Evaluated articles

eLife assessment

This study provides useful information on the evolution of gene expression levels and plasticity in tissues impacted by hypoxia during colonization of a high-altitude environment. Unfortunately, the evidence for the conclusions is incomplete because of the low sample size available.

eLife assessment

This important study describes the protective role of group 2 innate lymphoid cells (ILC2s) in tissue physiology and contributes to immunity, inflammatory pathology, and metabolism in maintaining homeostasis during pregnancy. The authors provide convincing evidence that ILC2s have new roles distinct from parasite protection and allergy inducers. Uterine ILC2s are key immune cells during normal and complicated pregnancies.

eLife assessment

This study presents valuable new insights into the role of the extracellular matrix component (ECM) Perlecan in axon integrity, with downstream consequences for the maintenance of synaptic structures. The evidence for Perlecan's role in this process is solid, although negative results for Perlecan's mechanism of action should be strengthened with the addition of appropriate controls centered on the relevant pathways and mechanisms involved as well as more careful analyses and interpretations. The authors provide convincing data identifying and describing the cellular sequence from ECM perturbations to axonal and synaptic degeneration, but additional data pinpointing the requirements of Perlecan for axonal maintenance would further improve the impact of this study.

eLife assessment

The present study offers valuable insights into the remodeling of Merkel cells and their innervating sensory axons in the skin. This remodelling seems to be mostly played out independently between the two synaptic partners revealing significant Merkel cell turnover and axonal plasticity. The authors employed live imaging and quantification tools using genetic models in which parts of the mechanosensory organs of the skin are labelled with distinct fluorescent proteins. While most of the data, and their interpretations are solid, the analyses of Merkel cell number homeostasis remain incomplete.

eLife assessment

This important work employed global proteomic and phosphorylation site analysis to examine adipose tissue and skeletal muscle samples collected at baseline from a sample of 10 women, including those with and without PCOS, both before and after 5 weeks of electrical stimulation treatment. This work significantly enhances our knowledge by demonstrating that women with PCOS who exhibit protein hyperandrogenicity have elevated extramyocellular lipid levels and a decreased number of oxidative insulin-sensitive type I muscle fibers. The convincing evidence supporting these conclusions makes this research of broad interest not only to scientists but also to clinicians.

eLife assessment

This manuscript describes rigorous experiments that provide a wealth of virologic, respiratory physiology, and particle aerodynamic data pertaining to aerosol transmission of SARS-CoV-2 between infected Syrian hamsters. The significance of the paper is fundamental because infection is compared between alpha and delta variants, and because viral load is assessed via numerous assays (gRNA, sgRNA, TCID) and in tissues as well as the ambient environment of the cage. The strength of evidence is compelling.

eLife assessment

In this useful study, Holzinger et al. present compelling evidence that scorpionfish bactericidal/permeability-increasing protein (scoBPI) exhibits remarkable antibacterial activity against multi-drug resistant Pseudomonas aeruginosa. These findings open new avenues of research for identifying novel chemotherapies to treat Pseudomonas infections and have broader implications in developing chemotherapies against other drug-resistant Gram-negative bacterial infections. The work will be of interest to individuals investigating novel cystic fibrosis antimicrobials.

eLife assessment:

This important paper highlights the clonal organization of the dorsal telencephalon, a major region of the vertebrate brain, and analyzes the distinctive gene expression and chromatin accessibility present in each clonal using the adult teleost fish medaka. High-quality data were collected using convincing and solid methods and these were used to identify synaptic genes with a distinct chromatin landscape and expression in one of the regions of the dorsal pallium, with the goal of ascribing an evolutionary origin to these neurons.

eLife assessment

This paper is of potential interest to both the hippocampal and computational neuroscience fields because it provides a framework for understanding how adult-born granule cells in the hippocampus contribute to network processing. It contains novel interesting ideas, such as the analysis of input-output transformation by SRM models and the establishment of "greedy networks". However, not all major conclusions are sufficiently supported by the data. The paper demonstrates that mixed networks show better encoding performance than pure networks, but the differences are small and only visible with specific performance metrics. Intuitive explanations are not provided.

eLife assessment

In this study, the authors use high-speed and high-resolution imaging to investigate the role of the yeast syntaxin homolog Tlg2p in endocytic vesicle sorting. They obtain compelling data to show that the Tlg2p-residing compartment within the trans-Golgi network functions as an early/sorting compartment, where endocytic cargos are sorted to either the recycling pathway or the endo-lysosomal pathway. The authors also describe additional molecular details of this sorting process, and overall provide important insights into the mechanism of endocytic vesicle sorting in budding yeast.

