Evaluated articles

eLife Assessment

This study provides important insights into mural cell dynamics and vascular pathology using a zebrafish model of cerebral small vessel disease. The authors present convincing evidence that partial loss of foxf2 function results in progressive, cell-autonomous defects in pericytes accompanied by endothelial abnormalities across the lifespan. By leveraging advanced in vivo imaging and genetic approaches, the work establishes zebrafish as a powerful and relevant model for dissecting the cellular mechanisms underlying cerebral small vessel disease.

eLife Assessment

The authors present a set of wrappers around previously developed software and machine-learning toolkits, and demonstrate their use in identifying endogenous sterols binding to a GPCR. The resulting pipeline is potentially useful for molecular pharmacology researchers due to its accessibility and ease of use. However, the evidence supporting the GPCR-related findings remains incomplete, as the machine-learning model shows indications of overfitting, and no direct ligand-binding assays are provided for validation.

eLife Assessment

This valuable study expands the inventory of polyadenylated RNAs cleaved by the double-stranded RNA endonuclease Rnt1 in budding yeast, using solid methodology based on high-throughput sequencing. Previous studies had anecdotally discovered mRNA substrates, and this global characterization is comprehensive with multiple complementary controls. This study sets the stage for deeper investigations into the biological function of Rnt1 and substrate cleavage.

eLife Assessment

This important study addresses the role of non-genetic factors in individual differences in phenotype. Using C. elegans, the study finds that non-genetic differences in gene expression, partly influenced by the environment, correlate with individual differences in two reproductive traits. This supports the use of gene expression data as a key intermediate for understanding complex traits. The clever study design makes for compelling evidence.

eLife Assessment

This useful study presents the potentially interesting idea that LRRK2 regulates cellular BMP levels and their release via extracellular vesicles, with GCase activity further modulating this process in mutant LRRK2-expressing cells. However, some of the evidence supporting these conclusions remains incomplete, and additional work is suggested under certain conditions. Overall, the study will be of interest to cell biologists working on Parkinson's disease.

eLife Assessment

This manuscript introduces a useful protein-stability-based fitness model for simulating protein evolution and unifying non-neutral models of molecular evolution with phylogenetic models. The model is applied to five viral proteins that are of structural and functional importance. While the general modelling approach is solid, and effectively preserves folding stability, the evidence for the model's predictive power remains limited, since it shows little improvement over neutral models in predicting protein evolution. The work should be of interest to researchers developing theoretical models of molecular evolution.

eLife Assessment

This study presents a valuable assessment of and solid evidence for increased similarity in visual appearance combined with increased chemical differences between two butterfly species in sympatry compared with differences between three populations of one of the two species in allopatry. The similarity in visual appearance hints to an evolutionary response to shared predators (but alternative explanations are possible). Thus, the difference in chemical signaling likely helps to avoid between-species mating in sympatry.

eLife Assessment

This study presents a valuable advance for the analysis of gene expression variation at the level of individual cells by introducing a novel reference-free framework that can detect splicing, fusion, editing, immune-receptor diversity and repeated elements in sequencing data. The evidence supporting these claims is solid, with rigorous validation on simulated datasets and extensive analysis of full-length single-cell sequencing data demonstrating improved performance over existing methods. This work will be of particular interest to researchers developing methods for high-resolution transcriptome analysis and to those studying cellular heterogeneity in health and disease.

eLife Assessment

This important study investigated whether the nuclear receptor Nur77 is regulated by a non-canonical mechanism of ligand-induced disruption of its interaction with RXRg, similar to the family member Nurr1. The overall evidence is compelling. This manuscript will be of interest to scientists focusing on mechanisms of transcriptional regulation.

eLife Assessment

This study presents an important finding on the role of GATA4 in aging- and OA-associated cartilage pathology. The conclusions are well supported by compelling in vitro and in vivo evidence. This work will be of broad interest to both cell biologists and orthopedic/skeletal health 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 findings are highly relevant to the fields of homologous recombination, DNA repair, and genome stability.

eLife Assessment

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

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 convincing 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 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 study reveals surprising morphological diversity of Drosophila sensory neurons. Using serial block-face electron microscopy, the authors created detailed 3D reconstructions of large neuronal populations, convincingly finding significant structural variation both within and across distinct classes. These results form the basis for testable hypotheses on how neuronal arborization is optimized for particular sensory functions. This research will be highly relevant to biologists in the fields of physiology, insect chemosensation, and neuroscience.

eLife Assessment

This important study presents findings on the patterned loss of Purkinje cells in the cerebellum during aging. The compelling data nicely support the conclusions of this study. This work advances understanding of mechanisms underlying neurodegeneration with aging and provides the basis for development of treatments for age-related neurological disorders.

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 in mice. The evidence supporting the claims was viewed as solid in revealing the dynamics and potential mechanisms supporting extradimensional shifts. 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.