities wanting to create their own Tripal platform. Covering their setup and customizations of the Tripal platform, and how they re-engineered modules for multi-omics data integration, and addition of many other custom features that can be reused. Peer review fixed a few minor bugs and added clarifications on how the platform will be updated.
*This evaluation refers to version 1 of the preprint *
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eLife Assessment
This important work advances our understanding of parabrachial CGRP threat function. The evidence supporting CGRP aversive outcome signaling is solid, while the evidence for cue signaling and fear behavior generation is incomplete. The work will be of interest to neuroscientists studying defensive behaviors.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents a valuable finding on the identification of a complex consisting of NHE1, hERG1, β1/integrin and NaV1.5 on the membrane of breast cancer cells. The evidence supporting the claims of the authors is somewhat incomplete. The inclusion of clarification of some experimental design and the amendment of cropping Western blot data 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
SGLT2 inhibitors (SGLT2i) have assumed important roles in reducing cardiovascular risk, particularly in those with diabetes. It has become appreciated that its protective effects are likely beyond their ability to lower blood sugar levels. This research presents a novel approach to studying the SGLT2i mechanism of action which is yet to be fully elucidated.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study provides a valuable new perspective on how motor learning occurring in one state generalizes to new states (for example, a different limb posture). The proposed model improves upon previous theories in its ability to predict patterns of generalization, but evidence supporting this specific proposed model over possible alternatives is incomplete. The newly proposed theory appears promising but would be more convincing if its conceptual and theoretical basis were clearer and more rigorously derived.
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www.medrxiv.org www.medrxiv.org
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eLife Assessment
This important work advances our understanding of factors influencing early childhood development. The large sample size and methodology applied make the findings of this study convincing; however, support for some of the claims made by the authors is incomplete. The work will be of interest to researchers in developmental science and early childhood pediatrics.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important work addresses the role of Marcks/Markcksl during spinal cord development and regeneration. The study is exceptional in combining molecular approaches to understand the mechanisms of tissue regeneration with behavioural assays, which is not commonly employed in the field. The data presented is convincing and comprehensive, using many complementary methodologies.
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www.biorxiv.org www.biorxiv.org
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Editors Assessment:
PhysiCell is an open source multicellular systems simulator for studying many interacting cells in dynamic tissue microenvironments. As part of the PhysiCell ecosystem of tools and modules this paper presents a PhysiCell addon, PhysiMeSS (MicroEnvironment Structures Simulation) which allows the user to accurately represent the extracellular matrix (ECM) as a network of fibres. This can specify rod-shaped microenvironment elements such as the matrix fibres (e.g. collagen) of the ECM, allowing the PhysiCell user the ability to investigate physical interactions with cells and other fibres. Reviewers asked for additional clarification on a number of features. And the paper now clear future releases will provide full 3D compatibility and include working on fibrogenesis, i.e. the creation of new ECM fibres by cells.
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 paper demonstrates that different PKA subtypes exhibit distinct subcellular localization at rest in CA1 neurons. The authors provide compelling evidence that when all tested PKA subtypes are activated by norepinephrine, catalytic subunits translocate to dendritic spines but regulatory subunits remain unmoved. Furthermore, PKA-dependent regulation of synaptic plasticity and transmission can be supported only by wildtype, dissociable PKA, but not by inseparable PKA.
