- Last 7 days
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This well-designed study combining psychophysical and fMRI data presents a valuable finding regarding how adaptation alters spatial frequency processing in the cortex. The evidence supporting the claims of the authors is solid, although inclusion of more participants and better quality of the fMRI data would have strengthened the study. The study will be of interest to cognitive and perceptual neuroscientists working on human and non-human primates.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study presents a meta-analysis confirming a statistically significant association between slow oscillation-spindle coupling and memory formation, although the reported effects are limited (~0.5% of variance). The evidence is overall convincing, but the statistical methods may be difficult to follow for readers unfamiliar with advanced techniques. This work will be of particular interest to neuroscientists studying the neural mechanisms of sleep and memory.
-
-
arxiv.org arxiv.org
-
eLife Assessment
This valuable paper uses a quantitative modeling approach to explore a well-studied transition in motor behavior in the nematode C. elegans. The authors provide convincing evidence that this transition, which has been interpreted as a two-state behavior, can instead be described as a process whose parameters are smoothly modulated within a single state. This finding provides insight into the relationships between latent internal states and observable behavioral states, and suggests that relatively simple neuronal mechanisms can drive behavioral sequences that appear more complex.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study describes distinctive characteristics of dentate gyrus granule cells and semilunar cells that are recruited during contextual memory processing. The study provides solid evidence to suggest mechanisms that may be involved in the recruitment of neurons into memory engrams in the dentate gyrus.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable work explores the timely idea that aperiodic activity in human electrophysiology recordings is dynamically modulated in response to task events in a manner that may be relevant for behavioral performance. Moreover, the authors present solid evidence that, in some circumstances, these aperiodic changes might be misinterpreted as oscillatory changes. While many aspects of the manuscript were intriguing, there was a sense that some of the interpretations were overstated - for instance the claim that aperiodic activity distorts interpretations of theta specifically, versus having a more nuanced impact on the time-frequency representation. Softening some of the language may further improve the manuscript.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study concerns how macaque visual cortical area MT represents stimuli composed of more than one speed of motion. The study is valuable because little is known about how the visual pathway segments and preserves information about multiple stimuli, and the study involves perceptual reports from both humans and one monkey regarding whether there are one or two speeds in the stimulus. The study presents compelling evidence that (on average) MT neurons shift from faster-speed-takes-all at low speeds to representing the average of the two speeds at higher speeds. Ultimately, this study raises intriguing questions about how exactly the response patterns in visual cortical area MT might preserve information about each speed, since such information could potentially be lost in an average response as described here, depending on assumptions about how MT activity is evaluated by other visual areas.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study uses tools of population and functional genomics to examine long non-coding RNAs (lncRNAs) in the context of human evolution. Analyses of computationally predicted human-specific lncRNAs and their genomic targets lead to the development of hypotheses regarding the potential roles of these genetic elements in human biology. The conclusions regarding evolutionary acceleration and adaptation, however, only incompletely take data and literature on human/chimpanzee genetics and functional genomics into account.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study presents a well-constructed multiscale simulation framework to investigate ATP-driven DNA translocation by prokaryotic SMC complexes, supporting a segment-capture mechanism. The strength of evidence is convincing, highlighting the necessity of a precise balance between electrostatic interactions and hydrogen bonding, as well as the critical role of kleisin asymmetry in ensuring unidirectional movement.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Research on push-pull systems has often focused on controlled environments, leaving significant gaps in our understanding of how these systems function under real-world conditions. This important and solid study makes a substantial contribution by investigating the volatile emissions and behavioral effects of Desmodium in natural and semi-field contexts which offer insights of broad interest for sustainable agriculture and pest management. While the authors rightly acknowledge some remaining limitations, the revised manuscript now provides a well-supported and transparent assessment of the ecological role of Desmodium volatiles in push-pull systems.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is a valuable study on how past sensory experiences shape perception across multiple time scales. Using a behavioural task and reanalysed EEG data, the authors identify two unifying mechanisms across time scales: a process resulting in faster responses to expected stimuli modulated by attention to task, and reduced early decoding precision for expected inputs interpreted as dampened feedforward processing. The manipulation to dissociate task-related and unrelated history effects over multiple timescales is novel and promising, but the evidence is incomplete and could be strengthened by clarifying the measures, justifying analyses choices, and the relationship to other work.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors study how apolipoprotein L1 variants impact inflammation and lipid accumulation in macrophages. The findings will be useful for researchers investigating macrophage metabolism and inflammation. The discovery that the polyamine spermidine in part mediates such effects is interesting, but the supporting evidence for a physiologically relevant role is currently incomplete due to the lack of relevant in vivo studies.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a valuable finding of novel markers that may potentially identify resident tendon stem/progenitor cells (TSPCs). The study also presents a comprehensive single-cell transcriptional dataset that will be of value to the field. The evidence supporting the identification of novel markers of a TSPC is incomplete, requiring clarification of current analyses and additional validation experiments to demonstrate that these markers are indeed specific and these cells are indeed TSPCs. This work will be of interest to biologists and engineers focused on tendons and ligaments.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study reanalyzed previously published scRNA-seq and TCR-seq data to examine the proportion and characteristics of dual-TCR-expressing Treg cells in mice, presenting some useful insights into TCR diversity and immune regulation. However, the evidence is incomplete, particularly with respect to data interpretation, statistical rigor, and the functionality of dual -TCR Treg cells. The study is potentially of interest to immunologists studying T-cell biology.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides an important perspective on the influence of parental care in the establishment of the amphibian microbiome. Through a combination of cross-fostering experimental work, comparative analysis, and developmental time series, the authors provide compelling evidence that vertical transmission through care is possible, and solid but somewhat preliminary evidence that it plays a significant role in shaping frog skin microbiomes in nature or across time. This work will be of interest to researchers studying the evolution of parental care and microbiomes in vertebrates.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study demonstrates the application of END-seq, originally developed to study genomewide DNA double-strand breaks, to telomere biology; the work packs a punch, concisely demonstrating the utility of this approach and the new insights that can be gained. The authors confirm that telomeres in telomerase-positive cells terminate with 5'-ATC in a Pot1-dependent manner, and demonstrate that this principle holds true in telomerase-negative ALT cells as well. S1-END-seq is similarly developed for telomeres, showing that ALT cells harbor several regions of ssDNA. The study is well-executed and convincing, the new insights are fundamental and compelling, and the optimized END-seq approaches will be widely utilized. The work will prompt additional studies that the reviewers look forward to, including combining telomeric END-seq with long-read sequencing to address the distribution and origin of variant telomere repeats and ssDNA along telomeres in ALT and telomerase-positive settings.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study addresses the role of non-genetic factors in individual differences in phenotype. Using C. elegans, the study finds that non-genetic differences in gene expression, partly influenced by the environment, correlate with individual differences in two reproductive traits. This supports the use of gene expression data as a key intermediate for understanding complex traits. The clever study design makes for compelling evidence.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors address a fundamental question for cell and tissue biology. They use the skin epidermis as a paradigm and ask how stratifying self-renewing epithelia induce differentiation and upward migration in basal dividing progenitor cells to generate suprabasal barrier-forming cells that are essential for a functional barrier formed by such an epithelium. The authors provide compelling evidence time that an increase in intracellular actomyosin contractility, a hallmark of barrier-forming keratinocytes, is sufficient to trigger terminal differentiation, providing in vivo evidence of the interdependency of cell mechanics and differentiation. To illustrate their points, the authors use a combination of genetic mouse models, RNA sequencing, and immunofluorescence analysis. Precisely how the changes in gene expression, cell morphology, mechanics, and cell position are instructive and whether consecutive changes in differentiation are required still remain unclear, but the paper takes a nice step in advancing our knowledge of the process.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This convincing study advances our understanding of the physiological consequences of the strong overexpression of non-toxic proteins in baker's yeast. The findings suggest that a massive protein burden results in nitrogen starvation and a shift in metabolism likely regulated via the TORC1 pathway, as well as defects in ribosome biogenesis in the nucleolus. The study presents findings and tools that are important for the cell biology and protein homeostasis fields.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This work presents potentially important findings suggesting that a combination of transcranial stimulation approaches applied for a short period could improve memory performance. However, the evidence supporting the conclusions is currently incomplete. In particular, the claims relating to the specific neural mechanisms and anatomical sites of action underlying effects were viewed as overstated in the current version. The results potentially have implications for non-invasive enhancement of cognitive functions.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife Assessment
