eLife assessment

This valuable work extends previous studies showing that the striatum multiplexes various aspects of locomotion, including velocity and movement transitions, by demonstrating that striatal neurons also encode single-limb gait. The authors present solid evidence to show that gait deficits induced by severe unilateral dopamine depletion are associated with an imbalance in the gait modulation of striatal firing. Although the source and function of this gait modulation remain unclear, this manuscript uncovers a role of striatal activity in gait, which may have implications for understanding gait disturbances in Parkinson's Disease.

eLife assessment

The manuscript by Jingsong Zhou and colleagues tries to uncover the reasons for the resistance of extraocular muscles (EOMs) to degenerative changes induced by amyotrophic lateral sclerosis (ALS). The findings of the study offer valuable information that EOMs are spared in ALS because they produce protective factors for the NMJ and, more specifically, factors secreted by EOM-derived satellite cells. While most of the experimental approaches are convincing, the use of sodium butyrate (NaBu) in this study needs further investigation, as NaBu might have a variety of biological effects. Overall, this work may help develop future therapeutic interventions for patients with ALS.

eLife assessment

This useful study uses a chemoinformatics pipeline to identify a list of candidate mosquito repellants that may be pleasant to smell and safe for humans. The computational methodology is solid, but insufficiently benchmarked against other leading models. At the high concentrations tested, there may also be off-target effects of the repellents on the mosquitoes that are not considered. This paper may be of interest to specialists interested in the discovery of new mosquito repellents.

eLife assessment

This study reports a potentially important discovery that testosterone-induced metabolic changes in seminal vesicle epithelial cells lead to the production of oleic acids in seminal plasma to enhance sperm fertility. The evidence to support metabolic changes in seminal vesicles and the identification of oleic acid as a key factor in seminal plasma is solid. However, the evidence for how oleic acids support enhanced sperm fertility in vivo is not well supported, thus currently remains incomplete, and requires further study.

eLife assessment

This work is potentially useful because it has generated a mineable yield of new candidate immune inhibitory receptors, which can serve both as drug targets and as subjects for further biological investigation. It is noted however that the work is rather incomplete, in that it does little to validate the putative new receptors, and instead makes a study of their putative distribution across cell types. Experimental follow-up to demonstrate the claimed properties for the proteins identified, or mining existing experimental data sources on gene expression across tissues to at least show that the pipeline correctly identified genes likely to be specific to immune cells, would make this work more complete.

eLife assessment

This study provides valuable new insights as to how two evolutionary conserved motifs in CD4 contribute to the CD4-mediated enhancement of TCR signaling independently of the CD4-LCK interaction. The data at hand are convincing, even if confined to a cell line model and not substantiated in vivo and with little new mechanistic insight provided regarding the domains of CD4 shown to have significant roles in the signaling process. Without the data from primary cells it is difficult to make statements about the quantitative contribution of LCK-dependent and independent functions of CD4 in TCR signaling.

eLife assessment

This solid study addresses the unresolved question of why many thousands of small-effect loci contribute more to the heritability of a trait than the large-effect lead variants. The authors explore resource competition within the transcriptional machinery as one possible explanation with a simple theoretical model, concluding that the effects of resource competition would be too small to explain the heritability effects. The topic and approximation of the problem are important and offer an intuitive way to think about polygenic variation, but there are concerns on the derivation of the equations with respect to dropping vs. including certain terms that deal inherently with small numbers.

eLife assessment

This important study examines the ancestral function of Hippo pathway kinases in contractility and cell density in the ameboid organism Capsaspora owczarzaki, a unicellular animal that is a close relative of multicellular animals. There is convincing evidence for Hippo kinases regulating contractility and cell density but not proliferation in C. owczarzaki. The work complements previous work on the Hippo effector Yorkie homolog in this species, although the unavailability of extensive genetic tools in this species precludes informative epistasis experiments. The work would be of interest to evolutionary and developmental biologists.

eLife assessment

This manuscript presents valuable findings that contribute to our understanding of how sphingolipids and membrane contact sites, formed by the tethering protein family tricalbins, are involved in regulating vacuolar morphology in S. cerevisiae. The evidence supporting the authors' claims is largely solid: while the reported correlation between sphingolipid levels and vacuole homeostasis is intriguing, the data do not completely substantiate the proposed mechanism. This study will be of interest to cell biologists focusing on intracellular organization and lipid metabolism.

eLife assessment

This manuscript presents valuable findings that contribute to our understanding of how sphingolipids and membrane contact sites, formed by the tethering protein family tricalbins, are involved in regulating vacuolar morphology in S. cerevisiae. The evidence supporting the authors' claims is largely solid. While the reported correlation between sphingolipid levels and vacuole homeostasis is interesting and intriguing, more work is needed to thoroughly substantiate the proposed mechanism. This study will be of interest to cell biologists focusing on intracellular organization and lipid metabolism.

eLife assessment

This manuscript presents a valuable approach to exploring CD4+ T-cell response in mice across stimuli and tissues through the analysis of their T-cell receptor repertoires. The authors use a transgenic mouse model with reduced diversity of the T-cell receptor repertoire to elicit more consistent T-cell responses across individuals, demonstrating challenge-specific and tissue-specific responses of regulatory T-cells. The evidence for the authors' conclusions is solid, and the work will be of interest to immunologists studying T cell responses.

eLife assessment

The study presents valuable findings on sexually dimorphic patterns of osteocytic transcriptomes and low calcium diet-induced osteocytic osteolysis in FNDC5-deficient mice. The authors present solid evidence for sex-specific changes in osteocyte morphology and gene expression under a calcium-demanding setting in this particular strain of mice, although the protective role of FNDC5-deficiency in lactation and low-calcium diet in female mice remains unclear due to lack of mechanistic studies. The study also lacks evidence that irisin, a proteolytically cleaved product of FNDC5, is responsible for the observed phenotypes, as irisin was not directly measured.

eLife assessment:

