eLife Assessment

This important work substantially advances our understanding of RNA structure analysis by introducing an innovative method that extends DMS probing to include guanosine residues, thereby enhancing our ability to detect complex tertiary interactions. The evidence supporting the conclusions is compelling, with detailed analyses demonstrating the method's capacity to differentiate structural contexts and improve RNA structure predictions. This work will be of broad interest to RNA structural biology, biochemistry, and biophysics researchers.

eLife Assessment

This study by Graca et al. explores ethanol metabolism pathways in mycobacteria. The enzyme, MftG, a flavoprotein dehydrogenase, is shown to act as an electron shuttle between an uncommon redox cofactor and the electron transport chain thereby regenerating mycofactocin. Whilst this study was conducted in Mycobacterium smegmatis, the findings are important and have general implications for elucidating broader mycobacterial metabolism. Overall, the data presented are convincing supported by well-designed experiments.

eLife Assessment

This important, clearly written, and timely manuscript links the timing of ART with the kinetics of total and intact proviral HIV DNA. The conclusions are interesting and somewhat novel, and the importance of the work is high because the focus is on African women and clade C virus, both of which are understudied in the HIV reservoir field. The strength of the evidence is convincing. Overall, this work will be of very high interest to scientists and clinicians in the HIV cure/persistence fields.

eLife Assessment

This study reports an important finding on the mechanism underlying the enhancement of anti-viral immune responses by febrile temperatures, especially the role of the conserved heat-shock factor, HSF-1. The data provide compelling support for the authors' model wherein increased temperature in the shrimp Litopenaeus vannamei activates HSF1, which in turn enhances anti-viral response via up-regulation of the nSWD protein and antibacterial peptides. The work, which will be of interest to virologists, immunologists, and cell biologists, would benefit from more discussion of the function and roles of HSF-1 at 25°C vs. 32°C.

eLife Assessment

In this important study, the authors set out to investigate the biogenesis of extracellular vesicles in mycobacteria and provide several observations to link VirR with vesiculogenesis, PG metabolism, lipid metabolism, and cell wall permeability. Whilst some of the evidence provided is convincing, there are still some shortcomings in the revised manuscript where the data to support the proposed mechanism remain incomplete. The work will be of interest to bacteriologists.

eLife Assessment

This fundamental work advances our understanding of the mechanisms underlying lactation-induced infertility. Compelling evidence supports the notion that prolactin inhibits kisspeptin activity and LH pulsatile release and that loss of this signal results in an early reestablishment of fertility during lactation. This work will be of interest to endocrinologists and reproductive biologists.

eLife Assessment

In this useful study, Wang and colleagues investigate the potential probiotic effects of Bacillus velezensis in a murine model. They provide convincing evidence that B. velezensis limits the growth of Salmonella typhimurium in lab culture and in mice, together with beneficial effects on the microbiota. The overall presentation of the manuscript has improved and the work will be of interest to infectious disease researchers.

eLife Assessment

This study reports the fundamental discovery of a novel structure in the developing gut that acts as a midline barrier between left and right asymmetries. Some of the evidence supporting the dynamics, composition, and function of this novel basement membrane in the chick is solid, some is even convincing, but investigation of its origin and impact on asymmetric organogenesis remains challenging and is not yet conclusive. This careful work is of broad relevance to patterning mechanisms, the importance of the extracellular matrix, and laterality disorders.

eLife Assessment

This potentially useful study introduces an orthogonal approach for detecting RNA modification, without chemical modification of RNA, which often results in RNA degradation and therefore loss of RNA molecules. While the authors have improved the work compared to a previous version, uncertainty regarding false positive and false negative rates leave the evidence for the broad applicability of the method incomplete. If properly validated, the approach might be of particular interest for sites where modifications are rare.

eLife Assessment

This interesting study focuses on a previously reported positive correlation between translational efficiency and protein noise. This is unexpected as typically noise is inversely related to expression and increasing translation efficiency would increase the protein expression and thus be expected to reduce noise in gene expression. Using mathematical modeling and analysis of experimental data the authors argue that this phenomenon arises due to ribosomal demand. However, the work appears incomplete, with the reviewers having raised questions regarding the validity of the assumptions used in the mathematical model as well as the clarity of the presentation.

eLife Assessment

This work presents a valuable finding on how the interplay between transcription factors SOX2 and OCT4 establishes the pluripotency network in early mouse embryos. Despite the high quality of the data, the evidence supporting the claims of the authors is currently incomplete and would benefit from more omics analysis such as H3K4me1 and H3K27ac CUT&Tag. The work will be of interest to biologists working on embryonic development.

eLife Assessment

This valuable study provides a detailed picture of the synapse distributions for a set of visual projection neurons and their downstream partners, in combination with multi-compartmental modelling fitted to electrophysiological data. The model reveals interesting consequences of synapse topography for neuronal computation. The analysis, however, seems incomplete as the authors only analyze passive models of these spiking neurons, and do not attempt to connect their analysis to the bigger picture at the behavioral level.

eLife Assessment

This valuable study on strategies used by Pseudomonas to subvert hots immunity identifies a new immune evasion strategy. The study presents solid evidence on the cleavage of VgrG2B by Caspase 11 and the generation of fragments that inhibit activity of the NLRP3 inflammasome. This work should be of interest to immunologists and microbiologists.

eLife Assessment

Wang et al's study addresses an important critical gap in our understanding of de novo epithelial polarization using MDCK cell doublets surrounded by ECM, providing convincing evidence through imaging and depletion studies on the role of conserved polarity proteins and the centrosome during this process. While the authors propose a clear hierarchical model, there is a need for further exploration of how microtubule organization contributes to this process. Specifically, live cell imaging of microtubules under mutants and their included ECM conditions, along with a more precise temporal mapping of microtubule dynamics in relation to proteins like Gp135, would strengthen the study's conclusions.

