eLife Assessment

This valuable study identifies a protein called adenosine deaminase-related growth factor (ADGF) as a key regulator of tip formation in the slime mold Dictyostelium discoideum. The authors convincingly show that ADGF catalyses the formation of ammonia from adenosine, allowing ammonia to initiate tip formation, and then elucidate pathways upstream and downstream from ADGF. The authors discuss the intriguing possibility that mammalian ADGF may also similarly regulate development.

eLife Assessment

This important study by Liu et al. presents a comprehensive structure-function analysis of the presynaptic protein UNC-13, leading to new insights into how its distinct domains control neurotransmitter release. The methods, data, and analyses are convincing, and the genetic and electrophysiological approaches support many of their conclusions. The work will be of interest to neuroscientists studying synaptic transmission, as it provides a foundation for future mechanistic studies of Munc13/UNC-13 family proteins.

eLife Assessment

This valuable work investigates the social interactions of mice living together in a system of multiple connected cages. It provides solid evidence for a statistical approach capturing changes in social interactions after manipulating prefrontal cortical plasticity. This research will be of broad interest to researchers studying animal social behaviour.

eLife Assessment

The study presents valuable insights into the role of periosteal stem cells in bone marrow regeneration. The evidence is convincing. The data broadly support their claims and in line with state-of-art methodology. Future study on their model will help to strengthen their discovery further.

eLife Assessment

This useful study introduces a deep learning-based algorithm that tracks animal postures with reduced drift by incorporating transformers for more robust keypoint detection. The efficacy of this new algorithm for single-animal pose estimation was demonstrated through comparisons with two popular algorithms. The strength of evidence is solid but would benefit from consideration of issues in multi-animal tracking. This work will be of interest to those interested in animal behavior tracking.

eLife Assessment

This useful manuscript reports on the crystal structures of two glycosaminoglycan (GAG) lyases from the PL35 family, along with in vitro enzyme activity assays and comprehensive structure-guided mutagenesis. The authors have addressed key concerns by incorporating additional docking analyses, validating the role of His188 in alginate degradation, and providing ICP-MS data to examine Mn²⁺ binding. While these improvements enhance the study, the study is incomplete due to the lack of enzyme-substrate complex structures and reliance on modeling which still limit mechanistic insight. Nonetheless, the revised manuscript presents a more complete analysis that will be of interest to specialists in carbohydrate-active enzymes.

eLife Assessment

This important work advances our understanding of how the SARS-CoV-2 Nsp16 protein is regulated by host E3 ligases to promote viral mRNA capping. Support for the overall claims in the revised manuscript is convincing . This work will be of interest to those working in host-viral interactions and the role of the ubiquitin-proteasome system in viral replication.

eLife Assessment

This study provides a valuable contribution to our understanding of causal inference in visual perception. The evidence provided through multiple well-designed psychophysical experiments is convincing. The current study targets very specific visual features of launch events, future work will be able to build on this to study the implementation of causal inference in general.

eLife Assessment

Cichlid fishes have attracted attention from a wide range of biologists because of their<br /> extensive species diversification at the ecological and phenotypic levels. In this important study, the authors have partially revealed the mechanism behind lip thickening in cichlid fishes, which has evolved independently across three lakes in Africa. To explore this phenomenon, the authors used histological comparison, proteomics, and transcriptomics, all of which are well suited for their objectives. With compelling evidence, this contribution provides insights into parallel evolution in polygenic traits and holds significant value for the field.

eLife Assessment

This important manuscript investigates the role of olfactory cues in Pieris brassicae larvae, focusing on their interactions with the host plant Brassica oleracea and the parasitoid wasp Cotesia glomerata. The authors' demonstration that impaired olfactory perception reduces caterpillar performance and increases susceptibility to parasitism is solid. These findings highlight the ecological significance of olfaction in mediating feeding behavior and predator avoidance in herbivorous insects.

eLife Assessment

This study presents a valuable open-source and cost-effective method for automating the quantification of male aggression and courtship in Drosophila melanogaster. The work as presented provides solid evidence that the use of the behavioral setup that the authors designed - using readily available laboratory equipment and standardised high-performing classifiers they developed using existing software packages - accurately and reliably characterises social behavior in Drosophila. The work will be of interest to Drosophila neurobiologists and particularly to those working on male social behaviors.

eLife Assessment

This study presents a valuable finding on predator threat detection in C. elegans and the role of neuropeptide systems in defensive behavioral strategies. The evidence supporting the conclusions is solid, although additional analyses and control experiments would strengthen the claims of the study. Overall, the work is of interest to the C. elegans community as well as neuroethologists and ecologists studying predator-prey interactions.

eLife Assessment

This useful study reports detailed molecular dynamics (MD) simulations of T-cell receptors (TCRs) in complex with a peptide/MHC complex, for a better understanding of the mechanism of T-cell activation. The MD simulations provide solid evidence supporting that different TCRs can respond mechanically in different ways upon binding to the same pMHC complex. The analyses are systematic and provide testable predictions that can be evaluated by future mutagenesis and force microscopy studies.

eLife Assessment

This important study shows a surprising scale-invariance of the covariance spectrum of large-scale recordings in the zebrafish brain in vivo. A convincing analysis demonstrates that a Euclidean random matrix model of the covariance matrix recapitulates these properties. The results provide several new and insightful approaches for probing large-scale neural recordings.

eLife Assessment

This study presents valuable insights into the involvement of miR-26b in the progression of metabolic dysfunction-associated steatohepatitis (MASH). The delivery of microRNA-containing nanoparticles to reduce MASH severity has practical implications as a therapeutic strategy. The authors use two sets of transgenic mouse models, conducted kinase activity profiling of mouse liver samples, and supplemented their findings with additional experiments on human liver and plasma, providing solid support for their findings.

eLife Assessment

This paper explores how diverse forms of inhibition impact firing rates in models for cortical circuits. In particular, the paper studies how the network operating point affects the balance of direct inhibition from SOM inhibitory neurons to pyramidal cells, and disinhibition from SOM inhibitory input to PV inhibitory neurons. This is an important issue as these two inhibitory pathways have largely been studied in isolation. A combination of analytical calculations and direct numerical simulations provides convincing evidence that the interplay of these inhibitory circuits can separately control network gain and stability.

eLife Assessment

This is an important study showing that people who are hungry (vs. sated) put more weight on taste (vs. health) in their food choices. The experiment is well-designed and includes choice behavior, eye-tracking, and state-of-the-art computational modeling, resulting in compelling evidence supporting the conclusions.