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eLife Assessment
In this potentially important study, the authors conducted atomistic simulations to probe the salt-dependent phase separation of the low-complexity domain of hnRN-PA1 (A1-LCD). The authors have identified both direct and indirect mechanisms of salt modulation, provided explanations for four distinct classes of salt dependence, and proposed a model for predicting protein properties from amino acid composition. There is a range of opinions regarding the strength of evidence, with some considering the evidence as incomplete due to the limitations in the length and statistical errors of the computationally intense atomistic MD simulations.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This manuscript presents a valuable new quantitative crosslinking mass spectrometry approach using novel isobaric crosslinkers. The data are solid and the method has potential for a broad application in structural biology if more isobaric crosslinking channels are available and the quantitative information of the approach is exploited in more depth.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful study by Nandy and colleagues examined relationships between behavioral state, neural activity in cortical area V4, and trial-by-trial variability in the ability to detect weak visual stimuli. They present solid evidence indicating that certain changes in arousal and eye-position stability, along with patterns of synchrony in the activity of neurons in different layers of V4, can show modest correspondences to changes in the ability to correctly detect a stimulus. These findings are likely to be of interest to those who seek a deeper understanding of circuit mechanisms that underlie perception.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful manuscript addresses some key molecular mechanisms on the neuroprotective roles of soluble TREM2 in neurodegenerative diseases. Thw study will advance our understanding of TREM2 mutations, particularly on the damaging effect of known TREM2 mutations, and also explain why soluble TREM2 can antagonize Aβ aggregation. However, the primary experimental method, MD simulations, suffers from limited sampling, rendering the results incomplete for definite conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study provides a valuable showcase of a workflow to perform large-scale characterization of drug mechanisms of action using proteomics in which on-target and off-targets of 166 compounds using proteome solubility analysis in living cells and cell lysates were determined. The evidence supporting the claims of the authors is solid, however, the inclusion of more replicate experiments and more statistical rigor would have strengthened the study. This will be of broad interest to medicinal chemists, toxicologists, computational biologists and biochemists.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This landmark study elucidates the intricate structural mechanisms by which both covalent and non-covalent synthetic ligands can co-occupy the binding pocket of the nuclear receptor transcription factor PPARγ. Through a compelling integration of structural, biochemical, and biophysical evidence, the authors challenge the reliability of two commonly used covalent inhibitors. These findings have far-reaching implications for the broader field of nuclear receptor research. This work will be of high interest to structural biologists and biochemists exploring ligand interactions within the nuclear receptor superfamily.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The manuscript presents an important model for the field of endosome maturation, providing perspective on the role of the deubiquitinating enzyme UPS-50/USP8 in the process. The evidence presented in the paper is clear, incorporating well-designed experiments that suggest the dual actions of UPS-50 and USP8 in the conversion of early endosomes into late endosomes. Overall, the work is convincing and centers on an intriguing subject.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study demonstrates mRNA-specific regulation of translation by subunits of the eukaryotic initiation factor complex 3 (eIF3) using convincing methods, data, and analyses. The investigations have generated important information that will be of interest to biologists studying translation regulation. However, the physiological significance of the gene expression changes that were observed is not clear.
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eLife Assessment
This study presents an important finding on durotaxis in various amoeboid cells that is independent of focal adhesions. The evidence supporting the authors' claims is compelling. The work will be of interest to cell biologists and biophysicists working on rigidity sensing, the cytoskeleton, and cell migration.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The study is considered important with solid evidence that demonstrates the impact of plasma membrane nano-domains and protein interactions in the plant defence response to viruses. It includes a molecular understanding of the role of a calcium dependent kinase (CPK3) and a remorin protein in the cell-to-cell spread of viruses and cytoskeletal dynamics demonstrating, conclusively, the role of CPK3 with multiple lines of evidence. The work opens avenues to investigate different viruses and other plasma membrane proteins to gain a fuller picture of the involvement of plasmodesmata and other nanodomains in virus spreading.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable work describes results from a set of simulation and empirical studies of a set-up assessing exploratory behavior in a potentially rewarding environment that contains danger. The core idea is that an instrumental agent can be helped to be both effective and safe, thus avoiding excessive danger, during exploratory behavior, if its influence is flexibly gated by an independent Pavlovian fear learning system. The conclusion that safe, but effective exploration can be achieved based on a flexibly weighted combination of a Pavlovian and an instrumental agent is solid.