eLife Assessment

This important study shows that Toxoplasma gondii uses paracrine mechanisms, in addition to cell-intrinsic methods, to evade the host immune system, with MYR1 playing a key role in transporting effector molecules into host cells. The authors present convincing evidence that in vivo, MYR1-deficient parasites can be rescued by wild-type parasites, revealing a limitation in pooled CRISPR screens, where such paracrine effects may obscure the identification of key parasite pathways involved in immune evasion.

eLife Assessment

This important study reports a detailed quantification of the population dynamics of Salmonella enterica serovar Typhimurium in mice. Bacterial burden and founding population sizes across various organs were quantified, revealing pathways of dissemination and reseeding of the gastrointestinal tract from systemic organs. Using various techniques, including genetic distance measurements, the authors present compelling evidence to support their conclusions, thus presenting new knowledge that will be of broad interest to scientists focusing on infectious diseases.

eLife Assessment

This important study uses a large dataset from both recent isolates and genomes in databases to provide an analysis of the population structure of the pathogen Salmonella gallinarum. The results regarding regional adaptation and the evolutionary trajectory of the resistome and mobilome remain incomplete, requiring additional details to fully support their claims and assess the value of these insights for future policy interventions regarding this and other pathogens. This work will interest microbiologists and researchers working on genomics, evolution, and antimicrobial resistance.

eLife Assessment

This study provides important information on pre-existing epigenetic modification in T cell plasticity. The evidence supporting the conclusions is compelling, supported by comprehensive transcriptional and epigenetic analyses. The work will be of interest to immunologists and colleagues studying transcriptional regulation.

eLife Assessment

The authors have developed a valuable approach that employs cell-free expression to reconstitute ion channels into giant unilamellar vesicles for biophysical characterisation. The work is convincing and will be of particular interest to those studying ion channels that primarily occur in organelles and are therefore not amenable to be studied by more traditional methods.

eLife Assessment

This important study reveals insights into how calcineurin influences C. elegans pathogen susceptibility and lifespan through its role in controlling the defecation motor program. The authors provide convincing evidence to support a new mechanism through which calcineurin impacts longevity. This work will be of interest to investigators studying host-pathogen interactions and aging in a number of experimental systems.

eLife Assessment

This important study presents a high-resolution cryoEM structure of the supercomplex between photosystem I (PSI) and fucoxanthin chlorophyll a/c-binding proteins (FCPs) from the model diatom Thalassiosira pseudonana CCMP1335, revealing subunits, protein:protein interactions and pigments not previously seen in other diatoms or red/green photosynthetic lineages. Combining structural, sequence and phylogenetic analyses, the authors provide convincing evidence of conserved motifs crucial for the binding of FCPs, accompanied by interesting speculation about the mechanisms governing the assembly of PSI-FCP supercomplexes in diatoms and their implications for related PSI-LHC supercomplexes in plants. The findings set the stage for functional experiments that will further advance the fields of photosynthesis, bioenergy, ocean biogeochemistry and evolutionary relationships between photosynthetic organisms.

eLife Assessment

This valuable study provides convincing evidence that mutant hair cells with abnormal, reversed polarity of their hair bundles in mouse otolith organs retain wild-type localization, mechanoelectrical transduction and firing properties of their afferent innervation, leading to mild behavioral dysfunction. It thus demonstrates that the bimodal pattern of afferent nerve projections in this organ is not causally related to the bimodal distribution of hair-bundle orientations, as also confirmed in the zebrafish lateral line. The work will be of interest to scientists interested in the development and function of the vestibular system as well as in planar-cell polarity.

eLife Assessment

The authors describe a model for tracking time-varying functional connectivity between neurons from multi-electrode spike recordings. This is an interesting and potentially useful approach to an open problem in neural data analysis, and could be an essential tool for investigating the neural code from large-scale in-vivo recordings of spiking activity. However, the evidence is incomplete: systematic comparisons with existing methods and/or demonstration of its utility relative to conventional methods are essential to demonstrate the usefulness of the method.

eLife Assessment

This work provides an important and novel framework for interpreting the interactions between recurrent dynamics across stages of neural processing. The authors report that two different kinds of dynamics exist in recurrent networks differing in the extent to which they align with the output weights. The authors also present convincing evidence that both types of dynamics exist in the brain.

eLife Assessment

This study presents useful findings on the role of the small GTPase Rab3A in homeostatic synaptic plasticity following activity suppression. While the study demonstrates that Rab3A is required for homeostatic scaling, the evidence supporting the model put forward by the authors is incomplete. The work will be of interest to the field of synaptic transmission and synaptic plasticity.

eLife Assessment

This study provides important findings that during credit assignment, the lateral orbitofrontal cortex (lOFC) and hippocampus (HC) encode causal choice representations, while the frontopolar cortex (FPl) mediates HC -lOFC interactions when the causality needs to be maintained over longer distractions. While this research offers compelling evidence and employs sophisticated multivariate pattern analysis, there are some concerns regarding a) task design which may have oversimplified real-world credit assignment complexities, and b) the interpretation of results. This work will be of interest to cognitive and computational neuroscientists who work on value-based decision-making and fronto-hippocampal circuits.

eLife Assessment

The study from Frank and colleagues reports potentially important cryo-EM observations of mouse glutamatergic synapses isolated from adult mammalian brains. The authors used a combination of mouse genetics to generate PSD95-GFP labeling in vivo, a rapid synaptosome isolation and cryo-protectant strategy, and cryogenic correlated light-electron microscopy (cryoCLEM) to record tomograms of synapses, which together provide convincing support for their conclusions. Controversially, the authors report that forebrain glutamatergic synapses do not contain postsynaptic "densities" (PSD), a defining feature of synapse structure identified in chemically-fixed and resin-embedded brain samples. The work questions a long-standing concept in neurobiology and is primarily of interest to specialists in synaptic structure and function.