eLife assessment

Using intracellular in vitro and in vivo recordings and a deep learning approach, this study shows that mouse dentate gyrus mossy cells (MCs) and CA3 pyramidal cells process information from an important electrophysiological hall mark of hippocampus, sharp wave-ripples (SWRs). The innovative use of deep learning to predict SWR waveforms from MC membrane potentials represents an interesting methodological advance. While the key findings are potentially fundamental, some of the evidence is currently incomplete and should be revised to better support the findings.

eLife Assessment

The authors describe an approach to construct hybrid neuraminidase molecules that express epitopes (loops) of a specific neuraminidase grafted onto another neuraminidase. The loops (epitopes) are from low-expressing neuraminidases and the scaffold is derived from a high-expressing neuraminidase. This paper is an important contribution giving new insights into the structure, function, and immunogenicity of influenza virus neuraminidases. The paper presents convincing evidence supporting the conclusions arrived at by the authors.

eLife Assessment

This manuscript presents a potentially important strategy for stimulating mammalian Müller glia to proliferate in vivo by manipulating cell cycle components. The results are convincing that a large number of Müller glia can be induced to re-enter the cell cycle without a damage stimulus. These findings are likely to appeal to retinal biologists and neuroscientists in general.

eLife Assessment

This study provides valuable insight into the role of Meis2 in whisker hair follicle formation and confirms prior work that nerves are dispensable for this process. The solid imaging techniques support the authors' conclusions, however the data provides limited evidence to support the mechanism of Meis2 in whisker formation.

eLife Assessment

This valuable study presents a computational model that simulates walking motions in Drosophila and suggests that, if sensorimotor delays in the neural circuitry were any longer, the system would be easily destabilized by external perturbations. The hierarchical control model is sensible and the evidence supporting the conclusions convincing. The modular model, which has many interacting components with varying degrees of biological realism, will serve as a well-grounded starting point for future studies that incorporate richer or more complete empirical data.

eLife Assessment

This important study uses Mendelian Randomisation to show that early life phenotypes (i.e. onset of age at menarche and age at first birth) have an influence on a multitude of health outcomes later in life. The provided empirical evidence supporting the antagonistic pleiotropy theory is solid. However, some results seem improbable and need to be checked to make sure they are correct.

eLife Assessment

This valuable study presents a deep learning framework for predicting synergistic drug combinations for cancer treatment in the AstraZeneca-Sanger (AZS) DREAM Challenge dataset. However, the evidence on the generalizability of the model is incomplete, as part of the validation seems to be flawed by overfitting, and only a modest correlation between predictions and observations was observed in the second, more independent test set. The reported tool, DIPx, could be of use for personalized drug synergy prediction and exploring the activated pathways related to the effects of drug combinations.

eLife Assessment

The authors have generated important resources such as a reference dataset of early primate development by utilizing single-cell transcriptomic technology together with induced pluripotent stem cells (iPSCs) from four primate species: humans, orangutans, cynomolgus macaques, and rhesus macaques. By analyzing marker gene expression and cell types across species during undirected differentiation of iPSCs, the authors provide solid evidence that the transferability of marker genes decreases as the evolutionary distance between species increases. This work demonstrates the extended usage of iPSCs for broader fields, which will benefit several scientific communities including anthropology, comparative biology, and evolutionary biology.

eLife Assessment

This is an important study that establishes how anti-sense oligonucleotides degrading a specific target protein called EMC10 can rescue neuronal function in models of chromosome 22.11.2 deletions. The authors use human iPSC-derived neurons and a mouse model to provide compelling data for the rescue of cellular and cognitive features of 22.11.2 phenotypes upon ASO regulation of EMC10. These pre-clinical data are of interest because they support reduction of ECM10 as a promising therapeutic strategy.

eLife Assessment

This study presents an important finding on the involvement of a Caspase 3-dependent pathway in the elimination of synapses for retinogeniculate circuit refinement and eye-specific territory segregation. This work fits well with the concept of "synaptosis" which has been proposed in the past. The evidence supporting the claims of the authors is convincing, demonstrating that caspase-3 activation is essential for microglial elimination of synapses during both brain development and neurodegeneration. The work will be of interest to investigators studying cell death pathways, neurodevelopment, and neurodegenerative disease.

eLife Assessment

This valuable study reports on the characteristics of premotor cortical population activity during the execution and observation of a moderately complex reaching and grasping task. By using new variants of well-established techniques to analyse neural population activity, the authors provide solid evidence that while the geometry of neural population activity changes between execution and observation, their dynamics are largely preserved. Although these findings are novel and robust, pending additional controls and analyses, the authors should further clarify the functional implications of their findings.

eLife Assessment

This important study provides solid evidence that glucosylceramide synthase (GlcT), a rate-limiting enzyme for glycosphingolipid (GSL) production, plays a role in the differentiation of intestinal cells. Mutations in GlcT compromise Notch signaling in the Drosophila intestinal stem cell lineage resulting in the formation of enteroendocrine tumors, and preliminary data suggests that a homolog of glucosylceramide synthase also influences Notch signaling in the mammalian intestine. While the outstanding strengths of the initial genetic and downstream pathway analyses are noted, there are weaknesses in the data regarding the potential role of this pathway in Delta trafficking. Nevertheless, this study opens the way for future mechanistic studies addressing how specific lipids modulate Notch signalling activity.

eLife Assessment

TrASPr is an important contribution that leverages transformer models focused on regulatory regions to enhance predictions of tissue-specific splicing events. The evidence supporting the authors' claims is convincing, with rigorous analyses demonstrating improved performance relative to existing models, although some aspects of the evaluation would benefit from further clarification. This work will be of particular interest to researchers in computational genomics and RNA biology, as it offers both a refined predictive model and a new tool to designing RNA sequences for targeted splicing outcomes.

eLife Assessment

Fleming et al sought to better understand DNAJC7's function in motor neurons as mutations in this gene have been associated with amyotrophic lateral sclerosis (ALS). Using iPSC-derived motor neurons, interactome, and transcriptomic data, they provide solid evidence that loss-of-function mutations in DNAJC7 disrupt RNA binding proteins and resistance to proteasomal stress. These important findings advance our understanding of DNAJC7 in motor neurons while providing clues to how its loss may be causal for ALS; nonetheless, the experiments were performed with a single iPSC line, while at least 3 are deemed to be required to validate the results. Furthermore, the mechanistic evidence is still incomplete with respect to how DNAJC7 mutations lead to HSF1 impaired activity, and whether it is direct or not.

