Evaluated articles

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 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 convincing 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.

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

This important study identifies the cribriform plate as a key neuroimmune interface that shapes myeloid cell responses during neuroinflammation. Using imaging, flow cytometry, and single-cell approaches in a mouse model of EAE, the authors provide convincing evidence that dendritic cells and macrophages accumulate in PDPN-rich niches and have transcriptional features consistent with tolerogenic or immunosuppressive states. The work is technically strong and novel, and future studies will be needed to define the functional consequences of these myeloid cell states in autoimmunity.

eLife Assessment

This study offers a valuable analysis of how moment-to-moment fluctuations in arousal are associated with structured, non-uniform patterns of brain-wide functional connectivity during wakefulness. Using data-driven analyses of resting-state and naturalistic fMRI with eye tracking, the authors present convincing evidence that arousal is a dynamic, continuous process that shapes brain activity in a structured way beyond a simple global effect. This paper sheds light on the link between brain activity and ongoing fluctuations in arousal and will be of interest to researchers studying large-scale brain functional organization and links between the brain and body.

eLife Assessment

In this important study, DNA and RNA are co-imaged in single cells to show that the proximity of topologically associated domain (TAD) boundaries is uncoupled from the transcriptional activity of nearby genes. The evidence supporting these conclusions is convincing for the regions examined, with high-throughput imaging providing robust statistics. This work will be of interest to researchers studying genome architecture and its relationship to gene regulation.

eLife Assessment

This study provides valuable data regarding gene expression and molecular changes that occur in the mouse spinal cord from exercise and motor activity. Overall, the findings and methods are solid, although additional independent validation experiments would improve the rigor of the study. The work provides resources for neuroscientists who investigate communication between neurons and non-neurons and both basic and translational scientists with interests in how physical activity impacts the nervous system function, with potential therapeutic outcomes.

eLife Assessment

This study provides valuable evidence regarding our expectations about task difficulty and how this might influence proactive attention. The findings suggest that anticipated demands enhance the strength of attentional selection at cued locations. The evidence is solid but not definitive, as the conclusions rely on the absence of changes in spatial breadth. Nevertheless, the manuscript puts forth an informative experiment with a well written and thoughtful discussion of the results.

eLife Assessment

Foucault and colleagues examine how human adaptive learning depends on the structure of the learning task. The authors provide useful findings clarifying the differences in how people learn in environments that are continuously versus discontinuously changing. While they provide solid evidence for most conclusions, support for some of the claims is incomplete in the current form.

eLife Assessment

This important study convincingly demonstrates how bacterial cells can modulate outer membrane-peptidoglycan tethering by expressing two different Lpp homologs with distinct cross-linking efficiencies, revealing that Salmonella typhimurium LppB forms disulfide-based homodimers (or heterotrimers with Lpp when present) and is covalently attached to peptidoglycan primarily via the L,D-transpeptidase LdtB at residue K58. The evidence supporting the authors' claims is solid, including the regulatory role of LppB dimerization for its abundance in E. coli and its ability to inhibit Lpp/A crosslinking to peptidoglycan, although additional analysis and quantification of muropeptides in wild-type E. coli overexpressing LppB would further strengthen the findings. Overall, the work will be of great interest to microbiologists studying cell envelope biogenesis.

eLife Assessment

This fundamental study describes long-range serial dependence of performance on a visual texture discrimination training task that manipulated conditions to induce differing degrees of location transfer of learning. The authors re-analyzed previously-published, behavioral data, generating compelling evidence from converging approaches that the serial dependence effects persist over multiple days of training, and may share a common causal mechanism with training-induced location transfer. By informing our understanding of the importance of temporal integration to long-term perceptual learning and its propensity towards specificity or generalizability, these results should interest neuroscientists who seek to uncover underlying neural mechanisms for these processes.

eLife Assessment

The new development of Neuroplex, a pipeline that links projection-defined neuronal identity to in vivo calcium activity within the same animal, is an important contribution to the field of neuroscience and beyond. The strength of evidence is convincing.

eLife Assessment

This study uses a Bayesian framework to characterize latent brain state dynamics associated with memory encoding and performance in children, as measured with functional magnetic resonance imaging. The novelty of the approach offers valuable insights into memory-related brain activity, but the consideration of developmental changes in memory and brain dynamics, and the evidence to support the proposed mapping between specific states and distinct aspects of memory, are incomplete. This work will be of interest to researchers interested in cognitive neuroscience and the development of memory.

eLife Assessment

This study provides important insights into how working memory shapes perceptual decisions, using a dual-task design, continuous mouse tracking, and hierarchical Bayesian modeling. By dissociating fast attentional capture effects from slower, sustained perceptual biases within single trials, the authors provide compelling evidence that working memory-perception interactions unfold through distinct dynamic processes rather than a single mechanism. This work will be of interest to researchers studying working memory, perception, decision-making, and mouse-tracking methodology.