The authors attempt to identify which patients with benign lesions will progress to cancer using a liquid biomarker. Although the study is valuable, the evidence provided for the liquid biopsy EV miRNA signature developed based on radiomics features remains incomplete. There remain key details missing and validation experiments that would better support the conclusions of the study.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study on the loss of DEGS1 in the developing larval brain convincingly shows the accumulation of dihydroceramide in the CNS which induces severe alterations in the morphology of glial subtypes as well as a reduction in glial number. The localization of DEGS1/ifc primarily to the ER is also compelling and interesting, and the loss of DEGS1/ifc clearly drives ER expansion and reduces the levels of TGs. This is an important contribution to the role of lipid metabolism in neural development and disease.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study employs optogenetics, genetically-encoded dopamine and serotonin sensors, and patch-clamp electrophysiology to investigate modulations of neurotransmitter release between striatal dopamine and serotonin neurons - a topic of interest to neuroscientists studying the basal ganglia. The results suggest that the dopamine and serotonin systems operate largely in parallel, with the activation of serotonin neurons resulting in a small, transient dopamine release. The authors suggest that this interaction occurs via glutamate release in the ventral tegmental area, findings that are closely related to previous work. Some conclusions are incomplete requiring larger samples-sizes and controls.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study is important as it highlighted how IL-4 regulates the reactive state of a specific microglial population by increasing the proportion of CD11c+ microglial cells and ultimately suppressing neuropathic pain. The study employs a combination of behavioral assays, pharmacogenetic manipulation of microglial populations, and characterization of microglial markers to address these questions. It provided convincing evidence for the proposed mechanism of IL-4-mediated microglial regulation in neuropathic pain.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides valuable findings regarding potential correlates of protection against the African swine fever virus. The evidence supporting the claims is solid, although analysis using a higher number of animals and other virus strains will be required to further evaluate the relevance of the immune parameters associated to protection. The work will be of broad interest to veterinary immunologists, and particularly those working on African swine fever.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a potentially fundamental analysis of a fossil feather from a 125-million-year-old enantiornithine bird. Using sophisticated 3D microscopic and numerical methods, the authors conclude that the feather was iridescent and brightly colored, possibly indicating that this was a male bird that used its crest in sexual displays. At present, the strength of evidence supporting the conclusions is considered incomplete based on methodological shortcomings and questions about taphonomy.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study explores the regulation of collective cell migration and tissue patterning in the zebrafish posterior lateral line primordium by SoxB1 transcription factors. The authors provide evidence that SoxB1 genes interact with Wnt and Fgf signaling pathways to control neuromast deposition and spacing, a process central to sensory organ development. The work offers mechanistic insight into the self-organization of migrating tissues and adds to the understanding of how transcriptional networks integrate with signaling pathways during morphogenesis. However, the strength of the evidence supporting several key conclusions is incomplete due to insufficient validation of mutant and knockdown tools, lack of quantitative analysis, and unclear experimental design details; additional quantification and more rigorous verification of gene knockdown or loss-of-function tools are needed to support the proposed model.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides an important method to model the statistical biases of hypermutations during the affinity maturation of antibodies. The authors show convincingly that their model outperforms previous methods with fewer parameters; this is made possible by the use of machine learning to expand the context dependence of the mutation bias. They also show that models learned from nonsynonymous mutations and from out-of-frame sequences are different, prompting new questions about germinal center function. Strengths of the study include an open-access tool for using the model, a careful curation of existing datasets, and a rigorous benchmark; it is also shown that current machine-learning methods are currently limited by the availability of data, which explains the only modest gain in model performance afforded by modern machine learning.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a valuable finding on the delivery of a nuclear envelop protein to lysosomes and the impact of C-terminal tagging on its traffic. The authors provide solid evidence for the potential artifacts introduced by large terminal tags, particularly in the context of membrane protein localization and stability.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study shows, for the first time, the structure and snapshots of the dynamics of the full-length soluble Angiotensin-I converting enzyme dimer. The combination of structural and computational analyses provides compelling evidence that reveals the conformational dynamics of the complex and key regions mediating the conformational change. This fundamental work illustrates how conformational heterogeneity can be used to gain insights into protein function.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Arecchi et al. demonstrate that polarized second-harmonic generation microscopy can be used to probe the ON/OFF states of myosin in both permeabilized and intact muscle, making this key measurement accessible to a greater number of labs. This has the potential to help with the study of disease-causing mutations and our understanding of drug function. The methodology is well defined, and the results are important; however, whilst this is overall a convincing study, there are some limitations to the interpretation of the data.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study demonstrates that yeast populations can rapidly evolve freeze-thaw tolerance by converging on a trehalose-rich, quiescence-like state, illuminating a general physiological route to extreme-stress adaptation. The evidence is solid, combining rigorous experimental-evolution design with multi-scale phenotyping, biophysical measurements, whole-genome sequencing, and quantitative modeling that together support the mechanistic conclusions. Questions about the novelty relative to prior growth/stress tolerance links, the precise genetic versus non-genetic drivers of trehalose up-regulation, and the breadth of independently evolved lines. These are areas for clarification, but these do not substantially weaken the overall contribution.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study reports the important development and characterization of next-generation analogs of the molecule AA263, which was previously identified for its ability to promote adaptive ER proteostasis remodeling. The evidence supporting the conclusions is convincing, with rigorous assays used to benchmark the changes in potency and efficacy of the AA263 analogs as well as AA263 targets. The ability of AA263 analogs to restore the loss of function associated with disease-associated proteins prone to misfolding will be of interest to pharmacologists, chemical biologists, and cell biologists, as well as those working on protein misfolding disorders.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This article presents valuable findings on how the timing of cooling affects the timing of autumn bud set in European beech saplings. The study leverages extensive experimental data and provides an interesting conceptual framework of the various ways in which warming can affect bud set timing. The support for the findings is incomplete, though extra justifications of the experimental settings, clarifications of the interpretation of the results, and alternative statistical analyses can make the conclusions more robust.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This landmark study describes the structure of the human RAD51 filament with a recombination intermediate called the displacement loop (D-loop). Using cryogenic structural, biochemical, and single-molecule analyses, the authors provide compelling evidence on how the RAD51 filament promotes strand exchange between single-stranded and double-stranded DNAs. The findings are highly relevant to the fields of homologous recombination, DNA repair, and genome stability.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This paper examines selection on induced epigenetic variation ("Lamarckian evolution") in response to herbivory in Arabidopsis thaliana. The authors find weak evidence for such adaptation, which contrasts with a recently published study that reported extensive heritable variation induced by the environment. The authors convincingly demonstrate that the findings of the previous study were confounded by mix-ups of genetically distinct material, so that standing genetic variation was mistaken for acquired (epigenetic) variation. Given the controversy surrounding the influence of heritable epigenetic variation on phenotypic variation and adaptation, this study is an important, clarifying contribution; it serves as a timely reminder that sequence-based verification of genetic material should be prioritized when either genetic identity or divergence is of importance to the conclusions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study presents a real-time transcriptomics analysis, with the aim of providing rapid access to sequenced data to reduce the costs associated with Oxford Nanopore long-read technology. The revised manuscript demonstrates the utilities with four sets of experiments with convincing evidence.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study uses brain stimulation and electroencephalography to study speech-gesture integration. It investigates the role of frontotemporal regions in integrating linguistic and extra-linguistic information during communication, focusing on the inferior frontal gyrus and posterior middle temporal gyrus. Reliance on activation patterns of tightly-coupled brain regions over short timescales leads to incomplete support for the study's conclusions due to conceptual and methodological limitations.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study uses all-optical electrophysiology methods to provide a valuable insight into the organization of cortical networks and their ability to balance the activity of groups of neurons with similar functional tuning. The all-optical approach used in this study is impressive and the claim that the effects of optical stimulation correspond to a specific homeostatic mechanism is solid. The work will be of interest to neurobiologists and to developers of optical approaches for interrogating brain function.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this manuscript, Lim and collaborators present an important system for developing self-amplifying RNA with convincing evidence that it does not provoke a strong host inflammatory response in cultured cells. This approach could be further strengthened going forward by testing these self-amplying RNAs in an in vivo system.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important work introduces a splitGFP-based labeling tool with an analysis pipeline for the synaptic scaffold protein bruchpilot, with tests in the adult Drosophila mushroom bodies, a learning center in the Drosophila brain. The evidence supporting the conclusions is solid. However, additional controls, validation of synapse-specificity, validation of activity-dependence, details on image processing, and additional functional experiments are needed to strengthen the study.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study identifies astrocyte-intrinsic mechanisms by which the LRRK2 G2019S, a mutation linked to familial Parkinson's disease, disrupts synaptic integrity in the anterior cingulate cortex. The findings are convincing, as they rely on a comprehensive set of in vivo and in vitro genetic, biochemical, proteomic, and electrophysiological approaches. They are important because of their translational value, being validated in both mouse models and post-mortem human samples.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this manuscript, Park et al. developed a multiplexed CRISPR construct to genetically ablate the GABA transporter GAT3 in the mouse visual cortex, with effects on population-level neuronal activity. This work is important, as it sheds light on how GAT3 controls the processing of visual information. The findings are compelling, leveraging state-of-the-art gene CRISPR/Cas9, in vivo two-photon laser scanning microscopy, and advanced statistical modeling.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study offers important insights into the development of infants' responses to music based on the exploration of EEG neural auditory responses and video-based movement analysis. The convincing results revealed that evoked responses emerge between 3 and 12 months of age, but data analysis requires further refinement to fully complement the findings related to movement in response to music. This study will be of significant interest to developmental psychologists and neuroscientists, as well as researchers interested in music processing and in the translation of perception into action.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This paper undertakes an important investigation to determine whether movement slowing in microgravity is due to a strategic conservative approach or rather due to an underestimation of the mass of the arm. While the experimental dataset is unique and the coupled experimental and computational analyses comprehensive, the authors present incomplete results to support the claim that movement slowing is due to mass underestimation. Further analysis is needed to rule out alternative explanations.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors proposed two hypotheses: first, that methamphetamine induces neuroinflammation, and second, that it alters neuronal stem cell differentiation. These are valuable hypotheses, and the authors provided in vivo observations of the methamphetamine response in mice. However, concerns remain regarding the interpretation of the data, and the current evidence is incomplete, requiring substantial experimental validation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study investigates the neural basis of bidirectional communication between the cortex and hippocampus during learning. The evidence supporting the identification of specific circuits and functional cell types involved is convincing. However, certain aspects of the behavioral analysis and statistical interpretation remain incomplete. Overall, the work will be of interest to neuroscientists studying learning and memory.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This revised paper provides valuable findings that altruistic tendency during moral decision-making is gain/loss context-dependent and oxytocin can restore the absence of altruistic choices in the loss domain. The methods and analyses are solid, yet the study could still benefit from better overall framing and more clarity and precision in the definition of key constructs, as pointed out by reviewers. If these concerns are addressed, this study would be of interest to social scientists and neuroscientists who work on moral decision-making and oxytocin.