eLife assessment

The authors made a useful finding that Zizyphi spinosi semen, a traditional Chinese medicine, has demonstrated excellent biological activity and potential therapeutic effects against Alzheimer's disease (AD). The researchers presented the effects, but the research evidence for the mechanism was incomplete. The main claims were only partially supported.

eLife Assessment

This useful study presents a possible solution for a significant problem - that of draining vein sensitivity in functional MRI, which complicates the interpretability of laminar-fMRI results. The addition of a low diffusion-weighted gradient is presented to remove the draining vein signal and obtain functional responses with higher spatial fidelity. However, the strength of the evidence is incomplete, and most tests appear to have been done only in a single subject. Significance thresholds in presented maps are very low and most cortical depth-dependent response profiles do not differ from baseline, even in the BOLD data shown as reference. Curiously, even BOLD group data fails to replicate the well-known pattern of draining towards the cortical surface.

eLife Assessment

In this useful study, Millard et al. assessed the effects of nicotine on pain sensitivity and peak alpha frequency (PAF). The evidence shown is incomplete to support the key claim that nicotine modulates PAF or pain sensitivity, considering the effect sizes observed. This raises the question of whether the chosen experimental intervention was the most suitable approach for investigating their research question. Nonetheless, the work can be incorporated into the literature investigating the relationship between nicotine and pain, and could be of broad interest to pain researchers.

eLife Assessment

This valuable study describes MerQuaCo, a computational and automatic quality control tool for spatial transcriptomics datasets. The authors have collected a remarkable number of tissues to construct the main algorithm. The exceptional strength of the evidence is demonstrated through a combination of empirical observations, automated computational approaches, and validation against existing software packages. MerQuaCo will interest researchers who routinely perform spatial transcriptomic imaging (especially MERSCOPE), as it provides an imperfection detector and quality control measures for reliable and reproducible downstream analysis.

eLife Assessment

This study presents important findings on the role of CXXC-finger protein 1 in regulatory T cell gene regulation and function. The evidence supporting the authors' claims is convincing, with mostly state-of-the-art technology. The work will be of relevance to immunologists interested in regulatory T cell biology and autoimmunity.

eLife Assessment

The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. These potentially important results suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, even though the estrogen responsive enhancer does not loop with the TFF3 promoter. To explain these results, the authors invoke a transcriptional condensate model. The claim of a temporal delay and effects of the target gene transcription on the non-target gene expression are supported by solid evidence but there is no direct evidence of the role of a condensate in mediating this effect. The reviewers appreciate that the authors have done a lot of work to strengthen the study. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

eLife Assessment

This important study developed a mathematical model to predict biological age by leveraging physiological traits across multiple organ systems. The results presented are convincing, utilizing comprehensive data-driven approaches. However, additional external validation could further strengthen its generalizability. The model provides a way to identify environmental and genetic factors impacting aging and lifespan, revealing new factors potentially affecting aging. It also shows promise for evaluating therapeutics aimed at prolonging a healthy lifespan.

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 information. Compared to previous versions, the most recent one is improved and sufficiently aligned with the standards of the field to merit consideration by the research community, making the evidence solid according to said standards. Nevertheless, uncertainty regarding false positive and false negative rates remains, as it does for some of the alternative approaches. With more rigorous validation, the approach might be of particular interest for sites in RNA molecules where modifications are rare.

eLife Assessment

The research presents valuable findings on the impact of FRMD8 loss on tumor progression and resistance to tamoxifen therapy. Through a series of convincing and systematic experiments, the author thoroughly investigates the role of FRMD8 in breast cancer and its underlying regulatory mechanisms. The study confirms that FRMD8 holds potential as a therapeutic target for reversing tamoxifen resistance, offering helpful insights for future treatment strategies.

eLife Assessment

This study shows that a peptide called galanin can decrease or increase seizure activity in experimental models of seizures depending on the model. The authors use zebrafish and several methods to address the effects of galanin. The study will be useful to researchers who use zebrafish as experimental animals and who are interested in how peptides like galanin regulate seizures. However, the strength of evidence was considered incomplete at the present time due to several limitations of the results.

eLife Assessment

This study presents valuable findings on the control of survival and maintenance of a specific set of brain resident immune cells. The authors generate a new animal model to enable sophisticated analysis of cell function in vivo. The sophisticated knock-in/knock-out alleles are compelling, although the work would ultimately be strengthened with further mechanistic analyses.

eLife Assessment

Du et al. present a valuable study on neural activation in medial prefrontal cortex (mPFC) subpopulations projecting to the basolateral amygdala (BLA) and nucleus accumbens (NAc) during behavioral tasks assessing anxiety, social preference, and social dominance. The study has innovative approaches and solid in vivo calcium imaging data, but the evidence linking neural physiology to behavioral outcomes is incomplete. Addressing these gaps would significantly enhance the understanding of how distinct mPFC→BLA and mPFC→NAc pathways influence anxiety, exploration, and social behaviors.

eLife Assessment

The authors of this important study investigate how telomere length regulates hTERT expression via non-telomeric binding of the telomere-associated protein TRF2. They conclusively show that TRF2 binding to long telomeres results in a reduction in its binding to the hTERT promoter, while short telomeres restore TRF2 binding in the hTERT promoter, recruiting repressor complexes like PRC2, and suppressing hTERT expression. There is convincing support for the claims and the findings should be of broad interest for cell biologists and those working in fields where telomeres alter function, such as cancer and aging.

eLife Assessment

This study provides an important method to model the statistical biases of hypermutations during the affinity maturation of antibodies. The authors show convincingly that their model outperforms previous methods with fewer parameters; this is made possible by the use of machine learning to expand the context dependence of the mutation bias. They also show that models learned from nonsynonymous mutations and from out-of-frame sequences are different, prompting new questions about germinal center function. Strengths of the study include an open-access tool for using the model, a careful curation of existing datasets, and a rigorous benchmark; it is also shown that current machine-learning methods are currently limited by the availability of data, which explains the only modest gain in model performance afforded by modern machine learning.

eLife Assessment

Using an unbiased approach, this important study discovered a role of Ezh2 in the differentiation of granule neuron precursors, the cell of origin for Shh group of medulloblastoma. Furthermore, the authors also provided solid evidence that combined inhibition of Ezh2 and CDK4/6 likely represents a promising strategy for the treatment of this subgroup of MB. Validation of these findings using the FDA-approved Ezh2 inhibitor is needed to further strengthen this preclinical study.

