Evaluated articles

eLife assessment

This useful study defines developmental roles for a protein kinase involved in endocytosis and reports a surprising finding that the kinase catalytic activity is unnecessary. However, several claims of the authors are only partially supported by the data. Although in its current form, this work is incomplete, it will be of broad interest to cell biologists and biochemists because this kinase was previously suggested to be a target of drug design efforts.

eLife assessment

The investigation of the functional significance of the X-linked ciliary protein OFD1 gene in regulating the fate of cranial neural crest-derived cells (CNCCs) and its potential effect on myogenic progenitors during tongue development is interesting because the Ofd1 conditional knockout mouse model has a very striking phenotype and nicely mimics the phenotype in humans. It is a valuable model to understand human disease. This study will require additional experiments to support their conclusions.

eLife assessment

This study presents a useful finding on a virally encoded immune-evasin which differentially inhibits antigen presentation by cellular protein complexes called Major histocompatibility complex (MHC) class I, thereby diminishing the activation of cytotoxic T cells. The evidence supporting the claims of the authors is solid, although the addition of more mechanistic insights would strengthen the study. The work will be of interest to virologists and immunologists working on the adaptive immune response to herpesviral infection. Some conclusions would require additional experimental support.

eLife assessment

The paper presents valuable insights into the success of the parasitoid Trichopria drosophilae on Drosophila suzukii, elucidating the importance of both molecular adaptations, such as specialized venom proteins and unique cell types, ecological strategies, including tolerance of intraspecific competition and avoidance of interspecific competition. Through convincing methodological approaches, the authors demonstrate how these adaptations optimize nutrient uptake and enhance parasitic success, highlighting the intricate coordination between molecular and ecological factors in driving parasitization success.

eLife assessment

This fundamental work describes the complex interplay between light exposure, hypothalamic activity, and cognitive function. The evidence supporting the conclusion is compelling with potential therapeutic applications of light modulation. The work will be of broad interest to basic and clinical neuroscientists.

eLife assessment

This useful study describes a role for acetylation in controlling the stability of acetyl-CoA synthetase 2, which converts acetate to acetyl-CoA for de novo lipid synthesis. While many aspects of the study are solid, some evidence supporting these findings is incomplete. Including direct demonstration of target deacetylation by sirtuin 2, revisiting statistical analyses, and confirming generalizability to adipocyte cell lines would further strengthen the study. This work will be of interest to researchers studying lipid metabolism and related diseases.

eLife Assessment

This is a fundamental study that addresses the key question of how the tetraspanin Tspan12 functions biochemically as a co-receptor for Norrin to initiate β-catenin signaling. The strength of the work lies in the rigorous and compelling binding analyses involving various purified receptors, co-receptors, and ligands, as well as molecular modeling by AlphaFold that was subsequently validated by an extensive series of mutagenesis experiments. The study advances the field by providing a novel mechanism of co-receptor function and shedding new light on how signaling specificity is achieved in the complex Wnt/Norrin signaling system.

eLife Assessment

This important study asks whether motor neurons within the vestibulo-ocular circuit of zebrafish are required to determine the identity, connectivity, and function of upstream premotor neurons. They provide compelling and comprehensive genetic, anatomical and behavioral evidence that the answer is, "No!". This work will be of general interest to developmental neurobiologists and will motivate future studies of whether motor neurons are dispensable for assembly of other sensorimotor neural circuits.

eLife assessment

The significance of the findings is valuable, with implications for immunotherapy design in pancreatic ductal adenocarcinoma. The evidence was considered incomplete and partially supportive of the major claims.

eLife assessment

This valuable paper first demonstrated that RGS10 was identified as a biomarker to evaluate the prognosis of breast cancer. To prevent the loss of RGS10 theoretically provide a new strategy for the treatment of breast cancer. The evidence supporting the claims of the authors is solid, although inclusion of a larger number of patient samples and an animal model would have strengthened the study. The work will be of interest to clinicians working on breast cancer.

