Evaluated articles

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 at this point incomplete.

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. 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, though the reduced performance in detecting chromatin accessibility represents a limitation. 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 peri-nuclear actomyosin network, present in some types of human cells, facilitates kinetochore-spindle attachment of chromosomes in unfavorable locations - thereby suppressing their missegregation rate. This actomyosin network and its general role have been studied previously, but this study convincingly clarifies the underlying mechanism using a light-controlled perturbation and detailed tracking of kinetochore movement. The generality of the mechanism could be further supported by confirming the findings in non-synchronized cells and additional cell lines. The results may have implications for understanding chromosome missegregation in cancer cells.

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

eLife Assessment

This 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. However, the research relies extensively on synthetic, non-physiological protein variants and a homozygous disease model, with limited mechanistic validation, leading to conclusions that remain largely correlative. Furthermore, limitations in the reporting of experimental replication and controls, as well as inconsistencies between cancer cell and neuronal models, diminish confidence in the robustness of the findings. Despite its technical strengths, the findings presented are currently incomplete and do not provide sufficient evidence to substantiate claims about the direct role of nuclear export in pathological protein aggregation and disease.

eLife Assessment

This important study addresses the unresolved and long-debated question of whether atypical protein kinase C is required for the maintenance of synaptic potentiation and long-term memory. The results confirm previous findings that persistent activity of PKMζ is required for lasting potentiation of hippocampal synapses and spatial memory. The study also adds new genetic evidence to support the earlier suggestion that enhanced expression of PKC iota/lambda compensates for the genetic reduction of PKM zeta to support synaptic potentiation and memory; however, the results as currently presented were viewed as incomplete.

eLife Assessment

This important study implicates that changes in cell regulation may contribute to the evolution of multicellularity. The evidence supporting the conclusions is convincing, with rigorous methods used to test alternative hypotheses. The work will be of broad interest to cell and evolutionary biologists and those studying the cell cycle and cancer.

eLife Assessment

This study presents a valuable finding on the mutational order for common alterations in colorectal cancer. The evidence of in vitro growth assays comparing mutations is solid, although inclusion of biological replicates for the transcriptional assessments and in vivo experiments would have strengthened the study. The work will be of interest to scientists working in the field of colon cancer.

eLife Assessment

Laaker et al. make an important finding that the cribriform plate acts as a unique neuroimmune interface that shapes local myeloid cell states during EAE-induced neuroinflammation. Using immuohistochemistry, flow cytometry, and single-cell RNAseq of doublets to interrogate cell-cell interactions, the authors provide solid evidence that macrophages, migratory dendritic cells (DCs), and fibroblasts interact at the site of CSF outflow, with DCs showing characteristics of immune tolerance. While the functional consequences of these cell states remain to be established, the work shows that the cribiform plate can play a key role in influencing immune cell composition and interactions with stromal cells.