Editors Assessment:

The Visayan spotted deer (Rusa alfredi), is a small, endangered, primarily nocturnal species of deer found in the rainforests of the Visayan Islands in the Philippines. The present study reports the first draft genome assembly for the species, addressing a critical gap in genomic data for this IUCN-redlisted cervid. Using Illumina sequencing, the resulting genome assembly spans 2.52 Gb in size with a BUSCO completeness score of 95.5% and encompasses 24,531 annotated genes. Phylogenetic analysis suggests a close evolutionary relationship between R. alfredi and Cervus species suggesting that the genus Rusa is sister to Cervus. Peer-review teased out more benchmarking results and the annotation files, demonstrating this genomic resource is useful and usable for advancing population genetics and evolutionary studies, thereby informing conservation strategies and enhancing breeding programs for the critically threatened species. Providing whole genome sequences for other native species of Rusa could further provide genomic resources for detecting hybrids, which will also help the management and monitoring of these species, especially for the reintroduction of captive populations in the wild.

This evaluation refers to version 1 of the preprint

eLife Assessment

This serostudy of blood donors in Bolivia (a country with very high COVID death rates in 2020-21) provides useful insights on the successive viral variants of SARS-CoV-2 over 2021 and 2022. Using compelling antibody and neutralization assays, the authors describe variant specific distributions in the different parts of Bolivia. The main methodological advance is to use serology to understand variant diversity, which in turn helps deepen understanding of "hybrid" immunity from widespread infection (and vaccination).

eLife Assessment

This study presents a valuable finding on the role of secretory leukocyte protease inhibitors (SLPI) in developing Lyme disease in mice infected with Borrelia burgdorferi. The evidence supporting the claims of the authors is solid. This paper will be of interest to scientists in the infectious inflammatory disease field.

Editors Assessment:

Teinturier grapes produce berries with pigmented skin and flesh, and are used in red wine blends, as they provide a deeper colour. This paper presents the genomes of two popular teinturier varieties (Dakapo and Rubired); sequenced, assembled, and annotated to provide additional resources for their use in breeding. Combining Nanopore and Illumina sequencing for Dakapo, scaffolding to the existing grapevine assembly to generate a final assembly of 508.5 Mbp and 36,940 gene annotations. For Rubired PacBio HiFi reads were assembled, scaffolded, and phased to generate a diploid assembly with two haplotypes 474.7-476.0 Mbp long and 56,681 genes annotated. Peer review has helped validate their high quality, these genomes hopefully enabling more insight into the genetics of grapevine berry colour and their other traits like frost and mildew-resistance.

This evaluation refers to version 1 of the preprint

eLife Assessment

This study presents valuable findings with practical and theoretical implications for drug discovery, particularly in the context of repurposing cipargamin CIP for the treatment of Babesia spp. The evidence is solid with the methods, data and analyses broadly supporting the claims. The paper will be of great interest to scientists in drug discovery, computational biology, and microbiology

eLife Assessment

This important study utilizes humanized mice, in which human immune cells are introduced into immune-deficient mice, to provide convincing evidence that two helper CD4 T-cell subsets, T-follicular helper (Tfh) and T-peripheral helper (Tph) cells, are able to drive both autoantibody production and induction of autoimmunity. The work will be of broad interest to medical scientists engaged in deciphering how human immune cells mediate immune responses and contribute to the development of autoimmune diseases.

eLife Assessment

This important paper on measuring molecular connectivity using combined serotonin PET and resting-state fMRI provides both novel methods for studying the brain as well as insights into the effects of ecstasy administration. The methods are convincing, with the high anaesthetic dose used likely limiting network activity.

eLife Assessment

This important work provides another layer of regulatory mechanism for TGF-beta signaling activity. The evidence convincingly supports the involvement of microtubules as a reservoir of Smad2/3, and association of Rudhira with microtubules is critical for this process. The work will be of board interest to developmental biologists in general and molecular biologists in the field of growth factor signaling.

eLife Assessment

The authors provide a compelling method for characterizing communication within brain networks. The study engages important, biologically pertinent, concerns related to the balance of dynamics and structure in assessing the focal points of brain communication. It will be of interest to researchers trying to dissect structure of complex interaction networks across scales, from cells to regions.

eLife Assessment

The paper addresses the problem of optimising the mapping of serum antibody responses against a known antigen. The manuscript describes a method using EM polyclonal epitope mapping to help elucidate endogenous antibodies. The work is interesting and valuable to the fields of immunology and serology, and the strength of evidence to support its findings is considered solid.

eLife Assessment

This valuable study presents an interesting analysis of the role of the polyamine precursor putrescine in the pili-dependent surface motility of a laboratory strain of Escherichia coli. The overall data convincingly demonstrate a role in this case. This study presents interesting findings for those studying uropathogenic bacteria, and those studying bacterial polyamine function.

eLife Assessment

This important study analyzes the effect of heat treatment on phage-bacterial interactions and convincingly shows that prior heat exposure alters the bacterial cell envelope, enhancing persistence and bacterial survival when exposed to lytic phages. The study will interest researchers working on antibiotic resistance, tolerance, and phage therapy.

eLife Assessment

This important study leverages the power of Drosophila genetics and sparsely-labeled neurons to propose an intriguing new model for neuronal injury signaling. The authors present convincing evidence to show that the somatic response to axonal injury can be suppressed if the injury is not complete, suggesting the presence of a new mode of injury 'integration.' While the underlying mechanism of this fascinating observation has yet to be determined, the phenomenon itself will be of broad significance in the field.

eLife Assessment

This study reports that the RNA binding and cardiomyopathy-associated protein RBM20 is expressed in specific populations of neurons in the CNS, where it binds to and regulates the expression of synapse-related RNAs. This is an important finding because it reveals a new mechanism for gene regulation in neurons by an RNA binding protein previously studied in the heart; the authors also provide data to suggest that the mechanism by which RBM20 acts in neurons may be distinct from the splicing regulation studied in cardiac tissue. The data in support of the binding and regulation of RNAs by RBM20 is compelling, using leading edge sequencing methods to determine RNA binding profiles, and cell type specific genetics for evaluation of function.

eLife Assessment

This study presents a useful method based on flow cytometry to study partitioning noise during cell division. The evidence supporting the claims of the authors is incomplete, as the method neglects other sources of noise present in cells. With the theoretical part extended, this paper would be of interest to cell biologists and biophysicists working on asymmetric partitioning during cell division.