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The authors identify a novel relationship between exosome secretion and filopodia formation that has implications for cancer cell metastasis and neuronal synapse formation. Further, they identify the exosomal cargo, THSD7A, as a regulator of this process. The data presented is convincing, and represents an important advancement in our understanding of how these two biological processes are linked and play roles in regulating cell migration and cell-cell communication.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study investigates how the size of an LLM may influence its ability to model the human neural response to language recorded by ECoG. Overall, solid evidence is provided that larger language models can better predict the human ECoG response. Further discussion would be beneficial as to how the results can inform us about the brain or LLMs, especially about the new message that can be learned from this ECoG study beyond previous fMRI studies on the same topic. This study will be of interest to both neuroscientists and psychologists who work on language comprehension and computer scientists working on LLMs.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study significantly enhances our understanding of how various ligands and receptors interact within the Notch signaling pathway. By developing novel cell-based assay systems, the authors systematically analyzed the effects of different ligand-receptor combinations on pathway activation. The convincing data reveal intriguing and unexpected differences and provide a foundation for interpreting Notch signalling in both normal and disease-related contexts.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study uses in vitro and in vivo methods to identify HpARI proteins from H. polygyrus as modulators of the host immune system. The data from comprehensive approaches for investigating differential roles of HpARI proteins are convincing. This paper is relevant to those who investigate host-pathogen interactions at the systems and molecular levels.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This is an important study on the damage-induced checkpoint maintenance and termination in budding yeast that provides novel and convincing evidence for a role of the spindle assembly checkpoint and mitotic exit network in halting the cell cycle after prolonged arrest in response to irreparable DNA double strand breaks (DSBs). The study identifies particular components from these checkpoints that are specifically required for the establishment and/or the maintenance of a cell cycle block triggered by such DSBs. The authors propose an interesting model for how these different checkpoints intersect and crosstalk for timely resumption of cell cycling even without repairing DNA damage that has been revised by addressing the bulk of the reviewers' comments to the first version of the manuscript.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study examines the role of Microrchidia (MORC) proteins in the human malaria parasite Plasmodium falciparum. Solid experimental results, including genome editing and chromatin profiling methods (ChIP-seq and Hi-C), provide a comprehensive picture of the critical role MORC plays in shaping parasite chromatin. Depletion of MORC results in a lethal collapse of heterochromatin and parasite death, nominating the factor as a new target of antimalarial therapies.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study focuses on the regulation of Notch signaling during the immune response in Drosophila. The authors provide solid evidence in support of roles for Su(H) and Pkc53E-induced phosphorylation in Drosophila immunity. The work will be of interest to colleagues in immunity and receptor signaling.
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eLife Assessment
This important study provides a new perspective on how human immunity shapes the antigenic evolution of pathogens. By combining theory and simulation the authors make a compelling case for the importance of eco-evolutionary interactions in population-level virus-host dynamics, which arise due to coupling between the dynamics of immune memories and viral variants. Although the work does not propose improved data-driven viral forecasting methods, it makes a conceptual contribution that advances the field's understanding of this problem's intrinsic difficulty.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents a valuable methodological advancement in quantifying thoughts over time. A novel multi-dimensional experience-sampling approach is presented, identifying data-driven patterns that the authors use to interrogate fMRI data collected during naturalistic movie-watching. The experimentation is inventive and the analyses carried out are convincing.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents an important finding on the involvement of a Caspase 3-dependent pathway in the elimination of synapses for retinogeniculate circuit refinement and eye-specific territory segregation. This work fits well with the concept of "synaptosis" which has been proposed in the past but lacked in vivo support. Despite its elegant design and many strengths, the evidence supporting the claims of the authors is incomplete, particularly regarding whether Caspase-3 expression can really be isolated to synapses vs locally dying cells, whether microglia direct or instruct synapse elimination, and whether astrocytes are also involved. The work will be of interest to investigators studying cell death pathways, neurodevelopment, and neurodegenerative disease.
