Evaluated articles

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.

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. However, the strength of the conclusions is limited by a reliance on specific analytical choices and the need for additional controls and robustness analyses. 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 valuable 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 and would benefit from clearer statistical justification and a more cautious interpretation of alternative mechanisms.

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 important 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 a previously-published behavioral data set, generating compelling evidence from converging approaches that serial dependence effects can persist across multiple days post-training, and are impacted by whether training promotes more or less location transfer. Although underlying mechanisms for these processes remain unclear, these results will interest neuroscientists in general by informing our understanding of the importance of temporal integration to long-term perceptual learning and its propensity towards specificity or generalizability.

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 a valuable contribution to the field of neuroscience and beyond. The strength of evidence is judged to be solid, as the methods, data, and analyses broadly support the stated claims.

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.

eLife Assessment

This important study links allelic expression imbalance with replication timing, suggesting a stochastic model for haploinsufficiency in dosage-sensitive disease. The integration of allele-specific RNA-seq and replication timing in clonal systems provides solid evidence for an association between asynchronous replication and allelic imbalance, although the scope and generality of some conclusions require more cautious interpretation. This study will interest epigeneticists and genome regulation researchers studying replication timing and monoallelic expression, as well as developmental biologists and human geneticists concerned with clonal heterogeneity, haploinsufficiency, and variable disease penetrance.

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

eLife Assessment

This valuable study demonstrates molecular changes associated with age related impairment in oligodendrocyte differentiation and ability to myelinate. The identification of particular genes that are associated with this decline will provide potential future targets for therapeutic interventions. The reviewers felt that the quality of the evidence was solid while identifying some minor weaknesses that if addressed would enhance the rigor of the study.

eLife Assessment

This study presents a high-quality cryo-EM structure of the human kinase PINK1 in complex with the HSP90-CDC37 chaperone complex, capturing a partially folded intermediate in which the C-lobe and C-terminal extension are structured while the N-lobe remains unfolded and engaged by the HSP90 clamp. The structural data are broadly consistent with a recently published structure of the same complex, providing useful insight into early steps of PINK1 maturation and highlighting residues linked to familial Parkinson's disease. However, the mechanistic conclusions remain incomplete because the manuscript does not experimentally validate key hypotheses raised by the structure, including the functional roles of the C-lobe interface, the HPNI motif, the C-terminal extension, or the proposed competition between HSP90 and TOM20.

eLife Assessment

This study investigates how RNA molecules modulate phase separation, aggregation, and cytotoxicity of the staphylococcal virulent peptide PSMα3 and the human host‑defence peptide LL‑37 using an array of biophysical and cell‑based assays. If validated, these findings would be important, as they suggest that nucleic acids can tune the material state and bioactivity of amyloids, with implications for host-pathogen interactions and for the design of therapeutics that target phase behaviour. However, the evidence is incomplete: many key claims rest on qualitative imaging and contested assumptions about "functional" amyloids, and the absence of quantitative binding data, phase diagrams, and appropriate controls limits confidence in the conclusions.

eLife Assessment

In their valuable study, Beaudet, Berger and Hendricks provide a mechanistic link between disease-associated tau hyperphosphorylation, loss of cooperative tau envelope formation on microtubules, and dysregulation of axonal transport prior to aggregation. Using complementary in vitro reconstitution and human iPSC-derived neuronal assays with phosphodeficient and phosphomimetic tau constructs targeting 14 disease-relevant sites, the authors convincingly show that phosphorylation state alters tau organization on microtubules and differentially impacts kinesin- and lysosome-based transport. The evidence is solid and well aligned with the conclusions, yet the work could be further strengthened by incorporating additional controls and motor-specific assays to refine the mechanistic depth.

eLife Assessment

Kambali et al use optogenetic manipulations to examine whether the ventral hippocampal Schaffer collateral (vCA3-to-vCA1) and temporoammonic (EC-to-vCA1) pathways regulate anxiety- and fear-related behaviors in mice. They find that both pathways regulate the expression of fear (freezing) responses to a context and auditory conditioned stimulus paired with foot shock (trace conditioning protocol), but only the Schaffer collateral pathway regulates the expression of anxiety-related behaviors in the elevated plus maze, open field test, and Vogel conflict test. Overall, the study is valuable: it detects bidirectional effects of optogenetic excitation and inhibition in both pathways. However, the strength of the evidence in support of its main claims is incomplete.

eLife Assessment

This fundamental work significantly advances our understanding of how contact-dependent antagonism enables keystone bacteria to establish and maintain their niche over time. The evidence obtained is convincing, supporting most of the conclusions drawn. This work will be of significant interest to the microbiome research community.

eLife Assessment

This study reports an important and novel finding that TENT5A, an enzyme involved in fine-tuning poly(A) tail length on selected mRNAs, is required for proper enamel mineralization in mice. The evidence supporting the authors' conclusion that reduced expression of enamel matrix proteins (EMPs) in TENT5A-deficient mice results from shortened poly(A) tails remains incomplete, as TENT5A may possess additional functions independent of post-transcriptional regulation that are not addressed in the current study.