eLife Assessment

This study presents valuable findings suggesting that the late maturation of prefrontal cortex-based control processes enhances conceptual learning by allowing a period of less-constrained knowledge acquisition. The authors provide convincing computational evidence that delayed semantic control promotes learning without compromising representation integrity, with the strongest benefits emerging when control connections target intermediate layers of the model. However, the model's narrow scope raises concerns about scalability to more complex, real-world learning environments, and the meta-analysis, while supporting the developmental trajectory, does not directly test the model's specific predictions regarding task outcomes or error patterns.

eLife Assessment

The study presents valuable findings regarding the incidence and clinical impact of a mutation in a cardiac muscle protein and its association with the development of atrial fibrillation. The authors provide some convincing evidence of electrophysiological disturbances in cells with this mutation which would be of interest to cellular electrophysiologists. However, evidence supporting the conclusion that this mutation causes atrial fibrillation would benefit from more rigorous electrophysiologic approaches.

eLife Assessment

Studying the biological roles of polyphosphates in metazoans has been a longstanding challenge to the field given that the polyP synthase has yet to be discovered in metazoans. This important study capitalizes on the sophisticated genetics available in the Drosophila system and uses a combination of methodologies to start to tease apart how polyphosphate participates in Drosophila development and in the clotting of Drosophila hemolymph. The data validating the tools are solid and well-documented and they will open up a field of research into the functional roles of polyP in a metazoan model.

eLife Assessment

This is an important study that examines the impact of Streptococcus pneumoniae genetics on its in vitro growth kinetics, aiming to identify potential targets for vaccines and therapeutics. The study identified significant variations in growth characteristics among capsular serotypes and lineages, linked to phylogeny and high heritability, but genome-wide association studies did not reveal specific genomic loci associated with growth features independent of the genetic background. The evidence supporting these findings is solid.

eLife Assessment

This important study examines the relationship between cognition and mental health and investigates how brain, genetics, and environmental measures mediate that relationship. The methods and results are compelling and well-executed. Overall, this study will be of interest in the field of population neuroscience and in studies of mental health.

eLife Assessment

This study establishes the methodology (machine vision and gaze pose estimation) and behavioral apparatus for examining social interactions between pairs of marmoset monkeys. Their results enable unrestrained social interactions under more rigorous conditions with detailed quantification of position and gaze. It has been difficult to study social interactions using artificial stimuli, as opposed to genuine interactions between unrestrained animals. This study makes an important contribution to studying social neuroscience within a laboratory setting; the approach is novel and well-executed, backed by convincing evidence.

Editors Assessment:

The accuracy of basecalling of nanopore sequencing still needs to be improved. With recent advances in deep learning this paper introduces SqueezeCall, a novel end-to-end tool for accurate basecalling. This uses Squeezeformer-achitecture which integrates local context extraction through convolutional layers and long-range dependency modeling via global context acquisition. Testing and peer review demonstrated that SqueezeCall outperformed traditional RNN and Transformer-based basecallers across multiple datasets, indicating its potential to refine genomic assembly and facilitate direct detection of modified bases in future genomic analytics. Future work is ongoing that will focus on training on highly curated datasets, including known modifications, to further increase research value. SqueezeCall is MIT licensed and available from GitHub here: https://github.com/labcbb/SqueezeCall

This evaluation refers to version 1 of the preprint

eLife Assessment

The study describes a useful tool for assessing microglia morphology in a variety of experimental conditions. The MorphoCellSorter provides a solid platform for ranking microglia to reflect their morphology continuum and may offer new insight into changes in morphology associated with injury or disease. While the study provides an alternative approach to existing methods for measuring microglia morphology, the functional significance of the measured morphological changes were not determined.

Evaluation Statement (30 January 2025)

Kay and Aminzare discuss a claim made in a prior publication that macromolecular condensation acts as a water buffering mechanism in cells to compensate for the effects of osmotic shock. The authors argue that, although such a buffer could temporarily maintain a transmembrane osmolality differential, this differential would drive water across the membrane to reach a steady-state in which osmolality within the cell equals osmolality outside the cell. Using the well-established pump-leak model for osmotic water transport, they further show that the timescale at which a water buffer could maintain a modest 10% osmolality differential across the membrane is at most one minute for a typical animal cell.

Biophysics Colab recommends this study to researchers working on membrane transport, intracellular water buffering, and condensate biology.

Biophysics Colab has evaluated this study as one that meets the following criteria:

• Rigorous methodology
• Transparent reporting
• Appropriate interpretation

(This evaluation refers to version 3 of this preprint, which has been revised in response to peer review of versions 1 and 2.)

eLife Assessment

This manuscript represents a fundamental contribution demonstrating that fentanyl-induced respiratory depression can be reversed with a peripherally-restricted mu opioid receptor antagonist. The paper reports compelling and rigorous physiological, pharmacokinetic, and behavioral evidence supporting this major claim, and furthers mechanistic understanding of how peripheral opioid receptors contribute to respiratory depression. These findings reshape our understanding of opioid-related effects on respiration and have significant therapeutic implications given that medications currently used to reverse opioid overdose (such as naloxone) produce severe aversive and withdrawal effects via actions within the central nervous system.

eLife Assessment

In this revised work, Barzó et al. assessed the electrophysiological and anatomical properties of a large number of layer 2/3 pyramidal neurons in brain slices of human neocortex across a wide range of ages, from infancy to elderly individuals, using whole-cell patch clamp recordings and anatomical reconstructions. This large data set represents an important contribution to our understanding of how these properties change across the human lifespan, supported by convincing data and analyses. The authors have addressed the concerns raised in previous reviews. Overall, this study strengthens our understanding of how the neural properties of human cortical neurons change with age and will contribute to building more realistic models of human cortical function.

eLife assessment:

This study describes a new set of genetic tools for optimized Cre-mediated gene deletion in mice. The advances are substantial and will facilitate biomedical research. Although the tools have been validated using solid methodologies, the quantitative assessment of their recombination efficiency is not yet sufficiently described. Evaluating their ability to mediate the deletion of multiple alleles in a mosaic setting would also be a highly valuable addition.

eLife Assessment

This is an important study that characterizes a surprising interaction between two different cytokine/hormone receptors using nanoscale resolution (dSTORM) microscopy. The study provides solid evidence that the interaction is ligand-dependent, and is mediated by the receptor-associated intracellular signalling molecule JAK2. While at present limited to growth hormone and prolactin receptors in a limited number of cell lines, there are potentially broad implications for cytokine signalling, as such JAK2-mediated interactions could occur between a range of different cytokines. Moreover, the specific hormone interactions shown in the manuscript may have significant implications for understanding how these hormones can have differential effects in breast cancer, under different conditions.

