Evaluated articles

eLife Assessment

This manuscript by Feng et al. provides valuable evidence regarding the hematopoietic differentiation of bone marrow endothelial cells in the adult mouse. Overall, the authors have addressed our main concerns. Solid data now more strongly support long-term multi-lineage reconstitution of the adult hemogenic endothelial cells. However, critical data, especially regarding the endothelial cells' hematopoietic identity and functional capacity, remain insufficient, which limits the strength of the hemogenic claim, especially the assertion that these adult hemogenic ECs generate bona fide HSCs. Additional experiments would be necessary to fully rule out alternative explanations.

eLife Assessment

This valuable study introduces MPS, an open-source pipeline that addresses a significant technical bottleneck by making miniscope data analysis more accessible. Characterized by speed and a low barrier to entry, the software's performance is supported by solid evidence. This work will be of interest to miniscope users seeking a streamlined, memory-efficient, end-to-end analysis solution.

eLife Assessment

This important study introduces LUNA, a new autofocusing method that achieves nanoscale precision and robustly corrects focus drift during time-lapse microscopy, improving imaging under temperature shifts. The authors exploit this technical advance to investigate the bacterial cold shock response, providing solid evidence that individual cells continue to grow and divide in a highly coordinated process that cannot be observed in population-level measurements. This work offers a technical and conceptual framework for reconciling discrepancies between bulk and single-cell growth measurements, with broad relevance for cell biology and microbiology.

eLife Assessment

This valuable study advances our understanding of best practices for analyzing population-level data using advanced functional alignment methods. It provides convincing evidence that demographic-specific functional templates improve functional neuroimaging studies that use hyperalignment. This study will be of interest to cognitive neuroscientists, neuroimaging methodologists, and computational researchers with an interest in the human brain.

eLife Assessment

This study systematically characterizes the activity patterns of a lateral supramammillary nucleus (SuM)-medial septum (MS)-hippocampus circuit across sleep-wake cycles and its role in memory consolidation. This work is fundamental because it identifies a previously unrecognized brain hub that helps coordinate how different types of memory are supported during a specific sleep state, advancing our understanding of how sleep contributes to memory organization. The work is well-designed, and the data are solid, supporting clear and significant conclusions; however, some mechanistic details and causal relationships would benefit from further clarification or additional experiments. The paper provides new insights into how distinct memory modalities could be processed by parallel, sleep-active subcortical-hippocampal circuits, which would be of general interest to a broad neuroscience audience.

eLife Assessment

This valuable manuscript demonstrates that embryonic exposure to the pesticide chlorpyrifos (CPF) impairs juvenile zebrafish social behavior and sets out to define the underlying mechanism. The authors provide solid evidence that butyrate and class I histone deacetylases are involved, as their modulation rescues the phenotype. However, claims that CPF acts through the microbiome and nitric oxide signaling remain correlative and incomplete. Additional validation would strengthen the intriguing hypotheses raised by this work.

eLife Assessment

This important study demonstrates that Mycobacterium tuberculosis suppresses protective Th17/IL-17 responses in C57BL/6 mice via a Tbet-dependent mechanism involving the virulence factors ESX-1 and PDIM, as mutants lacking these factors induce significantly higher IL-17-producing CD4 T cells and IL-17A in the lungs compared to wild-type bacteria. The experiments are rigorous and well-designed, combining host knockouts and bacterial mutants to yield solid evidence pointing to cross-regulation between Th1 and Th17 pathways, including reduced IL-23 in draining lymph node dendritic cells. However, some of the data on IFN-γ effects or lymph node-specific mechanisms are incomplete and require deeper mechanistic insight, such as direct T cell transcription factor analysis in lymph nodes and broader host validation, to strengthen the work. Overall, the findings provide insight into how bacterial virulence factors limit Th17 induction, thereby promoting persistence, and will interest immunologists and TB researchers focused on host-pathogen balance and vaccine strategies.

eLife Assessment

This work provides an important modeling-based framework for understanding the processes of temporal integration in the claustrum. These mechanisms could support a broader range of integrative brain function. However, at present, the evidence remains at least in part incomplete, primarily because of over-interpretation of the results and their connection to neurophysiology.

eLife Assessment

This important study investigates the impact of BRCA1/2 mutations on immunotherapy in lung adenocarcinoma using multi-omics approaches. The detailed genetic analysis of two cancer genes (BRCA1 and BRCA2) demonstrated new roles for these genes in causing the tumor microenvironment in lung cancer. Further experimental explorations of the immune-related changes may still be required. The solid findings of this study provide a foundation for further developing drugs targeting BRCA1/2 in lung cancer therapy.

eLife Assessment

This valuable study provides evidence that locus coeruleus activity is coordinated with heart rate during sleep, confirming previous work in mice and humans, with a possible role for sleep-dependent memory consolidation. The claims are supported by solid evidence, although the underlying mechanisms and the predictive value of the correlative dataset would benefit from additional controls. This work will be of interest to neuroscientists focusing on sleep, memory, and autonomic functions.