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study suggests that adolescent mice exhibit less accuracy than adult mice in a sound discrimination task when the sound frequencies are very similar. The evidence supporting this observation is solid and suggests that it arises from cognitive control differences between adolescent and adult mice. The adolescent period is largely understudied, despite its contribution to shaping the adult brain, which makes this study interesting for a broad range of neuroscientists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents valuable findings on the role of dopamine receptor D2R in dopaminergic neurons DAN-c1 and mushroom body neurons (Y201-GAL4 pattern) on aversive and appetitive conditioning. The evidence supporting the claims of the authors is solid in the context of their behavioural paradigm. Controls using a reciprocal training protocol would have broadened the scope of their conclusions. The work will be of interest to researchers studying the role of dopamine during learning and memory.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this highly innovative study, Carpenet C et al explore the use of nanobody-based PET imaging to track proliferative cells after in vivo transplantation in mice, in a fully immunocompetent setting. The development of a unique set of PET tracers and mouse strains to track genetically-unmodified transplanted cells in vivo is an important novel asset that could potentially facilitate cell tracking in different research fields. The evidence provided is compelling as the new method proposed might facilitate overcoming certain limitations of alternative approaches, such as full sized immunoglobulins and small molecules.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study focuses on a previously reported positive correlation between translational efficiency and protein noise. Using mathematical modeling and analysis of experimental data the authors reach the valuable conclusion that this phenomenon arises due to ribosomal demand. While some aspects of the work appear to be incomplete, the results have the potential to be of value and interest to the field of gene expression.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Floeder and colleagues provide an important investigation that describes the experimental conditions that systematically produce "ramps" in dopamine signaling in the striatum. This somewhat nebulous feature of dopamine has been a significant part of recent theoretical and computational debates attempting to formally describe the different timescales on which dopamine functions. The current results are convincing and add context to that ongoing work.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study by Wu and Zhou combines neurophysiological recordings and computational modelling to address an interesting question regarding the sequence of events from sensing to action. Neurophysiological evidence remains incomplete: explicit mapping of saccade-related activity in the same neurons and a better understanding of the influence of the spatial configuration of stimulus and targets would be required to pinpoint whether such activity might contribute, even partially, to the observed results and interpretations. These results are of interest for neuroscientists investigating decision-making.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The manuscript by Russell et al. investigates an important problem: the current lack of methods for early and accurate N. fowleri diagnosis, which is >95% fatal. The authors provide solid evidence that a small RNA secreted by N. fowleri is detectable in biological fluids like blood and urine in a mouse model, and is present in cerebrospinal fluid and blood for a limited number of patient samples. This could potentially help with earlier diagnosis, which could save lives.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This convincing study, which is based on a survey of researchers, finds that women are less likely than men to submit articles to elite journals. It also finds that there is no relation between gender and reported desk rejection. The study is an important contribution to work on gender bias in the scientific literature.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides valuable evidence indicating that SynGap1 regulates the synaptic drive and membrane excitability of parvalbumin- and somatostatin-positive interneurons in the auditory cortex. Since haplo-insufficiency of SynGap1 has been linked to intellectual disabilities without a well-defined underlying cause, the central question of this study is timely. The experimental data is solid, as in their revisions the authors successfully addressed questions related to changes in thalamocortical presynaptic excitability, the contradiction between spontaneous and mini EPSCs data, and the anatomical analysis of excitatory synapses.to the somatic region and technical problems regarding phase plots remain unresolved.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this useful study, the authors perform voltage imaging of CA1 pyramidal cells in head-fixed mice running on a track while local field potentials (LFPs) were recorded in the contralateral hemisphere. The authors conclude that synchronous ensembles of neurons are associated with theta rhythms but not with contralateral sharp wave-ripples. However, evidence for some of the paper's primary claims remains incomplete, due to limitations of the experimental approach.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study reveals surprising morphological diversity of Drosophila sensory neurons. Using serial block-face electron microscopy, the authors created detailed 3D reconstructions of large neuronal populations, convincingly finding significant structural variation both within and across distinct classes. These results form the basis for testable hypotheses on how neuronal arborization is optimized for particular sensory functions. This research will be highly relevant to biologists in the fields of physiology, insect chemosensation, and neuroscience.
-
-
-
eLife Assessment
This important work develops C. elegans as a model organism for studying effort-based discounting by asking the worms to choose between easy and hard to digest bacteria. The authors provide convincing evidence that the nematodes are effort-discounting. However, evidence regarding the role of dopamine is incomplete and this weakens the authors connection of the behavior in C. elegans with mammals.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides compelling evidence that action potential (AP) broadening is not a universal feature of homeostatic plasticity in response to chronic activity deprivation. By leveraging state-of-the-art methods across multiple brain regions and laboratories, the authors demonstrate that AP half-width remains largely stable, challenging previous assumptions in the field. These important findings help resolve longstanding inconsistencies in the literature and significantly advance our understanding of neuronal network homeostasis.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable work investigates cooperative behaviors in adolescents using a repeated Prisoner's Dilemma game. The computational modeling approach used in the study is solid and well established, yet evidence supporting certain claims remains incomplete. The work could be strengthened with the consideration of additional experimental contexts, non-linear relationships between age and observed behavior, and modeling details. If these concerns are addressed, the results will be of interest to developmental psychologists, economists, and social psychologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors investigated the potential role of IgG N-glycosylation in Haemorrhagic Fever with Renal Syndrome (HFRS), which may offer significant insights for understanding molecular mechanisms and for the development of therapeutic strategies for this infectious disease. The findings are useful to the field, although the strength of evidence to support the findings is incomplete. Several issues need to be addressed, including more detail on the background, methods, and results. Additional statistical tests should be performed, and the conclusions should reflect the correlational findings of the paper.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a valuable technical advance in the long-term live imaging of limb regeneration at cellular resolution in Parhyale hawaiensis. The authors develop and carefully validate a method to continuously image entire regenerating legs over several days while minimizing photodamage and optimizing conditions for robust cell tracking, together with post-hoc in situ identification of cell types. The data are convincing, the methodology is rigorous and clearly documented, and the results will be of interest to researchers in regeneration biology, developmental biology, and advanced live imaging and cell tracking software development.
[Editors' note: this paper was reviewed by Review Commons.]
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This fundamental study demonstrates how a left-right bias in the relationship between numerical magnitude and space depends on brain lateralization. The evidence is compelling and will be of interest to researchers studying numerical cognition, brain lateralization, and cognitive brain development more broadly.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is a fundamental study that provides a detailed single-cell transcriptomic and epigenomic map of the mouse trabecular meshwor, identifying three distinct trabecular meshwor subtypes with specific functional roles. It links the glaucoma-associated transcription factor LMX1B to mitochondrial regulation in TM3 cells and demonstrates that nicotinamide treatment prevents IOP elevation in Lmx1bV265D/+ mutant mice, highlighting a potential metabolic therapeutic strategy for glaucoma. This convincing work would be further supported by data that link the transcriptional data with mitochondrial functional assays.
-
- Jul 2025
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study introduces a powerful imaging approach that enables deep-tissue visualization in gastruloids using two-photon microscopy, combined with spectral imaging and unmixing to achieve four-color 3D image acquisition. The evidence is compelling that many of the established methods are very helpful (e.g., registration, corrections, signal normalisation, lazy loading bioimage visualisation, spectral decomposition analysis), facilitate the development of quantitative research, and would be of interest to the wider scientific community.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The findings of this important study substantially advance our understanding of the transcription factors that can induce hair cell-like cells from human pluripotent stem cells. The presented evidence supporting these findings is compelling, including rigorous characterization of the effects of hair cell induction using both single-cell RNA sequencing and electrophysiological assessments.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife Assessment
This important study examines the relationship between cognition and mental health and investigates how brain, genetics, and environmental measures mediate that relationship. The methods and results are compelling and well-executed. Overall, this study will be of interest in the field of population neuroscience and in studies of mental health.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study introduces a novel experimental and modeling framework to quantify passive joint torques in Drosophila, revealing that passive forces are insufficient to support body weight, contrary to prior assumptions based on larger insects. The approach is technically impressive, combining genetic silencing, kinematic tracking, and biomechanical modeling. However, the strength of evidence is incomplete, limited by concerns about the specificity of the genetic tools, simplifications in the mechanical model, and limited functional interpretation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important manuscript introduces a genetic tool utilizing mutant mitfa-Cas9 expressing zebrafish to knockout genes to analyze melanocyte function in development and tumorigenesis. The data are convincing and the authors cover potential caveats from their model that might impact its utility for future work. This work significantly adds to the existing approaches in the field, as the mitfa:Cas9 strategy taken here provides a roadmap for generating similar platforms for using other tissue-specific regulators and Cas proteins in the future.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study proposes a useful assay to identify relative social ranks in mice incorporating the competitive drive for two basic resources - food and living space. Using this new protocol, the authors provide solid evidence of stable ranking among male and female pairs, while reporting more fluctuant hierarchies among triads of males. The evidence is, however, limited by the lack of ethologically based validation, assessment of the influence of competitor recognition, and proof of concept of application to neuroscience. This manuscript may be of interest to those interested in social behavior and related neuroscience.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this study Wang et. al. mined publicly available RNA-seq data from The Genotype-Tissue Expression (GTEx) database spanning multiple tissues to ask the question of how transcriptomes are changed with age and in both sexes. The authors provide solid evidence reporting widespread gene expression changes and alternative splicing events that vary in an age- and sex-dependent manner. An important finding is that many of these changes coincide with the time sex hormones begin to decline; additionally, the rate of aging is faster in males than in females.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Peukes et al. report compelling ultrastructures of excitatory synapses in the mouse forebrain that will serve as a reference for future work in the field. Their important findings using correlated fluorescence and cryo-electron tomography challenge the textbook view of synaptic structure that emerged from chemically fixed and metal-stained tissues. Instead of a post-synaptic density, these authors reveal the architecture of the cytoskeletal, neurotransmitter receptor clusters, and organelles in the 'synaptoplasm'.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife Assessment