This valuable work substantially advances our understanding of the organization of neural dynamics relative to behavioral outputs within recurrent neural networks, with implications for biological neural networks. Evidence supporting the conclusions is convincing, with rigorous analyses of neural variance and robustness to noise. The work will be of broad interest to neuroscientists studying computation through dynamics.

eLife assessment

This work presents a valuable data-driven method to extract the "true" synaptic plasticity rule (or learning rule) operating in a neural circuit from empirical measurements of neural activity. The approach aims to train a generative adversarial network (GAN) to match neural activity measurements in terms of statistics, learning them from the data, rather than being pre-determined by the experimenter. The main conclusion is that the extracted learning rules are not unique, but rather degenerate, meaning that multiple plasticity rules can produce the same neural activity. Although the paper presents a thorough investigation using one learning rule as a case study (the Oja rule), the evidence that the results can be inferred beyond the specific numerical experiments presented in the paper is incomplete.

eLife assessment

This valuable study presents convincing evidence for an association between PARP-1 and H4K20me1 in transcriptional regulation, supported by biochemical and ChIP-seq analyses. The work contributes significantly to our understanding of how Parp1 associates with target genes to regulate their expression.

eLife assessment

This paper presents useful results that extend our understanding of how the visual cortex encodes temporal structure, providing new information about sequence representations in superficial layers of the visual cortex. The evidence for prediction errors is solid, however, support for other claims regarding sparsification and simplification of activity following training is incomplete.

eLife assessment

The authors analyze the role of newborn astrocytes in the modulation of glial scar formation in a middle carotid artery occlusion (MCAO) hypoxia lesion model. The findings are valuable because they have implications for understanding the molecular and cellular processes contributing to brain repair in response to ischemia. The results are currently incomplete, in the absence of data showing: (i) cell-target specificity of molecular markers for newborn astrocytes; (ii) consistent phenomena across different rodent species.

eLife assessment

This valuable paper by Yao, Dai, and colleagues describes a viral gene drive against herpes simplex virus 1 in cell culture. The authors provided solid evidence that an engineered gene drive sequence, expressing either spCas9 or Un1Cas12f1 nuclease, could spread efficiently in the population of wild-type viruses and induce fewer drive-resistant mutations than spCas9. Limitations include a mechanistically inaccurate title, several methodologic flaws, and a paucity of descriptions of possible therapeutic applications.

eLife assessment

This fundamental work significantly advances our understanding of how FOG1 nuclear localization is regulated during erythropoiesis and megakaryopoiesis, including the role of EPO and MPL/TPO signaling in this process. The authors provide compelling evidence using both K562 and CD34+ cells that heat shock cognate B (HSCB) can promote the proteasomal degradation of TACC3 to regulate the nuclear localization of FOG1, and that this function is independent of its role in iron-sulfur cluster (ISC) biogenesis. The conclusions would be strengthened in the future by the use of in vivo model systems, however, as written, this work will be of broad interest to cell biologists.

eLife assessment

This study is an important contribution to our insights into the impact of heat stress on sexual reproduction in plants and provides information about how centromere integrity is affected by heat stress during male meiosis in Arabidopsis thaliana. The evidence supporting the claims, specifically the dynamics of tagged proteins in meiocytes by live cell imaging is solid, even though a deeper mechanistic understanding is still lacking.

eLife assessment

This manuscript provides important insights into the degradation of the host tRNA modification enzyme TRMT1 by the SARS-CoV-2 protease Nsp5 (nonstructural protein 5 or MPro). The data convincingly support the main conclusions of the paper. These results will be of interest to virologists studying the alterations in tRNA modifications, host methyltransferases, and viral infections.

eLife assessment

This article provides a review and test of image-analysis methods for bacteria growing in the 'mother-machine' microfluidic device, introducing also a new graphical user interface for the computational analysis of mother-machine movies based on the 'Napari' environment. The tool allows users to segment cells based on two previously published methods (classical image transformation and thresholding as well as UNet-based analysis), with solid evidence for their robust performance based on comparison with other methods and use of datasets from other labs. While it was difficult to assess the user-friendliness of the new GUI, it appears to be valuable and promising for the field.

eLife assessment

This valuable study informs on the regulation of metabolic flux between glycolysis and respiration in yeast, mediated by inorganic phosphate. The authors propose a novel mechanism involving Ubp3/Ubp10 that potentially mitigates the Crabtree effect, based on an array of assays that offer substantial insight into mitochondrial biogenesis under high glucose conditions. However, the evidence supporting the conclusions remains incomplete because of a limited number of replicates, particularly in protein blot analyses with insufficient normalization methods, which undermines the robustness of the findings. This work could influence the subfield significantly if the methodological weaknesses are addressed to provide more support for the proposed model.

eLife assessment

This valuable study examines the evolution of the pillars in the shell architecture of organo-phosphatic brachiopods. The phylogenetic implications of this shell structure in relation to other early Cambrian brachiopod families are interpreted based on solid evidence. As such, this paper with interesting ideas regarding the evolution of brachiopod shell structure contributes to our understanding of the ecology and evolution of brachiopods as a whole.

eLife assessment

This study investigated the factors related to understudied genes in biomedical research. It showed that understudied genes are largely abandoned at the writing stage, and it identified a number of biological and experimental factors that influence which genes are selected for investigation. The study is an important contribution to this branch of meta-research, and the evidence in support of the findings is solid.

eLife assessment

This study presents a valuable contribution towards understanding the protein target and mechanism of action of an herbicide, which could be applied to the development of herbicide-based technologies to improve crop yields. Evidence is gathered using a variety of technical approaches that enrich and support the findings, but the methodology and the presentation of the results are incomplete.

eLife assessment

This study provides a detailed evaluation of how HIV evades nascent immune pressure from people living with HIV followed nearly immediately after infection. There is convincing evidence that H173 mutations in the V2 loop was a key determinant of selection pressure and escape. These data are congruent with protection in the RV144 clinical trial, the only trial that showed protection from infection. Overall, this study is an important contribution to the field.

