Evaluated articles

eLife Assessment

This work describes a circadian regulation in the expression of HERP, a regulator of endoplasmic reticulum calcium, in primary astrocytic cultures. This work is important because it highlights the potential importance of circadian rhythms in astrocytes, even though making a direct comparison between these rhythms in vitro and in vivo remains challenging. The technical approaches used in this work (RNA-seq, siRNA, Ca2+ imaging) are a solid support for data interpretation.

eLife assessment

The authors report that optogenetic inhibition of hippocampal axon terminals in retrosplenial cortex impairs the performance of a delayed non-match to place task. Elucidating the role of hippocampal projections to the retrosplenial cortex in memory and decision-making behaviors is important. However, the strength of evidence for the paper's claims is incomplete.

eLife Assessment

In this useful study, the authors present convincing evidence linking the enzyme D-alanine-D-alanine ligase (Ddl), crucial for cell wall fortification, to organic acid exposure in Staphylococcus aureus. While it's established that organic acids impede bacterial growth, the researchers reveal a novel coping mechanism where S. aureus maintains elevated levels of D-alanine, the substrate for Ddl, to counteract this inhibition. This discovery illuminates a bacterial strategy for organic acid tolerance, offering new insights for microbiologists and potentially informing future antimicrobial approaches.

eLife assessment

This important study reports a novel approach to studying cerebellar function based on the idea of selective recruitment using fMRI. It provides convincing evidence for task-dependent gating of neocortical input to the cerebellum during a motor task and a working memory task. The study will be of interest to a broad cognitive neuroscience audience.

eLife assessment

This elegant study presents important findings into how small molecules that were originally developed to inhibit the oncogenic kinase, BRAF, instead trigger activation of this kinase target. Compelling and comprehensive evidence supports a new allosteric model to explain the paradoxical activation. This rigorous work will be of great interest to biochemists, structural biologists, and those working on strategies to inhibit kinases in the context of human disease.

eLife Assessment

This valuable study provides convincing evidence that white matter diffusion imaging of the right superior longitudinal fasciculus might help to develop a predictive biomarker of chronic back pain chronicity. The results are based on a discovery-replication approach with different cohorts, but the sample size is limited. The findings will interest researchers interested in the brain mechanisms of chronic pain and in developing brain-based biomarkers of chronic pain.

eLife Assessment

In this valuable study the authors use electrophysiology in brain slices and computer modeling and suggest that layer 2/3 pyramidal neurons of the mouse cortex have functional HCN channels on the proximal apical dendrite which allows distinct processing of input at that location from the input to distal apical dendrites. The revisions improved the solid paper but some of the concerns were not addressed sufficiently and many of these concerns could be addressed by further revision.

eLife assessment

In this important study, the authors use a genetically engineered mouse model to reveal a tumor suppressive role for focal adhesion kinase in right-sided colon cancer. The evidence in support of the authors' claims is generally solid, although the data supporting the mechanism through which FAK deletion promotes tumorigenesis are incomplete. This work will be of interest to cancer researchers and others studying the biological consequences of tuning signal transduction pathways.

eLife Assessment

This valuable study focuses on gene regulatory mechanisms essential for hindbrain development. Through molecular genetics and biochemistry, the authors propose a new mechanism for the control of Hox genes, which encode highly conserved transcription factors essential for hindbrain development. The strength of evidence is solid, as most claims are supported by the data. This work will be of interest to developmental biologists.

eLife assessment

This valuable study demonstrates how proximity labeling with streptavidin can be used to boost fluorescence signals in otherwise hard-to-label regions of cells. The experimental verification of amplification of fluorescence near epitope tags in phase-separated compartments is solid, demonstrating enhanced signal-to-noise compared to immunofluorescence. This study will be of particular interest to those using correlative light and electron microscopy or expansion microscopy when the signal is limiting or inaccessible.