eLife assessment

This valuable study shows that new, virulent genotypes of Xanthomonas oryze pv. oryzae, that are similar to strains present in east Asia, cause outbreaks of bacterial blight of rice in Tanzania. The authors' use of CRISPR-based gene editing on multiple pathogen targets in an elite African rice variety to create lines resistant to both endemic and emerging pathogen strains in Africa makes for a compelling contribution to meet this alarming development. The work describing the new strains of the pathogen is solid but could be stronger if there were genome sequence data for all strains examined and a clearer presentation of recent disease outbreaks and their severity.

eLife assessment

The findings in this study are important, as this brainstem region is implicated in a multitude of functions. The experimental procedures are difficult to implement and the preparation used and the skill required are impressive. The methods and data are solid, however, some analyses are incomplete, and the strength of evidence is also incomplete because the claims are only partially supported by the data. This work will interest those who study respiration, airway protection, and other oral behaviors.

eLife assessment

This manuscript explores the potential regulatory role of a previously unstudied phosphorylation site in the Src kinase SH3 domain. A mutant intended to mimic the phosphorylation of this site, Y90E, shows enhanced activity and transforming capacity, reduced mobility in the lipid bilayer, and a more open catalytic structure. In general, these findings are supported by compelling evidence. The paper will be of interest to biochemists and structural biologists studying new mechanisms that are capable of modulating the allosteric regulation of multi-domain protein kinases.

eLife assessment

Using chemogenetic manipulation, the authors induce or suppress activity in D1 spiny neurons in the dorsomedial striatum of mice. The results effectively demonstrate that excitation or inhibition of this class of neurons results in a consistent behavioral effect that is linked to an impact on local dynamics in thalamic regions that project to this part of the thalamus, as well as cortical regions that can be more readily defined as unimodal as identified by a classification approach. This work has clear relevance to the field of neuroimaging, getting at the broader hemodynamic signatures of direct pathway stimulation in the striatum, but requires critical revisions to justify their main conclusions.

Using chemogenetic manipulation, the authors induce or suppress activity in D1 spiny neurons in the dorsomedial striatum of mice. The results effectively demonstrate that excitation or inhibition of this class of neurons results in a consistent behavioral effect that is linked to an impact on local dynamics in thalamic regions that project to this part of the thalamus, as well as cortical regions that can be more readily defined as unimodal as identified by a classification approach. This work has clear relevance to the field of neuroimaging, getting at the broader hemodynamic signatures of direct pathway stimulation in the striatum, but requires critical revisions to justify their main conclusions.

eLife assessment

This paper reports a detailed functional analysis of the Rab1 effector Uso1, and it provides a fundamental advance in our understanding of how ER-derived vesicles deliver their cargo. The authors provide compelling evidence that the key function of Uso1 is promoting SNARE complex formation rather than tethering vesicles as generally assumed. These insights will be of interest to cell and structural biologists who study membrane traffic.

eLife assessment

This important study defines signaling mechanisms in tendinopathy development, which is significant as there is a clear need to identify therapeutic targets to prevent or reverse tendon pathology. The evidence supporting the conclusions are compelling combining an existing human tendinopathy transcriptomics dataset with ex-vivo assembloid model, and an in vivo injury model using genetic reporter mice. This work will be of interest to developmental and stem cell biologists.

eLife assessment

This paper describes valuable results from studies investigating circuits in the brain that underlie behavioral responses in fearful situations. The authors identified a role for a class of neurons that are sufficient to cause these stereotyped behaviors including freezing behaviors. These solid studies increase our understanding of brain pathways regulating these types of behaviors.

eLife Assessment

This study presents a valuable finding about the role of Perk (Protein kinase RNA-like endoplasmic reticulum kinase) and Atf4 (Activating Transcription Factor-4) in the integrated neurodegenerative and regenerative responses following the optic nerve injury. The authors present solid evidence, combining newly generated transcriptomic data with publicly available datasets to strengthen their findings. Despite some limitations in data quality and interpretation, the study is likely to be of interest to researchers studying optic neuropathies and axonal regeneration.

eLife assessment

This paper describes an important new marine reptile specimen. A solid ostelogical description of the saurosphargid Prosaurosphargis yingzishanensis, the earliest known member of this group, combined with a large-scale phylogenetic analysis enhances our understanding of the affinities of a wide range of Triassic reptiles. As such the relevance of this paper goes far beyond the immediate importance of this remarkable fossil - it also sheds light on the position of several important Triassic groups, including Testudinata and Archosauromorpha.

eLife assessment

Vocalizations are controlled by neural circuits connecting the amygdala and periaqueductal gray. This study presents valuable measures of the neurons that suppress vocalization in appropriate contexts using a rich variety of behavioural, imaging, optogenetic, and tracing methodologies. The evidence supporting the claims of the authors is solid, although their results only hint at the mechanisms that could underlie the hierarchical control of vocalization. The work will be of interest to neurobiologists working on motor control and vocalization.