Evaluated articles

eLife Assessment

This is a valuable study on the metabolic adaptations upon succinate dehydrogenase loss in cancer cells. If confirmed, this study will offer some therapeutic vulnerabilities in treating SDH-deficient cancer. However, the evidence supporting the authors' claim is incomplete and would benefit from additional experimental evidence. This study will be of broad interest for cancer biologists focusing on metabolism.

eLife Assessment

This valuable study documents, for the first time, the degree of preference for contralateral versus ipsilateral forelimb movements in the motor cortex of mice, revealing subtly distinct profiles across cortical areas, with the orofacial region showing comparatively little limb selectivity relative to the forelimb motor areas. The experiments and analyses are, in general, solid and well-designed, and the data support the paper's conclusions.

eLife Assessment

This important study addresses how the molecular identity of a single neuron specifies its hard-wired synaptic connectivity, using repeated single-cell RNA sequencing of identified Drosophila sensory neurons together with functional perturbation of candidate cell-surface molecules. It demonstrates remarkably low transcriptomic variability across animals for the same identified neuron, defines a tractable set of differentially expressed cell-surface molecules that distinguish mechanosensory from chemosensory neurons, and links several of these molecules to axonal targeting and circuit function. The evidence is solid, with the single-neuron transcriptomic datasets and Dscam isoform repertoires offering a lasting resource for the field, though clearer articulation of the experimental logic, additional controls in the RNAi screen, and a more complete characterization of the neuronal re-wiring would further strengthen the central claims.

eLife Assessment

This study investigates the role of Interleukin-2-inducible T cell kinase (ITK) deficiency in autoimmune lung injury using a pristane-induced pulmonary hemorrhage (PH) model, suggesting that ITK-deficient regulatory T cells (Tregs) restrict severe tissue pathology. The work represents an important addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. The experimental evidence supporting the core ideas is solid and provides mechanistic insight into how ITK deficiency promotes a tissue-protective Treg phenotype, although additional studies will be needed to further define the molecular pathways involved.

eLife Assessment

This important study by Otgonbaatar and colleagues employs advanced live microscopy, optogenetics, and an endogenous fluorescent timer system to investigate short- and long-term stabilization dynamics of β-catenin/Armadillo (Arm) during Drosophila development. The authors identify an unexpected and functionally relevant enrichment of stabilized junctional Arm in leading-edge cells during dorsal closure, providing evidence for a stabilization mechanism that appears independent of canonical Wingless signaling. These findings are significant because they expand current understanding of β-catenin/Arm beyond its canonical signaling functions and suggest a role in tissue mechanics and force transmission during dorsal closure. The proposed model represents a key advance in the field, but the strength of evidence is currently incomplete: the main conclusions regarding Wingless independence, JNK-mediated regulation, and the mechanical role of stabilized Arm are only partially supported by the available data and would benefit from further experimental testing and corroboration.

eLife Assessment

This useful study investigates how plasticity and homeostatic adaptation can lead to the emergence of synchronization patterns associated with different sleep phases. The ideas are novel and interesting, but the evidence at present remains incomplete. Further work is needed to determine whether the reported states persist for larger system sizes, longer integration times, and how robust the results are to different initial conditions.

eLife Assessment

This valuable study presents a comparative analysis of the transcriptomic features underlying C. elegans longevity, providing insights into how different changes in gene expression can promote longevity. The authors present solid evidence with analysis and selected functional validation showing that some long-lived animals share common changes while others appear to use opposing strategies. The datasets and analyses contained within and the user-friendly website developed will be of interest to researchers interested in complicated transcriptomic analyses and/or the biology of aging.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

The report by Liu and colleagues reports on an analysis of environmental adaptation across diverse lineages of the grass Phragmites australis differing by their level of ploidy. These results represent important findings for understanding the environmental adaptation of species complexes with mixed ploidy and the analysis reports solid evidence that lineages with distinct levels of ploidy occupy different climate niches. The use of regional survey in tandem with common garden experiment represents a convincing approach to suggest a correlation between ploidy and climate adaptation. This manuscript will be of interest to a broad community of ecological genomicists interested in how structural variation in gene dosage potentially affects the pattern of adaptation.

eLife Assessment

This important study combines peptide engineering, molecular docking, and functional assays to define the molecular basis of ligand recognition and activation of the human Y4 receptor and to identify three novel small-molecule agonists. The evidence supporting the conclusions is convincing, with complementary experimental and computational approaches providing strong support for the proposed receptor-ligand interactions. While concentration-response analyses of the small-molecule agonists and additional structural or mutagenesis studies would further strengthen the work, these are not essential to support the main conclusions. The work will be of interest to researchers studying GPCR pharmacology, structural biology, and ligand discovery.