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eLife Assessment
This valuable paper provides an unbiased landscape for the cerebellar cortical outputs to the brainstem nuclei. By conducting anatomical and physiological analyses of the axonal terminals of Purkinje cells, the data provide convincing evidence that Purkinje cells innervate brainstem nuclei directly. The results show that in addition to previously known inputs to vestibular and parabrachial nuclei, Purkinje cells synapse onto the pontine central grey nucleus but have little effect on the locus coeruleus and mesencephalic trigeminal neurons.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study reports that the neurohormone, bursicon, and its receptor, play a role in the seasonal polyphenism of the bug Cacopsylla chinensis. Low temperature activates the bursicon signaling pathway during the transition from the summer to the winter form, affecting cuticle pigment and thickness as well as chitin content. The solid experiments reveal how bursicon signaling, which is modulated by the microRNA miR-6012, regulates features of polyphenism related to the exoskeleton, although it is less clear what the upstream regulatory events are.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents valuable findings on what networks of genes were impacted by introgression from Denisovans, to identify the biological functions involved in high-altitude adaptation in Tibet. This study applies solid and previously validated methodology to identify genes with signatures of both introgression and positive selection. This paper would be of interest to population geneticists, anthropologists, and scientists studying the genetic basis underlying high-altitude adaptation.
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intelligence.org intelligence.org
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- Humans have a very general ability to solve problems and achieve goals across diverse domains.
- AI systems could become much more intelligent than humans.
- If we create highly intelligent AI systems, their decisions will shape the future.
- Highly intelligent AI systems won’t be beneficial by default.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
ProtSSN is a valuable approach that generates protein embeddings by integrating sequence and structural information, demonstrating improved prediction of mutation effects on thermostability compared to competing models. The evidence supporting the authors' claims is solid, with well-executed comparisons. This work will be of particular interest to researchers in bioinformatics and structural biology, especially those focused on protein function and stability.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental work provides creative and thoughtful analysis of rodent foraging behavior and its dependence on body reference frame-based vs world reference frame-based cues. Compelling evidence demonstrates that a robust map, capable of supporting taking novel shortcuts, is learned primarily if not exclusively based on self-motion cues, which has rarely if ever been reported outside of the human literature. The work, which will be of interest to a broad audience of neuroscientists, provides a rich discussion about the role of the hippocampus in supporting the behavior that should guide future neurophysiological investigations.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This fundamental work provides creative and thoughtful analysis of rodent foraging behavior and its dependence on body reference frame-based vs world reference frame-based cues. Compelling evidence demonstrates that a robust map, capable of supporting taking novel shortcuts, can be learned primarily if not exclusively based on self-motion cues, which has rarely if ever been reported outside of the human literature. The work, which will be of interest to a broad audience of neuroscientists, provides a rich discussion about the role of the hippocampus in supporting the behavior that should guide future neurophysiological investigations.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study addresses potential roles of the master regulator of X chromosome inactivation, the Xist long non-coding RNA, in autosomal gene regulation. Using data from mouse cells, the authors propose that Xist can coat specific autosomal promoters, which in turn leads to the attenuation of their transcriptional activity, complementing recently published results from humans. While the evidence from individual genes is suggestive, shortcomings in the data and statistical analyses leave the evidence currently incomplete. The work would be of interest to anyone studying gene regulation and noncoding RNAA
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study provides important insights into the mechanistic basis of neurological manifestations of RNA polymerase III-related disease by creating a mutant mouse to dissect transcriptional changes. The data provide compelling evidence for disease progression initiated by a global reduction in tRNA levels leading to integrated stress and innate immune responses and neuronal loss. The work will be of interest to those engaged in the study of chromosome biology, developmental biology and neurodegeneration.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study advances our understanding of the mechanisms controlling lipid flux and ion permeation in the TMEM16 and OSCA/TMEM63 family channels. The study provides compelling new evidence indicating that side chains along the TM4/6 interface play a key role in gating lipid and ion fluxes in these channels. The authors suggest that the transmembrane channel/scramblase family proteins may have originally functioned as scramblases but lost this capacity over evolution.