eLife Assessment

In their valuable study, Lee et al. explore a role for the Hippo signaling pathway, specifically wts-1/LATS and the downstream regulator yap, in age-dependent neurodegeneration and microtubule dynamics using C. elegans mechanosensory neurons as a model. The authors demonstrate that disruption of wts-1/LATS leads to age-associated morphological and functional neuronal abnormalities, linked to enhanced microtubule stabilization, and show a genetic connection between yap and microtubule stability. Overall, the study employs robust genetic and molecular approaches to reveal a convincing link between the Hippo pathway, microtubule dynamics, and neurodegeneration.

eLife Assessment

This important study aims to understand the function of ProSAP-interacting protein 1 (Prosapip1) in the brain. Using a conditional Prosapip1 KO mouse (floxed prosapip1 crossed with Syn1-Cre line), the authors performed analysis including protein biochemistry, synaptic physiology, and behavioral learning. Convincing evidence from this study supports a role of Prosapip 1 in synaptic protein composition, synaptic NMDA responses, LTP, and spatial memory.

eLife Assessment

This valuable study investigates how the neural representation of individual finger movements changes during the early period of sequence learning. By combining a new method for extracting features from human magnetoencephalography data and decoding analyses, the authors provide incomplete evidence of an early, swift change in the brain regions correlated with sequence learning, including a set of previously unreported frontal cortical regions. The addition of more control analyses to rule out that head movement artefacts influence the findings, and to further explain the proposal of offline contextualization during short rest periods as the basis for improvement performance would strengthen the manuscript.

eLife Assessment

This work investigates the functional difference between the most commonly expressed form of PTH, and a mutant form of PTH, identified in a patient with chronic hypocalcemia and hyperphosphatemia which characterizes hypoparathyroidism. The authors investigate the hypothesis that this mutant PTH assumes a dimeric form in vivo and serves anabolic functions in the bone. The data are compelling and the translational aspects are fundamental in understanding PTH-1 Receptor activation.

eLife Assessment

Catani and colleagues provide data on antigenic properties of neuraminidase proteins of pandemic H1N1 and show that antigenic diversity of the neuraminidase from 2009 to 2020 largely falls into two groups. These antigenic groups map to two phylogenetic groups, and substitutions at positions 432 and 321 are likely associated with the antigenic change. These data and results allow useful insights into the antigenic properties of N1 influenza and the evidence supporting the conclusions is solid.

eLife Assessment

The study by Chi and colleagues presents important new tools for precise genetic manipulation and lineage tracing in mice. The characterization of these new models was conducted using validated, state-of-the-art methodologies and convincingly demonstrates their ability to enhance the precision of genetic manipulation in distinct cell types. This work will be of great interest to many laboratories worldwide and will facilitate future research across various biomedical disciplines.

eLife Assessment

This important study examined orientation representations along the visual hierarchy during perception and working memory. The authors provide results suggesting that during working memory there is a gradient where representations are more categorical in nature later in the visual hierarchy. The evidence presented is solid, most notably a match between behavioral data, though minor weakness can be attributed to the tasks and behaviors not being designed to address this question. The findings should be of interest to a relatively broad audience, namely those interested in the relationship between sensory coding and memory.

eLife Assessment

The songbird vocal motor nucleus HVC contains cells that project to the basal ganglia, the auditory system, or downstream vocal motor structures. In this fundamental study, the authors conduct optogenetic circuit mapping to clarify how four distinct inputs to HVC act on these distinct HVC cell types. They provide compelling evidence that all long-range projections engage inhibitory circuits in HVC and can also exhibit cell-type specific preferences in monosynaptic input strength. Understanding the HVC microcircuit at this microcircuit level is critical for informing models of song learning and production.

eLife Assessment

This work presents important findings that the human frontal cortex is involved in a flexible, dual role in both maintaining information in short-term memory, and controlling this memory content to guide adaptive behavior and decisions. The evidence supporting the conclusions is compelling, with a well-designed task, best-practice decoding methods, and careful control analyses. The work will be of broad interest to cognitive neuroscience researchers working on working memory and cognitive control.

eLife Assessment

This study presents a fundamental finding on how levels of m6A levels are controlled, invoking a consolidated model where degradation of modified RNAs in the cytoplasm plays a primary role in shaping m6A patterns and dynamics, rather than needing active regulation by m6A erasers and other related processes. The evidence is compelling through its use of transcriptome-wide data and mechanistic modeling. Relevant for any reader with an interest in RNA metabolism, this new framework consolidates previous observations and highlights the importance of careful experimentation for evaluation m6A levels.

eLife Assessment

This valuable study builds on previous work by the authors by presenting a potentially key method for correcting optical aberrations in GRIN lens-based microendoscopes used for imaging deep brain regions. By combining simulations and experiments, the authors provide convincing evidence showing that the obtained field of view is significantly increased with corrected, versus uncorrected microendoscopes. Because the approach described in this paper does not require any microscope or software modifications, it can be readily adopted by neuroscientists who wish to image neuronal activity deep in the brain.

eLife Assessment

This paper represents an important contribution to the field. Summarizing results from neural recording experiments in mice across ten labs, the work provides compelling evidence that basic electrophysiology features, single-neuron functional properties, and population-level decoding are fairly reproducible across labs with proper preprocessing. The results and suggestions regarding preprocessing and quality metrics may be of significant interest to investigators carrying out such experiments in their own labs.

eLife Assessment

This study provides valuable insights into the evolutionary histories and cellular infection responses of two Salmonella Dublin genotypes. While the evidence is compelling, a more phylogenetically diverse bacterial collection would enhance the findings. This research is relevant to scientists studying Salmonella and gastroenteritis-related pathogens.

eLife Assessment

This valuable study reports that epididymal proteins are required for embryogenesis after fertilization. The data presented are generally supportive of the conclusion and considered solid. This work will be of interest to reproductive biologists and andrologists.

eLife Assessment

This study provides valuable information on a novel gene that regulates meiotic progression in both male and female meiosis. The evidence supporting the conclusions of the authors is solid. This study will be of interest to developmental and reproductive biologists.

eLife Assessment

This important study shows that a very slow (infraslow) oscillation occurs in voltage recordings from the dentate gyrus of the adult mouse. The authors suggest that it is related to sleep stage and serotonin acting at one type of serotonin receptor in the dentate gyrus. The results are significant because they suggest new insight into how a slow oscillation affects memory through serotonin receptors in the dentate gyrus. Convincing data are provided to support the claims.

