Evaluated articles

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 but these are discussed by the authors. 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 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.

eLife Assessment

This study presents valuable findings for identifying biotypes of depression patients using white matter measures, which are under-utilised and under-appreciated in current biological and computational psychiatry work. The evidence supporting the claims is solid, although enhanced interpretability of the identified biotypes across both white matter and symptom levels, and better justification of the choice of models would strengthen the paper. Overall, this study will be of interest to the broad community of neuroimagers, clinicians, and biological and computational psychiatry researchers.

eLife Assessment

This study uses the yeast two-hybrid assay to identify proteins that may interact with yeast Set1 and other subunits of COMPASS/Set1C, the histone H3K4 methyltransferase, providing also some evidence for Set1 sumoylation and a role of SET1C methylating other factors in vitro. The results are valuable and they should contribute to understanding the functions of the conserved SET1C complex, as they suggest potential functional connections with RNA biogenesis, chromatin remodeling, and non-histone methylation whose implications would yet need to be explored. Nevertheless, apart from the fact that only a small subset of the Y2H interactions is further examined, the validating experiments are only partial or inconclusive, the strength of evidence being incomplete at this point, although with improvements over the previous version.

eLife Assessment

This study provides valuable insights into the protein composition of the C2a projection in mouse motile cilia, building upon prior work in Chlamydomonas. The evidence supporting the claims of the authors is solid. The work will be of interest to biologists and clinicians studying cilia and ciliopathies.

eLife Assessment

This important work identifies phlda2 as a specific marker for primordial cardiomyocytes in the adult zebrafish heart and demonstrates their essential role in myocardial morphogenesis and coronary vascularization, but not in heart regeneration. The conclusions are well supported by single-cell transcriptomics, new genetic tools, and cell-specific ablation experiments. Overall, the evidence is solid and provides insight into the difference between developmental and regenerative cardiac programs. This work will be of interest for those studying cardiac development and regeneration.

eLife Assessment

This manuscript identifies temperature-dependent alternative splicing of PIF4 in Arabidopsis thaliana and shows that heat stress promotes the accumulation of a short exon 5-skipping isoform that is predicted to encode a non-functional protein. This finding is important, and it provides an intriguing new layer of regulation for PIF4; however, the strength of the mechanistic conclusions is limited, and several key conclusions rely on indirect evidence. As a result, while the data robustly demonstrate heat-regulated alternative splicing of PIF4, the causal role of PIF4 isoforms' balance in shaping heat-induced developmental responses remains only partially supported and the strength of the evidence presented is incomplete. This work will be of interest to biologists working on alternative splicing.

eLife Assessment

This important paper presents a rigorous and comprehensive deep mutational analysis of the kinase TYK2, revealing how single amino acid substitutions influence protein abundance, signaling activity, and responses to pharmacological inhibitors. By combining high‑quality experimental design with dose‑response signaling assays and multiple inhibitor conditions, the authors generate a robust dataset that identifies variants across all domains of TYK2, including clusters at functionally critical sites and protein-protein interfaces. The study highlights mutations that drive drug resistance or potentiation and shows that reduced TYK2 abundance aligns with protective autoimmune‑associated variants, underscoring the therapeutic relevance of modulating TYK2 stability. Overall, the work provides compelling insights with clear implications for biochemistry, immunology, clinical genetics, and drug discovery.

eLife Assessment

This study presents a useful methodological advance that better enables the simultaneous measurement of gene expression and chromatin accessibility in individual cells. The evidence supporting the improved detection of gene expression is solid. The method has the potential to be more broadly impactful if it were expanded to include orthogonal validation strategies. This method will be of interest to those studying transcription and gene regulation.

eLife Assessment

This study presents valuable findings that could potentially allow a deeper understanding of the immunopathogenesis underlying influenza infection in aged mice. The results are based on solid evidence that define putative immune determinants underlying immunopathology in the aged lung. This study will be of interest to researchers pursuing aging research, as well as to immunologists.

eLife Assessment

In this valuable study, Robben et al. describe a 3D beta-cell spheroid platform, a tool allowing high-throughput monitoring of cytoplasmic calcium concentrations and insulin secretion, with calcium signals comparable to those recorded in primary pancreatic islets. The authors demonstrate the method by culturing MIN6 cells in a 3D culture system, and show solid evidence of its utility by recording calcium signals in a high-throughput format and characterizing these calcium signals using pharmacological tools. This highlights the potential utility of the 3D beta-cell spheroids for screening new pharmacological modulators of pancreatic beta-cell function.

eLife Assessment

This important study demonstrates that a perinuclear actomyosin network, present in some types of human cells, facilitates kinetochore-spindle attachment of chromosomes in unfavorable locations, thereby reducing their missegregation rate. This actomyosin network and its general role have been studied previously, but this study convincingly clarifies the underlying mechanism and expands the investigation to additional cell lines. The results are relevant to understanding chromosome missegregation in cancer cells.

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

eLife Assessment

This revised study presents valuable findings implicating nuclear export in the regulation of protein condensate behaviour and TDP-43 phase behaviour, suggesting a link to pathogenic aggregation in ALS/FTD. The work contains several observations that will be of interest to the field; however, the underlying mechanistic links proposed by the authors remain insufficiently supported by the current data. The research relies extensively on synthetic, non-physiological protein variants and a homozygous disease model, with limited mechanistic validation, leaving many of the conclusions largely correlative. Thus, despite its technical strengths, the findings presented are currently incomplete, and while the results are invaluable to the field, these do not provide sufficient evidence to substantiate claims about the direct role of nuclear export in pathological protein aggregation and disease.