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study aims to analyse the effect of polymorphism on meiotic recombination in subspecies of Saccharomyces. The detection of reciprocal and non-reciprocal events is based on sequencing the haploid products of meiosis, and frequencies are compared between strains having introgressed genomic segments and strains lacking such segments. Unfortunately, the method used are inadequate for quantifying the non-reciprocal events.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents a valuable finding in understanding the role of plectin in the development and progression of hepatocellular carcinoma (HCC). The evidence supporting the conclusions is convincing because multiple orthogonal ways were used to demonstrate the requirement of this target in liver cancer models. However, the study is incomplete as the downstream molecular activities of plectin that mediate the cancer phenotypes were not fully evaluated.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study presents a valuable examination of the prevalence of interactions between amino acids from different periods of Earth's history and coenzymes. While the premise of this work is well founded and the analysis is solid, with more data, the interpretation could change. This manuscript would be of interest to evolutionary biologists and biophysicists.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This revised study provides valuable information on the single nucleus RNA sequencing transcriptome, pathways, and cell types in pig skeletal muscle in response to conjugated linoleic acid (CLA) supplementation. Based on the comprehensive data analyses, the data are considered compelling and provide new insight into the mechanisms underlying intramuscular fat deposition and muscle fiber remodeling. The revised study clarifies major aspects of its methodology and analysis, addresses previous reviewer concerns, and contributes significantly to the understanding of nutritional strategies for fat infiltration in pig muscle.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study addresses two questions: (i) how danger signaling is altered for people with childhood adversities, and (ii) how this differs across different operationalizations of adversity. The latter is of particularly broad interest to multiple fields, given that childhood adversity is operationalized very differently across the literature. The study provides compelling evidence using a large sample size and rigorous statistical methods. These data will be of interest to scientists and clinicians interested in early life adversity, statistical approaches for quantifying stress exposure, or aversive learning.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study explores the mechanistic link between glycosylation at the N162 site of the Fc gamma receptor FcγRIIIa and the modulation of NK cell-mediated antibody-dependent cytotoxicity. Using innovative isotope labeling strategies and advanced NMR spectroscopy techniques, the authors provide compelling evidence of how glycan composition influences receptor stability and immune function. These findings offer fundamental insights that may contribute to the development of more effective therapeutic antibodies. The manuscript will be of significant interest to immunologists and researchers focused on therapeutic antibody design.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study focuses on gene regulatory mechanisms essential for hindbrain development. Through molecular genetics and biochemistry, the authors propose a new mechanism for the control of Hox genes, which encode highly conserved transcription factors essential for hindbrain development. The strength of evidence is solid, as most claims are supported by the data. This work will be of interest to developmental biologists.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This work reports an important new method for activity-dependent neuronal labeling in Drosophila using in situ hybridization, with the potential to establish a new standard in the field. The authors demonstrate the method's applicability by generating compelling evidence of the function of male-specific neurons in both aggression and courtship behaviors. These results and the new method will be of great interest to the neuroscience community.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The manuscript by Kolbeck and co-workers is an important contribution to understanding the physical mechanism that controls a key step in the retroviral infectious cycle. The authors employ a wide range of experimental techniques, complemented with Montecarlo simulations, that result in convincing evidence of compaction of HIV DNA by the viral integrase. This manuscript would benefit from in-depth discussion and analysis of the biophysical implications of the results.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable paper reports image analysis pipelines for the automated segmentation of micronuclei and the detection and sorting of micronuclei-containing cells, which could be powerful tools for researchers studying micronuclei. While the development of the pipelines is solid, a proof-of-principle experiment is not entirely conclusive and leaves open the possibility that additional refinements are required, which would be facilitated by a more detailed explanation of the methods used.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This manuscript provides valuable mechanistic insight into NSCLC progression, both in terms of tumour metastasis and the development of chemoresistance. The authors draw upon a range of techniques and assays and although the evidence shown is solid, suggestions by the two reviewers will strengthen the message. The work presented will be of interest to cancer biologists and more broadly to those interested in NSCLC translational studies.