eLife assessment

This study presents two valuable new mouse models that individually tag proteins from the SMAD family to identify distinct roles during early pregnancy. Convincing evidence is provided that SMAD1 and SMAD5 target many of the same genomic regions as each other and the progesterone receptor. Given the broad effect of these signaling pathways in multiple systems, these new tools will most likely interest readers across biological disciplines.

eLife assessment

In this useful study, Wang and colleagues investigate the potential probiotic effects of Bacillus velezensis to prevent colitis in a mouse model. They provide solid evidence that B. velezensis limits the growth of Salmonella typhimurium in lab culture and in mice, together with beneficial effects on the microbiota. The work will be of interest to infectious disease researchers and those studying the microbiome.

eLife assessment

This study addresses an important long-standing controversy in the field of reproductive biology. Using cutting-edge techniques the authors provide compelling evidence supporting a pivotal role of prolactin as the mediator of lactational infertility. Some methodological, technical, interpretive, stylistic, and typographical aspects of the paper need to be strengthened.

eLife assessment

Spermiogenesis is a complex process allowing the emergence of specific sperm organelle, including the acrosome, a sperm giant vesicle of secretion. This important study reports the key role of Cylicin-1 in acrosome biogenesis and identifies the molecular partners necessary for acrosome anchoring. The compelling demonstration is based on infertile patient samples and two animal models. Overall, this provides results that will be invaluable to the male reproduction community, including scientists and andrologists.

eLife assessment

This manuscript provides useful findings to further explore the heterogeneity of hematopoietic stem cells and myeloid-biased hematopoiesis during aging. The results presented in this study are incomplete and additional data is needed to strengthen the conclusions. Some of the methods and data analyses, including the replicates and statistical robustness, remain inadequate to support the primary claims.

eLife assessment

This is a useful study that provides solid, yet confirmatory findings about the complex (FtsEX) that controls peptidoglycan remodeling during bacterial cell division. The authors capitalize on the finding that ATP binding stabilizes the FtsEX complex allowing structural characterization for this system. A model is then developed using biochemical approaches to explain ATP regulation. The resulting model would be strengthened were the authors to incorporate their structural findings as well as previously published work.

eLife assessment

This important study identifies a novel link between the early keratinocyte response to wounds and the subsequent regenerative capacity of local sensory neurons. The evidence supporting the claims of the authors is solid, although the inclusion of additional pharmacological and genetic manipulations might have strengthened the mechanistic aspects. The work will be of interest to cell and developmental biologists interested in tissue regeneration and cell interactions in a broader context.

eLife assessment

This study presents an important application of high-content image-based morphological profiling to quantitatively and systematically characterize induced pluripotent stem cell-derived mixed neural cultures cell type compositions. Convincing evidence through rigorous experimental and computational validations supports new potential applications of this cheap and simple assay.

eLife assessment

This work demonstrates an important regulatory role of the N-terminal disordered tail of small ubiquitin-like modifier (SUMO) proteins, which modulates the function of a variety of proteins in eukaryotic cells. The authors present convincing evidence that the N-terminal region of SUMO inhibits its own interaction with downstream effector proteins and SUMOylation targets. This new discovery significantly advances the field by providing a possible explanation of how SUMO paralogues select their effectors and SUMOylation targets.

eLife assessment

This manuscript reports important data on the stability of nucleosomes. Convincing evidence obtained by single-molecule FRET experiments shows that DNA unwrapping is found to be slower when a single CC base pair mismatch is introduced at three different positions. The work is carefully conducted and described clearly, but the biological significance and implications of the findings on cellular DNA metabolism remain unclear.

eLife assessment

This study reports an important finding highlighting the essential role of the putative ion channel, TMC7 (transmembrane channel-like 7) in male fertility, thereby significantly advancing our understanding of the function of the previously uncharacterized protein in sperm development. The evidence supporting TMC7's requirement in acrosome biogenesis during spermatogenesis is solid, and its function as an ion channel requires more study.

eLife assessment

This valuable study addresses how distinct cilia lengths of different cell types in zebrafish are regulated and proposed an interesting mechanism. While the quality of imaging and the resources generated in this study are excellent, key experimental information is not always provided and the strength of evidence to support the proposed hypothesis on ciliary length regulation is currently incomplete.

eLife assessment

This fundamental study employs a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry to elucidate the role of α-tubulin acetylation at the lumenal lysine 40 residue (αK40) within the cilium. Compelling evidence shows αK40 acetylation to impact the structure and stability of doublet microtubules in cilia by affecting the lateral rotational angle. The work will be of relevance to those interested in cytoskeleton and structural biology.

eLife assessment

The solid study addresses the role of extracellular matrix (ECM) in neuronal migration. The authors showed that the interaction between the ternary complex formed by tenascin-C, the chondroitin sulfate proteoglycan neurocan, and hyaluronic acid is important for the multipolar to bipolar transition in the intermediate zone (IZ) of the developing cortex

eLife assessment

This study provides an important insight into the mechanisms of cooperation between Hsp70 and its cochaperones during protein disaggregation. Based on compelling evidence, the authors demonstrate that Hsp110 increases Hsp70 recruitment to protein aggregates. This work is of broad interest to biochemists and cell biologists working in the protein homeostasis field.

eLife assessment

This manuscript highlights single-stranded DNA exo- and endo-nuclease activities of ExoIII as a potential caveat and an underestimated source of decreased efficiency in its use in biosensor assays. The data present convincing evidence for the ssDNA nuclease activity of ExoIII and identifies residues that contribute to it. The findings are useful, but the study remains incomplete as the effect on biosensor assays was not established.

eLife assessment

This valuable study presents findings that suggest the need for postoperative type 2 diabetes screening and that this should be prioritized in colorectal cancer survivors with overweight/obesity regardless of the type of colorectal cancer treatment applied. The evidence supporting the claims of the authors is solid and the authors use a population-based cohort study including all Danish colorectal patients who had undergone colorectal cancer surgery between 2001-2018. The work will be of interest to medical biologists, endocrinologists and oncologists working on colorectal cancer.