eLife Assessment

This important study provides new and nuanced insights into the evolution of morphs in a textbook example of Batesian mimicry. The evidence supporting the claims about the origin and dominance relationships among morphs is convincing, but the interpretation of signals needs improvement with complementary analysis and some nuanced interpretation. Pending a revision, this work will be of interest to a broad range of evolutionary biologists.

eLife Assessment

This important study advances our understanding of the temporal dynamics and cortical mechanisms of eye movements and the cognitive process of attention. The evidence supporting the conclusions is convincing and based on measuring the time course of the eye movement-attention interaction in a novel, carefully-controlled experimental task. This study will be of broad interest to psychologists and neuroscientists interested in the dynamics of cognitive processes.

eLife Assessment

This study reports differences in proteomic profiles of embryonic versus induced pluripotent stem cells. This important finding cautions against the interchangeable use of both types of cells in biomedical research, although the mechanisms responsible for these differences remains unknown. The proteomic evidence is convincing, even though there is limited validation with other methods.

eLife Assessment

The main idea tested in this work is that host galectin-9 inhibits Mycobacterium tuberculosis (Mtb) growth by recognizing the Mtb cell wall component arabinogalactan (AG) and, as a result, disrupting mycobacterial cell wall structure. Moreover, a similar effect is achieved by anti-AG antibodies. While the hypothesis is intriguing and the work has the potential to make a valuable contribution to Mtb therapy, the evidence presented is incomplete and does not explain several critical points including the dose-independent effect of galectin-9 on Mtb growth and how anti-AG antibodies and galectin-9 access the AG layer of intact Mtb.

eLife Assessment

This important work uses in vivo foveal cone-resolved imaging and simultaneous microscopic photostimulation to investigate the relationship between ocular drift - eye movements long thought to be random - and visual acuity. The surprising result is that ocular drift is systematic - causing the object to move to the center of the cone mosaic over the course of each perceptual trial. The tools used to reach this conclusion are state-of-the-art and the evidence presented is convincing. This work advances our understanding of the visuomotor system and the interplay of anatomy, oculomotor behavior, and visual acuity.

eLife Assessment

This valuable study provides a novel method to detect sleep cycles based on variations in the slope of the power spectrum from electroencephalography signals. The method, dispensing with time-consuming and potentially subjective manual identification of sleep cycles, is supported by solid evidence and analyses but some aspects could be better illustrated and the source of the discrepancies between classical and fractal cycles should be identified. This study will be of interest to researchers and clinicians working on sleep and brain dynamics.

eLife Assessment

Liu and colleagues' study provides important insights into the neural mechanisms of narrative comprehension by identifying three distinct brain states using a hidden Markov model on fMRI data. The work is compelling, as it demonstrates that the dynamics of these brain states, particularly their timely expression, are linked to better comprehension and are specific to spoken language processing. The study's robust findings, validated in a separate dataset, will be of broad interest to researchers exploring the neural basis of speech and language comprehension, as well as those studying the relationship between dynamic brain states and cognition.

eLife assessment

This study seeks to expand the understanding of insulin and glucose responses in the brain, specifically by implicating a family of protein kinases responsive to insulin. The significance of the study to the field is valuable. The evidence supporting the conclusions about brain glucose utilization is convincing, although there are several aspects that could benefit from additional validation to strengthen the claims.

eLife Assessment

This important study examines the stability and compensatory plasticity in the retinotopic mapping in patients with congenital achromatopsia. It provides convincing evidence for a stable mapping of the visual field in V1, alongside changes of the readout from V1 into V3, which shows revised receptive field location and size. With the controlling for potential confounding variables, this paper would be of interest to scientists studying the visual system, brain plasticity, and development.

eLife Assessment

This work provides important findings characterizing potential synaptic mechanisms supporting the role of midline thalamus-hippocampal projections in fear memory extinction in mice. The methods and approaches used were solid. However, the evidence itself is incomplete, as there are concerns with whether the findings fully support the conclusions drawn.

eLife Assessment

This valuable report describes the changing antiviral activity of IFIT1 across mammals and in response to distinct viruses, likely as a result of past arms races. One of the main strengths of the manuscript is the breadth of mammalian IFIT1 orthologs and viruses that were tested. Overall the evidence is solid, but the analysis of positive selection could benefit from more thorough validation with complementary selection tests and also from assessing or more extended discussion of the impact of recombination and/or physical interactions with other IFITs.

eLife Assessment

This valuable study reports on a novel role of PD-1 in early T cell differentiation, showing that PD-1 stimulation impairs Th2 differentiation more effectively than that of Th1, with implications for the treatment of allergies. However, whereas the series of well-designed experiments using OVA-specific CD4 T cells from DO.11.10 mice and the use of an allergy model generated compelling data, the study is still incomplete since it shows gaps in the rationale for the experimental protocols, contradictory data regarding IFN-gamma and IL-4 production, and the lack of in vivo experiments on Th2 differentiation to further support the main hypothesis. Nonetheless, the reported data would be of interest to immunologists working on T cell differentiation and allergy.

eLife Assessment

The presented soft tissue data of pterosaur tail vanes represent a valuable contribution to ongoing research efforts to decipher the flight abilities of pterosaurs in the fields of paleontology, comparative biomechanics, and bioinspired design. The new methods are compelling and give new detail on tail morphology that has the potential to resolve how pterosaurs were able to control and maintain tail stiffness to furnish flight control.

eLife Assessment

This study presents numerical results on a potentially useful framework for understanding the dynamics of subthreshold waves in a network of electrical synapses modeled on the connectome data of the C elegans nematode. However, the strength of the evidence presented in favor of interference effects being a major component in subthreshold wave dynamics is inadequate.

eLife Assessment

Gil Ávila et al. evaluated the aperiodic component in the medial prefrontal cortex using resting-state EEG recordings from 149 individuals with chronic pain and 115 healthy participants. The authors present compelling evidence that the aperiodic component of the EEG does not differentiate between those with chronic pain and healthy individuals. The study was well-designed and rigorously conducted, and the clear and conclusive results provide important insights that can guide future research in the field of pain neuroscience.