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This manuscript reports on the crystal structures of two glycosaminoglycan (GAG) lyases from the PL35 family, along with in vitro enzyme activity assays and comprehensive structure-guided mutagenesis. While the study provides structural insights into the broad substrate specificity of these enzymes, the incomplete structural models, lack of key data such as Mn²⁺ binding confirmation, and reliance on basic docking methods diminish the overall impact. Although the work is useful for specialists in carbohydrate-active enzymes, additional data, and more rigorous analysis are required to present a complete study.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
In this potentially important study, the authors conducted extensive atomistic and coarse-grained simulations as well as a lattice Monte Carlo analysis to probe the driving force and functional impact of supercomplex formation in the inner mitochondrial membrane. The study highlighted the importance of membrane mechanics to the supercomplex formation and revealed differences in structural and dynamical features of the protein components upon complex formation. In its current form, the analysis is considered incomplete, especially concerning the contributions of membrane mechanics and allosteric coupling of key regions.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This manuscript presents a valuable finding on the impact of FRMD8 loss on tumor progression and the resistance to tamoxifen therapy. The author conducted systematic experiments to explore the role of FRMD8 in breast cancer and its potential regulatory mechanisms, confirming that FRMD8 affects tamoxifen resistance and convincingly validating this hypothesis through a series of experiments.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
In this valuable manuscript, the authors propose that the lysosomal protein LAPTM4B plays a role in suppressing the TGF-β/SMAD signaling pathway and suggest that enhancing LAPTM4B function could be a potential therapeutic strategy for alleviating bleomycin-induced lung fibrosis. The findings will be of interest to the lung disease field, and the data presented to support the authors' conclusions is solid. However, it remains unclear whether the suppressive effect of LAPTM4b on idiopathic pulmonary fibrosis is mediated by Nedd4l.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study describes how a single effector of the Type Six Secretion System (T6SS) has two distinct enzymatic functions that together may contribute to bacterial survival and dynamics in a community and provide potential for developing new antimicrobial compounds. The authors have deployed a range of methods in biochemistry, microbiology, and microscopy, generating solid data that support the main assertions. While the manuscript could benefit from additional clarifying experiments and a more detailed discussion of the methods, it will appeal to those studying T6SS, particularly those interested in effectors and bacterial enzymes.
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eLife Assessment
This work provides a potentially valuable framework for understanding the primary causes of disease. However, the evidence supporting the utility of the approach is incomplete given the reliance on strong assumptions about the underlying causal mechanisms.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
In this work, the authors propose that astrocytic aquaporin 4 (AQP4) is the main pathway for tonic water efflux, without which astrocytes undergo cell swelling. These findings are important, because they shed light on key molecular mechanisms implicated with the regulation of brain water homeostasis. The authors use a broad set of experimental tools (e.g., acute brain slices, in vivo recording, and diffusion-weighted MRI) but the evidence remains incomplete without ruling out non-specific effects of TGN-020, and without evidence that changes in sulforhodamine B fluorescence can be used as reliable readouts of cell volume dynamics.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
The authors utilized single-cell RNA-seq profiling of non-small cell lung cancer (NSCLC) patient tumor samples to generate useful insights into the determinants of immune checkpoint inhibitor (ICI) responsiveness in NSCLC patients. While some of the findings add weight to the current literature, the analysis is incomplete due to the small cohort size and heterogeneous population which has limited their ability to draw statistically supported conclusion after adjusting for multiple hypothesis testing, as well as the lack of functional characterization of the findings. This study would benefit from external cohorts to both validate the findings and justify the statistical analysis undertaken.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This comprehensive and compelling study presents a robust, cost-effective method for expanding pluripotent stem cells. The authors have identified a media condition that maintains iPSCs in suspension cultures by inhibiting the PKCβ and Wnt signaling pathways. The manuscript is important for the pluripotent stem cell field as it seeks robust and economical approaches to expand iPSCs at scale for high throughput screens and preclinical studies. While the authors have tested their media and protocol on a few lines, given the variability of iPSCs, further testing across more cell lines and in different laboratory settings will be crucial to evaluate its reproducibility.