This paper is an important overview of the currently published literature on low-intensity focussed ultrasound stimulation (TUS) in humans, providing a meta-analysis of this literature that explores which stimulation parameters might predict the directionality of the physiological stimulation effects. The overall synthesis, except for the section on TPS and AD, is convincing though could be streamlined at places. The database proposed by the paper has the potential to become a key community resource if carefully curated and developed.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study presents a new method for longitudinally tracking cells in two-photon imaging data that addresses the specific challenges of imaging neurons in the developing cortex. It provides compelling evidence demonstrating reliable longitudinal identification of neurons across the second postnatal week in mice. The study should be of interest to development neuroscientists engaged in population-level recordings using two-photon imaging.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is an important study providing molecular insight into how cross-talk between histone modifications regulates the histone H3K36 methyltransferase SETD2. The manuscript contains excellent quality data, and the conclusions are convincing and justified. This work will be of interest to many biochemists working in the field of chromatin biology and epigenetics.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this important manuscript, Cassell and colleagues set out on a mechanistic and pharmacological exploration of an engineered chimeric small conductance calcium-activated potassium channel 2 (SK2). They show convincing evidence that the SK2 channel possesses a unique extracellular structure that modulates the conductivity of the selectivity filter, and that this structure is the target for the SK2 inhibitor apamin. While the interpretations are sound and the writing is clear, the manuscript would be strengthened by providing more detailed information for the electrophysiological experiments and the structural analyses attempted, in addition to relating dilation of the filter to mechanisms of inactivation in other potassium channels. This high-quality study will be of interest to membrane protein structural biologists, ion channel biophysicists, and chemical biologists, and will inform future drug development targeting SK channels.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is a potentially useful study that provides solid, yet confirmatory structural findings about the complex (FtsEX) that controls peptidoglycan remodeling during bacterial cell division. The authors capitalize on the fact that ATP binding stabilizes the FtsEX complex allowing structural characterization for this system. A model is then developed to explain ATP regulation but there is a gap between the model presented here and in vivo data reported previously.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable work used molecular biology, cell biology, and genetic approaches to unravel individual genes and potential pathways that contribute to paternal mitochondrial inheritance using C. elegans as the model organism. Their microscopy method is cutting edge, with sufficient biological replicates, proper control, and appropriate statistics. These findings are convincing and are of general interest for understanding mitochondrial inheritance in C. elegans, which could have implications for understanding similar biological processes in other organisms.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study addresses the structural basis of voltage-activation of BK channels using atomistic simulations of several microseconds, to assess conformational changes that underlie both voltage-sensing and gating of the pore. The findings, including movement of specific charged residues, combined with the degree to which these movements are coupled to pore movements, provide a solid basis for understanding voltage-gating mechanisms in this class of channels. This paper will likely be of interest to ion channel biologists and biophysicists focused on voltage-dependent channel gating mechanisms.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The open-source software Chromas tracks and analyses cephalopod chromatophore dynamics. The software features a user-friendly interface alongside detailed instructions for its application, with compelling exemplary applications to two widely divergent cephalopod species, a squid and a cuttlefish, over time periods large enough to encompass new chromatophore development among existing ones. It demonstrates accurate tracking of the position and identity of each chromatophore. The software and methods outlined therein will become an important tool for scientists tracking dynamic signaling in animals.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a rather valuable finding that a combination of arginine methyltransferase inhibitors synergize with PARP inhibitors to kill ovarian and triple negative cancer cells. The evidence supporting the claims of the authors is solid, although some comments and elaborations in the main text would have enhanced the comprehension and clarity of the data. The work will be of interest to scientists working in the field of breast cancer.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a valuable finding that the biomechanical force of heart contractility is required for robust endocardial id2b expression, which in return promotes valve development and myocardial function through upregulation of Neuregulin 1. The data were collected and analyzed using solid methodology and can be used as a starting point for deeper mechanistic insights into the genetic programs regulating endocardial-myocardial crosstalk during heart development.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important 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 and solid findings regarding the importance of thymic epithelial cells. This study would be of interest to oncologists, immunologists, and mathematical modelers.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors investigate arrestin2-mediated CCR5 endocytosis in the context of clathrin and AP2 contributions. Using an extensive set of NMR experiments, and supported by microscopy and other biophysical assays, the authors provide convincing data on the roles of AP2 and clathrin in CCR5 endocytosis. This important work will appeal to an audience beyond those studying chemokine receptors, including those studying GPCR regulation and trafficking. The distinct role of AP2 and not clathrin will be of particular interest to those studying GPCR internalization mechanisms.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this manuscript, Franco and colleagues present compelling evidence that fecal extracts containing high concentrations of indole, a known repellent, enhance rather than protect against invasion of colonic tissue by Salmonella. The authors describe important findings that lead to the conclusion that the competing effects of attractants present in fecal matter, including L-serine, also sensed by the Tsr chemoreceptor that senses indole, override the repulsive effect of indole.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study introduces ambisim, a rigorously validated and well-documented simulation framework that enables the generation of synthetic, genotype-aware single-cell RNA and ATAC sequencing datasets under realistic conditions. The authors provide solid evidence of its utility by benchmarking multiple demultiplexing methods and proposing a new variant consistency metric. While the tool is valuable for guiding method selection, the interpretation of the new metric requires further clarification.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study dissects the function of 3 outputs of a specific population of modulatory neurons, dorsal raphe dopamine neurons, in social and affective behavior. It provides valuable information that both confirms prior results and provides new insights. The strength of the evidence is convincing, based on cutting-edge approaches and analysis. This study will be of interest to behavioral and systems neuroscientists, especially those interested in social and emotional behavior.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This paper reports on an important study that aims to move beyond current experimental approaches in speech production by (1) investigating speech in the context of a fully interactive task and (2) employing advanced methodology to record intracranial brain activity. Together these allow for examination of the unfolding temporal dynamics of brain-behaviour relationships during interactive speech. This approach and the analyses presented in support of the authors' claims pose convincing evidence.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study introduces a Bayesian method to determine bacterial counts that accounts for the experimental noise inherent to dilution and plating methods, and distinguishes it from biological uncertainty. The evidence supporting the conclusions is convincing, combining simulated data and experimental data. The method will be of interest to microbial ecologists, and potentially to the broader community interested in inference from biological data, even more so if the domain of application and the limitations are further clarified.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study addresses a gap in our understanding of how the size of the attentional field is represented within the visual cortex. The evidence supporting the role of visual cortical activity is convincing, based on a novel modeling analysis of fMRI data. The results will be of interest to psychologists and cognitive neuroscientists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important work offers a fresh perspective central to merozoite surface biology and potential implications on vaccine design, challenging the dogma that MSPs are indispensable invasion engines. Although the authors only deleted bp 132-819, the data based on Western blot, IFA, and RNA‐seq provide compelling evidence that while MSP2 is dispensable for growth, it serves as an immune modulator for AMA1. This work will be of particular interest to scientists working on different aspects of Plasmodium biology and vaccinology.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable work explores how synaptic activity encodes information during memory tasks. All reviewers agree that the work is of very high quality and that the methodological approach is praiseworthy. Although the experimental data support the possibility that phospholipase diacylglycerol signaling and synaptotagmin 7 (Syt7) dynamically regulate the vesicle pool required for presynaptic release, concerns remain that the central finding of paired-pulse depression at very short intervals may be more likely due to Ca²⁺ channel inactivation rather than vesicle pool depletion. Overall, this is a solid study although the results warrant consideration of alternative interpretations.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study presents an evaluation of several tools used for detecting Identity-By-Descent (IBD) segments in highly recombining genomes, using simulated data to replicate the high recombination and low marker density of Plasmodium falciparum, the parasite responsible for malaria. The evidence presented by the authors is convincing demonstrating that users should be cautious calling IBD when SNP density is low and recombination rate is high. This study will be of interest to scientists working in the field of genome evolution and infectious diseases
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study investigates the role of Drp1 in early embryo development. The authors have addressed most of the original comments and the work now presents convincing evidence on how this protein influences mitochondrial localization and partitioning during the first embryonic divisions. The research employs the Trim-Away technique to eliminate Drp1 in zygotes, revealing critical insights into mitochondrial clustering, spindle formation, and embryonic development.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable manuscript describes cryo-EM structures of archaeal proteasomes that reveal insights into how occupancy of binding pockets on the 20S proteasome regulates proteasome gating. The evidence supporting these claims is convincing, although the extrapolation of these findings to the more complex eukaryotic proteasome may prove challenging. This work will be of high interest to researchers interested in proteasome structure and regulation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study describes expression profiling by scRNA-seq of thousands of cells of recombinant yeast genotypes from a system that models natural genetic variation. The rigorous new method presented here shows promise for improving the efficiency of genotype-to-phenotype mapping in yeast, providing convincing evidence for its efficacy. This manuscript focuses on overcoming technical challenges with this approach and identifies several new biological insights that build upon the field of genotype-to-phenotype mapping, a central question of interest to geneticists and evolutionary biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important 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 new insights into general aspects of cortical development.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This manuscript by Li, Lu et al., presents important findings on the role of cDC1 in atherosclerosis and their influence on the adaptive immune system. Using Xcr1Cre-Gfp Rosa26LSL-DTA ApoE-/- mouse models, these data convincingly reveal an unexpected, non-redundant role of the XCL1-XCR1 axis in mediating cDC1 contributions to atherosclerosis.