Evaluated articles

eLife assessment

This study reports a new approach to determine the architecture of peptidoglycan (PG), the primary component of the bacterial cell wall, validating the pipeline through an architectural analysis of several members of the human gut microbiota. The technique is potentially valuable for this sub-field as it would enable researchers interested in peptidoglycan in a range of organisms to easily assess muropeptide composition in an easy, automated manner. However, there is some uncertainty about whether the pipeline was fully automated and it was noted that the pipeline requires prior knowledge of the peptidoglycan composition of an organism. Additionally, the use of the technique to investigate whether PG cross-bridge length is a determinant of cell wall stiffness produced evidence that would need more direct support and is therefore so far incomplete.

eLife assessment

This important and compelling study investigates the problem of intracellular acidification induced by commonly-used optogenetic stimulating opsins. The low proton permeability of two high-performance opsins is shown to reduce photostimulated acidification. The findings may be of broad interest in the fields of neuroscience research and optogenetic therapies.

eLife Assessment

The specific questions taken up for study by the authors-in mice of HDAC and Polycomb function in the context of vascular endothelial cell (EC) gene expression relevant to the blood-brain barrier, (BBB)-are potentially useful in the context of vascular diversification in understanding and remedying situations where BBB function is compromised. The strength of the evidence presented is incomplete, and to elaborate, it is known that the culturing of endothelial cells can have a strong effect on gene expression.

eLife assessment

This important paper addresses the challenging problem of dating the origin of several groups of marine microorganisms. However, while much of the analyses are solid, the lack of robustness analysis in molecular dating component such as using alternative time calibrations, clock models, and input gene sets makes the study incomplete. Despite some concerns, this work is a commendable attempt at an extremely difficult problem and will be of broad interest to microbiologists, geologists, and evolutionary biologists.

eLife assessment

This manuscript describes useful data on the mechanisms underlying the activation of the receptor tyrosine kinase FGFR1 and stimulation of intracellular signaling pathways in response to FGF4, FGF8, or FGF9 binding to the extracellular domain of FGFR1. Solid evidence for quantitative differences in the downstream responses induced by the three ligands is presented. This manuscript will be of interest to biochemists and cell biologists working on receptor tyrosine kinases and general cell signalling across membranes.

eLife assessment

This study describes a useful method to monitor the behavior of Drosophila larvae in a uniform environment over much longer time scales than was possible with previous methods. The authors provide a solid characterization of aspects of the method and show that the behavior of single larvae can be quantified over several hours. The experiments offer a proof-of-concept for a robotic device that will enable the investigation of behavior in long-term experiments in ways that were previously unimaginable.

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.