eLife Assessment

This work presents a software and hardware suite for targeted photostimulation that can be used in vivo. The package is a well-designed and documented hardware/software suite with a comprehensive build guide. This tool will likely promote important neuroscience advances through targeted real-time perturbation of the cerebral cortex. Overall, this manuscript makes a compelling case on how to design and make available power tools for the research community.

eLife Assessment

This study presents a valuable metagenomic analysis of the gut microbiome in sickle cell disease (SCD) patients, revealing associations between bacteriophage, host immunity, and SCD pathophysiology. This solid dataset and in-depth analysis will be of broad interest to researchers studying SCD, immunology, phage biology, and the microbiome, adding to the small but growing literature suggesting a microbial component to SCD.

eLife Assessment

This manuscript presents openretina, an open-source platform that integrates retinal datasets, model training, benchmarking, and in silico analysis tools within a unified framework. The resource is valuable because it addresses long-standing challenges in reproducibility, accessibility, and cross-study comparison in computational retina research, while providing a foundation for community-driven model development and evaluation. The supporting evidence is solid, with the authors demonstrating a functional and well-documented platform across multiple datasets and species, although a clearer discussion of model interpretability, current performance limitations, and data quality standards would strengthen the resource.

eLife Assessment

The authors describe a cell-specific mechanism by which glutamate transporters regulate the fidelity with which T-stellate cells in the mouse ventral cochlear nucleus relay information from auditory nerve inputs. The study is supported by solid electrophysiological data. It provides valuable insights into how the rapid binding of glutamate to transporters shapes auditory information processing at specific synapses.

eLife Assessment

This valuable study provides a cross-species single-cell transcriptomic resource for early female gonadal development in mammals. The data supporting the main conclusion remain incomplete, and experimental validation is needed to strengthen the conclusions. The work will be of interest to reproductive biologists and developmental biologists.

eLife Assessment

This manuscript describes an important development of several variants of optogenetic tools to control endogenous p53 activity. They are based on peptides competing with Mdm2/MdmX for binding to p53, thus releasing p53 from its negative regulators and stabilizing its cellular levels. In principle, the data are convincing but should be complemented by investigations of p53 target genes at endogenous levels (instead of only reporter constructs). The study therefore remains incomplete but will be of interest to scientists working on optogenetics as well as the p53 field.

eLife Assessment

Verma and colleagues interrogate the mechanisms of phagosome maturation arrest during Mycobacterium tuberculosis infection. While cellular events that culminate in this arrest have been largely elucidated, involvement of other organelles, such as mitochondria, has not been highlighted mechanistically. In this valuable study, elements of mitochondrial quality control, such as mitophagy and mitochondrial-derived vesicles involvement, are shown to be paramount in the host-pathogen tussle. The evidence supporting the main conclusions is solid, based on multiple complementary approaches and appropriate controls, although some central mechanistic aspects of the proposed pathway remain only partially resolved.

eLife Assessment

This study investigates the cellular mechanisms underlying theta-nested gamma oscillations in the medial entorhinal cortex; the experiments are rigorous, and the analyses and modeling provide potentially useful insights into cell-type-dependent circuit dynamics. However, the evidence supporting several key conclusions remains incomplete. The study is limited by conceptual constraints in the experimental design and a modeling approach that does not fully address underlying physiological mechanisms. Overall, this is a careful study that addresses how distinct neuronal populations in superficial MEC participate in theta-gamma coordination and provides new data linking cell-type-specific activity patterns to oscillatory network structure.

eLife Assessment

In this useful Tools & Resources article, the authors describe a new cryogenic light microscopy design and characterize its temperature and spatial stability. This compelling system avoids the challenges associated with vacuum-based designs, particularly vacuum transfer systems, which are difficult to engineer. A key advantage of the system is that it reduces ice contamination and drift, which are the primary challenges in open cryostat systems.

eLife Assessment

This study presents an important large-scale behavioral and transcriptomic analysis of Drosophila that are heterozygous for putative loss-of-function alleles of homologs of human genes that have been linked to autism spectrum disorders. The authors consider 48 genes as hits from their screen, which show significant behavioral alterations in sleep, basal activity, and/or social behavior, and significant sexual dimorphism. The authors then focus on the domino/SRCAP gene as a candidate regulator of sleep, social behavior, transcriptional programs, and RNA splicing. The work generates a solid dataset and applies quantitative analytical approaches that will be of interest to researchers in the field, yet the evidence presented remains incomplete because issues of genetic background need to be further addressed.

eLife Assessment

This manuscript describes a valuable study of the mechanism by which acetylation on the histone H3 core domain regulates RNA polymerase II transcription passing through nucleosomes. The authors provide convincing evidence that acetylation influences transcription in a context-specific fashion. Some questions relating to the static nucleosome structures and the polymerase passage remain, but this manuscript will be of considerable interest to researchers in the chromatin and transcription fields.