eLife Assessment

This important study presents results for the theory of odor coding in hyperbolic spaces by revealing spiral trajectories in the dynamics of odors during natural, ethologically relevant processes such as ripening. In the current manuscript, the strength of the evidence is solid and would be strengthened by answering several technical points raised by reviewers.

eLife Assessment

This technical study presents a novel sampling strategy for detecting synaptic coupling between neurons from dual pipette patch-clamp recordings in acute slices of mammalian brain tissue in vitro. The authors present solid evidence that this strategy, which incorporates automated patch clamp electrode positioning and cleaning for reuse with strategic neuron targeting, has the potential to substantially improve the efficiency of neuronal sampling with paired recordings. This technique and the extensions discussed will be useful for neuroscientists wanting to apply or already conducting automated multi-pipette patch clamp recording electrophysiology experiments in vitro for neuron connectivity analyses.

eLife Assessment

This important study provides proof of principle that C. elegans models can be used to accelerate the discovery of candidate treatments for human Mendelian diseases by detailed high-throughput phenotyping of strains harboring mutations in orthologs of human disease genes. The data are compelling and support an approach that enables the potential rapid repurposing of FDA-approved drugs to treat rare diseases for which there are currently no effective treatments. The authors should provide a clearer explanation of how the statistical analyses were performed, as well as a link to a GitHub repository to clarify how figures and tables in the manuscript were generated from the phenotypic data.

eLife Assessment

This valuable study explores the sequence characteristics and conservation of high-occupancy target loci, regions in the human genome such as promoters and enhancers that are bound by a multitude of transcription factors. The computational analyses presented in this study are solid. This study would be a helpful resource for researchers performing ChIP-seq based analyses of transcription factor binding.

eLife Assessment

This important study identifies biallelic variants of DNAH3 in unrelated infertile men and reports infertility in DNAH3 knockout mice. The authors demonstrate that compromised DNAH3 activity decreases the expression of IDA-associated proteins in the spermatozoa of human patients and knockout mice, providing convincing evidence that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and male infertility. The study will be of substantial interest to clinicians, reproductive counselors, embryologists, and basic researchers working on infertility and assisted reproductive technology.

eLife Assessment

This study, which proposes a new role of ATG6 in plant immune response, makes a valuable contribution to our understanding of plant immunity. The results suggest a direct interaction between ATG6 and NPR1, a salicylic acid receptor protein, and they will be of interest to scientists studying the regulation of plant immunity. The data presented are convincing, although the discrepancies between data from fluorescence microscopy and protein blots, particularly in the interpretation of ATG6-mCherry fusion proteins. Addressing these inconsistencies would enhance the study's overall impact.

eLife Assessment

This important work substantially advances our understanding of nocturnal animal navigation and the ways that animals use polarized light. The evidence supporting the conclusions is convincing, with elegant behavioural experiments in actively navigating ants. The work will be of interest to biologists working on animal navigation or sensory ecology.

eLife Assessment

In this compelling study, the authors examine the interactions between stellate cells and PV+ interneurons in the medial entorhinal cortex. Huang et al. focus on the spatial distribution of synaptic inputs and demonstrate that closely located neuron pairs receive common inputs, suggesting a structured functional organization in the entorhinal cortex. Advanced dual whole-cell patch recordings further reveal patterns of postsynaptic activation, indicating intensive interactions within clusters of these neurons, with weaker interactions between clusters. These findings offer significant insights into the functional dynamics of the entorhinal cortex and the circuit mechanisms that shape grid cell activity. This study is important not only for the field of MEC and grid cells, but also for broader fields of continuous attractor networks and neural circuits.

eLife Assessment

The research has the potential to be a valuable addition to the field, and the conclusions are solid, but there is a need for more reproducible data to address existing discrepancies and enhance its impact.

eLife Assessment

The authors tested the hypothesis that age-dependent factors in human sera affect the core circadian clock or its outputs in cultured fibroblasts, and they provide compelling evidence that genes involved in the cell cycle and transcription/translation remain rhythmic in both conditions, genes associated with oxidative phosphorylation and Alzheimer's Disease lose rhythmicity in the aged condition, while the expression of cycling genes associated with cholesterol biosynthesis increase in the cells entrained with old serum. Together, the findings suggest that yet to be identified age-dependent blood-borne factors affect circadian rhythms in the periphery. The paper provides fundamental insights and a possible explanation for previous observations showing that circadian gene expression in peripheral tissues tends to dampen or phase-shift with age.

eLife Assessment

The manuscript represents a valuable conceptual and technical contribution to our understanding of ciliogenesis and intraflagellar transport in vertebrates. Through a series of solid and technically superb live imaging experiments to directly visualize intraflagellar transport in various zebrafish ciliated tissues, the authors unveil the surprising breadth of intraflagellar transport speed among differing organs and link this to cell type-specific differences in cilia length and intraflagellar transport train size. This work will be of broad interest to researchers in numerous fields, including development, cell biology, and imaging.

eLife Assessment

This study provides an important resource by thoroughly benchmarking multiple sequencing-based tRNA quantification methods. The suggested best practice is supported by convincing evidence from in silico experiments in multiple scenarios.

eLife Assessment

Research on push-pull systems often focuses on controlled environments, limiting our understanding of their effectiveness under real-world conditions. This important study has validated how push-pull systems work in natural settings. However, the manuscript remains incomplete, since the findings have only been partially supported, as acknowledged by the authors.

eLife Assessment

This study attempts to understand the functional roles of the human DCP1 paralogs in regulating RNA decay by DCP2. Using a combination of cellular-based assays and in vitro assays, the authors conclude that DCP1a/b plays a role in regulating DCP2 activity. While this revised version presents some new and interesting observations on human DCP1, the underlying data to support its claims remain incomplete. Overall, these results will be useful to the RNA community.