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www.medrxiv.org www.medrxiv.org
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eLife Assessment
This valuable study reports machine learning models derived from large-scale data to predict the risk of post-stroke epilepsy. The evidence supporting the conclusions is convincing, although there are some validation issues (lack of cross-validation, possible bias in external validation results). The study may be of interest in the field of clinical neurology
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study provides interesting insights into the mechanisms of action of adjuvants. It shows that adjuvants, MPLA and CpG especially, modulate the peptide repertoires presented on the surface of antigen presenting cells, and surprisingly, adjuvant favored the presentation of low-stability peptides rather than high-stability peptides by antigen presenting cells. As a result, the low stability peptide presented in adjuvant groups elicits T cell response effectively. Evidence in support of these conclusions is solid, and this paper would be of interest to vaccinologists and immunologists.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important work explores the modulation of pain by intense stress. The authors employed a series of cutting-edge techniques and provided convincing evidence suggesting that the dorsal lateral septum-> lateral hypothalamus-> rostral ventromedial medulla circuit is responsible for mediating stress-induced analgesia. This work will be of interest to neuroscientists interested in the neural circuits of behavior, and scientists interested in stress or pain.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study uses C. elegans, a poikilothermic ("cold-blooded") animal, to investigate the interesting question of how cells and organisms adapt to prolonged exposure to cold temperature. The study employed ribosome profiling and RNAseq analyses and provides a useful inventory of genes changed in cold adapted nematodes. However, the overall conclusions that 1) translation is ongoing at a low rate and 2) IRE mediated transcriptional changes play a significant role in cold adaptation are incompletely supported by the evidence provided. The authors are encouraged to conduct additional bioinformatic analyses and rewrite the manuscript to more accurately reflect the evidence provided.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study develops a high throughput version of expansion microscopy that can be performed in 96-well plates. The engineered technology is convincing and compatible with standard microplates and automated microscopes and thus will be of broad interest. The application to hiPCS-derived cardiomyocytes treated with doxorubicin provides a solid proof-of-concept demonstrating the potential for high-throughput analysis.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This useful study examines relationships between tumor mutational burden and the response to immunotherapy, using new data sets along with publicly available data sets. The authors conclude that tumor mutational burden cut-offs are unreliable proxies for predicting the response to therapy, underpinned by solid evidence, but with several caveats and assumptions that leave the central question subject to further inquiry. In summary, this is an interesting study that adds to a growing body of work investigating the particular conditions governing the effectiveness of immunotherapy.
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eLife assessment
This work presents a valuable new approach for self-supervised segmentation for fluorescence microscopy data, which could eliminate time-consuming data labeling and speed up quantitative analysis. The experimental evidence supplied is currently incomplete as the comparison with other methods is only done on a single dataset, lacks common metrics, and could not be easily reproduced for other sample data listed in the manuscript.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study combines agent-based modelling and in vivo experiments in medaka embryos to provide new insights into the role of the thymic niche in T cell development. The modelling yields some interesting findings regarding the importance of thymic epithelial cells, for some of which the evidence is incomplete. This study would be of interest to oncologists, immunologists, and mathematical modelers.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
In this valuable study, the authors attempt to reconstruct the evolutionary history of a large and widespread group of freshwater fishes (Nemacheilidae) across Eurasia since the early Eocene, based on molecular phylogenetic analysis with very comprehensive samplings including 471 specimens belonging to 250 living species. The authors infer that range expansions of the family were facilitated by tectonic connections, favourable climatic conditions, and orogenic processes, adding to our understanding of the effects of climatic change on biodiversity during the Cenozoic. The molecular evidence is overall solid, but the calibration points from the fossil records used in the analysis have not been clearly demonstrated or cited; the different dates for the calibration points might impact the discussion on the evolutionary history relating to past climatic changes.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study focuses on the regulation of GLP-1 in enteroendocrine L cells and how this may be stimulated by the mechanogated ion channel Piezo1 and the CaMKKbeta-CaMKIV-mTORC1 signaling pathway. The work is innovative and is considered valuable, as the hypothesis that is being tested may have significant mechanistic and translational implications. Data to support the proposed mechanism were considered incomplete, yet data to support the overall physiological characterization were considered solid.