eLife assessment

This study presents a valuable inventory of immune signatures that are correlated with cancer treatment-related pneumonitis. The data were collected and analysed using validated methodology and can be used as a starting point for further prospective studies. The authors have provided a scRNA-Seq analysis with an HD baseline using publicly available dataset and the evidence for their claims is convincing.

eLife assessment

Pin1 as an essential prolyl cis/trans isomerase has attracted considerable attention because this enzyme family is implicated in cancer and neurodegenerative diseases. However, the requirement for its catalytic function remains a matter of dispute. The authors provide solid evidence that Pin1 modulates the activity of an important cell signaling kinase, Protein Kinase C, by a non-catalytic mechanism, acting as a chaperone to regulate the stability of this kinase.

eLife assessment

This computational study is a valuable empirical investigation into the common trait of neurons in brains and artificial neural networks: responding effectively to both objects and their mirror images and it focuses on uncovering conditions that lead to mirror symmetry in visual networks and the evidence convincingly demonstrates that learning contributes to expanding mirror symmetry tuning, given its presence in the data. Additionally, the paper delves into the transformation of face patches in primate visual hierarchy, shifting from view specificity to mirror symmetry to view invariance. It empirically analyzes factors behind similar effects in two network architectures, and key claims highlight the emergence of invariances in architectures with spatial pooling, driven by learning bilateral symmetry discrimination and importantly, these effects extend beyond faces, suggesting broader relevance. Despite strong experiments, some interpretations lack explicit support, and the paper overlooks pre-training emergence of mirror symmetry.

eLife assessment

This manuscript presents a detailed phenotyping of the role of dietary iron in a large number of genetically distinct mouse strains. There are exciting and convincing data that could be valuable in their impact on the fields of nutrition, iron metabolism and anemia.

• insulates nerve and speeds up the impulses between cells while supporting the neural pathways
• improves coordination, thought process and movement.
• present in adolescents but most dramatic first years

• helps master our complex skills. experience will determine which connections are kept in our brains.
• occurs during childhood and adolescence after blooming period

eLife assessment

This valuable study provides new insight into potential subtle dynamics in effector biology. The data presented generally support the claims, but in some cases controls are missing and so the overall work is currently incomplete. If the limitations can be addressed, this work should be of broad relevance for biologists interested in molecular plant-microbe interactions.

eLife assessment

This important study reveals the molecular basis of mutualism between a vector insect and a bacterium responsible for the most devastating disease in citrus agriculture worldwide. The evidence supporting the conclusions is compelling, with biochemical and gene expression analysis demonstrating the phenomenon. However, there are concerns related to the presentation, as well as lack of sufficient information about data analysis, both of which should be clarified and/or extended. With these matters addressed, this work will be of great interest to the fields of vector-borne disease control and host-pathogen interaction.

eLife assessment

This study presents valuable findings that expand our view of dopamine release in different brain regions and show that dopamine release in the lateral hypothalamus is related to the activity of orexin neurons. The evidence supporting the claims of the authors is solid, although inclusion of tests that directly assess causality of the noble pathways would have been even more conclusive. The work will be of interest of neuroscientists who study the neural basis of motivation.

eLife assessment

This manuscript claims to have found evidence for coordinated membrane potential oscillations in E. coli biofilms that can be linked to a putative K+ channel and that may serve to enhance photo-protection. The finding of waves of membrane potential would be of interest to a wide audience from molecular biology to microbiology and physical biology. Unfortunately, a major issue with the experimental technique affects the interpretation of the observations: the dye used has been previously shown not to report membrane potential, leaving the evidence inadequate.

eLife assessment:

The study answers the important question of whether the conformational dynamics of proteins are slaved by the motion of solvent water or are intrinsic to the polypeptide. The results from neutron scattering experiments, involving isotopic labelling, carried out on a set of four structurally different proteins are convincing, showing that protein motions are not coupled to the solvent. A strength of this work is the study of a set of proteins using spectroscopy covering a range of resolutions, however, it suffers from some scholarly shortcomings and limited discussion of results. The work is of broad interest to researchers in the fields of protein biophysics and biochemistry.

eLife assessment

This is an important study examining the role of prediction error in state allocation of memories. The data are convincing and largely support the conclusion that a gradual change between acquisition and extinction maintains the memory state of acquisition and, thus, results in extinction that is resistant to restoration. This paper is of interest to behavioural and neuroscience researchers studying learning, memory, and the neural mechanisms of those processes, as well as to clinicians using extinction-based therapies in treating anxiety-based disorders.

eLife assessment

Wound infections are very common and can lead to delayed wound healing or poor wound healing which significantly impacts morbidity and overall quality of life for patients. This manuscript uses scRNA-Seq to try to understand the impact of infection on various cell types during wound healing in a mouse model. The methodology is solid and the results provide a valuable 'atlas' of the cellular changes associated with infected and uninfected wounds which will of interest to the field.

eLife assessment

The paper investigates a potential cause of a type of severe epilepsy that develops in early life because of a defect in a gene called KCNQ2. The significance is fundamental because it substantially advances our understanding of a major research question. The strength of the evidence is convincing because appropriate methods are used that are in line with the state-of-the art, although there are some revisions/corrections that would strengthen the evidence further.

eLife assessment

The findings in this manuscript are important and novel, and the genomic analyses are convincing. This study expands upon our understanding of the role of hnRNP proteins in lncRNA function and the evidence is compelling, suggesting shared mechanism(s) in the regulation of ASARs and Xist RNAs by RBPs that bind Cot1 sequences in these lncRNAs. This manuscript should be of interest to the noncoding RNA and chromatin biology communities.

eLife assessment

This valuable study provides insights into how the brain parses the syntactic structure of a spoken sentence. Convincing evidence is provided that distributive cortical networks are engaged for incremental parsing of a sentence, and neural activity recorded by MEG correlates with sentence structure measures extracted by a deep neural network language model, i.e., BERT. A contribution of the work is to use a deep neural network model to quantify how the mental representation of syntactic structure updates as a sentence unfolds in time.