eLife Assessment

In this manuscript, the authors present valuable findings on the apparent role of a salience-network anterior insula node in directing fronto-parietal and default-mode network activity within a tripartite network during control of memory, drawn from an impressive invasive human neurophysiological dataset. Overall, the authors have presented a convincing set of analyses. We also commend the use of a large intracranial EEG dataset to approach this question.

eLife Assessment

This important study uses the Jurkat T cell model to study the role of Formin-like 1 β phosphorylation at S1086 on actin dynamics and exosome release at the immunological synapse. The evidence supporting these findings is compelling within the framework of the Jurkat model. As the Jurkat model is known to have a bias toward formin-mediated actin filament formation at the expense of Arp2/3-mediated branched F-actin foci observed in primary T cells, it will be beneficial in the future to confirm major findings in primary T cells.

eLife Assessment

This is an important piece of work that sheds light on our understanding of early lung development. There is solid evidence that there is a key new role for Svep1, which may be acting via FGF9. A more precise understanding of the interactions between Svep1 and FGF9, with a possibility of other ECM factors, would add value.

eLife Assessment

The study presents a very well-illustrated specimens of the artiopodan Cindarella eucalla from the Chengjiang Biota, using computer tomography (CT) scanning to illustrate multiple specimens with preserved appendages, a rarity in artiopodans. The description of these fossils is important for expanding our understanding of this taxon and its relatives. The imaging and morphological description are followed by a discussion of how this morphology relates to other Cambrian arthropods and its potential ecological function. The evidence provided in this section about resulting function and ecology is presently incomplete and the conclusions are put forward too strongly. This assessment could be improved if the work is revised with more careful wording and additional data.

eLife Assessment

The paper presents a new pipeline for functional validation of genes known to underlie fragile bone disorders, using CRISPR-mediated knockouts and a number of phenotypic assessments in zebrafish. The solid data demonstrate the feasibility and validity of the approach, which presents a valuable tool for rapid functional validation of candidate gene(s) associated with heritable bone diseases identified from genetic studies.

eLife Assessment

This important work advances our understanding of trained immunity, especially in the context of Bacillus Calmette-Guérin (BCG) administration and host-pathogen interactions. The evidence supporting the conclusions are convincing, based on a combination of state-of-the-art omics techniques such as bulk and single-cell RNA sequencing with the use of JAK/STAT signaling inhibitors. The work will be of broad interest to immunologists and infection biologists.

eLife Assessment

This useful study reports that the exogenous expression of the microRNA miR-195 can partially compensate in early B cell development for the loss of EBF1, one of the key transcription factors in B cells. While this finding will be of interest to those studying lymphocyte development, the evidence, particularly with regard to the molecular mechanisms that underpin the effect of miR-195, is currently incomplete.

eLife Assessment

This important study presents a new method for generating cell-type restricted knockouts in zebrafish and it reports several interesting applications of this method to study pigmentation and melanomagenesis. The evidence supporting the conclusions is convincing, with rigorous characterization of several knock out mutations that provide a proof of principle. The work will be of broad interest to cell, skin, and cancer biologists.

This article contributes to the development of LIS literature by highlighting a blind-spot which exists in popular conversation around libraries. It also goes a step further and highlights how those blind-spots fall short of desired outcomes, and offers them as points of discussion to develop ideas around the best implementation of makerspaces into libraries, and ultimately still argues for their existence.

Journal name

Dr. Rebekah Willett is a professor at the Information School of the University of Wisconsin-Madison. She received a PhD in Education from the University of London, and she researches a variety of topics relevant to this article, including childhood studies, new literacies, and public library makerspaces (Willett, Rebekah, 2017).

The author concludes that while there are problems that arise from the contradictory and often under-baked reasonings that push for maker education, wrestling with these concerns directly can only lead to a more focused vision for how best to utilize makerspaces and maker education for specific learning goals.

This analysis finds that often, discussions of makerspaces in educational and library settings are contradictory, disjointed, and lack evidence to support their claims.

While not a typical empirical research article, there is a methodology used for identifying relevant sources for its literature review and analyzing those sources.

This section of the abstract highlights that the article is a literature review that will be looking at other published articles on Maker education

This first line of the conclusion succinctly relays the purpose of this article - to collect, analyze, and discuss common themes and conclusions in conversations and research around Maker education in libraries.

eLife Assessment

This is a valuable manuscript analyzing single-cell RNA-sequencing data from the mouse vomeronasal organ. Convincing evidence in this manuscript allows the authors to identify and verify the differential expression of genes that distinguish apical and basal vomeronasal neurons. The authors also show that Gnao1 neurons exhibit enriched expression of ER-related genes, which they verify with in situ hybridizations and immunostaining and also explore via electron microscopy.

eLife Assessment

This observational study from the UK Biobank provides an important investigation into the associations between menopausal hormone therapy and brain health in a large, population-based cohort of females in the UK. A solid model of brain aging using an open source algorithm is used. While some modest adverse brain health characteristics were associated with current mHT use and older age at last use, the findings do not support a general neuroprotective effect of mHT nor severe adverse effects on the female brain. This work addresses a topic that is of grave importance since menopausal hormone therapy and its effect on the brain should be better understood in order to provide individualized effective medical support to women going through menopause.

eLife Assessment

This is an important study, supported by solid data, that suggests a model for diet selection in C. elegans. The significance is that while C. elegans has long been known to be attracted to bacterial volatiles, what specific bacterial volatiles may signify to C. elegans is largely unknown. This study also provides evidence for a possible odorant/GPCR pairing.

eLife assessment

This important study advances our understanding of the role energy metabolism, specifically anaerobic glycolysis, plays during development. Convincing genetic and pharmacological evidence demonstrates that glycolytic flux is not only necessary during retinogenesis but also controls the rate of retinal progenitor cell proliferation and photoreceptor maturation. Interesting evidence suggests potential downstream roles for intracellular pH and Wnt/β-catenin signaling; however, more direct evidence is needed to show they are the key mediators of glycolysis. This work is expected to stimulate broad interest and possible future studies investigating the link between metabolism and development in other tissue systems.