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study investigates the role of Hox genes in determining the position of the forelimb bud using experimental loss- and gain-of-function approaches in chicken embryos, concluding that Hox4 and Hox5 provide permissive signals for forelimb formation throughout the neck region, while the final forelimb position is determined by the instructive signals of Hox6/7 in the lateral plate mesoderm. These results could potentially be fundamental to our understanding of Hox patterning. However, the evidence supporting these conclusions is incomplete; while the gain-of-function experiments are well supported, the loss-of-function experiments using dominant-negative constructs lack sufficient controls, and could be the result of an experimental artifact.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study provides insights into the role of maternal behavior in the learning and ontogeny of vocalization, finding evidence that the maternal behavior of sac-winged bats (Saccopteryx bilineata) can influence the learned territorial songs of their pups. The behavioral analyses are solid, although a more comprehensive and quantitative description of the babblings and the female displays would have strengthened the study. The work will interest biologists and neuroscientists studying vocal learning and its evolution.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
These are valuable findings for those interested in how neural signals reflect auditory speech streams, and in understanding the roles of prediction, attention, and eye movements in this tracking. However, the evidence as it stands is incomplete. Further details are needed on how the observed quantities relate to the relevant theoretical claims and mathematical models. Moreover, additional motivation is required for several analytical choices.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This study provides convincing evidence that the Kinesin protein family member KIF7 regulates the development of the cerebral cortex and its connectivity and the specificity of Sonic Hedgehog signaling by controlling the details of Gli repressor vs activator functions. This study provides important new insights into general aspects of cortical development.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This is an important study demonstrating that cholecystokinin is a key modulator of auditory thalamocortical plasticity during development and in young adults but not aged mice, though the cortical application of this neuropeptide in older animals appears to go some way to restoring this age-dependent loss in plasticity. A strength of this work is the use of multiple experimental approaches, which together provide convincing support for the proposed involvement of cholecystokinin. Nevertheless, the specificity of the electrical and optical stimulation experiments requires further validation and some key details are missing in the presentation and discussion of these findings. This work is likely to be influential in opening up a new avenue of investigation into the roles of neuropeptides in sensory plasticity.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study highlights the key role of the gut-liver axis mediated by LPS in causing hepatic steatosis. The authors provide solid evidence, in vivo, in vitro, and in silico, for the role of acyloxyacyl hydrolase in mediating this effect using KO mice subjected to MASD-inducing diets. The findings are significant for the liver research community and others interested in the gut-liver axis.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This important study provides solid in-vivo evidence that CCR4 regulates the early inflammatory response during atherosclerotic plaque formation. The authors propose that altered T-cell response plays a role in this process, shedding light on mechanisms that may be of interest to medical biologists, biochemists, cell biologists, and immunologists. Further in vivo validation, mechanistic studies, and discussion of results in vitro suggested would be helpful to cement the significance and implications of these findings.
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eLife Assessment
In this useful study, the authors use published scRNA-seq data to highlight the importance of mast cells (MCs) in TB granulomas, reporting a comparative assessment of chymase- and tryptase-expressing MCs in the lungs of tuberculosis-infected individuals and non-human primates, with MC-deficient mice showing reduced lung bacterial burden and pathology during infection. Whilst the findings are helpful, the evidence to support conclusions is inconsistent across models and thus incomplete. Specifically, the data supporting a role for MCs in coordinating cytokine responses to modulate pathology, susceptibility to tuberculosis, and dissemination during infection are weak.
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eLife Assessment
Wittkamp et al. investigated the spatiotemporal dynamics of expectation of pain using an original fMRI-EEG approach. The methods are solid and the evidence for a substantially different neural representation between the anticipatory and the actual pain period is convincing. These important findings are discussed within a general framework that encompasses their research questions, hypotheses, and analysis of results. Although the choice of conditions and their influence on the results might accept different interpretations, the manuscript is strong and contributes beneficial insights to the field.
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www.biorxiv.org www.biorxiv.org
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eLife Assessment
This valuable study provides convincing evidence that white matter diffusion imaging of the right superior longitudinal fasciculus might help to develop a predictive biomarker of chronic back pain chronicity. The results are based on a discovery-replication approach with different cohorts, but the sample size is limited. The findings will interest researchers interested in the brain mechanisms of chronic pain and in developing brain-based biomarkers of chronic pain.
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