eLife Assessment

The findings of this study are important since they cover the repurposing of small molecules as metalloprotease and phospholipase inhibitors for early intervention in the treatment of bothropic envenoming in the Neotropics, and thus provide a strong rationale for the progression of these inhibitors into future preclinical and clinical evaluation for snakebite indications across various ecological zones. The strength of the evidence is solid; however, there are some weaknesses, such as a lack of translatability of the in vivo model and insufficient venom characterisation. Thus, the strength of the evidence can be enhanced by the use of a mouse model. The paper remains of interest to ophiologists, biochemists and medicinal chemists.

eLife Assessment

This useful study supplements previous publications of willed attention by addressing a frontoparietal network that supports internal goal generation. The evidence is solid in analyzing two datasets collected at different independent sites, using the same willed-attention paradigm and combining fMRI and EEG. This work will interest cognitive psychologists and neuroscience researchers.

eLife Assessment

This study presents a valuable examination of two measurements of physical activity (self-report and objective) in relation to widely studied structural MRI measures of the brain (hippocampal volume and BrainAGE) and cognitive function (Trail Making Test). Cross-sectional and longitudinal data were analyzed using established and validated methodology. The results convincingly suggest that brain health is more likely a cause of physical activity than an outcome of it, although limitations to the data could mask evidence of benefits to brain health. This work will be of interest to neurologists and epidemiologists studying the etiology of cognitive decline, to clinicians interested in advising patients on strategies for preserving brain health in aging, and to members of the lay public.

eLife Assessment

The authors establish solid theoretical principles for designing brain perturbations under the assumption that brain activity evolves under a linear model. By prioritizing low-variance components, resonant frequencies, and hub nodes, this framework provides an important foundation for optimizing information gain, neural state classification, and the control of neural dynamics. However, the lack of investigation of model mismatch makes the study incomplete.

eLife Assessment

This study provides valuable contributions to establish canonical Dhh signaling as a primary mediator in the differentiation of Leydig cells and their steroidogenic capacity. Together, the experimental design using their established stem Leydig cell line alongside relevant genetically mutated models, both derived using the relevant Nile tilapia animal system, provided largely convincing evidence to support their conclusions. The work could benefit from a more rigorous dissection of current literature on this pathway that might better inform their conclusions. The work will be of broad interest to developmental biologists interested in differentiation of steroidogenic or hormone producing cells.

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

eLife Assessment

This study used pupillometry to provide an objective assessment of a form of synesthesia in which people see additional color when reading numbers. It provides convincing evidence that subjective color ratings are matched by changes in pupil size that recapitulate brightness-mediated changes when exposed to the real color. The work provides a valuable contribution to the literature on both synesthetic perception and the use of pupillometry to probe perception and related psychological processes.

eLife Assessment

This important study experimentally probes potential antibiotic activity against hypothetical "mirror bacteria" with reversed chirality, showing that D-enantiomers of several approved antibiotics largely lack activity against natural bacteria (as a proxy for mirror organisms) and that conjugated D-peptides can elicit strong binding antibody responses in mice when adjuvanted. The evidence is solid for these core observations but incomplete on issues of chiral purity, functional antibody assays, replicates, and pharmacodynamic readouts; the work also overreaches in extrapolations without deeper mechanistic integration or native-format validation. Overall, the work offers a cautious, relevant contribution to mirror microbiology discussions and will interest infectious disease researchers.

eLife Assessment

This paper describes useful findings on the effects of isoflurane anesthesia on the visual cortical circuitry of the mouse. It provides solid evidence that the visual spatial frequency sensitivity becomes coarser (lower resolution) during anesthesia, with distinct effects described in excitatory neurons, and parvalbumin (PV) and somatostatin (SOM) positive interneurons. This study should be of interest to neuroscientists studying the mouse visual cortex and the effects of anesthesia on cortical circuitry.

eLife Assessment

AIRE has been well known to contribute to immune self-tolerance in the thymus by expressing auto-antigens; in this manuscript, the authors describe unexpected findings about the interaction of AIRE with AID in B cells, and its function in the immune system, thereby contributing to a fundamental understanding of the broader functions of AIRE. The strength of this manuscript is that, by employing biochemical and genetic experiments, the authors convincingly show interaction between AIRE and AID and subsequent AIRE's function in the GC responses. However, two weak points exist: first, the connection between AIRE, auto-anti IL17 Abs, and IL17-positive effector T cells, and second, like the thymus, expression of auto-antigens by AIRE in the GC B cells has not been tested.

eLife Assessment

This study provides valuable insights through the elucidation of the first full-length structure of the heterohexameric (MmpS4)₃-(MmpL4)₃ transporter complex from Mycobacterium tuberculosis, advancing understanding of its transport mechanism, linked to virulence and drug resistance. The structural analysis is convincing, offering a clear framework for future mechanistic studies. Major strengths include a comprehensive structural characterization of the complex, though some conclusions require further validation.