eLife Assessment

This important study asks whether motor neurons within the vestibulo-ocular circuit of zebrafish are required to determine the identity, connectivity, and function of upstream premotor neurons. They provide compelling and comprehensive genetic, anatomical and behavioral evidence that the answer is, "No!". This work will be of general interest to developmental neurobiologists and will motivate future studies of whether motor neurons are dispensable for assembly of other sensorimotor neural circuits.

eLife Assessment

The findings of this valuable manuscript advance our understanding of the significance of Bestrophin isoform 4 (BEST4) in suppressing colorectal cancer (CRC) progression. The authors used appropriate and validated methodology, such as the knockout of BEST4 using CRISPR/Cas9 in CRC cells, to provide a solid foundation for elucidating the potential link between BEST4 and CRC progression.

eLife Assessment

This study provides a useful set of experiments showing the relative contribution of the Noradrenergic system in reversing the sedation induced by midazolam. The evidence supporting the claims of the authors is solid, although specificity issues in the pharmacology and neural-circuit investigations narrow down the strengths of the conclusions. Dealing with these limitations will make the paper attractive to medical biologists working on the neurobiology of anesthesia.

eLife Assessment

This fundamental study advances substantially our understanding of sound encoding at synapses between single inner hair cells of the mouse cochlea and spiral ganglion neurons. Dual patch-clamp recordings-a technical tour-de force-and careful data analysis provide compelling evidence that the functional heterogeneity of these synapses contributes to the diversity of spontaneous and sound-evoked firing by the neurons. The work will be of broad interest to scientists in the field of auditory neuroscience.

eLife Assessment

This manuscript tackles a significant problem in addiction science: how interdependent are measures of "addiction-like" behavioral phenotypes? The manuscript provides compelling evidence that, under these experimental conditions, escalation of intake, punishment-resistant responding, and progressive ratio break points reflect a single underlying construct rather than reflect distinct unrelated measures. The exceptionally large sample size and incorporation of multiple behavioral endpoints add strength to this paper, and make it an important resource for the field.

eLife Assessment

This valuable study applies transcranial direct current stimulation (tCDS) to the prefrontal cortex of non-human primates during two states: (1) propofol-induced unconsciousness; and (2) wakeful performance of a fixation task. The analysis offers incomplete evidence to indicate that the effect of tDCS on brain dynamics, as recorded with functional magnetic resonance imaging, is contingent on the state of consciousness during which the stimulation is applied. The findings will be of interest to researchers interested in brain stimulation and consciousness.

eLife Assessment

This valuable study uses an original approach to address the longstanding question of why reaching movements are often biased. The combination of a wide range of experimental conditions and computational models is a strength. However, the modeling assumptions are not well-substantiated, the modeling analysis is insufficient with its focus on fits to average and not individual subject data, and the results are limited to biases in reach direction and do not consider biases in reach extent. Taken together, the evidence supporting the main claims is incomplete.

eLife Assessment

This important study shows that sound exposure enhances drug delivery to the cochlea via outer hair cell electromotility acting as a "fluid pump". Although others have proposed that electromotility subserves cochlear amplification, this is the first report to have tested the pumping effect in vivo and considered its possible implications for cochlear homeostasis and drug delivery. The manuscript provides convincing evidence for OHC-based fluid flow within the cochlea.

eLife Assessment

This study presents valuable findings to the field interested in inattentional blindness (IB), reporting that participants indicating no awareness of unexpected stimuli through yes/no questions, still show above-chance sensitivity to specific properties of these stimuli through follow-up forced-choice questions (e.g., its color). The results suggest that this is because participants are conservative and biased to report not noticing in IB. The authors conclude that these results provide evidence for residual perceptual awareness of inattentionally blind stimuli and that therefore these findings cast doubt on the claim that awareness requires attention. Although the samples are large and the analysis protocol novel, the evidence supporting this interpretation is still incomplete, because effect sizes are rather small, the experimental design could be improved and alternative explanations have not been ruled out.

eLife Assessment

This valuable study introduces a novel split-belt treadmill learning task to reveal distinct and parallel learning sub-components of gait adaptation: slow and gradual error-based perceptual realignment, and a more deliberate and flexible "stimulus-response" style learning process. While the behavioural results convincingly support the presence of a non-error-based learning process during continuous movements, the computational modelling provides incomplete evidence for establishing the nature of this secondary learning process.

eLife Assessment

This study offers valuable information on how titin derived from different nuclei within the syncytium is organized and integrated during skeletal muscle development and remodeling. The authors developed a novel mCherry titin knock-in mice with the fluorophore mCherry inserted into titin's Z-disk region to track the titin during cell fusion. The approach using mcherry adds to understanding of the role and localization of titin in controlling stiffness of striated muscles and fine tuning contraction. The results demonstrate that the integration of titin into the sarcomere is tightly regulated, with its unexpected mobility aiding in the uniform distribution of titin post-cell fusion. Although the experimental approach is convincing, the work is very qualitative in its approaches, and the data needs rigorous statistical analysis. There is a need for some clarification concerning numbers of animals and control groups. Future studies will need more rigorous data analysis and interpretation.

eLife Assessment

The landmark significance of this manuscript is based on the mechanistic description of purine metabolism by Lactobacillus plantarum, which helps to alleviate hyperuricemia, which is a phenotype that underlies multiple disease symptoms. The evidence provided for L. plantarum's involvement in reducing hyperuricemia was exceptional, combining microbiomics, whole genomics, in vitro bacterial culture, gene knock-outs, and metabolomics. Collectively, the study shows a clear link between the gut microbiota and hyperuricemia, providing a pathway for modification to help alleviate this condition.