eLife Assessment

This important manuscript proposes a dual behavioral/computational approach to assess emotional regulation in humans. The authors present solid evidence for the idea that emotional distancing (as routinely used in clinical interventions for e.g. mood and anxiety disorders) enhances emotional control.

eLife Assessment

This important study has modified ChIP-seq and 4C-seq procedures with a urea step and shows that this drastically changes the pattern of chromatin interactions observed for SATB1 but not other proteins (CTCF, Jarid2, Suz12, Ezh2). Multiple controls make the data convincing. The findings shed new light on the role of SATB1 in genome organization and will be of interest to those who study chromosome structure and nuclear organization.

eLife Assessment

This important study investigates the different mechanisms that provide instructions for a missing body part to regenerate its appropriate identity. The authors use two species of planarians to identify a key role for bodywide canonical Wnt gradients in controlling the outcome of regeneration. The study provides convincing evidence for variable regeneration efficiency among planarian species that will be of interest to developmental biologists interested in regeneration. However, some of the results are over-interpreted and the additional experiments could provide better support for the authors' claims.

eLife Assessment

This valuable study reports a potential connection between the seminal microbiome and sperm quality/male fertility. The data are generally convincing. This study will be of interest to clinicians and biomedical researchers who work on microbiome and male fertility.

eLife Assessment

This compelling study introduces a set of novel genetically encoded tools for the selective and reversible ablation of excitatory and inhibitory synapses. These new tools enable selective and efficient ablation of excitatory synapses, and photoactivatable and chemically inducible methods for inhibitory synapse ablation in specific cell types, providing valuable methods for disrupting neural circuits. This approach holds broad potential for investigating the roles of specific synaptic input onto genetically determined cells.

eLife Assessment

The paper describes a novel approach for inferring features of synaptic networks from recordings of individual cells within the network. The paper will be a valuable contribution to those studying central pattern generators, including those involved in respiration. However, the theoretical approach to drawing inferences regarding the underlying synaptic currents is incomplete as it relies on unsupported simplifying assumptions.

eLife Assessment

This neuroimaging and electrophysiology study in a small cohort of congenital cataract patients with sight recovery aims to characterize the effects of early visual deprivation on excitatory and inhibitory balance in visual cortex. While contrasting sight-recovery with visually intact controls suggested the existence of persistent alterations in Glx/GABA ratio and aperiodic EEG signals, it provided incomplete evidence supporting claims about the effects of early deprivation itself. The reported data were considered valuable, given the rare study population. However, methodological limitations will likely restrict usefulness to scientists working in this particular subfield.

eLife Assessment

van Vliet and colleagues show a useful correlation between internal states of a convolutional neural network (CNN) trained on visual word stimuli with three specific components of evoked MEG potentials during reading in humans. The findings are solid, though quantitative evidence that model can produce any of the phenomena that the human visual system is known to have (e.g., feedback connections, sensitivity to word frequency), or that it has comparable performance to human behaviour (i.e., similar task accuracy with a comparable pattern of mistakes) would make the conclusions much stronger.

eLife Assessment

Hardly anything is known about the genetic basis and mechanism of male-killing. Recently, a gene called oscar, in the bacterium Wolbachia, was implicated in killing male corn borer moths by interfering with moth genes that control sex determination and proper dosage of sex-specific genes. In this paper, the authors show that a distantly related oscar gene in another strain of Wolbachia kills male tea tortrix moths in a similar mechanism. This valuable study cements our understanding of the sophisticated way that Wolbachia kills male moths and butterflies (Lepidoptera) so early in their development. The conclusions are supported by solid evidence.

eLife Assessment

The authors have developed a biosensor for programmed cell death. They use this biosensor to provide cell death measurements in a specific early development time. The findings useful in a specific context; however, the application of this biosensor is incomplete as it does not take into account existing literature and is missing controls.

eLife Assessment

It is known from model organisms that genes' effects on traits are often modulated by environmental variables, but similar gene-by-environment (GxE) interactions have been difficult to detect using statistical analyses of genomic data, e.g., in humans. This study introduces a new framework to estimate gene-by-environment effects, treating it as a bias-variance tradeoff problem. The authors convincingly show that greater statistical power can be achieved in detecting GxE if an underlying model of polygenic GxE is assumed. This polygenic amplification model is a truly novel view with fundamental promise for the detection of GxE in genomic datasets, especially with continued development to detect more complex signals of amplification.

eLife Assessment

This important study reports numerous attempts to replicate reports on transgenerational inheritance of a learned behavior – pathogen avoidance – in C. elegans. While the authors observe parental effects that are limited to a single generation (also called intergenerational inheritance), the authors failed to find evidence for transmission over multiple generations, or transgenerational inheritance. The experiments presented are meticulously described, making for compelling evidence that in the authors' hands transgenerational inheritance cannot be observed. There remains the possibility that different assay setups explain the failure to reproduce previous observations, although the authors present data suggesting that details of the assay are not that significant. There also remains the possibility that differences in culture conditions or lab environment explain the failure to reproduce previous observations, with updates to the paper having further reduced the probability that this applies here. Even if this were the case, it would imply that the original experimental paradigm was dependent on a very specific context. Given the prominence of the original reports of transgenerational inheritance, the present study is of broad interest to anyone studying genetics, epigenetics, or learned behavior.

[As also pointed out by the authors of this study, the authors of the original reports have provided a response on bioRxiv (DOI: https://doi.org/10.1101/2025.01.21.634111).]

eLife Assessment

This work investigates ZC3H11A as a cause of high myopia through the analysis of human data and experiments with genetic knockout of Zc3h11a in mouse, providing a useful model of myopia. The evidence supporting the conclusion is still incomplete in the revised manuscript as the concerns raised in the previous review were not fully addressed. The article will benefit from further strengthening the genetic analysis, full presentation of human phenotypic data, and explaining the reasons why there was no increased axial length in mice with myopia. The work will be of interest to ophthalmologists and researchers working on myopia.

eLife Assessment

This study follows up on Arimura et al's powerful new method MagIC-Cryo-EM for imaging native complexes at high resolution. Using a clever design embedding protein spacers between the antibody and the nucleosomes purified, thereby minimizing interference from the beads, the authors concentrate linker histone variant H1.8 containing nucleosomes. From these samples, the authors obtain convincing atomic structures of the H1.8 bound chromatosome purified from interphase and metaphase cells, finding a NPM2 chaperone bound form exists as well. Caveats previously noted have been addressed nicely in the revision, strengthening the overall conclusions. This is an important new tool in the arsenal of single molecule biologists, permitting a deep dive into structure of native complexes, and will be of high interest to a broad swathe of scientists studying native macromolecules present at low concentrations in cells.

