Evaluated articles

eLife Assessment

This valuable study examines the role of E2 ubiquitin enzyme, Uev1a in tissue resistance to oncogenic RasV12 in Drosophila melanogaster polyploid germline cells and human cancer cell lines. The solid evidence suggests that Uev1a works with the E3 ligase APC/C to degrade Cyclin A. This work would be of interest to researchers in germline biology and cancer.

eLife Assessment

Using advanced CryoEM and mass spectrometry, the authors provide compelling evidence of how tubule formation occurs in an oxygen-dependent manner. These fundamental findings offer a novel mechanism by which rubrerythrin tubules encapsulate encapsulin to prevent oxidative stress in Pyrococcus furiosus. However, there are a few reasonable concerns about biochemical validations and the lack of adequate description of results and methodology.

eLife Assessment

This study provides new and interesting findings that SCoR2 acts as a denitrosylase to control cardioprotective metabolic reprogramming and prevent injury following ischemia/reperfusion. The compelling evidence is supported by a novel multi-omics approach, but questions remain regarding the stability and human relevance of BDH1 as well as the sufficiency of SCoR2. Overall, the work will be of interest to cardiovascular researchers and provides valuable information to the field, though some mechanistic aspects require further clarification.

eLife Assessment

This manuscript focuses on developing a structural model of how the multidomain ECM protein SVEP1 enables Angiopoietin (ANG) binding to the orphan receptor TIE1, resulting in downstream receptor phosphorylation and signaling. This is a potentially important study, however, it currently lacks key controls and is therefore incomplete. The data will be of interest to scientists working in vascular biology and RTK signaling.

eLife Assessment

This fundamental study advances our understanding of population-level immune responses to influenza in both children and adults. The strength of the evidence supporting the conclusions is compelling, with high-throughput profiling assays and mathematical modeling. The work will be of interest to immunologists, virologists, vaccine developers, and those working on mathematical modeling of infectious diseases.

eLife Assessment

This study presents a useful finding on the effects of arginine vasopressin (AVP) on islet cells in pancreatic tissue slices, using technically sophisticated spatio-temporal calcium recordings to confirm that AVP influences α and β cells differently depending on glucose concentrations. While the study’s methods – particularly the calcium imaging techniques and peptide ligand design targeting V1b receptors – are strong, the reviewers were concerned about several aspects of the experimental design. The results on β-cell responses are incomplete and insufficient to support the manuscript’s claims, especially due to the high variability of islet responses and lack of mechanistic and functional (hormone release) data. There are also concerns about the possibility of off-target effects and suboptimal receptor specificity: the study would be significantly strengthened by inclusion of signaling pathway interrogation, hormone output assays, genetic validation (e.g., β cell-specific deletion of V1br), and receptor localization. The work will still be of interest to researchers studying islet physiology in the context of health and diabetes.

eLife Assessment

By screening an FDA-approved small-molecule library against a leucine-dependent M. tuberculosis strain, this study identifies semapimod as an inhibitor of Mtb growth that functions by impairing leucine import. The work is useful in linking leucine uptake to cell wall lipid biology in Mtb. However, the mechanistic understanding remains incomplete. Additional experimental evidence is required to clarify how PDIM contributes to or regulates leucine uptake.

eLife Assessment

This study presents an alternative to conventional and UV-based tetramers, which are easy to use and reliable for the identification of antigen-specific CD8 T cells. The authors demonstrate that tetramers for HLA alleles A0301, A1101, B0702, and C0702 can be subjected to specific temperatures that facilitate peptide exchange, whilst maintaining structural integrity. Whilst the strength of the evidence is currently incomplete, further development and validation of this approach is likely to provide a useful alternative to generating reagents for examining T cell specificities.

eLife Assessment

This useful study shows a protective role of type 1 IFN during Mycobacterium tuberculosis infection. It shows that the type 1 IFN response in human skin TST inversely correlates with TB severity, suggesting its protective role. Considering that type I IFN is usually shown to be pro-pathogenic, the higher vulnerability of zebrafish larvae lacking stat2 to M marinum infection is a strong result. However, the conclusion that IFN-I is protective during mycobacterial infection remains indirect and incomplete; the study requires additional mechanistic insights and validation.

eLife Assessment

Engineering of adeno-associated virus (AAV) replication proteins may provide new insights into Parvoviral replication. The authors created a useful collection of Rep protein variants with changes that alter the amino acid sequence, but these did not lead to clear improvements in how the virus worked. Instead, their screen showed that changes that do not alter the protein ("synonymous" mutations) and changes to the promoter were more common. As it stands the results are incomplete due to potential issues with the screening design. We encourage a more complete characterization, which may enhance the translational potential of the approach.