eLife Assessment

This work explores the physical principles underlying fluid flow and luminal transport within the endoplasmic reticulum. Its important contribution is to highlight the strong physical constraints imposed by viscous dissipation in nanoscopic tubular networks. In particular, the work presents convincing evidence based on theoretical analysis that commonly discussed mechanisms such as tubular contraction are unlikely to be at the origin of the observed transport velocities. As such, it will be of relevance to cell biologists and physicists interested in organelle dynamics. As this study is solely theoretical and deals with order of magnitude estimates, its main conclusions await experimental validation.

eLife Assessment

The useful studies described here are broadly applicable to all antibody discovery subfields, even though they are not a significant improvement over published methods. The findings are incomplete with respect to the methodology, since details that are crucial in order to repeat the experiments are lacking (such as a timestamp). They also do not take into account multiple recent papers that have tested similar strategies. These studies will be of interest to a specialized audience working on generating antibodies to infectious agents.

eLife Assessment

This important study shows the effect of gut dysbiosis on the colonization of mycobacteria in the lung. The data with comprehensive analysis of gene expression profiles in the lung with dysbiotic mice is compelling and goes beyond the current state of the art. However, the mechanistic insight, where the lung epithelial cell line was used, and the experiments with Mtb infection are currently incomplete.

eLife Assessment

This valuable study investigated the appearance of ultrasonic vocalizations around 44 kHz that occurs in response to prolonged fear conditioning in male rats. Evidence in support of the conclusions is solid and may be of interest to some researchers also investigating distress-related ultrasonic vocalizations.

eLife Assessment

This is a potentially interesting study regarding the role of gasdesmin D in experimental psoriasis. The study contains useful data from murine models of skin inflammation, however the main claims (on neutrophil pyroptosis) are incompletely supported in its current form and require additional experimental support to justify the conclusions made.

eLife Assessment

This valuable study presents a machine learning model to recommend effective antimicrobial drugs from patients' samples analysed with mass spectrometry. The evidence supporting the claims of the authors is convincing. This work will be of interest to computational biologists, microbiologists, and clinicians.

eLife Assessment

This important work compares the strain properties of a-synuclein fibrils isolated from LBD and MSA patient samples with the resulting amplified fibrils following SAA. Using orthogonal biochemical and structural approaches to strengthen their analyses, the authors provide solid evidence that the SAA-amplified fibrils do not recapitulate the disease-relevant strains present in the patient samples. CryoEM would further strengthen this data but it is outside the scope of the work. This work should be considered in the widespread applications of SAA in synucleopathies and its potential limitations.

eLife Assessment

This study presents useful, yet preliminary, findings on the transcriptomic changes in cardiac lymphatic cells after myocardial infarction in mice. The conclusions of the authors remain uncertain as sample sizes for lymphatic endothelial cells are very low. The single-cell transcriptomic data were analyzed using solid advanced methodology and may be used as a starting point for future studies of the impact of lymphatic cells on heart disease.

eLife Assessment

The study by Tsai et al. employed multi-omics approaches, including transcriptomic, methylomic, and single-cell RNA-seq, and provided a solid and comprehensive analysis of the correlation between retrotransposable element (RTE) expression and biological aging in human blood. Their findings highlight the differential roles of RTE families, providing valuable insights for understanding the mechanisms of human aging.

eLife Assessment

This valuable study contributes to the understanding of phase separation in Dishevelled (DVL) proteins, by investigating the endogenous complexes of DVL2 using ultracentrifugation and contrasting them with DVL1 and DVL3 behaviour and the functional validation of the DVL2 intrinsically disordered regions mediating the protein condensate. The study includes a solid characterisation of several overexpression constructs, including in KO cells. However, investigations of the roles of the described DVL2 regions at the endogenous level remain to be carried out.

eLife Assessment

This work describes a highly complex automated algorithm for analyzing vascular imaging data from two-photon microscopy. This tool has the potential to be extremely valuable to the field and to fill gaps in knowledge of hemodynamic activity across a regional network. The biological application provided, however, has several problems that make many of the scientific claims in the paper incomplete.

eLife Assessment

This is a fundamental research study which identifies some of the molecular mechanisms underlying the energy costly process of memory consolidation. The strength of evidence is exceptional. The paper should be of broad interest because it establishes a clear mechanistic link between long-term memory processes and the energy-producing machinery in neurons.

eLife Assessment

This manuscript provides important new insight into the mechanisms underlying seasonal physiology, using medaka fish as a functional genetic model that naturally exhibits photoperiodic responses. The authors provide a range of data that implicate agrp1 in feeding regulation in response to photoperiod and reproductive status. This paper provides solid evidence connecting the effects of long and short photoperiods on the food intake of female medaka fish and egg production. It will be of relevance for biologists interested in understanding the molecular and cellular underpinnings of environmental effects on animal biology.

eLife Assessment

This study presents a valuable conceptual approach that cell lineage can be determined using methylation data. However, the evidence supporting the claims of the author is currently inadequate. If the author could carry out some additional experiments as well as explore alternative explanations for the current data, this approach could be of broad interest to neuroscientists and developmental biologists.

eLife Assessment

This paper undertakes a valuable theoretical treatment of the potential role of foraging-related concepts in several forms of intertemporal choice. While the computational evidence and methodologies employed are novel, some issues with clarity and generality result in incomplete support for the paper's claims.

eLife Assessment

SCARF1 is a scavenger membrane-bound receptor that binds modified versions of lipoproteins and has a significant role in maintaining lipid homeostasis. This useful study reports the crystal structure of SCARF1 and identifies putative binding sites for modified lipoproteins. Supported by a convincing set of experimental approaches, this study advances our knowledge of how scavenger receptors clear modified lipoproteins to maintain lipid homeostasis.

eLife Assessment

The article uses a cell-based model to investigate how mutations and cells spread throughout a tumour. The paper uses published data and the proposed model to understand how growth and death mechanisms lead to the observed data. This work provides an important insight into the early stages of tumour development. From the work provided here, the results are convincing, using a thorough analysis.