eLife assessment

This work contributes to the study of H3-K27M mutated pediatric gliomas. It convincingly demonstrates that the concomitant targeting of histone deacetylases (HDACs) and the transcription factor MYC results in a notable reduction in cell viability and tumor growth. This reduction is linked to the suppression of critical oncogenic pathways, particularly mTOR signaling, emphasizing the role of these pathways in the disease's pathogenesis. The current version of the manuscript is important because it unveils a vulnerability from dual targeting HDACs and MYC in the context of pediatric gliomas. This work will be of interest to cancer epigenetics and therapeutics research, with a focus on the neuro-oncology field.

eLife assessment

This fundamental study advances our understanding of the role of bacterial-derived extracellular ATP in the pathogenesis of sepsis. The evidence supporting the conclusions is compelling, although not all concerns from a previous round of reviews were adequately addressed. The work will be of broad interest to researchers on microbiology and infectious diseases.

eLife assessment

In this useful study, the authors show that N-acetylation of synuclein increases clustering of synaptic vesicles in vitro and that this effect is mediated by enhanced interaction with lysophosphatidylcholine. While the evidence for enhanced clustering is largely solid, the biological significance remains unclear.

eLife Assessment

This manuscript reports important data providing evidence that a 42 amino acid region of Rev7 is necessary and sufficient for interaction with the Rad50-Mre11-Xrs2 complex in budding yeast. The authors conclude that Rev7 inhibits the Rad50 ATPase and the Mre11 nuclease with the exception of ssDNA exonuclease activity. The convincing data largely support the conclusions, although the effect of Rev7 on homologous recombination is less well documented and the observed effect on resection is moderate. Specifically, the result that the Rev7 C-terminal truncation lacking the 42 amino acid region still suppresses homologous recombination is unexpected and unexplained.

eLife Assessment

This study presents a useful investigation of the use of small, de novo-designed protein binding domains (mini-binders) against the Spike protein of SARS-CoV-2 and EGFR, as ligand binding domains on two classes of synthetic receptors, second-generation synNotch (SNIPR) and CAR. The methods and evidence supporting the focused claims are solid. This work will be of interest to synthetic biologists and cell engineers as a starting point to map out the rules for receptor engineering based on mini-binders and ultimately to advance them in biomedical applications.

eLife assessment

This important article presents the results of a large screen for non-genetic transgenerational effects that may influence gene expression and other phenotypes in mice. An extraordinary amount of mouse breeding, phenotyping, and RNA sequencing data provide compelling evidence that, for the phenotypes and genomic regions interrogated in these mouse strains, non-genetic transgenerational effects of appreciable magnitude are likely to be extremely rare. This paper will be of broad interest to geneticists and of particular interest to those studying epigenetic inheritance.

eLife assessment

This study presents valuable findings on how the endocannabinoid system is involved in endometriosis progression using CNR1 and CNR2 knockout (KO) mouse models. The evidence supporting the authors' claims is incomplete; including bulk RNA-seq, flow cytometry, and imaging mass cytometry would have strengthened the study. This work might be of interest to medical scientists working on endometriosis.

eLife assessment

This important study investigates, from Drosophila to mammals, the role of the Forkhead box O (FoxO) transcription factors in airway epithelial cells' response to stressors including hypoxia, temperature variations, and oxidative stress. The findings suggest a conserved role of FoxO in maintaining airway homeostasis across species. However, limitations in the specificity and concerns with the loss-of-function experiments render the evidence presented incomplete. Nonetheless, this study highlights FoxO's potential relevance in respiratory diseases like asthma and offers insights into potential therapeutic targets for conditions affecting airway health.

eLife Assessment

This important study reveals how Drosophila may be used to investigate the role of missense variants in the PLCG1 phospholipase gene in human diseases. The experimental evidence is compelling and brings together rigorous analysis of clinical and model organism phenotypes with a structural analysis of the PLCG1 protein.

eLife assessment

This fundamental study provides insights into how pathogens respond, on a systemic level including several gene targets and clusters, to selected antimicrobial molecules. Compelling evidence is provided, through multi-omics and functional approaches, that very similar molecules originally designed to target the same bacterial protein act differently within the context of the whole set of cellular transcripts, expressed proteins, and pre-lethal metabolic changes. Given the rapid accumulation of omics data and the much slower capacity of extracting biologically relevant insights from big data, this work exemplifies how the development of sensitive data analysis is still a major necessity in modern research.