Evaluated articles

eLife assessment

This manuscript provides a structural analysis of bushy cells in the mouse cochlear nucleus. These neurons receive a large synaptic contact from the auditory nerve termed an endbulb that preserves the temporal information present in the auditory nerve and are key elements of binaural sound localization circuits. The analysis combines volume electron microscopy techniques with computational models to predict heterogeneous bushy cell responses. The analysis takes morphological analysis of bushy cells to a new level, and the modeling is well done.

eLife assessment

This potentially important paper investigates the mechanisms that contribute to building inhibitory synapses through differential protein release from microtubules. The experiments are generally designed well, but the evidence supporting the conclusions is incomplete. This manuscript will be of interest to neuroscientists and cell biologists interested in intracellular trafficking and synapse maturation.

eLife assessment

These valuable findings presented by Wu et al. advance our understanding in novel cell signaling regulators of hepatic metabolism. The evidence supporting these conclusions are solid, utilizing in vivo and in vitro gain and loss of function studies. These work will be of interest to biologists working in the field of hepatic steatosis.

eLife assessment

The paper provides important insight into the function of FAM76B protein as a regulator of inflammation. The knockout/overexpression data are solid, however, the mechanism of regulation and the role of FAM76B in neurodegeneration is incomplete and requires additional experimentation. The work will be of interest to researchers studying inflammation, particularly neuroinflammation.

eLife assessment

This important study shows that exercise improves cerebrovascular function during aging using convincing methods, the authors show that aerobic exercise reverses aging-induced deficits in microvascular perfusion and oxygenation and potentially improves short-term memory. This work will be of broad interest to researchers and clinicians studying vascular function, age-related cognitive decline, and the effects of aerobic exercise on reversing age-related dysfunction.

eLife assessment

This valuable study identifies three independent patient mutations in MAD2L1BP (p31 comet) that cause infertility. Consistent with the known functions of p31 comet, solid experiments in mouse oocytes imply that infertility could be caused by a failure to silence the spindle assembly checkpoint, though the mechanism was not determined. Although the sample size is small, a rescue experiment in human oocytes promises the potential for therapy.

eLife assessment

This report is a useful demonstration of how to predict the mutational pathways to antimicrobial resistance (AMR) emergence, particularly in the enzyme DHFR (dihydrofolate reductase). The methodology is overall solid but some of the claims are only partially supported. The work will be of interest to microbiologists and evolutionary biologists interested in antimicrobial resistance and its population genetics dynamic.

eLife assessment

In this interesting manuscript, Pietsch et al. develop innovative machine learning approaches for automated analysis of budding yeast live-cell imaging data obtained with a dedicated microfluidic device that retains mother cells. Developing such tools is crucial to enable high-throughput image analysis. These methods will be useful for researchers studying these cells, and may also inspire similar approaches for other types of cells.

eLife assessment

Extracellular vesicles (EVs) are emerging as important mediators of cell-to-cell signaling. Lee et al show convincingly that Stranded at second (Sas), a Drosophila cell surface protein, is trafficked by and localized to Drosophila EVs. However, the data supporting interaction with dArc and whether Sas facilitates the intercellular transfer of dArc protein or mRNA is incomplete. Moreover, almost all experiments rely on gain-of-function and over-expression of Sas, thus the relevance to normal physiological signaling is unclear.

eLife assessment

This is an elegant study combining virally-delivered lineage-tracing with single cell RNA-sequencing of the developing chicken enteric nervous system, showing potentially differential contribution of cell identities from the sacral and vagal neural crest. Addressing this important issue is pivotal to understanding basic enteric nervous system development as well as to devise therapeutic approaches to enteric neuropathies. The study is therefore generally interesting and in particular to researchers in the fields of enteric neuroscience and peripheral nervous system development. Lack of a basic classification scheme of neuronal cell types in the chicken, limited computational and functional analysis on a relatively immature stage and makes the conclusions of this work preliminary in its current state.