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study presents an innovative noninvasive immunotherapeutic strategy for hepatocellular carcinoma by combining ultrasound stimulation with calcium-loaded nanodroplets to activate splenic immune responses. The authors provide solid preclinical data, including single-cell transcriptomic analyses and evidence of tumor growth suppression, supported by a creative and well-executed methodology. Further validation of the calcium signaling mechanisms and assessment of long-term safety will strengthen the translational potential of this approach. The work will be of broad interest to researchers in oncology, immunotherapy, and biomedical engineering.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a valuable finding on the neural representation of time from two distinct egocentric and allocentric reference frames. The presentation of evidence in the version of the original submission is incomplete, as further conceptual clarifications, methodological details, and addressing potential confounds would strengthen the study. The work will be of interest to cognitive neuroscientists working on the perception and memory of time.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study describes a computational model of the rat spinal locomotor circuits and how they could be plastically reconfigured after lateral hemisection or contusion injuries to replicate gaits observed experimentally in vivo. Overall, the simulation results convincingly mirror the gait parameters observed experimentally. The model suggests the emergence of detour circuits after lateral hemisection, whereas after a midline contusion, the model suggests plasticity of left-right and sensory inputs below the injury.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful manuscript addresses some key molecular mechanisms on the neuroprotective roles of soluble TREM2 in neurodegenerative diseases. The study will advance our understanding of TREM2 mutations, particularly on the damaging effect of known TREM2 mutations, and also provides solid evidence why soluble TREM2 can antagonize Aβ aggregation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study convincingly demonstrates that odors evoke a feeding response in Drosophila, mediated by gustatory receptors and observed as a proboscis extension. The evidence is comprehensive, encompassing behavior, functional imaging and electrophysiology. This important results on the molecular and cellular basis of multimodal integration across olfaction and gustation will be of interest for the study of chemosensation, sensory biology, and animal behavior.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study reports important new insights into the roles of a long noncoding RNA, lnc-FANCI-2, in the progression of cervical cancer induced by a type of human papillomavirus. Through a blend of cell biological, biochemical, and genetic analyses of RNA and protein expression, protein-protein interaction, cell signaling, and cell morphology, the authors provide convincing evidence that lnc-FANCI-2 affects cervical cancer outcome by regulating the RAS signaling pathway. These findings will be of interest to scientists in the fields of cervical cancer, long noncoding RNA, and cell signaling.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The paper addresses the question of gene epistasis and asks what is the correct null model for which we should declare no epistasis. By reanalyzing synthetic gene array datasets regarding single and double-knockout yeast mutants, and considering two theoretical models of cell growth, the authors reach the valuable conclusion that the product function is a good null model. While the justification of some assumptions is incomplete, the results have the potential to be of value to the field of gene epistasis.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This paper highlights an important physiological function of PGAM in the differentiation and suppressive activity of Treg cells by regulating serine synthesis. This role is proposed to intersect with glycolysis and one-carbon metabolism. The study's conclusion is supported by solid evidence from in-vitro cellular and in-vivo mouse models.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study fills an gap in our knowledge of the evolution of GPCRs in holozoans, as well as the phylogeny of associated signaling pathway components such as G proteins, GRKs, and RIC8 proteins. The evidence supporting the conclusions is compelling, with the analysis of extensive new genomic data from choanoflagellates and other non-animal holozoans. Overall, the study is thorough and well-executed. It will be a resource for researchers interested in both the comparative genomics of multicellularity and GPCR biology more broadly, especially given the importance of GPCRs as highly druggable targets.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important theoretical study examines the possibility of encoding genomic information in a collective of short overlapping strands (e.g., the Virtual Circular Genome (VCG) model). The study presents convincing theoretical arguments, simulations and comparisons to experimental data to point at potential features and limitations of such distributed collective encoding of information. The work should be of relevance to colleagues interested in molecular information processing and to those interested in pre-Central Dogma or prebiotic models of self-replication.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is a valuable study that uses single-cell RNA sequencing to define tumor-intrinsic transcriptional programs that characterize distinct types of small intestine neuroendocrine tumors. The evidence supporting the claims of the authors is solid, but would benefit from a larger sample size. The work will be of interest to cancer biologists studying neuroendocrine tumors, as well as those studying tumor heterogeneity more broadly.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife Assessment
This study offers a valuable assessment of the impact of antibiotics on the human gut microbiota across diverse observational cohorts. The findings presented are convincing, despite the observational design and residual confounding that may still contribute to discrepancies between the cross-sectional and longitudinal data. The work is relevant for researchers and clinicians interested in antimicrobial resistance and the impact of antibiotics on the host.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides important insights into the evolution of pesticide resistance, demonstrating that resistance can arise rapidly and repeatedly, which complements prior work on parallel evolution across species. The combination of extensive temporal sampling in the field, experimental evolution, and genomics makes for compelling findings. The authors are to be commended for acknowledging the main limitations of their study in the Discussion. Framing the work in a broader context of resistance beyond arthropod pests would further increase the appeal of the study, which is of relevance for both agronomic practitioners and evolutionary biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study reports the first characterization of the CG14545 gene in Drosophila melanogaster, which the authors name "Sakura." Acting during germline stem cell fate and differentiation, Sakura is required for both oogenesis and female fertility, although some mechanistic details require further investigation. This solid study presents a wide-ranging and well-controlled characterization of Sakura, and accordingly the findings and associated reagents described will be of use to scientists interested in oogenesis and early development.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study identifies a population of CD81-positive fibroblasts showing senescence signatures that can activate neutrophils through the C3/C3aR1 axis, hence contributing to the inflammatory response in periodontitis. Solid evidence, combining in vitro and in vivo analyses and mouse and human data, supports these findings. The revised manuscript has addressed many concerns significantly. The work would be of interest to researchers working in the senescence and oral medicine fields.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is a valuable study showing that differentiated cells of the zebrafish skin form membrane protrusions called cytonemes that contact and likely transmit Notch signals to cells of the undifferentiated layer below. The data are convincing that cytoneme like protrusions from the periderm are required for proper periderm structure, proliferation, gene expression, and Notch signaling. Evidence that inflammatory signaling through IL-17 affects epidermal differentiation, Notch and cytoneme formation is solid, but whether these are through a single common or two parallel pathways requires further investigation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This fundamental manuscript presents a practical modification of the orthogonal hybridization chain reaction (HCR) technique, a promising yet underutilized method with broad potential for future applications across various fields. The authors advance this technique by integrating peptide ligation technology and nanobody-based antibody mimetics-cost-effective and scalable alternatives to conventional antibodies-into a DNA-immunoassay framework that merges oligonucleotide-based detection with immunoassay methodologies. Notably, they demonstrate with compelling evidence that this approach facilitates a modified ELISA platform capable of simultaneously quantifying multiple target protein expression levels within a single protein mixture sample.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
With a computational analysis of a neuroanatomical network model in C. elegans, this valuable work investigates the synaptic mechanism for memory-dependent klinotaxis, i.e., salt concentration chemotaxis. By incorporating experimental data altering the ASER neuron's basal glutamate release into their model, the authors demonstrate the possibility of a transition between excitatory and inhibitory signaling at the ASER-AIY synapse, depending on environmental and cultivated salt concentrations. These solid findings offer a proposal for how synaptic plasticity plays a role in sensorimotor navigation, and will be of interest to worm biologists and theoretical neuroscientists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a valuable finding on the molecular mechanisms that govern GABAergic inhibitory synapse function. The authors propose that Endophilin A1 serves as a novel regulator of GABAergic synapses by acting as a component of the inhibitory postsynaptic density. The authors have added substantial new analyses that take a wide range of approaches to provide solid support for their conclusions, although one of the reviewers concludes that the premise that gephyrin and endophilin A1 interact requires more robust analysis. The findings are likely to interest a broad audience of scientists focusing on inhibitory synaptic transmission, the excitation-inhibition balance, and its disruption in disorders such as epilepsy.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The manuscript by Ross, Miscik, and others describes an intriguing series of observations made when investigating the requirement for podxl during hepatic development in zebrafish. Understanding how genetic compensation pathways are involved in gene function is an important question. However, there is incomplete evidence provided in the manuscript at this point to conclude that discrepancies between observed phenotypes are due to genetic compensation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this important study, the authors set out to determine the molecular interactions between the AQP2 from Trypanosoma brucei (TbAQP2) and the trypanocidal drugs pentamidine and melarsoprol in order to clarify the origins of clinically observed drug resistance and facilitate future drug design. Using cryo-EM, molecular dynamics simulations, and lysis assays, the authors present a solid theory for how drug resistance mutations in TbAQP2 prevent drug uptake. Overall, even though a few methodological issues still need minor clarification, this study will be of interest to those working on aquaporins and the development of drugs targeting aquaporins.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable manuscript presents findings supported by solid data to identify a surprising glia-exclusive function for betapix in vascular integrity and angiogenesis. The manuscript also describes the optimisation of a modified CRISPR-based Zwitch approach to generate conditional knockouts in zebrafish.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study provides a spatial transcriptomic analysis of the mouse adrenal gland that could have implications for future research and applications. The authors present solid results that allow the dissection of the cell signalling pathways and cellular composition of different zones of the adrenal glands in the mouse model; they propose new zone-specific gene markers and specific intra- and inter-zonal signaling pathways based on receptor-ligand expression patterns. Their web tool is user-friendly and will be helpful for adrenal scientists; however, the validation of crucial results of the large dataset is necessary. There are also several contradictory results/interpretations, and the opportunity to dissect the sexually dimorphic gene expression pattern and mouse-human interspecies differences is a missed opportunity.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study asks how the neural representation of individual finger movements changes during the early periods of sequence learning. By combining a new method for extracting features from human magnetoencephalography data and decoding analyses, the authors provide solid evidence of an early, swift change in the brain regions correlated with sequence learning, including a set of previously unreported frontal cortical regions. The authors also show that offline contextualization during short rest periods is the basis for improved performance. Further confirmation of these results on multiple movement sequences would further strengthen the key claims.
