Evaluated articles

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

eLife assessment

This is a 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.

eLife assessment

This study presents an interesting set of findings that connects N-cadherin and glypican-4 to Slit signaling during the regulation of contact inhibition of locomotion of Schwann cells in culture. Solid evidence is provided showing that N-cadherin not only regulates cell recognition but also proper trafficking of Slit to the cell surface. An ex-vivo model demonstrates the importance of Slit signaling during cell migration but the molecular details of how N-cadherin traffics Slit to the surface and role of glypican are unclear. The data would have been strengthened with a similar interrogation of N-cadherin in this system. The work will be of interest to cell biologists studying the mechanisms behind peripheral nervous system regeneration.

eLife assessment

This fundamental work advances our understanding of the role of Cbfβ in maintaining articular cartilage homeostasis and the underlying mechanisms. The evidence supporting the conclusion is mostly convincing, although including additional experiments and discussions would have strengthened the study. This paper is of potential interest to skeletal biologists and orthopaedic surgeons who study the pathogenesis and the therapeutics of osteoarthritis.

eLife assessment

This important study provides a new, apparently high-performance algorithm for B cell clonal family inference. The new algorithm is highly innovative and based on a rigorous probabilistic analysis of the relevant biological processes and their imprint on the resulting sequences, however, the strength of evidence regarding the algorithm's performance is incomplete, due to (1) a lack of clarity regarding how different data sets were used for different steps during algorithm development and validation, resulting in concerns of circularity, (2) a lack of detail regarding the settings for competitor programs during benchmarking, and (3) method development, data simulation for method validation, and empirical analyses all based on the B cell repertoire of a single subject. With clarity around these issues and application to a more diverse set of real samples, this paper could be fundamental to immunologists and important to any researcher or clinician utilizing B cell receptor repertoires in their field (e.g., cancer immunology).

eLife assessment

This important study combines in vivo and in vitro models to characterise the role of CYRI-B, an interactor of the small GTPase Rac1, in controlling pancreatic cancer progression towards a higher proliferative and metastatic stage. The evidence supporting the claims of the authors is convincing in characterizing a novel Rac1 binding protein, CYRI-B, as a regulator of metastatic potential in vivo, with distinct functions at different stages of tumour progression. CYRI-B reduces the typical hyperactivation of Rac1 in the early stages of tumour progression; subsequently, CYRI-B mediates internalization of lysophosphatidic acid receptor 1 (LPAR1) uptake through macropinocytosis, thus regulating chemotactic migration of cancer cells towards lysophosphatidic acid (LPA). Although the inclusion of human pancreatic cancer cell lines would have strengthened the study, the work will be of broad interest to cell biologists and the signalling research communities.

eLife assessment

This work presents a potentially important behavioral finding: that perceptual learning may not only improve but also distort the appearance of visual stimuli. The strength of the presented evidence in support of the main claim is however incomplete, and requires further analyses to confirm that perceptual learning does increase overestimation bias, and clarify why a very large baseline overestimation bias is present in the data.

eLife Assessment

The authors present a critique of current usage of principal component analysis in geometric morphometrics, making a compelling case with benchmark data that standard techniques perform poorly. The work is an important contribution to the field and will hopefully lead to a reassessment of the methodology most scientists in morphometrics currently use. This work challenges a very commonly used analytical approach and is bound to raise some controversy in the community, but the authors' critique is based on a well-founded and well-thought out analysis.

eLife Assessment

In this study, the authors present compelling data illustrating a potential mechanism for a hitherto not described form of extracellular vesicle biogenesis. Their model suggests that small extracellular vesicles are secreted from cells within larger vesicles, termed amphiectosomes, which subsequently rupture to release their smaller vesicle contents. This discovery represents an important advancement in the field.

eLife assessment

This important work addressed the identifcation of antimalarial drug resistance mutations that do not readily transmit to new human hosts, focusing on azithromycin resistance. The technically challenging analyses of azithromycin-resistant parasites as they traverse the mosquito host and human liver are conducted using state-of-the-art tools, including humanized mice. While the claim regarding the lack of transmission by atovaquone-resistant P. berghei is convincing, the evidence for the lack of transmission by atovaquone-resistant P. falciparum is insufficient. This work will appeal to biologists and biomedical scientists in parasitology and drug discovery, offering insights into combating antimalarial drug resistance and understanding the fitness costs associated with drug-resistant parasites.