Evaluated articles

eLife Assessment

This study presents an important finding on the role of GATA4 in aging and OA-associated cartilage pathology. The evidence supporting the conclusions is compelling, with rigorous in vitro and in vivo data. The work will be of broad interest to cell biologists and orthopedic clinicians.

eLife Assessment

This important study applies an innovative multi-model strategy to implicate the ribosomal protein (RP) encoding genes as candidates causing Hypoplastic Left Heart Syndrome. The evidence from the screen in stem cell-derived cardiomyocytes and whole genome sequencing of human patients, followed by functional analyses of RP genes in fly and fish models, is convincing and supports the authors' claims. This work and methodology applied would be of broad interest to medical biologists working on congenital heart diseases.

eLife Assessment

This study clarifies that stalled RNA pol II is not sufficient for AID targeting, which is important to the field. The authors provide solid experimental evidence that RNA poll II stalling is not the driving mechanism for AID targeting, and even though the results are generally "negative", they are highly relevant to our current understanding of SHM. The authors propose premature transcription termination as a possible mechanism to determine V gene mutability, but the study does not experimentally address such possibilities. This paper makes investigators rethink the model with which AID finds single-strand DNA in the genome.

eLife Assessment

This landmark study describes the structure of the human RAD51 filament with a recombination intermediate called the displacement loop (D-loop). Using cryogenic structural, biochemical, and single-molecule analyses, the authors provide compelling evidence on how the RAD51 filament promotes strand exchange between single-stranded and double-stranded DNAs. The work will be of interest to the community of homologous recombination and DNA repair, as well as genome stability more generally.

eLife Assessment

This fundamental study demonstrates how a left-right bias in the relationship between numerical magnitude and space depends on brain lateralization. The evidence is compelling, and the manuscript could be strengthened by improving its contextualization, presentation, and discussion. The results will be of interest to researchers studying numerical cognition, brain lateralization, and cognitive brain development more broadly.

eLife Assessment

This paper presents a valuable software package, named "Virtual Brain Inference" (VBI), that enables faster and more efficient inference of parameters in dynamical system models of whole-brain activity, grounded in artificial network networks for Bayesian statistical inference. The authors have provided solid evidence, across several case studies, for the utility and validity of the methods using simulated data from several commonly used models, but more thorough benchmarking could be used to demonstrate the reliability, generalizability, and practical utility of the toolkit. This work will be of interest to computational neuroscientists interested in modelling large-scale brain dynamics.

eLife Assessment

This valuable work uses serial block face electron microscopy to reconstruct detailed morphologies of large populations of Drosophila sensory neurons to determine the degree of diversity both within and across distinct neuronal populations. The authors convincingly show that there is considerable morphological diversity even within classes, and develop testable hypotheses about how arbors are optimized for particular sensory function and physiology. This work will be of interest to biologists working in physiology, insect chemosensation, and neuroscience.

eLife Assessment

This study presents valuable findings on the patterned loss of Purkinje cells in the mouse cerebellum during aging. Convincing evidence shows that Purkinje cell loss with aging occurs in a pattern of parasagittal stripes in relationship with the zebrin-II expression pattern. Further evidence supporting the Purkinje cell aging loss pattern as it relates to human cerebellar aging would strengthen the study.

eLife Assessment

This study presents a valuable finding on how the locus coeruleus modulates the involvement of medial prefrontal cortex in set shifting using calcium imaging. The evidence supporting the claims was viewed as incomplete, although a more rigorous statistical comparison of intradimensional vs. extradimensional stages of the task, either in behavior or in the calcium imaging data, would help to address this concern. The work is of broad interest to those studying flexible cognition.

eLife Assessment

This is valuable work with theoretical implications for possible mediation by MMP12 in the link between atherosclerosis and intracranial aneurysms, using Mendelian Randomization for causal inference. Additional analysis would be required to verify the claims, which currently have incomplete support in terms of the strength of evidence. Given that most of the identified causal associations do not hold after correcting for multiple tests, the conclusions should be carefully reviewed in order to be fully supported by the results.

eLife Assessment

The reported cryo-EM imaging of a pentameric ligand-gated ion channel in liposomes as opposed to nanodiscs has both broad implications and contributes valuable methodological advances to the structural investigation of membrane receptors. The comparison of structures assigned to distinct functional states in liposomes versus nanodiscs is convincing, and will aid membrane protein structural biologists in selection of functionally relevant membrane reconstitution environments. This work could be strengthened by a more quantitative presentation of the pore dimension profile leading to the proposed 9' desensitization gate with discussion of the additional apparent constriction at 2' in the desensitized structure, and by a more thorough description of the biochemistry methods for which core parts are not described and/or discussed in sufficient detail.

