Evaluated articles

eLife Assessment

This important study advances our understanding of how FGF13 variants confer seizure susceptibility. By acting in a set of inhibitory interneurons, FGF13 regulates synaptic transmission and excitability. The data presented here are convincing and combine cell type-specific knockouts and electrophysiology, complemented by histology/RNA studies. Collectively, this research will be of interest to a wide audience, particularly those involved in the study of epilepsy, inhibitory neurons, and ion channels.

eLife assessment

The methods and findings of the current work are important and well-grounded. The strength of the evidence presented is convincing and backed up by rigorous methodology. The work, when elaborated on how to access the app, will have far-reaching implications for current clinical practice.

eLife Assessment

This work describes a new software platform for machine-learning-based segmentation of and particle-picking in cryo-electron tomograms. The program and its corresponding online database of trained models will allow experimentalists to conveniently test different models and share their results with others. The paper provides convincing evidence that the software will be valuable to the community.

eLife Assessment

The manuscript by Hills, et al. presents data that support multiple conclusions regarding the gene expression patterns of cells, especially chemosensory neurons. The evidence is largely solid, with transcriptomic analysis combined and validated by spatially resolved expression in tissue sections, but is incomplete in other ways with some claims not fully supported. This large-scale single-cell transcriptomics dataset is an important resource, alongside a thorough exploration of the molecular features of the different cell types within the mouse vomeronasal organ, including expression of chemosensory receptors.

eLife Assessment

This study provides an important resource by thoroughly benchmarking multiple sequencing-based tRNA quantification methods. The suggested best practice is supported by convincing evidence from in silico experiments in multiple scenarios.

eLife assessment

This study presents a valuable strategy to co-deliver peptides and adjuvants to antigen-presenting cells by engineering the Virus-like particle (VLP). The evidence supporting the claims of the authors is convincing, but the antitumour efficacy is unimpressive and would benefit from more antitumor experiments. The work will be of broad interest to bioengineers and medical biologists focusing on cancer vaccines.

eLife Assessment

The study presents valuable findings on the molecular mechanisms of glucose-stimulated insulin secretion from pancreatic islets, focusing on the main regulatory elements of the signaling pathway in physiological conditions. While the evidence supporting the conclusions is solid, the study can be strengthened by the use of a beta cell line or knockout mice. The work will be of interest to cell biologists and biochemists working on diabetes.

eLife assessment

This important study investigates the sensitivity to endogenous cosolvents of three families of intrinsically disordered proteins involved with desiccation. The findings, drawn from well-designed experiments and calculations, suggest a functional synergy between sensitivity to small molecule solutes and convergent desiccation protection strategy. The evidence is found to be convincing, and the authors provide appropriate caveats since the study's conclusions are based on a small number of proteins. This work will be of interest to biochemists and biophysicists interested in the conformation-function relationship of intrinsically disordered proteins.

eLife Assessment

This study presents fundamental findings that could redefine the specificity and mechanism of action of the well-studied Ser/Thr kinase IKK2 (a subunit of inhibitor of nuclear factor kappa-B kinase (IkB) that propagates cellular response to inflammation). Solid evidence supports the claim that IKK2 exhibits dual specificity that allows tyrosine autophosphorylation and the authors further show that auto-phosphorylated IKK2 is involved in an unanticipated relay mechanism that transfers phosphate from an IKK2 tyrosine onto the IkBa substrate. The findings are a starting point for follow-up studies to confirm the unexpected mechanism and further pursue functional significance.

eLife Assessment

In this valuable study, the authors investigate how inflammatory priming and exposure to irradiated Mycobacterium tuberculosis or the bacterial endotoxin LPS impact the metabolism of primary human airway macrophages and monocyte-derived macrophages. The work shows that metabolic plasticity is greater in monocyte-derived macrophages than alveolar macrophages, with solid experimental methods and overall evidence. The findings are relevant to the field of immunometabolism.