eLife Assessment

This important study advances our understanding of maladaptive innate immune training. The experimental evidence supporting the conclusions is convincing with only a few clarifications required. The work will be of high interest to both researchers in the trained immunity field and clinician scientists.

eLife Assessment

This useful manuscript shows a set of interesting data including the first cryo-EM structures of human PIEZO1 as well as structures of disease-related mutants in complex with the regulatory subunit MDFIC, which generate different inactivation phenotypes. The molecular basis of PIEZO channel inactivation is of great interest due to its association with several pathologies. This manuscript provides some structural insights that may help to ultimately build a molecular picture of PIEZO channel inactivation. While the structures are of use and clear conformational differences can be seen in the presence of the auxiliary subunit MDFIC, the strength of the evidence supporting the conclusions of the paper, especially the proposed role for pore lipids in inactivation, is incomplete and there is a lack of data to support them.

eLife Assessment

This valuable paper seeks to determine the role of endogenous CNS hemoglobin in protecting mitochondrial homeostasis in hypoxia. There is merit in the work, although it remains incomplete as there is a question as to the validity of the hypoxia model as relevant to CNS-specific ischemia/hypoxia that should be considered. In particular, a whole-body hypoxia model may liberate exosomes from other hypoxic organs, which should be addressed by the authors. Overall, this work has the potential to be of broad interest to the neuroscience and hypoxia communities.

eLife Assessment

This manuscript reports on the 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 valuable and have theoretical or practical implications for a subfield. The strength of the evidence is solid, with the methods, data, and analyses broadly supporting the claims with only minor weaknesses.

eLife Assessment

This study presents a useful characterisation of the topographical organisation of the human pulvinar, an associative thalamic subregion crucial for visual perception and attention. The evidence supporting the conclusions is solid given the multimodal validation and replication across datasets, although even higher-resolution imaging data would have strengthened the study. The manuscript would also be strengthened by clarifying how the work extends previous assessments of thalamic connectivity and expanding the results with a more digested interpretation of the findings and validation of the segmentation quality. With these components strengthened, the work would be of interest to neuroscientists, neurologists, and neuropsychiatrists working on pulvinar functioning in health and disease.

ID (digest/hash) is calculated on the normalized data 3. Embed the ID

I like to think of this as a way to "normalize the data" or "standardize the data" - Data normalization is a common practice

Three steps said simply: 1. Normalize the data (put #'s where there ID will be) 2. Compute ID on the normalized data 3. Embed ID in data

An "Address" is a way to find something. or "Search" for something.

The "SA" of SAID means the ID is embedded within the data it is ID'ing

a SAID is an ID

eLife Assessment

This important study uncovers a surprising link between two self-cleaving RNAs that belong to the same structural family. The evidence supporting the main conclusions is convincing and based on extensive biochemical and bioinformatic analysis. This research will be of broad interest to RNA molecular biologists and biochemists.

eLife Assessment

This valuable study delineates the cellular contributions of BMP signaling in liver development and function. The findings are convincing, and the study employs state-of-the-art molecular, genetic, and cellular approaches to demonstrate that hepatic stellate cells play a central role in liver health by mediating cell-to-cell crosstalk via the production of specific BMP proteins. This study will be of interest to scientists interested in developmental biology and organ physiology.

eLife Assessment

This study offers important insights into the generation and maintenance of monosomic yeast lines and is, to our knowledge, the first to evaluate gene expression in yeast monosomies. The research introduces an innovative method to assess epistasis between genes on the same chromosome, providing solid evidence for positive epistatic interactions affecting fitness. Although the authors have substantially improved the methodology and interpretation during revision, questions regarding the interpretation of the transcriptome data have not been completely addressed.

eLife Assessment

In this valuable study, Huffer et al posit that non-cold sensing members of the TRPM subfamily of ion channels (e.g., TRPM2, TRPM4, TRPM5) contain a binding pocket for icilin that overlaps with the one found in the cold-activated TRPM8 channel. After examining a body of TRP channel cryo-EM structures to identify the conserved site, this study presents convincing electrophysiological evidence supporting the presence of an icilin binding pocket within TRPM4. This study shows that icilin has modulatory effects on the TRPM4 channel and will be of direct interest to those working in the TRP-channel field, but it also has implications for studies of somatosensation, taste, as well as pharmacological targeting of the TRPM subfamily.

eLife Assessment

This study demonstrates a novel role for SIRT4; a mitochondrial deacetylase, shown to translocate into nuclei where it regulates RNA alternative splicing by modulating U2AF2 and the gene expression of CCN2 in tubular cells in response to TGF-β. This fundamental work substantially advances our understanding of kidney fibrosis development and offers a potential therapeutic approach. The evidence supporting the conclusions of a SIRT4-U2AF2-CCN2 axis activated by TGF-β is compelling and adds a new layer of complexity to the pathogenesis of chronic kidney disease.

eLife Assessment

This study uses ex vivo live imaging of uteri post-mating to test the role of the sperm hook in the house mouse sperm in sperm movement that would be interesting to evolutionary biologists. The significance of the work is useful as live imaging can reveal information not seen in fixed images. The strength of evidence is incomplete as they cannot directly test the role of the sperm hook in facilitating movement along the uterine wall.

eLife Assessment

This useful manuscript presents an interesting multi-modal omics analysis of lung adenocarcinoma patients with distinct clinical clusters, mutation hotspots, and potential risk factors identified in cases linked to air pollution. The findings show potential for clinical and therapeutic impact. Some of the conclusions remain incomplete as they are based on correlative or suggestive findings, and would benefit from further functional investigation and validating approaches.

eLife Assessment

The study elucidates a detailed molecular mechanism of the initial stages of transport in the medically relevant Na+-coupled GABA neurotransmitter transporter GAT1 and thus generates important new insights into this protein family. In particular, it presents convincing evidence for the presence of a "staging binding site" that locally concentrates Na+ ions to increase transport activity, whilst solid evidence for how Na+ binding influences larger scale dynamics.