Evaluated articles

eLife assessment

This study presents useful findings regarding the role of formin-like 2 in mouse oocyte meiosis. Some of the data are supported by incomplete methodological details and analyses, and several conclusions are overstated. This paper would be of interest to reproductive biologists.

eLife assessment

This valuable study reports that miR-199b-5p is elevated in human osteoarthritis patients. There is solid evidence for the finding that inhibiting miR-199b-5p alleviates symptoms in mice with knee osteoarthritis. Additionally, potential targets of miR-199b-5p are identified but whether miR-199b-5p truly functions through Fzd6 and/or Gcnt2 requires further investigation.

eLife assessment

This important study provides new insights into the development and function of medullary thymus epithelial cells (mTEC). The authors provide compelling evidence to support their claims as to the differentiation and lineage outcomes of CCL21+ mTEC progenitors, which further our understanding of how central tolerance of T cells is enforced within the thymus.

eLife assessment

Building on on the observation of an increase in miR-182-5p in diabetic patients, the authors investigated the role of miR-182-5p and its target gene LRP6 in dysregulated glucose tolerance and fatty acid metabolism in obese type 2 diabetics. The use of human livers complemented by supporting data in mice and cells are strengths, but the evidence presented remains incomplete. The findings provide valuable insights into the role of miRNAs in the regulation of liver metabolism and insulin sensitivity in individuals with diabetes and fatty liver disease.

eLife assessment

This valuable study seeks to disentangle the different selective forces shaping the evolutionary dynamics of transposable elements (TEs) in the wild grass Brachypodium distachyon. Using haplotype-length metrics, and genetic and environmental differentiation tests, the authors present convincing evidence that positive selection on TE polymorphisms is rare and that the distribution of TE ages points to purifying selection being the main force acting on TE evolution in this species. This study will be relevant for anyone interested in the role of TEs in evolution and adaptation.

eLife assessment

This important study describes exhaustive deep mutational scanning (DMS) of the gonadotropin-releasing hormone wild-type receptor and for two single point mutations that impact its folding and structure, monitoring how plasma membrane expression levels are influenced by the introduced mutations. With solid evidence, the authors have pioneered an exploration of the interaction between mutations (epistasis) in a membrane protein, with a potential for explaining membrane protein evolution and genetic diseases.

eLife assessment

This fundamental study presents a method to restore muscle innervations in ALS mouse models using optogenetics. It is convincing that embryonic stem cell derived motor neurons can be transplanted into and applied to reinnervate the muscles in an ALS mouse model. The work will be of broad interest to researchers and medical biologists to develop new strategies for the treatment of neurodegenerative disorders resulting from denervated skeletal muscles.

eLife Assessment

This valuable work provides solid evidence that a neuronal metallothionein, GIF/MT-3, incorporates metal-persulfide clusters. A variety of well-designed assays support the authors' hypothesis, revealing that sulfane sulfur is released from MT-3. However, the sufane sulfur content in the canonical induced MT-1 and MT-2 has not been demonstrated. Thus, the biological role of the persulfidated form is not yet clearly defined. There are caveats to the findings that limit the study, but the work will nevertheless prompt major follow-up work.

eLife assessment

This important work by Park et al. demonstrates an open-top two-photon light sheet microscopy (OT-TP-LSM) for lesser invasive evaluation of intraoperative 3D pathology. The authors provide convincing evidence for the effectiveness of this technique investigating various human cancer cells. This article will be of broad interest to biologists and, specifically, pathologists utilizing 3D optical microscopy.

eLife assessment

This important study combines experimental and computational data to address crucial aspects of RNA methylation by a vital RNA methyltransferase (MTase). The authors have provided compelling, strong evidence, utilizing well-established techniques, to elucidate aspects of the methyl transfer mechanism of methyltransferase-like protein 3 (METTL3), which is a part of the METTL3-14 complex. This work will be of broad interest to biochemists, biophysicists, and cell biologists alike.