eLife Assessment

Endothelial cell-specific loss of TGF-beta signaling in mice leads to CNS vascular defects, specifically impairing retinal development and promoting immune cell infiltration. The data are solid, showing that loss of TGF-beta signaling triggers vascular inflammation and attracts immune cells specific to CNS vasculature. These findings are important, highlighting TGF-beta's role in maintaining vascular-immune homeostasis and its therapeutic potential in neurovascular inflammatory diseases.

eLife Assessment

This study presents an important finding linking the bacterial metabolite trimethylamine and its receptor to circadian rhythms and olfaction. The current evidence supporting the claims of the authors is compelling. This work will be of broad interest to researchers interested in nutrition, microbial metabolism, circadian rhythms, and host-microbiome interactions.

eLife Assessment

This valuable study addresses the role of sphingolipid metabolism in maintaining endolysosomal membrane integrity and its impact on tau pathology in Caenorhabditis elegans and human cell culture models. The methods are solid and the proposed mechanisms are conceivable. However, the current evidence is incomplete and could be strengthened, due to reliance on imaging data and insufficient biochemical validation. The work will be of broad interest to cell biologists and biologists working on Alzheimer's disease and related proteinopathies.

eLife Assessment

This important series of studies provides converging results from complementary neuroimaging and behavioral experiments to identify human brain regions involved in representing regular geometric shapes and their core features. Geometric shape concepts are present across diverse human cultures and possibly involved in human capabilities such as numerical cognition and mathematical reasoning. Identifying the brain networks involved in geometric shape representation is of broad interest to researchers studying human visual perception, reasoning, and cognition. The evidence supporting the presence of representation of geometric shape regularity in dorsal parietal and prefrontal cortex is solid, but does not directly demonstrate that these circuits overlap with those involved in mathematical reasoning. Furthermore, the links to defining features of geometric objects and with mathematical and symbolic reasoning would benefit from stronger evidence from more fine-tuned experimental tasks varying the stimuli and experience.

eLife Assessment

This fundamental study combines in vitro reconstitution experiments and molecular dynamics simulations to elucidate how membrane lipids are transported from the outer to the inner membrane of mitochondria. The authors provide convincing evidence that a positive membrane curvature is critical for membrane lipid extraction. The work will be of broad interest to cell biologists and biochemists.

eLife Assessment

This study identifies 53BP1 as an interaction partner of GMCL1 (a likely CUL3 substrate receptor). The study proposes a novel mechanism by which cancer cells evade the mitotic surveillance pathway through GMCL1-mediated degradation of 53BP1, leading to reduced p53 activation and paclitaxel resistance. These data are the most useful aspect of the study, but the data supporting the authors' conclusions as to the clinical relevance of the study are inadequate. The authors have not taken relevant data about the clinical mechanism of taxanes into account.

eLife Assessment

This study provides important insights into mural cell dynamics and vascular pathology using a zebrafish model of cerebral small vessel disease. The authors present convincing evidence that partial loss of foxf2 function results in progressive, cell-autonomous defects in pericytes accompanied by endothelial abnormalities across the lifespan. By leveraging advanced in vivo imaging and genetic approaches, the work establishes zebrafish as a powerful and relevant model for dissecting the cellular mechanisms underlying cerebral small vessel disease.

eLife Assessment

The authors present a set of wrappers around previously developed software and machine-learning toolkits, and demonstrate their use in identifying endogenous sterols binding to a GPCR. The resulting pipeline is potentially useful for molecular pharmacology researchers due to its accessibility and ease of use. However, the evidence supporting the GPCR-related findings remains incomplete, as the machine-learning model shows indications of overfitting, and no direct ligand-binding assays are provided for validation.

eLife Assessment

This valuable study expands the inventory of polyadenylated RNAs cleaved by the double-stranded RNA endonuclease Rnt1 in budding yeast, using solid methodology based on high-throughput sequencing. Previous studies had anecdotally discovered mRNA substrates, and this global characterization is comprehensive with multiple complementary controls. This study sets the stage for deeper investigations into the biological function of Rnt1 and substrate cleavage.

eLife Assessment

This important study addresses the role of non-genetic factors in individual differences in phenotype. Using C. elegans, the study finds that non-genetic differences in gene expression, partly influenced by the environment, correlate with individual differences in two reproductive traits. This supports the use of gene expression data as a key intermediate for understanding complex traits. The clever study design makes for compelling evidence.