eLife assessment

This study enhances our understanding of the relationship between cortico-hippocampal interactions and behavioral performance. Using an inter-areal coherence metric to gate trial initiation in real time, the authors provide solid evidence that links high hippocampal-prefrontal theta coherence to correct performance on spatial working memory and cue-guided decision-making tasks. Although reviewers agreed that the results do not demonstrate causality between hippocampal-prefrontal synchrony and behavioral performance, the findings are viewed as important given their potential implications for brain-machine interface applications in humans.

eLife assessment

The reprocessing and reanalysis of archived samples can yield further insights from past experiments. Here, a useful procedure to perform tissue clearing and immunolabeling on large-scale formalin-fixed paraffin-embedded brain specimens is convincingly evaluated on a set of archival pathology specimens, and its applicability to further such samples is analyzed. This method will be of interest to both neuroscientists and pathologists.

eLife assessment

This important study presents relevant information about the involvement of TOR pathway in aflatoxin production by Aspergillus flavus. However, some of the presentation is confusing, leaving the study in its current form is incomplete. The strength of the evidence could be augmented with additional experiments and reorganization of the manuscript aiming to fully understand and characterize the involvement of TOR pathway in A. flavus aflatoxin production.

eLife assessment

This useful study, which systematically addresses off-target effects of a commonly used chemotherapy drug on bone and bone marrow cells and which therefore is of potential interest to a broad readership, presents evidence that reducing systemic inflammation induced by doxorubicin limits bone loss to some extent. Although the work does not inform in detail on the underlying mechanisms of doxorubicin action, the demonstration of the effect of systemic inflammation on bone loss is convincing. While not a new finding, the work sets the scene for additional genetic and pharmacologic experiments and a deeper analysis of the bone phenotype presented here, which should speak to the mechanisms involved in doxorubicin-induced bone loss and which may substantiate the clinical relevance of targeting inflammation in order to limit the negative impact of chemotherapies on bone quality.

eLife assessment

The results from this study, which investigates the mechanisms necessary for initiating tissue invagination using a cellular Potts modelling approach, suggests that apical constriction is not sufficient to drive the process by itself. The study highlights how choices inherent to modelling - such as permitting straight or curved cell edges - may affect the outcome of simulations and, consequently, their biophysical interpretation. Despite incomplete evidence supporting their major claims due to a rather coarse-grained exploration of the model, this work is useful for biophysicists investigating complex tissue deformation through computational frameworks.

eLife assessment

This important study reports the generation of genetic tools for manipulating several tissues at the same time in Drosophila. The authors provide convincing evidence that this allows for the generation of LexA and QF2 driver lines, which will be of great utility for understanding inter-organ communication. Making the tools available through the Drosophila stock center and plasmid depository will ensure that they are easily accessed by many researchers.

eLife assessment

In this important manuscript, Abd El Hay and colleagues reveal a clear role of TRPV1 and TRPM2 receptors in warm temperature perception and present a technically unique experimental strategy to measure and analyze temperature preference behavior, which will have a lasting impact on the field. In addition to the behavioral data, which is strong, the study provides an analysis of cultured sensory neurons to controlled warmth stimuli - in this case, the evidence relating the activity of TRPM2 channels to the behavioral responses of animals is incomplete. Overall, the findings are of importance for neuroscientists, physiologists, and biophysicists, as there is still substantial discussion in the field regarding the contribution of TRP channels to different aspects of thermosensation.

eLife assessment

This work presents an important online platform designed to facilitate the exploration of genes and genetic pathways implicated in human aging. Leveraging a new inference methodology, the tool enables the identification and visualization of key genes and tissues impacted by aging, facilitating scientific discovery. The methods and analyses are convincing and will be broadly used by scientists aiming to mine human aging RNA-seq data.

eLife assessment

This work will be of interest to the motor control community as well as neuroAI researchers interested in how bodies constrain neural circuit function. The authors present "MotorNet", a useful software package to train artificial neural networks to control a biomechanical model of an effector. The manuscript provides solid evidence that MotorNet is easy to use and can reproduce past results in the field, both at the neural and behavioural levels. Validation is limited to planar arm-like plants or point-masses, so future work exploring three-dimensional movements and other types of plants would strengthen the impact of the tool.

eLife assessment

The authors address the function of keratin 17 (K17), a marker of the most aggressive pancreatic ductal adenocarcinomas (PDACs). While this potentially useful study addresses a significant area of pancreatic cancer research, the lack of evidence demonstrating nuclear localization of K17 in human PDAC and the excessive reliance on a single cell line reduce the significance of the work. Moreover, the weak phenotypes of K17 phosphosite mutants provide incomplete support for the authors' mechanistic model.

eLife assessment

This potentially important paper addresses the question of how numerical information is represented in the human brain. Experimental findings are interpreted as providing evidence for a sensorimotor mechanism that involves channels, each tuned to a particular numerical range. While this is an interesting application of methodologies used to identify the presence of channels, the evidence supporting the claim that these have a sensorimotor basis is incomplete.

eLife assessment

In this manuscript, the authors present a wealth of fMRI data at both 3T and 7T to identify a scene-selective region of the intraparietal gyrus ("PIGS") that appears to have some responsivity to characteristics of ego-motion. In a series of experiments, they delineate the anatomical location of PIGS and functionally differentiate it from nearby V6 and OPA. Evidence for these important findings is solid, but further investigations as to the role of this region in processing ego-motion will be needed to confirm this conclusion.

eLife assessment

This valuable study showed convincing evidence that archerfishes can adapt their shooting behaviors to airflow perturbations. The fish also exhibits adaptive behaviors indicative of an egocentric representation of the perturbation, though direct evidence is missing. Hence, this work will be of interest to those interested in cross-species comparisons for motor learning.