eLife assessment

This valuable study demonstrates that genomic insertion of a G4-containing sequence can be sufficient to induce chromosome loops and alter gene expression. The evidence supporting the conclusions is convincing. Effects were shown by Hi-C as well as qPCR for chromatin modifications and expression, and the specificity of the effects was controlled by mutating the G4-containing sequence or treating with LNA probes to abolish G4 structure formation. The work will be of interest to researchers working on chromatin organization and gene regulation.

eLife Assessment

This important study presents a significant methodological advance by leveraging previously discarded, unmapped DNA sequence reads to estimate pest infestation loads across plant accessions, and map variation in these apparent pest loads to defense genes. The bioinformatics approach is compelling, and the results should bear broad implications for phenotype-genotype prediction, especially regarding the use of unmapped reads for GWAS.

eLife Assessment

It is well established that cellulose synthesis in higher plants requires three different but related catalytic subunits known as CESA proteins. Here the authors provide cryo electron microscopy structural information on soybean CESA1, CESA3, and CESA6 and find substantial differences between the structure of these CESA homotrimers and the previously-resolved secondary cell wall CESAs. They present an important model with convincing evidence in which the multi-subunit cellulose synthase complexes are made of multiple homotrimers.

eLife assessment

This valuable study investigates the effect of noncaloric monosaccharides, sugar substitutes that are commonly used by diabetic patients, on angiogenesis in the zebrafish embryo. The authors show that noncaloric monosaccharides and glucose similarly induce excessive blood vessel formation due to the increased formation of tip cells by endothelial cells through the foxo1a-marcksl1a pathway. This solid study is of interest for the medical community in charge of the prevention and of the treatment of diabetes and other metabolic diseases.

eLife assessment

This study presents an important computational tool for the quantification of the cellular composition of human tissues profiled with ATAC-seq. The methodology and its application results on breast cancer tumor tissues are convincing. It advances existing methods by utilizing a comprehensive reference profile for major cancer-relevant cell types, compatible with a widely-used cell type deconvolution tool.

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 solid biological application provides a demonstration of their pipeline's capabilities and suggests intriguing hypotheses around prolonged vascular tone changes, but will need to be followed up by further experiments to be conclusively demonstrated.

eLife assessment

This is a valuable study that describes the effects of T. pallidum on neural development by applying single-cell RNA sequencing to an iPSC-derived brain organoid model. The evidence supporting the claims of the authors is solid, although further evidence to understand the differences in infection rates would strengthen the conclusions of the study. In particular, the conclusions would be strengthened by validating infection efficiency as this can impact the interpretation of single-cell sequencing results, and how these metrics affect organoid size as well as comparison with additional infectious agents. Furthermore, additional functional validations of downstream effectors could be insightful.

eLife assessment

This is an important study on changes in newborns' neural abilities to distinguish auditory signals at 37 weeks of gestation. The evidence of change in neural discrimination as a function of gestational age is convincing, but, as the authors acknowledge, further control of the acoustic signals and infants' language environment is necessary for the results to be used in clinical applications. The work contributes to the field of neurodevelopment.

eLife assessment

By developing a framework to integrate metagenomic and metabolomic data with genome-scale metabolic models, this study establishes a toolkit to investigate trophic interactions between microbiota members in situ. The authors apply this method to the native rhizosphere bacterial communities of apple rootstocks, producing solid evidence and numerous detailed hypotheses on specific trophic exchanges and resource dependencies. The framework represents a valuable method to disentangle features of microbial interaction networks and will be of interest to microbiome scientists as well as plant and computational biologists.

eLife assessment

This manuscript describes the mapping of natural DNA sequence variants that affect gene expression and its noise, as well as cell cycle timing, using as input single-cell RNA-sequencing of progeny from crosses between wild yeast strains. The method represents an important advance in the study of natural genetic variation. The findings, especially given the follow-up validation of the phenotypic impact of a mapped locus of major effect, provide convincing support for the rigor and utility of the method.