-
- Jun 2025
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The microbiome field is constantly providing insight on various health-related properties elicited by the commensals that inhabit their mammalian hosts. Harnessing the potential of these commensals for knowledge about host-microbe interactions, as well as properties with therapeutic implications, will likely remain a fruitful field for decades to come. In this valuable study, Wang et al use various methods, encompassing classic microbiology, genomics, chemical biology, and immunology, to identify a potent probiotic strain that protects nematode and murine hosts from Salmonella enterica infection. The authors provide compelling evidence identifying gut metabolites that are correlated with protection, and show that a single metabolite can recapitulate the effects of probiotic administration.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study identifies a novel bacteriophage that can use the exopolysaccharide Psl of Pseudomonas aeruginosa to infect and disrupt biofilms. The work is convincing and suggests a novel approach to control biofilms that is relevant to researchers working on biofilms, specifically in Pseudomonas, on phage physiology and discovery, and on alternatives to controlling bacterial pathogens.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study analyzed 335 Mycobacterium tuberculosis Complex genomes and found that MTBC has a closed pangenome with few accessory genes. The research provides solid evidence for gene presence-absence patterns which support the appending conclusions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents potentially valuable insights into the role of climbing fibers in cerebellar learning. The main claim is that climbing fiber activity is necessary for optokinetic reflex adaptation, but is dispensable for its long-term consolidation. There is evidence to support the first part of this claim, though it requires a clearer demonstration of the penetrance and selectivity of the manipulation. However, support for the latter part of the claim is incomplete owing to methodological concerns, including the robustness of the CF marking and manipulation approach and the unclear efficacy of longer-duration climbing fiber activity suppression.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The study introduces new tools for measuring the intracellular calcium concentration close to transmitter release sites, which may be relevant for synaptic vesicle fusion and replenishment. This approach yields important new information about the spatial and temporal profile of calcium concentrations near the site of entry at the plasma membrane. This experimental work is complemented by a coherent, open-source, computational model that successfully describes changes in calcium domains. Some of the conclusions are strongly supported by the data, but a few gaps in the data presented mean that the evidence for other conclusions is incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors take a synthetic approach by introducing synaptic ribbon proteins into HEK cells to analyze how these assemblies cluster calcium channels at the active zone. Using a synapse-naive heterologous expression system and overexpression-based strategy is valuable, as it establishes a promising model for studying molecular interactions at the active zone. The study is built on a solid combination of super-resolution microscopy and electrophysiology, though it currently falls short of replicating the full functional properties of native ribbon synapses and instead resembles a multiprotein complex that partially mimics ribbon-type active zones.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The reported cryo-EM imaging of a pentameric ligand-gated ion channel in liposomes as opposed to nanodiscs has both broad implications and contributes valuable methodological advances to the structural investigation of membrane receptors. The comparison of structures assigned to distinct functional states in liposomes versus nanodiscs is convincing and will aid membrane protein structural biologists in selection of functionally relevant membrane reconstitution environments.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study makes the valuable claim that people track, specifically, the elasticity of control (that is, the degree to which outcome depends on how many resources - such as money - are invested), and that control elasticity is impaired in certain types of psychopathology. A novel task is introduced that provides solid evidence that this learning process occurs and that human behavior is sensitive to changes in the elasticity of control. Evidence that elasticity inference is distinct from more general learning mechanisms and is related to psychopathology remains incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study establishes bathy phytochromes, a unique class of bacterial photoreceptors that respond to near-infrared light (NIR), as important tools for bacterial optogenetics. NIR light is a key control signal in optogenetics due to its deep tissue penetration and the ability to combine with existing red- and blue-light sensitive systems, but thus far, NIR-activated proteins have been poorly characterized. The strength of the evidence is solid overall, with comprehensive in vitro characterization, modular design strategies, and validation across different hosts. There are some questions that remain – such as the rationale for linker choices, characterization of growth and performance relative to controls, and the physiological significance of color blind effects at alkaline pH – but overall, this study should advance the fields of optogenetics and photobiology and inspire future work.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This work models reinforcement-learning experiments using a recurrent neural network. It examines if the detailed credit assignment necessary for back-propagation through time can be replaced with random feedback. In this important study the authors show that it yields a satisfactory approximation and the evidence to support that it holds within relatively simple tasks is solid.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important manuscript presents a thorough analysis of trans-specific polymorphism (TSP) in Major Histocompatibility Complex gene families across primates. The analysis makes the most of currently available genomic data and methods to substantially increase the amount and evolutionary time that TSPs can be observed. Both false negative TSPs due to missing genes at the assembly and/or annotation level, as well as false positives due to read mismapping with missing paralogs, are well assessed and discussed. Overall the evidence provided is compelling, and the manuscript clearly delineates the path for future progress on the topic.
-
-
-
eLife Assessment
This study reports valuable findings on the role of Layilin in the motility and suppressive capacity of clonal expanded regulatory T cells (Tregs) in the skin. Although the strength of the study is utilizing conditional knock-out mice and human skin samples, the analysis of the molecular mechanism by which Layilin affects Treg function is incomplete. The study will be of interest to medical scientists working on skin immunology.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This revised study describes an important new model for in vivo manipulation of microglia, exploring how mutations in the Adar1 gene within microglia contribute to Aicardi-Goutières Syndome. The methodology is validated with exceptional data, supporting the authors' conclusions. The paper underscores both the advantages and limitations of using transplanted cells as a surrogate for microglia, making it a resource that is of value for biologists studying macrophages and microglia.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable work proposes a novel, rapid S. aureus entry mechanism via Ca²⁺-dependent lysosomal exocytosis and acid sphingomyelinase release, which influences bacterial sub-cellular fate. However, reliance on chemical inhibitors and the absence of a knockout phenotype weakens the overall impact, making the study incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors modified a common method to induce epilepsy in mice to provide an improved approach to screen new drugs for epilepsy. This is important because of the need to develop new drugs for patients who are refractory to current medications. The authors' method evokes seizures to circumvent a low rate of spontaneous seizures and the approach was validated using two common anti-seizure medications. The strength of evidence was solid, making the study invaluable, but there were some limitations to the approach and methods.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This useful study characterises motor and somatosensory cortex neural activity during naturalistic eating and drinking tongue movement in nonhuman primates. The data, which include both electrophysiology and nerve block manipulations, will be of value to neuroscientists and neural engineers interested in tongue use. Although the current analyses provide a solid description of single neuron activity in these areas, both the population level analyses and the characterisation of activity changes following nerve block could be improved.
-
-
www.biorxiv.org www.biorxiv.org
-
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 weak transcriptomics data that might be a good resource for the field. However, experimental evidence, methods, and data analyses supporting the main claims of the manuscript are incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors present useful findings on the use of a single-fly behavioral paradigm for assessing different Drosophila genetic models of neurodegeneration. The experimental design and analyses are solid and can be used for quick behavioral assessment in fly models of various neurodegenerative diseases, especially those having an impact on locomotion. The work will be of interest to Drosophila biologists using behavior as a readout for their studies.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is an important study that combines replications of findings and novel detailed MRI investigations to assess the impact of environmental enrichment and maternal behavior on mice brain structure at different stages of development. The results and evidence supporting the conclusions are convincing, but in detail, the interpretation is challenging, in particular due to inter-individual and inter-litter variability. The extent to which maternal care mediates the impact of enrichment on brain development during the perinatal period also remains unclear because behavior was observed only during short periods, and the performed analyses are still incomplete. This study will nevertheless be of significant interest to neuroscientists and researchers interested in neurodevelopment in relation to environmental factors because of its in-depth use of MRI to study brain plasticity in mice.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This manuscript aims to identify the pacemaker cells in the lymphatic collecting vessels - the cells that initiate the autonomous action potentials and contractions needed to drive lymphatic pumping. Through the exemplary use of existing approaches (genetic deletions and cytosolic calcium detection in multiple cell types), the authors convincingly determine that lymphatic muscle cells are the origin of the action potential that triggers lymphatic contraction. The inclusion of scRNAseq and membrane potential data enhances a tremendous study. This fundamental discovery establishes a new standard for the field of lymphatic physiology.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important work advances our understanding of the impact of malnutrition on hematopoiesis and subsequently infection susceptibility. Support for the overall claims is convincing in some respects and incomplete in terms of identifying mechanism as highlighted by reviewers. This work will be of general interest to those in the fields of hematopoiesis, malnutrition, and dietary influence on immunity.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study explores the role of SIRT2 in regulating Japanese encephalitis virus replication and disease progression in rodent models. The findings presented are novel as sirtuins are known for their roles in aging, metabolism, and cell survival, but have not been studied in the context of viral infections until recently. The evidence supporting the claims is solid, although additional experiments to further characterize the clinical outcomes and directly test the link between acetylated NF-kB and SIRT2 expression would have strengthened the study. The work will be of interest to biologists studying viruses, sirtuins, and inflammation.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife Assessment
This valuable study tested whether several months of dolutegravir intensification alters the size of the HIV reservoir as well as immune activation in individuals already on suppressive ART. While the general study approach is appropriate and the paper is well written, the evidence supporting the claims of the authors is incomplete. The title of the paper is only partially supported by the data, based on specific issues with the study design and analysis plan highlighted by Reviewer 1. Specifically, the primary study outcomes were not clearly described a priori, the plausibility of a biologic effect is uncertain based on lack of a consistent effect across participants, and sample size is small. Given a possible observed partial effect and relevant hypothesis, this approach warrants study in a larger trial.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Tropical single-island endemic bird populations are particularly vulnerable to climate change. The authors investigate genetic evidence of how such species dealt with climate changes in the past as a possible predictor for how they will respond to change in the future, which could provide an important example for the fields of conservation genetics and island biogeography. The authors' integration of genomics and habitat modeling is commendable, but we find that the support for their conclusions is incomplete: at times, the results presented appear to contradict each other, the authors do not fully account for key variables, and the limited taxonomic scope may cause problematic biases for the conclusions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents important findings that enhance our understanding of immune cell interactions in the context of chronic HIV-1 infection. The evidence supporting the conclusions is convincing. The authors have employed appropriate and validated methodologies, including detailed data reprocessing and batch correction to account for inter-donor variability. The inclusion of supplementary figures and analyses, such as cell communication inference, further substantiates the robustness of the findings. Overall, this work contributes to our understanding of HIV-1 immune evasion and highlights potential therapeutic targets for reservoir eradication.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents valuable findings on the relationship between nutrient availability and NAD/NADH levels, which in turn regulate biomass production in cancer cells. The authors provide solid evidence to support their claims, offering insight into why it is difficult to predict which nutrients limit cancer cell growth: both cell type and nutrient availability together determine the oxidative capacity that constrains the synthesis of various metabolic intermediates. The manuscript will be of interest to researchers working in cancer and cell metabolism.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Weiss et al. provide important new insights and convincing evidence to further our mechanistic understanding of how antigen presentation shapes skin persistence of CD8+ TRM. Using a mouse model for inducible genetic ablation of transforming growth factor beta receptor 3 (TGFBR3) in CD8+ T cells, they demonstrate TGFBR3's role in regulating CD8+ TRM persistence in skin. Furthermore, they show that the strength of T cell receptor (TCR) engagement upon initial CD8+ TRM skin seeding has a positive influence on subsequent TRM expansion following a secondary antigen-reencounter. Together, these mechanisms add to our understanding of how the skin CD8+ T cell repertoire is dynamically responsive to topical antigen.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents a useful framework to extract the individuality index to predict subjects' behavior in the target tasks. However, the evidence supporting such a framework is somewhat incomplete and would benefit from overall framing and clarity on its approaches. Overall, this study would be of interest to cognitive and AI researchers who work on cognitive models in general.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This manuscript makes important contributions to the methodology commonly used to assess representational structures in human and animal brain activity recorded using various techniques (especially fMRI). The evidence in the form of mathematical analysis and simulations is solid. The impact of this contribution could be improved by extending the simulations to assess the effects of violations of explicit and implicit assumptions.