eLife assessment

This useful study addresses the brain correlates underlying technical reasoning by a set of fMRI experiments and locates it to PF. If confirmed, this study provides an intriguing framework for our understanding of different types of problem-solving processes. However, the current evidence supporting the claims is incomplete, due to the existence of alternative explanations for the main overlapping results and potential confounding variables across conditions.

eLife assessment

This important study advances our understanding of the mechanisms of neuronal large dense-core vesicle (LDCV) secretion, which mediates neuropeptide and neurotrophin release. It describes a negative regulatory process involving the interaction of the Rab3-effector Rabphilin-3A with the SNARE fusion protein SNAP25, which limits LDCV secretion and neurite growth. The evidence in support of the authors' claims is solid overall, but some conclusions, e.g regarding the exact synaptic localization of Rabphilin-3A, its association with large dense-core vesicles, or the role of Rabphilin-3A-controlled neurotrophin signaling in neurite growth, are incompletely supported. This study will be of interest to the fields of cell biology, cellular neuroscience, and neuroendocrinology.

eLife assessment

This study provides valuable insights into understanding bone fragility in T2D patients through the use of human skeletal tissue, reinforcing previous pre-clinical studies or observational studies using serum samples that the Wnt signaling pathway may play a critical role in T2D-related bone impairment. The methods are solid, but a limited number of subjects and a small set of genes with lack of data in terms of cellular properties of skeletal tissue are viewed as weaknesses.

eLife assessment

This valuable study combines the use of Fisher Kernels with Hidden Markov models aiming to improve brain-behaviour prediction. The evidence supporting the authors' conclusions is solid, comparing brain-behaviour prediction accuracies across a range of different traits. This work is timely and will be of interest to neuroscientists working on functional connectivity for brain-behaviour association.

eLife assessment

This valuable study presents findings characterising the genomic features of E. coli isolated from neonatal meningitis from seven countries, and documents bacterial persistence and reinfection in two case studies. The genomic analyses are solid, although the inclusion of a larger number of isolates from more diverse geographies would have strengthened the generalisability of findings. The work will be of interest to people involved in the management of neonatal meningitis patients, and those studying E. coli epidemiology, diversity, and pathogenesis.

eLife assessment

This valuable study uses a model to determine when catalytic self-replication of polymers can emerge from a random pool of replicating polymers. The model accounts for the folding and function of polymers in addition to abstract evolutionary dynamics, providing solid evidence for the claims of the authors. The work will be of relevance to those interested in the origin of life, artificial cells, and evolutionary dynamics.

eLife assessment

In this fundamental study, the authors analyzed associations between circulating immune cells and periodontitis. Convincing evidence identifies three immune cell types related to periodontitis, which substantially advances our understanding of periodontitis.

eLife assessment

This valuable study combines in vitro and in vivo experiments designed to test if a deoxycytidine kinase inhibitor provides therapeutic benefit during infection with Staphylococcus aureus. Several in vitro methods used to measure therapeutic efficacy are thorough and compelling with appropriate conclusions drawn, however, the overall analysis is incomplete and would benefit from a more rigorous study design. With a strengthened study design, and more nuanced considerations of the strengths and limitations of the study, this paper would be of interest to bacteriologists, immunologists, and those studying host-microbe interactions.

eLife assessment

This valuable study combines in vitro and in vivo experiments designed to test if a deoxycytidine kinase inhibitor provides therapeutic benefit during infection with Staphylococcus aureus. The authors provide compelling evidence that this putative host-directed therapy has good potential to promote natural clearance of infection without targeting the bacterium. This paper would be of interest to bacteriologists, immunologists, and those studying host-microbe interactions.

Editors Assessment:

This is a Data Release paper describing data sets derived from the Pomar Urbano project cataloging edible fruit-bearing plants in Brazil. Including data sourced from the citizen science iNaturalist app, tracking the distribution and monitoring of these plants within urban landscapes (Brazilian state capitals). The data was audited and peer reviewed and put into better context, and there is a companion commentary in GigaScience journal better explaining the rationale for the study. Demonstrating this data providing a platform for understanding the diversity of fruit-bearing plants in select Brazilian cities and contributing to many open research questions in the existing literature on urban foraging and ecosystem services in urban environments.

This evaluation refers to version 1 of the preprint

eLife assessment

The authors provide solid evidence that any contribution of oligodendrocyte precursors to the developing cortex from the lateral ganglionic eminence is minimal in scope. The methods used support the conclusions, with some technical concerns that the authors can address with further experimentation. These are considered valuable additions to our understanding of the origins of oligodendrocytes in the forebrain during development.

eLife assessment

This useful study presents data regarding the presence of synaptic proteins in the extracellular vesicle pool present in the blood of Parkinson's patients and non-parkinson neurological outpatients, trying to correlate changes in such levels with the progression of Parkinson's symptoms. The results are semi-quantitative and preliminary, suggesting that these biomarkers could be used in the follow up of a specific group of Parkinson patients. The evidence is incomplete at this point, and more quantitative approaches are required to propose this correlation. The isolation of extracellular vesicles was appropriate as revealed by their sizes, but they are not exclusively from neuronal origin. The presented approach is not ready to be used in the clinical setting.

eLife assessment

This study unveils important mechanistic insights into postnatal lung development and bronchopulmonary dysplasia (BPD) pathology. Using two BPD models enhances our comprehension of the disease, utilizing compelling evidence from single-cell sequencing and flow cytometry, revealing a myofibroblast loss. Pharmacological and genetic approaches convincingly argue against the presumed increase in TGFb signaling causing alveolar simplification; instead, it appears to be a compensatory response. The identified weakness is the absence of validation in tissue, leaving the question unanswered regarding whether myofibroblast loss is due to a lack of myofibroblast proliferation or myofibroblast differentiation/specification.

eLife assessment

Herein, Xie and colleagues use a hamster model to show that Leptospira infection leads to gut pathology, an altered gut microbiota, and increased translocation. A combined use of antibiotics and LPS neutralization prolonged survival, providing a potential new therapeutic approach. This fundamental study uses compelling methods to provide new insights into this emerging disease, which could be dissected further in future studies aimed at gaining mechanistic insight and assessing the translational relevance of these discoveries.

