Evaluated articles

eLife Assessment

This important study investigates the self-assembly activity of all 109 human death-fold domains. The data collected using advanced microscopy and distributed amphifluoric FRET-based flow cytometry methods are compelling to support the "phase change battery" model that explains how signal amplification can occur without ATP consumption. This paper provides new insight into the thermodynamic control of protein phase behaviors within cells and will be of interest to those studying a variety of biological pathways involved in inflammatory responses and various forms of cell death.

eLife Assessment

This study in the Drosophila antennal lobe, which contains multiple non-equivalent sensory channels, provides valuable new insight into how early-life sensory experience can produce lasting, cell-type-specific changes in neural circuit function. The work convincingly demonstrates that glial-mediated pruning during a defined developmental window leads to persistent suppression of odor responses in one olfactory neuron type, while sparing another. The evidence is solid and supported by multiple complementary approaches, although some mechanistic interpretations remain speculative and would benefit from additional functional testing.

eLife Assessment

The authors used three genetically diverse mouse models to investigate the impact of genome diversity on metabolic disease outcomes, such as obesity and glucose tolerance. This study is important because it integrates comprehensive metabolic analyses and multi-tissue phenotyping across sexes to reveal pathways relevant to obesity and its complications; the data are convincing and uncover several pathways that advance understanding of disease etiology while suggesting potential therapeutic avenues to prevent obesity-related health risks. There are limitations, such as a limited number of mouse strains used in the work, the 9-week feeding regime may be too short to capture full metabolic remodeling, and the mechanisms by which the immune-adipose axis impacts the broader phenotype are not fully described. Overall, the study is compelling, but the manuscript could be improved by justifying the strain selection, addressing the concern about the feeding duration, and providing stronger mechanistic support or discussion.

eLife Assessment

This work provides an important resource identifying 72 proteins as novel candidates for plasma membrane and/or cell wall damage repair in budding yeast, and describes the temporal coordination of exocytosis and endocytosis during the repair process. The data are convincing; however, additional experimental validation will better support the claim that repair proteins shuttle between the bud tip and the damage site.

eLife Assessment

This study offers important insights into how entorhinal and hippocampal activity support human thinking in feature spaces. It replicates hexagonal symmetry in entorhinal cortex, reports a novel three-fold symmetry in both behavior and hippocampal signals, and links these findings with a computational model. The task and analyses are sophisticated, and the results appear convincing and of broad interest to neuroscientists.

eLife Assessment

This manuscript presents useful insights into the molecular basis underlying the positive cooperativity between the co-transported substrates (galactoside sugar and sodium ion) in the melibiose transporter MelB. Building on years of previous studies, this convincing study improves on the resolution of previously published structures and reports the presence of a water molecule in the sugar binding site that would appear to be key for its recognition, introduces further structures bound to different substrates, and utilizes binding and transport assays, as well as HDX-MS and molecular dynamics simulations to further understand the positive cooperativity between sugar and the co-transported sodium cation. The work will be of interest to biologists and biochemists working on cation-coupled symporters, which mediate the transport of a wide range of solutes across cell membranes.

eLife Assessment

The study showcases a significant and important enhancement of the MAGIC transgenesis method, by extending it genome-wide to all chromosomes. The authors provide compelling evidence to demonstrate that the MAGIC mosaic clones can be generated for genes from all, including the 4th chromosome. With this toolkit extension, the method is set to complement the classical FRT/Flp recombination system for gene manipulation in flies.

eLife Assessment

This is a valuable study that presents human single nuclei RNA-seq and spatial transcriptomics data of the developing outflow tract and adult aortic valves that will facilitate research in this area. Data presented are solid, with bioinformatics analyses showing cell lineage and trajectory relationships, intriguingly suggesting persistence of embryonic signature in adult aortic valve cells. The latter results would be strengthened by experimental validation.

eLife Assessment

This valuable study describes an interesting infection phenotype that differs between adult male and female zebrafish. The authors present data indicating that male-biased expression of Cyp17a2 appears to mediate viral infection through STING and USP8 activity regulation. Through experimentation on male fish, the authors present solid evidence linking this factor to direct and indirect antiviral outcomes through ubiquitination pathways. These findings raise interesting questions about immune mechanisms that underlie sex-dimorphism and the selective pressures that might shape it.

eLife Assessment

This study presents valuable findings on the ability of a state-of-the-art method, Temporally Delayed Linear Modelling (TDLM), to detect the replay of sequences in human memory. The investigation provides compelling evidence that TDLM has significant limitations in its sensitivity to detect replay in extended (minutes-long) rest periods. The work will be of strong interest to researchers investigating memory reactivation in humans, especially using iEEG, MEG, and EEG.

eLife Assessment

The study by Reed et al. provides fundamental findings defining the topological changes that occur during tumorigenesis. These compelling findings enhance the understanding of stable long-range connections among genes that reprogram cancer-related functions.

eLife Assessment

This manuscript reports important findings that have theoretical or practical implications beyond a single subfield. However, despite the combination of numerous analytical tools established and applied in the study, the work has substantial experimental limitations leading to incomplete evidence, indicating that the conclusions may be an over-interpretation of the findings.

eLife Assessment

This valuable study introduces CAAMO, a computational framework that combines structure prediction, in silico mutagenesis, molecular simulations, and energy calculations to design RNA aptamers with improved binding affinity. The computational methodology is solid, demonstrating strong theoretical foundations and systematic integration of multiple prediction techniques. Many of the previously identified methodological weaknesses that limit the strength of support for the computational predictions have been addressed.

eLife Assessment

This study is a valuable contribution to the evidence base. However, the evidence provided is incomplete as the study results only partially support the study conclusions. Addressing the methodological and reporting issues raised by the peer reviewers and properly aligning the claim made for providing a tool for early warning with the study analysis/results would improve the study quality and usefulness of its findings.

eLife Assessment

This study reports on the development and characterization of chickens with genetic deficiencies in type I or type III interferon receptors, which is an important contribution to the field of avian immunology. The data reflecting the development of the new interferon-receptor-deficient chickens is compelling. The initial characterization of IFN biology and infection responses in these knockout chickens provides a solid foundation for future studies on the distinct contributions of type I and type III interferon signaling to antiviral responses.

eLife Assessment

This important study examines the evolution of virulence and antibiotic resistance in Staphylococcus aureus under multiple selection pressures, specifically host immune function and antibiotic exposure. The evidence presented is convincing, supported by rigorous phenotypic and genomic data from within-host evolution experiments. The manuscript now provides a nuanced and robust interpretation of how pathogens adapt to complex selective landscapes.

eLife Assessment

Non-essential amino acids such as glutamine have been known to be required for T cell general activation through sustaining basic biosynthetic processes, including nucleotide biosynthesis, ATP generation, and protein synthesis. In this important study, the authors found that extracellular asparagine (Asn) is required not only for T cells to generally refuel metabolic reprogramming, but to produce helper T cell lineage-specific cytokine, for instance, IL17. In particular, the importance of Asn in IL17 production was convincingly demonstrated in the mouse experimental autoimmune encephalomyelitei (EAE) model, mimicking human multiple sclerosis disease.