-
-
-
eLife Assessment
This study makes an important contribution by showing that humans adapt learning rates rationally to environmental volatility yet systematically misattribute noise as volatility, demonstrating approximate rationality with simplified internal models. The evidence is compelling, encompassing a cleverly designed volatility-versus-noise paradigm, innovative lesion-based comparisons between reinforcement-learning and degraded Bayesian Observer Models, and convergent behavioural and pupillometric data. Expanding formal model comparisons (e.g., BIC/AIC) and directly contrasting RL and Bayesian fits to physiological markers would further enhance the work, but these are minor limitations that do not detract from the core findings.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study, from the group that pioneered migrasome, describes a novel vaccine platform of engineered migrosomes that behave like natural migrasomes. Importantly, this platform has the potential to overcome obstacles associated with cold chain issues for vaccines such as mRNA. In the revised version, the authors have addressed previous concerns and the results from additional experiments provide compelling evidence that features methods, data, and analyses more rigorous than the current state-of-the-art. Although the findings are important with practical implications for the vaccine technology, results from additional experiments would make this an outstanding study.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors provide compelling evidence that a chloride ion stabilizes the protonated Schiff base chromophore linkage in the animal rhodopsin Antho2a. This important finding is novel and of major interest to a broad audience, including optogenetics researchers, protein engineers, spectroscopists, and environmental biologists. The study combines state-of-the-art research methods, such as spectroscopic and mutational analyses, which are complemented by QM/MM calculations, and was further improved based on the comments from the reviewers.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study employs transition-metal FRET (tmFRET) and time-correlated single-photon counting to investigate allosteric conformational changes in both isolated cyclic nucleotide-binding domains (CNBDs) and full-length bacterial CNG channels, demonstrating that transmembrane domains stabilize CNBDs in their active state. By comparing isolated CNBD constructs with full-length channels, the authors reveal how allosteric networks couple domain movements to gating energetics, providing insights into ion channel regulation mechanisms. The rigorous methodology and compelling quantitative analysis establish a framework for applying tmFRET to study conformational dynamics in diverse protein systems.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors provide a convincing summary of ten years of Brain Initiative funding including the historical development, the specific funding mechanisms, and examples of grants funded and work produced. It is particularly valuable at this moment in history, given the cataclysmic changes in the US government structure and function occurring in early 2025.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This manuscript provides valuable insights into the heterogeneity of hematopoietic stem cells and age-associated myeloid-biased hematopoiesis. While several aspects of the study are intriguing and merit further investigation, the current results remain incomplete and additional data are necessary to substantiate the conclusions. Some of the methods and data analyses partially support the claims.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this valuable study, Taber et al used a battery of biophysical and structural approaches to characterize the impact of erythrocytosis-related mutations in prolyl hydroxylase domain protein 2 (PHD2). The authors show that PHD2 mutant proteins are destabilized, thus supporting the tenet that dysregulation of PHD2/hypoxia induced factor (HIF) axis underpins erythrocytosis, while providing incomplete evidence that N-terminal ODD prolyl hydroxylation of HIF is indispensable for these phenotypes. Notwithstanding that this study was found to be of broad interest for a variety of fields focusing on oxygen sensing in homeostasis and pathological states, resolving inconsistencies in the biophysical analysis (e.g., NMR, SEC, and BLI/MST) was thought to be warranted to further corroborate the proposed model.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Based on several lines of interesting data, the authors conclude that FMRP, though associated with stalled ribosomes, does not determine the position on the mRNAs at which ribosomes stall. Although this conclusion would be valuable if clearly established, the current set of data are incomplete and it is unclear if the methodologies applied in this paper are fully adequate to address this gap.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this study, the authors investigate the role of ZMAT3, a p53 target gene, in tumor suppression and RNA splicing regulation. Using quantitative proteomics, the authors uncover that ZMAT3 knockout leads to upregulation of HKDC1, a gene linked to mitochondrial respiration, and that ZMAT3 suppresses HKDC1 expression by inhibiting c-JUN-mediated transcription. This set of convincing evidence reveals a fundamental mechanism by which ZMAT3 contributes to p53-driven tumor suppression by regulating mitochondrial respiration.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In their study, Neiswender et al. provide important insights into how BicD2 variants linked to spinal muscular atrophy alter dynein activity and cargo specificity. While the findings suggest disease-relevant changes in BicD2's binding partners, the evidence connecting these changes to disease mechanisms remains incomplete and would benefit from further experimental validation. The work lays a strong foundation for future research, but could be strengthened by deeper functional analysis of key interactions, such as the BicD2/HOPS complex.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study identifies asymmetric dimethylarginine (ADMA) histones as potential determinants of the initial genomic binding of Rhino, a Drosophila-specific chromatin protein essential for piRNA cluster specification. The authors provide correlative genomic and imaging data to support their model, although functional validation of the proposed mechanism remains incomplete. The authors could revise the manuscript to reflect that they have uncovered a small subset of piRNA clusters dependent on ADMA-histones, which may not be the general rule.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is a useful study in the role of CHI3L1 in Kupffer cells, the macrophages of the liver, showing that CHI3L1 alters glucose regulation in obesity. Specifically, Chi3l1 protects glucose-dependent Kupffer cells during Metabolic dysfunction-associated steatotic liver disease (MASLD) by inhibiting glucose uptake, preventing metabolic stress and death. These data are compelling, yet require further validation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable manuscript provides convincing evidence that BK and CaV1.3 channels can co-localize as ensembles early in the biosynthetic pathway, including in the ER and Golgi. The findings, supported by a range of imaging and proximity assays, offer insights into channel organization in both heterologous and endogenous systems. However, mechanistic questions remain unresolved, particularly regarding the specificity of mRNA co-localization, the dynamics of ensemble trafficking, and the functional significance of pre-assembly at the plasma membrane. While the data broadly support the central claims, certain conclusions would benefit from more restrained interpretation and additional clarification to enhance the manuscript's impact and rigor.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides valuable insights into a new toxin-antidote element in C. elegans, the first naturally occurring unlinked toxin-antidote system where endogenous small RNA pathways post-transcriptionally suppress the toxin. The strength of evidence is solid, using a combination of genomic and experimental methods. Enthusiasm, however, is tempered by its reliance on meta-analysis of existing data sets and limited experimental evaluation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study uses long-term behavioural observations to understand the factors that influence female-on-female aggression in gorilla social groups. The evidence supporting the claims is convincing, as it includes novel methods of assessing aggression and considers other potential factors. The work will be of interest to broad biologists working on the social interactions of animals.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important work by Malita et al. describes a mechanism by which an intestinal infection causes an increase in daytime sleep through signaling from the gut to the blood-brain barrier. Their findings suggest that cytokines upd3 and upd2 produced by the intestine following infection act on glia of the blood brain barrier to regulate sleep by modulating Allatostatin A signaling. The evidence is compelling and elegantly performed using the ample Drosophila genetic toolbox, making this work appealing for a broad group of neuroscience researchers interested in sleep and gut-brain interactions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable study investigates the selectivity of neuronal responses in the neocortex and thalamus to visual stimuli presented far outside their receptive fields. The study shows convincing evidence for a long-latency surround-induced response in primary visual cortex that is absent in the dorsal lateral geniculate nucleus and does not depend strongly on the visual characteristics of the surround stimulus. The paper should be of interest to neurophysiologists interested in vision and contextual modulations.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study addresses how wing morphology and kinematics change across hoverflies of different body sizes. The authors provide convincing evidence that there is no significant correlation between body size and wing kinematics across 28 species and instead argue that non-trivial changes in wing size and shape evolved to support flight across the size range. Overall, this paper illustrates the power and beauty of an integrative approach to animal biomechanics and will be of broad interest to biologists, physicists and engineers.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This is an overall valuable set of findings on the role of centrally produced estrogens in the control of behaviors in male and female medaka. The significance of the findings rests on the revealed potential mechanism between brain derived estrogens modulating social behaviors in males as well as females. The results are supported by the analysis of multiple transgenic lines although the evidence is incomplete, and further validation would be necessary to fully validate the conclusions on the role of brain-derived estrogens. Nonetheless, the findings have led to helpful hypotheses on the hormonal control of behaviors in teleosts that can be tested further.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study combines imaginative experiments to demonstrate the relevance of poroelasticity in the mechanical properties of cells across physiologically relevant time and length scales. Through innovative experiments and a finite element model, the authors present solid evidence that cytosolic flows and pressure gradients can persist in cells with permeable membranes, generating spatially segregated influx and outflux zones. These findings will be of interest to the cell biology and biophysics communities. Nevertheless, a more in depth discussion of why other possible explanations for the long time scales associated to mechanical propagation are less effective could further strengthen their message.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife Assessment
This study makes a novel and valuable contribution by adapting step selection functions, traditionally used in animal ecology, to explore human movement and environmental risk exposure in urban slums, offering a promising framework for spatial epidemiology, particularly regarding leptospirosis. The integration of GPS telemetry with environmental data and the stratification by gender and serostatus are notable strengths that enhance the study's relevance for public health applications. The strength of evidence is compelling.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Alignment and sequencing errors are a major concern in molecular evolution, and this valuable study represents a welcome improvement for genome-wide scans of positive selection. This new method seems to perform well and is generally convincing, although the evidence could be made more direct and more complete through additional simulations to determine the extent to which alignment errors are being properly captured.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
In this valuable study, the authors provide a simple yet elegant approach to identifying therapeutic targets that synergize to prevent therapeutic resistance in ovarian cancer using cell lines, data-independent acquisition proteomics, and bioinformatic analysis. The authors convincingly identify several combinations of pharmaceuticals that were able to overcome or prevent therapeutic resistance in culture models of ovarian cancer, a disease with an unmet diagnostic and therapeutic need. However, the extent to which these findings may extend to more complex models of ovarian cancer remains unclear.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife Assessment