eLife assessment

This manuscript provides potentially valuable information suggesting that the earliest appearing T-cells during ontogeny may have properties that are fundamentally distinct from those appearing later in life. At this stage, weaknesses in the experimental design and data interpretation provide inadequate support for the conclusions. With modifications, the paper should be of interest to those interested in T-cell development.

eLife assessment

This study characterizes the composition and immune diversity of the zebrafish kidney, the immune organ equivalent to human bone marrow, with convincing single-cell transcriptomic data of hematopoietic cells and immunocytes. The key findings suggest that zebrafish kidney is a secondary lymphatic organ, and that hematopoietic stem cells in zebrafish may exhibit trained immunity, which are the unique features of the fish immune system. This study provides new and valuable insights into the antiviral response in teleost fish, which will be of interest to biologists in general, and to immunologists and cancer researchers in particular.

eLife assessment

This work describes a valuable new technique involving proximity labelling to identify Drosophila proteins modified by GlcNAcylation in subsets of cells in vivo. A solid set of experiments shows that several ribosomal proteins are modified in the fly mushroom body. Consistent with a role for GlcNAcylation of ribosomal proteins in control of memory related translational control, the authors show that perturbation of GlcNAc modification in KCs prevents efficient consolidation of long-term memory.

eLife assessment

This important work substantially advances our understanding of how resistant leukemia can arise without changes in mutational patterns by displaying epigenetic changes. The evidence supporting the conclusions is compelling, with rigorous genomic assays done on primary samples. and state-of-the-art microscopy. The work will be of broad interest to hematologists and cancer biologists.

eLife assessment

This important study outlines how the agr quorum sensing system in Staphylococcus aureus confers long-lived protection against oxidative stress, thereby linking bacterial metabolism to virulence in this pathogen. While the findings, which are supported by solid data, seem at first glance to contradict earlier findings that show increased fitness of agr mutants under oxidative stress, the core conclusions of the study are well-substantiated. The authors should, however, re-evaluate their interpretations related to the impact of agr inactivation on bacterial metabolic and redox status following oxidative stress. The topic of the paper holds broad relevance to microbiologists, especially those focusing on host-pathogen interactions and bacterial responses to ROS.

eLife assessment

The report presents the cryo-EM structure of human vesicular monoamine transporter 2 (VMAT2) bound to tetrabenazine, a clinical drug. VMAT2 is critical for neurotransmission, and the study constitutes an important milestone in neurotransmitter transport research. The evidence presented in the report is convincing and provides new opportunities for developing improved therapeutic interventions and furthering our understanding of this vital protein's function.

eLife assessment

This study provides valuable observations indicating that human pyramidal neurons propagate information as fast as rat pyramidal neurons despite their larger size. Solid evidence demonstrates that this property is due to several biophysical properties of human neurons. This study will be of interest to neurophysiologists.

eLife assessment

Varadharajan et al. explore the mechanistic basis of MBOAT7 SNP association with steatotic liver disease and link its function in LPI acylation to altered lipidomics of endosomal/lysosomal system and impaired TFEB mediated lysosomal biogenesis. The findings are important with theoretical and practical implications in MAFLD, alcohol-induced hepatic steatosis, and lysosomal diseases. The strength of evidence is convincing using methodology in line with current state-of-the-art.

eLife assessment

This important study follows up on previous work defining the anti-leukemic effects of a previously characterized cannabis extract on Notch-activated T cells and identifies several pathways that mediate its anti-cancer activity including the ER calcium and integrated stress response. The evidence is solid, but several concerns remain including the over reliance on a single cell line for the majority of the studies and lack of integration of the observations with existing literature

eLife assessment

Using state-of-the-art fate-mapping models and genetic and pharmacological targeting approaches, this study provides important findings on the distinct functions exerted by resident and recruited macrophages during cardiac healing after myocardial ischemia. Evidence supporting the conclusions are solid with the use of the FIRE mouse model in combination with fate-mapping to target fetal-derived macrophages. This study will be of interest for the macrophage biologists working in the heart but also in others tissues in the context of inflammation.

eLife assessment

The study presents important findings regarding a transcription-independent component of the early recovery of proteasome activity from a short pulse of proteasome inhibitor treatment, which has not been appreciated before and which is independent of the DDI2-NRF2 axis. While the evidence is in principle solid, with recapitulation in several cell line models, the proposed alternative underlying mechanism, namely regulation at the level of proteasome assembly, lacks experimental support, and at this point remain speculative.

eLife assessment

The authors build upon prior data implicating the secreted peptidoglycan hydrolase SagA produced by Enterococcus faecium in immunotherapy. Leveraging new strains with sagA deletion/complementation constructs, the investigators reveal that sagA is non-essential, with sagA deletion leading to a marked growth defect due to impaired cell division, and sagA being necessary for the immunogenic and anti-tumor effects of E. faecium. In aggregate, the study utilizes compelling methods to provide both fundamental new insights into E. faecium biology and host interactions and a proof-of-concept for identifying the bacterial effectors of immunotherapy response.

eLife assessment

This study, which seeks to identify factors from the glial niche that support and maintain neural stem cells, unveils a novel role for ferritin in this process. Furthermore, the work shows that defects in larval brain development resulting from ferritin knockdown can be attributed to impaired Fe-S cluster activity and ATP production. These findings will be valuable to both oncologists and neurobiologists, though the supporting evidence is currently incomplete.

eLife assessment

This important work presents a new methodology for the statistical analysis of fiber photometry data, improving statistical power while avoiding the bias inherent in the choices that are necessarily made when summarizing photometry data. The reanalysis of two recent photometry data sets, the simulations, and the mathematical detail provide convincing evidence for the utility of the method and the main conclusions, however, the discussion of the re-analyzed data is incomplete and would be improved by a deeper consideration of the limitations of the original data. In addition, consideration of other data sets and photometry methodologies including non-linear analysis tools, as well as a discussion of the importance of the data normalization are needed.