eLife assessment

This useful study investigates two secreted Mycobacterium tuberculosis proteins, ESAT-6 and CFP10, using biochemical assays, including a Biolayer Interferometry assay. Solid experimental evidence demonstrates that ESAT-6 forms a tight interaction with CFP10 as a heterodimer at neutral pH and that ESAT-6 also forms a homodimer at acidic pH. Additional, more definitive evidence is required to describe how these proteins disrupt the phagosomal membrane. While improved compared to a previous version, the revised manuscript did not address these concerns adequately.

eLife assessment

In this important study, Gaikwad and colleagues employed ribosome profiling in conjunction with standard biochemical approaches to investigate the role of eIF2A in translation initiation in yeast under optimal growth conditions or stress. The authors provide convincing data that eIF2A is not implicated in translation initiation in yeast, a finding that is anticipated to inspire future investigations to identify the cellular role(s) of eIF2A in yeast. Considering the broad scope of cellular functions attributed to eIF2A, this study should be of interest to a wide spectrum of biomedical researchers ranging from those studying mechanisms of translation regulation to virologists and cancer biologists.

eLife assessment

This valuable study employs a diverse array of techniques encompassing cell biological manipulations, biophysical measurements, and mouse models to elucidate the impact of target cell stiffness on CD8+ cytotoxic T cell activation, with a particular focus on the actin nucleator protein WASP. The finding that WASP is essential for the stiffness-dependent phosphorylation of ZAP70 in CD8 T cells is convincing. However, the data regarding the role of WASP in mechanosensing within CD8 T cell-mediated anti-tumor immunity is incomplete and would benefit from a more rigorous study design. This work would be of interest to cell biologists and investigators studying mechanosensing within the immune system.

eLife assessment

In this important study, chromatin is simulated as a polymer at the scale of genes, and the 3D organization of chromatin is analyzed at nucleosome resolution. There is convincing evidence for the emergence of chromatin microdomains due to the action of transcription factors, based on the simulation incorporating well-known biophysical properties of DNA, of nucleosomes, of linker histones, and of the transcription factor pair Myc:Max, as well as considering how the 3D organization of chromatin results from bending and looping of DNA. The work greatly improves our understanding of how the joint action of transcription factors and chromatin features affects chromatin structure and accessibility, which is of interest to anyone studying gene regulation.

eLife assessment

In this valuable study, the discovery and subsequent design of the AF03-NL chimeric antibody led to a tool for studying filoviruses and provides a possible blueprint for future therapeutics. In general, the data presented are solid, although further improvements can be made in the overall presentation of the results. The work will be of interest to virologists studying antibodies.

eLife assessment

This paper provides useful information about how the ionome of Arabidopsis thaliana adapts to very high CO2-levels, backed up by solid evidence and carefully designed studies. The work will be of interest to anyone studying natural genetic variation as well as the response of plants to altered CO2 levels in the atmosphere.

eLife assessment

The authors further corroborated their model that Netrin signaling promotes survival and dissemination of non-proliferating ovarian cancer cells. These valuable results were found to be of significant potential interest to cancer biologists in as much as they address gaps in knowledge pertinent to the mechanisms underpinning ovarian cancer spread. In general, it was thought that solid experimental evidence was provided to support the role of Netrin signaling in fueling ovarian cancer progression.

eLife assessment

This study presents fundamental insights into the heterogeneity of chronic myeloid leukemia (CML) stem cells and their response to tyrosine kinase inhibitor therapy, shedding light on potential mechanisms underlying treatment failure. The study's robust methodology, supported by validation with bulk RNA-seq data and surface marker analysis, provides compelling evidence for the identified associations between cellular composition and treatment outcome. These findings contribute to our understanding of CML pathogenesis and may inform the development of more targeted therapeutic strategies.

eLife assessment

This work describes a connection between inflammation and metabolism, in which itaconate stabilizes the mitochondrial fatty acid uptake enzyme Cpt1a to enhance fatty acid oxidation. The mechanism for itaconate action may be generalizable to other protein targets. This is an important advance, which is supported by solid experimental data.