eLife Assessment

This study presents two main findings regarding HIV-1 genomic integration. The first, based on convincing evidence in primary cell models, is that HIV-1 induces R loop formation, though the viral driver of this process remains undefined. The second, based on model cell systems with limited physiological relevance to HIV-1, is that a portion of HIV-1 genomes integrates in the vicinity of where R loops form. This finding has the potential to offer fundamental insight into HIV-1 integration, but the strength of the presented evidence was viewed as incomplete and needing additional validation by more direct experimental methods in order to understand what the mechanistic relationship between the formation of R loops and HIV-1 integration is.

eLife Assessment

This paper addresses a significant question regarding the low overlap between genetic discoveries for human complex diseases and those for gene expression by emphasizing the contribution of cell-type-specific chromatin accessibility QTLs. The analyses supporting the main claims are convincing, and the key conclusions are valuable and of interest to readers in the fields of human genetics and functional genomics.

eLife Assessment

This important study reports that the neurohormone, bursicon, and its receptor, play a role in the seasonal polyphenism of the bug Cacopsylla chinensis. Low temperature activates the bursicon signaling pathway during the transition from the summer to the winter form, affecting cuticle pigment and thickness as well as chitin content. The solid experiments reveal how bursicon signaling, which is modulated by the microRNA miR-6012, regulates features of polyphenism related to the exoskeleton, although it is less clear what the upstream regulatory events are.

eLife Assessment

In this important study the authors develop an elegant lung metastasis mouse model that closely mimics the events in human patients. They provide convincing evidence for the effectiveness of IL-15/12-conditioned NK cells in this design, which was also critical for the authors being able to conclusively reveal the T cell-dependency of NK-cell-mediated long-term control of experimental metastasis. Of note, an investigator-initiated clinical trial demonstrated that similar NK cell infusions in cancer patients after resections were safe and showed signs of efficacy, which is of promising clinical application value.

eLife Assessment

This valuable study employed a multi-omics approach to elucidate the regulatory mechanism underlying parturition and myometrial quiescence. The data presented to support the main conclusion are solid. This work will be of interest to both basic researchers who work on reproductive biology and clinicians who practice reproductive medicine.

eLife assessment

In this valuable study, the authors sought to investigate the associations of age at breast cancer onset with the incidence of myocardial infarction and heart failure. Based on results from a series of compelling statistical analyses, the authors conclude that a younger onset age of breast cancer is associated with myocardial infarction and heart failure, highlighting the need to carefully monitor the cardiovascular status of women who have been diagnosed with breast cancer.

eLife Assessment

This study presents important findings on the function of enteric glia expressing proteolipid protein 1 (PLP1+ glia). The evidence supporting the claims of the authors is solid, although the inclusion of additional data showing the mechanisms by which PLP1+ enteric glia acts on Paneth cells would have strengthened the study. The work will be of interest to colleagues studying intestinal biology.

eLife Assessment

This study focuses on the regulation of GLP-1 in enteroendocrine L cells and how this may be stimulated by the mechanogated ion channel Piezo1 and the CaMKKbeta-CaMKIV-mTORC1 signaling pathway. The work is innovative and is considered valuable, as the hypothesis that is being tested may have significant mechanistic and translational implications. Data to support the proposed mechanism were considered incomplete, yet data to support the overall physiological characterization were considered solid.

eLife Assessment

Using experiments in the white fly, this manuscript provides evidence that the bacterial symbiont Wolbachia can be transmitted from parasitoid wasps to their insect hosts. Characterizing the transfer of Wolbachia between insect species is a valuable attempt to explain the widespread of this intracellular bacterium. This paper is incomplete as it does not furnish sufficient data to support several of its claims for which additional methods and data are necessary.

eLife Assessment

This study combines genetic, cell biological, and interaction data to propose a model of meiotic double-strand break regulation in C. elegans. Solid evidence supports the main conclusions, while by nature of a screening-type study, more may be needed to solidify speculations in future studies. Yet, comprehensive cataloging of the physical and genetic interactions of factors required for meiotic double-strand break is useful information for the field.