eLife Assessment

The formation of the Z-ring at the time of bacterial cell division interests researchers working towards understanding cell division across all domains of life. The manuscript by Jasnin et al reports the cryoET structure of toroid assembly formation of FtsZ filaments driven by ZapD as the cross linker. The findings are important and have the potential to open a new dimension in the field, but the evidence to support these exciting claims is currently incomplete, mostly because of the suboptimal "resolution of the toroids", so in the absence of additional experiments, the interpretations would need to be toned down.

eLife Assessment

Combining experimental and computation approaches, this manuscript provides convincing evidence for a post-transcriptional mechanism that provides robust control over the protein expression level of RecB in E. coli. In addition to uncovering how DNA damage drives higher levels of RecB protein, this work also reveals important tenets for how broader mechanisms that suppress noise and underlie responsive tuning of protein levels can be achieved.

eLife Assessment

In this detailed study, Cohen and Ben-Shaul characterized Accessory Olfactory Bulb (AOB) cell responses to various conspecific urine samples in female mice across the estrous cycle. The authors found that AOB cell responses varied depending on the strain and sex of the sample, but no clear differences were observed between estrous and non-estrous females. These findings provide convincing evidence that the AOB functions as a stable sensory relay, without directly modulating responses based on reproductive state, which supports the role of downstream brain regions in integrating reproductive state. Overall, this study provides valuable insights for researchers in the fields of olfaction and social neuroscience.

eLife Assessment

Pinho et al use in vivo calcium imaging and chemogenetic approaches to examine the involvement of hippocampal sub-regions across the different stages of a sensory preconditioning task in mice. They find convincing evidence for sensory preconditioning in male mice. They also find that, in these mice, CaMKII-positive neurons in the dorsal hippocampus: (1) encode the audio-visual association that forms in stage 1 of the task, and (2) retrieve/express sensory preconditioned fear to the auditory stimulus at test. These findings are supported by evidence that ranges from incomplete to convincing. The study will be valuable to researchers in the field of learning and memory.

eLife Assessment

In this paper, the authors report important structural and functional findings on the interaction of how the group A streptococci (GAS) M3 protein (expressed on GAS strains emm3, which are associated with invasive disease) binds to human collagens. They demonstrate an unusual T-shaped structure within the N-terminal hypervariable region of M3 protein that can bind two copies of collagen triple helix in parallel. These solid data advance understanding of how GAS M3 interacts with human collagen, information relevant to understanding and developing treatments for GAS infection. A major limitation of the work is the lack of mutational work to test if the T-shaped structure is necessary for binding collagen.

eLife Assessment

This important theoretical study introduces an extension to the commonly used SIR model for infectious disease dynamics, to explicitly consider the role of larger group sizes. Instead of the commonly used individual-based network models, the authors developed a simplified approach based on group sampling, with discrete high- and low-risk groups, which makes the results easier to produce and interpret, at the cost of less detail in the model. The evidence is convincing in terms of the soundness of the theoretical projections and the impact that accounting for group sizes may have on inferences from surveillance data. However, it has not yet been demonstrated that the predictions provide more realistic projections when based on real-world data.

eLife Assessment

The study introduces new tools for measuring the intracellular calcium concentration close to transmitter release sites, which may be relevant for synaptic vesicle fusion and replenishment. This approach yields important new information about the spatial and temporal profile of calcium concentrations near the site of entry at the plasma membrane. This experimental work is complemented by a coherent, open-source, computational model that successfully describes changes in calcium domains. Key gaps in the data presented mean that the evidence for the main conclusions is currently incomplete.

eLife Assessment

This study presents valuable findings on the increased prevalence of pain in women with polycystic ovary syndrome and its relationship to health outcomes. The evidence supporting the conclusions is compelling with a large number of patients and sound methodology, and can be used as a starting point for studies of etiology and mechanisms of pain in women with polycystic ovary syndrome and comorbidities. The work will be of interest to medical biologists working on polycystic ovary syndrome pathophysiology and clinicians.

eLife Assessment

This valuable study characterises the activity of motor units from two of the three anatomical subdivisions ("heads") of the triceps muscle while mice walked on a treadmill at various speeds. Although this is the most thorough characterisation of motor unit activity in walking mice to date, the evidence supporting some of the claims, especially pertaining to probabilistic recruitment of motor units, is incomplete. Further investigating whether the differences in motor unit recruitment across muscle heads go beyond their different mechanical functions would also strengthen the paper.

eLife Assessment

This important study identifies a novel role for Hes5+ astrocytes in modulating the activity of descending pain-inhibitory noradrenergic neurons from the locus coeruleus during stress-induced pain facilitation. The role of glia in modulating neurological circuits including pain is poorly understood, and in that light, the role of Hes5+ astrocytes in this circuit is a key finding with broader potential impacts. However, the impact of this work is limited by incomplete evidence, notably the fact that acute restraint stress is generally anti-nociceptive rather than pro-nociceptive, and a lack of specificity in defining this novel circuit.

eLife Assessment

This is a useful follow-up on previous work on the same LGI1-ADAM22 complex using cross-linking to stabilize a trimeric state that the authors had previously observed by SEC-MALS and small-angle X-ray scattering (the previous crystal structure was determined in a dimeric form). A strength of this solid work is that oligomeric states do not affect the critical interaction between LGI1 and ADAM23, so the previous conclusions are still valid. A weakness is that the physiological relevance of the trimeric assembly is unclear.

eLife Assessment

This paper presents the important finding that BNIP3/NIX, a mitophagy receptor, and its binding to ATG18 are required for mitophagy during muscle cell reorganization in Drosophila. Although the involvement of the BNIP3-ATG18/WIPI axis in mitophagy induction has been reported in mammalian cell culture systems, this study provides the first compelling evidence for this pathway in vivo in animals. The physiological significance of this BNIP3-dependent mitophagy will require further investigation.

eLife Assessment

This paper provides a compelling and rigorous quantitative analysis of the turnover and maintenance of CD4+ tissue-resident memory T cell clones, in the skin and the lamina propria. It provides a fundamental advance in our understanding of CD4 T cell regulation. Interestingly, in both tissues, maintenance involves an influx from progenitors on the time scale of months. The evidence that is based on fate mapping and mathematical inference is strong, although open questions on the interpretation of the Ki67-based fate mapping remain.