This is a valuable study that suggests that HPV-human DNA junctions can be identified from cfDNA in women with cervical cancer and that detection of these junctions is indicative of recurrence. The evidence supporting the conclusions is incomplete, in part because the numbers of reads identifying breakpoints in tumor samples or in circulating cell-free serum samples are not provided. More quantitative analysis will be required to confirm that the breakpoints represented in cell-free DNA can be used as a surrogate to monitor the recurrence of cervical cancer cells, and additional patient studies would also be needed to strengthen the study. This work will be of interest to those who study and treat cervical cancer as well as other HPV-related malignancies.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This manuscript reports an important finding for understanding the molecular mechanisms of mutagenesis, carcinogenesis, and senescence. It follows a previous report showing that the Werner syndrome protein WRN and its interacting protein WRNIP1 are indispensable for translesion DNA synthesis (TLS) by Y-family DNA polymerases (Pols). The manuscript provides convincing evidence that WRN and WRNIP1 ATPases, in addition to the previously reported role of the WRN 3'>5' exonuclease activity, are essential for promoting the fidelity of replication through DNA lesions by Y-family Pols in human cells.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study presents important findings on increased ground beetle diversity in strip cropping compared with crop monocultures. Solid methods are used to analyze data from multiple sites with heterogeneous systems of mixed crops, allowing broad conclusions, albeit at the expense of lacking taxonomic specificity. The work will be of interest to all those applying plant diversity treatments to improve the diversity of associated animals in agricultural fields.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study investigates how hummingbird hawkmoths integrate stimuli from across their visual field to guide flight behavior. Cue conflict experiments provide solid evidence for an integration hierarchy within the visual field: hawkmoths prioritize the avoidance of dorsal visual stimuli, potentially to avoid crashing into foliage, while they use ventrolateral optic flow to guide flight control. These findings will be of broad interest to enthusiasts of visual neuroscience and flight behavior.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
By combining the 'pinging' technique with fMRI-based multivariate pattern analysis, this important study provides convincing evidence for a dual-format of attentional representation during preparatory period. The result reconciles the competing views between the sensory-like versus non-sensory accounts of attentional template and advances our understanding of how the brain flexibly utilizes different versions of template to guide attention. This work will be of interest to researchers in psychology, vision science, and cognitive science.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study aims to clarify the effects of cochlear neural degeneration on auditory processing in listeners with normal audiograms (sometimes referred to as 'hidden hearing loss'). The authors provide important new data demonstrating associations between cochlear neural degeneration, non-invasive assays of auditory processing, and speech perception. Based on a cross-species comparison, the findings pose compelling evidence that cochlear synaptopathy is associated with a significant part of hearing difficulties in complex environments.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides valuable findings on the effects of mating experience on sweet taste perception. The data as presented provide convincing evidence that the dopaminergic signaling-mediated reward system underlies this mating state-dependent behavioral modulation. The work will interest neuroscientists and particularly biologists working on neuromodulation and the effects of internal states on sensory perception.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The authors examine the effect of cell-free chromatin particles (cfChPs) derived from human serum or from dying human cells on mouse cells in culture and propose that these cfChPs can serve as vehicles for cell-to-cell active transfer of foreign genetic elements. The work presented in this paper is intriguing and potentially important, but it is incomplete. At this stage, the claim that horizontal gene transfer can occur via cfChPs is not well supported because it is only based on evidence from one type of methodological approach (immunofluorescence and fluorescent in situ hybridization (FISH)) and is not validated by whole genome sequencing.
-
-
www.biorxiv.org www.biorxiv.org
-
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 three types of downstream PPN neurons - GABAergic, glutamatergic, and cholinergic neurons - and carefully map connectivity along the rostrocaudal axis of the PPN. Overall, this important study provides convincing data on PPN connectivity with two key input structures that will provide a basis for further understanding PPN function.
-
-
-
eLife Assessment
This useful modeling study shows how spatial representations similar to experiment emerge in a recurrent neural network trained on a navigation task by requiring path integration and decodability, but without relying on grid cells. The network modeling results are solid, although the link to experimental data may benefit from further development.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important work by Diallo et al. substantially advances our understanding of the chemosensory system of a non-hymenopteran eusocial insect by identifying the first olfactory receptor for the trail pheromone in termites. The evidence supporting the conclusions that the receptor PsimOR14 is very narrowly tuned for the pheromone neocembrene is compelling. The work will be of broad interest to entomologists, chemical ecologists, neuroscientists, and molecular biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This manuscript reports effects of a single dose of methamphetamine vs placebo on a probabilistic reversal learning task with different levels of noise, in a large group of young healthy volunteers. The paper is well written and the methods are rigorous. The findings are important and have theoretical or practical implications beyond a single a subfield. The strength of the evidence is convincing, with the methods, data, and analyses broadly supporting the claims in the paper, which are sufficiently qualified given the lack of a significant effect of the binary baseline performance variable, and the nonlinear effect of individual differences in baseline performance.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
Bonnifet et al. present data on the expression and interacting partners of the transposable element L1 in the mammalian brain. The work includes important findings addressing the potential role of L1 in aging and neurodegenerative disease. The reviewers conclude that several aspects of the study are well done. However, the experimental evidence presented supporting the L1 increase with aging is not fully conclusive and this finding remains incomplete in its current form.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This fundamental study describes patterns of anatomical connectivity between the cortex and the thalamus using magnetic resonance imaging data in humans and non-human primates. The measures are related to numerous other modalities to develop a robust understanding of the organisation of the system. The authors provide convincing evidence that there is a difference between sensory and association cortices in terms of their connectivity with the thalamus, which may have downstream effects on brain function. This work will be of interest to neuroscientists interested in the organization and dynamics of cortico-thalamic circuits.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The manuscript reports fundamental findings supported by convincing data that supports the biological mechanism for optimal nodulation in soybean. The results are of relevance to understanding the signaling pathways (specifically those dependent on RIN4/RPM1-interacting protein 4) underpinning beneficial rhizobia symbiosis, while repressing the immune response.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This paper shows that it is possible to optogenetically activate single retinal ganglion cells in vivo in monkeys. This is an important step towards towards causal tests of the role of specific ganglion cell types in visual perception. The paper presents convincing evidence for the promise of the approach but further work will be needed to full explore its limitations and specificity.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
The study reports an important finding on the role of the global metabolic regulator Crp/cAMP in the formation of antibiotic persister Escherichia coli. The evidence supporting the claims is solid including metabolomic analysis and characterization of many mutant strains.
-
-
-
eLife Assessment
This study introduces a valuable spring-bead model for epithelial cell layers, designed to improve previous cell-resolved approaches and to understand the connection between the biophysics of cell-cell contacts and the tissue mechanics. While the model is not entirely new and does not fully settle open questions such as the role of adhesion in tissue fluidity, it provides solid evidence and stands out as simple and efficient. A more comprehensive comparison with previous cell-revolved approaches and, in particular, with experimental data, would further strengthen the proposed model as a conceptual and practical tool.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This important study utilizes the nematode C. elegans and mammalian cell culture to investigate the role of MML-1/Mondo in conserved regulation of metabolism and aging. The evidence supporting the conclusions is convincing and covers a range of areas including localization, upstream pathways, and conservation. The paper will be of interest to a broad range of biologists studying aging, metabolism, and transcriptional regulation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This Research Advance manuscript further elucidates the roles of SMC5/6 loader proteins and associated factors in the silencing of extrachromosomal circular DNA by the SMC5/6 complex. While the findings are largely in line with expectations, they are useful, representing a meaningful advance beyond the recent study (reference 33), contributing to a growing foundation for further comparative and mechanistic investigations. Solid evidence is presented for a role for SIMC1/SLF2 in the localization of the SMC5/6 complex to plasmid DNA, and the distinct requirements, as compared to the recruitment of SMC5/6 to chromosomal DNA lesions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This paper discusses the cognitive implications of potential intentional burial, wall engraving creation, and fire as light source use behaviors by relatively small-brained Homo naledi hominins. The discussion presented in the paper is valuable theoretically in its healthy questioning of prior assumptions concerning the socio-biological constraints of hominin meaning-making behavior. The discussion also contributes practically given that these behaviors have been ascribed to Homo naledi in two associated papers. Still, the present paper does not fully engage with the extent to which the strength of evidence supporting the H. naledi behavior conclusions across the two associated papers remains actively questioned, and thus the inferences here may be considered incomplete. The ultimate assessment of this work will vary among individual readers depending on how they view this debate, at least until further evidence leading to a broader consensus is published.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This study provides an important understanding of the contribution of different striatal subregions, the anterior Dorsal Lateral Striatum (aDLS) and the posterior Ventrolateral Striatum (pVLS), to auditory discrimination learning. The authors have included robust behavior combined with multiple observational and perturbation techniques. The data provided are convincing of the relevance of task-related activity in these two subregions during learning.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This valuable paper used a longitudinal cohort of individuals initiating ART to suggest that CD8+ T cells may contribute to the clearance of intact HIV DNA during long-term antiretroviral therapy (ART) for HIV, which is relevant to our understanding of the mechanisms driving reservoir persistence in people living with HIV. The reviewers concluded that the evidence presented is incomplete to fully support these claims, as the cohort sampling is relatively infrequent, and the association direction could be bi-directional or due to other confounding variables.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife Assessment
This paper examines selection on induced epigenetic variation ("Lamarckian evolution") in response to herbivory in Arabidopsis thaliana. The authors find weak evidence for such adaptation, which contrasts with a recently published study that reported extensive heritable variation induced by the environment. The authors convincingly demonstrate that the findings of the previous study were confounded by mix-ups of genetically distinct material, so that standing genetic variation was mistaken for acquired (epigenetic) variation. Given the controversy surrounding the influence of heritable epigenetic variation on phenotypic variation and adaptation, this study is an important, clarifying contribution; it serves as a timely reminder that sequence-based verification of genetic material should be prioritized when either genetic identity or divergence is of importance to the conclusions.
-