eLife assessment

This manuscript presents a valuable, lightweight software package that aims to accelerate the implementation of experiment pipelines running on heterogeneous computer environments. The authors present solid evidence of the advantages of their chosen approach, including demonstrating the flexibility, ease of use, and practical utility of this new system. However, questions remain regarding the maturity of the project and its specific advantages in relation to existing widely adopted software packages.

eLife assessment

This important study investigated transcriptional profiles of midbrain dopamine neurons using single nucleus RNA (snRNA) sequencing. The authors found more nuanced subgroups of dopamine neurons than previous studies, and identified some genes that are preferentially expressed in subpopulations that are more vulnerable to neurochemical lesions using 6-hydroxydopamine (6OHDA). The results are convincing and provide critical information on the heterogeneity and vulnerability of dopamine neurons which will be a foundation for future studies.

eLife assessment

This work addresses the connectivity of giant excitatory neurons in a part of CA1 of the hippocampus. Recordings in rat brain slices provide new evidence that these cells excite bistratified and basket inhibitory neurons, and have weak inhibitory input from basket cells, as well as other findings. This circuitry gives these cells unique potential, making the work valuable, however the strength of the evidence is currently incomplete.

eLife assessment

In this important study, Xiong and colleagues studied PKA regulation in synaptic plasticity. They provide convincing evidence that dissociation of PKA catalytic subunits is essential for the proper function of the kinase. Experiments using a PKA regulatory-catalytic subunit fusion establish that dissociative activation is required for both structural long-term potentiation and basal priming of AMPA receptors.

eLife assessment

This useful manuscript reports on a new mouse model for LAMA2-MD, a rare but very severe congenital muscular dystrophy; the knockout mice were generated by removing exon3 in the Lama2 gene, which results in a frameshift in exon4 and a premature stop codon. These animals lack any laminin-alpha2 protein and confirm results from previous Lama2 knockout models. Additionally, this study includes transcriptomics data that might be a good resource for the field. However, the experimental evidence supporting the main claims of the manuscript is incomplete, citations of previous Lama2 null mice studies are lacking, and both data presentation and interpretation need improvement.

eLife assessment

This valuable study addresses one way in which animals identify predator-associated cues and respond in a manner that reflects the imminence of the potential threat. The report shows that, in mice, fresh saliva from a natural predator (cat) elicits a greater defensive response compared to old cat saliva and implicates the vomeronasal organ and ventromedial hypothalamus as part of a circuit that underlies this process. While the study has potential, the results are somewhat preliminary, and as such support for the primary conclusions is incomplete.

eLife assessment

This important study by Lee and colleagues examined how neural representations are transformed between the olfactory tubercle (OT) and the ventral pallidum (VP) using single neuron calcium imaging in head-fixed animals trained in classical conditioning. They show that the dimensionality of neural responses is lower in the VP than in the OT and suggest that VP responses represent values in a more abstract form while OT contains more odor information, potentially enhancing odor contrast. The reviewers found the results overall convincing although the nature of OT responses needs to be investigated further.

eLife assessment

This study addresses the role of FMRP in the migration of newborn neuroblasts in the postnatal brain. Through extensive and convincing analysis of living imaging videos, the authors showed that neurons with FMRP deletion migrate aberrantly and exhibit defects in nucleokinesis and centrokinesis. The study presents a valuable finding on the mechanism of neuroblast migration in the postnatal brain.

eLife assessment

The authors use reinforcement learning modeling to study the alterations following acute ketamine in macaques. The evidence supporting the conclusion that ketamine reduces the impact of losses vs. neutral/gains is solid. In this version of this valuable study, the authors make more measured interpretations about the relationship between the processing of losses and ketamine's antidepressant effects.

eLife assessment

This important study uses calcium imaging in mice to advance our understanding of the effect of antipsychotic drugs on neural functioning. The evidence supporting the conclusions is convincing, and this work will be of interest to neuroscientists working on visual processing and psychosis researchers.

eLife assessment

This is a fundamental resource of snRNA-seq and and chromatin accessibility data from human aortic endothelial cells (ECs), treated with relevant perturbations such as IL1b, TGFB2, or si-EGR. The authors show that ECs can be categorized by distinct subpopulations of differing plasticity. The support for the existence of these subpopulations is compelling, supported also by three publicly available scRNA-seq datasets, and differential enrichment of coronary artery disease associated SNPs in open chromatin in these subpopulations.

eLife assessment

In this valuable study, the discovery and subsequent design of the AF03-NL chimeric antibody led to a tool for studying filoviruses and provides a possible blueprint for future therapeutics. In general, the data presented are solid, although further improvements can be made in the overall presentation of the results. The work will be of interest to virologists studying antibodies.

eLife assessment

This study reports comparative biochemical and structural analysis of two PLP decarboxylase enzymes from plants. The work is useful because of the potential application of these enzymes in industrial theanine production. The results, particularly the x-ray crystal structures, provide a solid basis for understanding substrate specificity. The paper will be of interest to enzymologists studying PLP enzymes and those working on enzyme engineering in plants.

eLife assessment

This study presents valuable data on the antigenic properties of neuraminidase proteins of human A/H3N2 influenza viruses sampled between 2009 and 2017. The antigenic properties are found to be generally concordant with genetic groups. Additional analysis have strengthened the revised manuscript, and the evidence supporting the claims is solid.

eLife assessment

This important study reports comprehensive multi-omics data on the changes induced in young and aged male mouse tail fibroblasts after treatment with chemical reprogramming factors. The authors provide solid evidence to support their claim that chemical reprogramming factors induce changes consistent with a reduction of cellular 'biological' age (e.g., correlations with established aging markers in whole tissues).

eLife assessment

This solid study presents valuable insights into the role of Cers1 on skeletal muscle function during aging, although further substantiation would help to fully establish the experimental assertions. It examines an unexplored aspect of muscle biology that is a relevant opening to future studies in this area of research.