eLife assessment

The creation of a single-cell atlas of normal and degenerative human anterior cruciate ligament (ACL) tissues using a single-cell RNA sequencing method is an important approach to understanding the pathological mechanisms of ACL degeneration. The data of this study showed the existence of fibroblasts, endothelial cells, pericytes, and immune cells in healthy ACL, and their ratios altered in the degenerative ACL, mainly exhibited as an increase in fibroblasts and immune cells. The data analysis suggests that alterations of spatial transcriptome and changes in gene expression and signaling pathways may contribute to ACL degeneration.

eLife assessment

This important study pinpoints nitrite oxide synthase 2 activity and decreased microtubule acetylation as distinct regulators of altered autophagic flux that may contribute to pathogenesis in a mouse model of Duchenne muscular dystrophy. While most of the evidence to support these claims is convincing, the claim that autophagy is improved with increased microtubule acetylation is incompletely supported. This work may be of broad interest to muscle biologists and has translational potential for the treatment of Duchenne muscular dystrophy.

eLife assessment

The authors used the Multiethnic Cohort (MEC) study to study how COVID-19 impacted access to cancer screenings and treatment. This study's important findings served to identify key factors associated with cancer-related screening and healthcare-seeking during the pandemic. This investigation provides solid evidence to inform future policies, particularly in older and vulnerable populations.

eLife assessment

This is an important study that examined multiple biological age measures in children, which has been lacking in literature. The findings of this study provided convincing evidence to interpret and understand the aging and developmental processes in children.

eLife assessment

The authors analyze changes in the gene expression of different immune cells during heart regeneration using single-cell RNA-sequencing and assess changes upon drug treatment that depletes macrophages. They find that drug treatment affects the gene expression profiles of different and abundance of immune cells. The work provides a wealth of gene expression data and a nice analysis supporting immune cell interactions during heart regeneration, so will be a useful resource.

eLife assessment

Roe et al. provide a large-sample analysis of hemispheric lateralisation in brain structure, synthesising local cortical thickness and surface area data from 7 different datasets. The study provides a rich descriptive catalogue of phenomena related to hemispheric anatomical asymmetries. These results are convincing and will prove an important point of reference to neuroscientists who might want to compare their own future results to the ones from this large and varied data set.

eLife Assessment

This fundamental study substantially advances our current understanding of mechanotransduction within endothelial cells. The evidence provided by the authors in the revised manuscript is compelling, which taken together, provides strong support for the authors' major findings. The work will be of broad interest to cell biologists and vascular biologists.

eLife assessment

In this important study, the authors present a human telencephalon-eye organoid model that exhibits remarkable pathfinding and growth of retinal ganglion cell (RGC) axons. The identification of cell-surface markers for RGCs could have value for understanding the molecular mechanisms involved in RGC axon development and regeneration. The strength of evidence is compelling for future studies to investigate RGC neurite outgrowth and brain-eye connectivity in humans.

eLife assessment

This important manuscript reveals signatures of co-evolution of two nucleosome remodeling factors, Lsh/HELLS and CDCA7, which are involved in the regulation of eukaryotic DNA methylation. The results suggest that the roles for the two factors in DNA methylation maintenance pathways can be traced back to the last eukaryotic common ancestor and that the CDC7A-HELLS-DNMT axis shaped the evolutionary retention of DNA methylation in eukaryotes. The solid evolutionary analyses form a strong basis for experimental follow-up studies. The work should be of interest to colleagues in the fields of evolutionary biology, chromatin biology and genome biology.

eLife assessment

This important study describes the coordinated regulation of cellular size and protein translation in response to chronic stress as an adaptive mechanism, termed the 'rewiring stress response' regulated by the heat shock response. The evidence supporting this conclusion is solid, utilizing diverse methods to monitor and manipulate cell size and evaluate stress resistance. The study could be strengthened by the inclusion of more experiments focused on defining the mechanistic basis of this coordination and broadening the scope of the specific role of the 'rewiring stress response' across different chronic cellular stresses. This work will be of broad interest to researchers interested in diverse fields including cellular proteostasis, stress-responsive signaling, and aging and senescence.