eLife Assessment

In this valuable study, the authors report on an innovative chemostat propagation system to reduce eukaryotic viruses while retaining phages in mixtures used for FVTs (fecal virome transplant). The authors hypothesized that chemostat-propagated viromes could modulate the gut microbiota and reduce necrotizing enterocolitis (NEC) lesions while avoiding potential side effects, such as earlier onset of diarrhea. The study is solid in that it integrates in vitro fermentation, high-resolution metagenomics, immunogenicity assays, and in vivo validation, demonstrating the potential of FVT using eukaryotic-free virome-based therapeutics. However, the study overall has some conceptual and technical limitations.

eLife Assessment

This paper presents valuable findings on the processing of sound mixtures in the auditory cortex of ferrets, a species widely used for studies of auditory processing. Using the convenient and relatively high-resolution method of functional ultrasound imaging, the authors provide solid evidence that background noise invariance emerges across the auditory cortical processing hierarchy. However, differences between this and other methods limit the comparisons that can be made across different species, and additional controls are needed to fully substantiate the paper's claims. This work will nonetheless be of interest to researchers studying the auditory cortex and the neural mechanisms underlying auditory scene analysis and hearing in noise.

eLife Assessment

This manuscript provides a single-cell transcriptomic atlas for AML (222 samples comprising 748,679 cells) integrating data from multiple studies. They use this dataset to investigate t(8;21) AML, and they reconstruct the Gene Regulatory Network and enhancer Gene Regulatory Network, which allowed identification of interesting targets. This aggregation is useful and can help infer differences in genetic regulatory modules based on the age of disease onset, which may help explain age-related variations in prognosis and disease development. However, result interpretations and the motivation and critical analysis of the applied computational methods are incomplete, and the statistical analyses lack control experiments and should be improved to avoid potential selection bias in the later analyses.

eLife Assessment

This valuable paper explores the idea that transient modulations of neural gain promote switches between distinct perceptual interpretations of ambiguous stimuli. The authors provide solid evidence for this idea by pupillometry (an indirect proxy of neuromodulatory activity), fMRI, neural network modeling, and dynamical systems analyses. The highly integrative nature of this approach is rare in the field.

eLife Assessment

This valuable study demonstrates that the GSK-3 inhibitor AZD2858 inhibits the formation of TOPBP1 condensates and hence DNA damage responses in colorectal cancer cells. The evidence supporting the claims of the authors is convincing, although uncovering how this drug blocks bio-condensate formation would have strengthened the study. The work will be of interest to cancer researchers searching for synergistic drug combination strategies.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This valuable study focuses on defining how the HSP70 chaperone system utilizes J-domain proteins to regulate the heat shock response-associated transcription factor HSF1. Using a combination of orthogonal techniques in yeast, this manuscript provides compelling evidence that the J-domain protein Apj1 facilitates attenuation of HSF1 transcriptional activity through a mechanism involving its dissociation from heat shock gene promoter regions. This work improves our understanding of HSF1 regulation and will be of broad interest to cell biologists interested in proteostasis, chaperone networks, and stress-responsive signaling.

eLife Assessment

This valuable study proposes a network implementation of the "re-aiming" learning strategy, which has been hypothesized to underlie brain-computer interface learning. Combining theoretical arguments, numerical simulations, and analysis of experimental data, the authors provide convincing evidence for their hypothesis. This paper will likely be of broad interest to the systems neuroscience community.

eLife Assessment

This valuable study reports the conservation of sperm-egg envelope binding by demonstrating successful recognition of the micropyle in fish eggs by the mouse sperm. However, the evidence supporting the conclusions drawn remains incomplete. In particular, the proposed specific role of CatSper in micropyle recognition and passage is not fully demonstrated. This study will be of interest to reproductive biologists and clinicians studying the biology of fertilization and fertility.

eLife Assessment

This important study combines an innovative experimental approach with mathematical modeling to demonstrate that genes separated by strong topological boundaries can exhibit coordinated transcriptional bursting, providing new insights into how regulatory information is transmitted across the genome. The evidence is solid within the studied locus, but the interpretation and generality of the findings would be strengthened by additional validation using simulated data and broader application beyond a single genomic region. This work will be of interest to cell biologists and biophysicists working on transcription and chromatin.