Evaluated articles

eLife Assessment

This important study provides the first in vivo evidence that nonsense-mediated mRNA decay (NMD) in mature astrocytes regulates astrocyte function, synaptic plasticity, and anxiety-related behavior. Using a broad range of approaches, the authors show that conditional deletion of Upf2 alters astrocyte morphology and calcium signaling while impairing synaptic transmission and plasticity, providing solid support for the central conclusion that astrocytic NMD influences neural circuit function. Some key mechanistic claims remain incompletely supported, including whether phenotypes reflect astrocyte remodeling versus loss, the interpretation of synaptic engulfment data, the link between NMD targets and calcium signaling, and the extent to which calcium dysregulation explains the observed synaptic and behavioral effects.

eLife Assessment

This fundamental manuscript describes a key role for the integrated stress response-regulated transcription factor CHOP in regulating liver biology in response to endoplasmic reticulum stress through both the downregulation of transcription factors involved in regulating hepatic identity and altering the capacity for integrated stress response and unfolded protein response signaling to induce protective signaling. The data supporting this model is convincing, but including some additional discussion on the mechanism and importance of the work in the context of the published literature would be helpful to better define the complex importance of CHOP signaling. This work will be of interest to a wide range of biologists interested in liver biology, stress-responsive signaling, and ER stress.

eLife Assessment

This is a valuable paper looking at nanoscale organization of the membrane associated periodic cytoskeleton in mouse sciatic nerve axons. Despite previous studies, the precise organisation of the structure remains unclear, especially in vivo, and this manuscript significantly adds to this knowledge with solid data. An unexpected observation is the presence of discrete nanoscale clusters, regularly distributed around sections of axons. However, the paper misses a description of these clusters along the longitudinal axis of the axons.

eLife Assessment

This useful study reports on lifespan extension in C. elegans males that carry a mutation in a gene for an insulin receptor; while the observations are striking, the strength of evidence is currently incomplete. The central claim of male-specificity is undermined by the absence of direct hermaphrodite healthspan comparisons, and the reliance on a single mutant allele leaves open the possibility that background mutations, rather than daf-2 loss-of-function, drive the phenotype. Methodological details critical for reproducibility are also lacking, particularly regarding male housing density, censoring of plate-leaving animals, and the adequacy of replication for the key epistasis experiment. The work could be substantially strengthened by a targeted set of additional experiments and fuller engagement with the existing literature on sex-specific aging in C. elegans.

eLife Assessment

Building on earlier studies, this manuscript reports a role for pol kappa in cisplatin resistance in the very specific scenarios of head and neck squamous cell carcinoma, providing evidence that the PIP box of Pol kappa is critical for cisplatin resistance in these cells. The findings are of a highly focused relevance and will be useful in the field, but the conclusions are limited to very specific cancer cells. Conclusions cannot be generalized to all cisplatin resistance mechanisms and cell types and are based on incomplete evidence that presents uncertainties and discrepancies that need to be resolved.

eLife Assessment

This is a potentially important study comparing LTP mechanisms between primates and rodents. The experimental methods have some possible confounds, and the power (replicates) and design of the statistical methods could be strengthened, hence the support for the central claims of species differences is currently incomplete.

eLife Assessment

This important study assessed the replicability of a selection of lab-based biomedical experiments in papers published by authors based in Brazil. The study adds a unique perspective to the literature on replication, and provides rich data on the approach taken, the outcomes, and the challenges involved in conducting large-scale crowd-sourced research. The evidence supporting the claims is convincing, but there is scope for clarifying the presentation of the results and extending the discussion section.

eLife Assessment

This study shows that the compound Yoda potentiates the function of the PIEZO2 channel, challenging the assumption that they selectively activate PIEZO1. This is an important finding and the evidence supporting this claim is solid. The authors have addressed the methodological and conceptual issues raised during review. Overall, this work will be of broad interest to researchers working with PIEZO channels across various biological scales.

eLife Assessment

The authors describe a new member of the KCNE auxiliary subunits of potassium channels from a lamprey. This new subunit represents an early evolutionary member which confers new properties when expressed along with KCNQ channels. In the revised version of the manuscript, the authors present convincing evidence from several experimental approaches. The contents of this manuscript are important and should be relevant to understanding both the mechanism of modulation of KCNQ channels by KCNE subunits and the evolutionary history of these subunits, which this manuscript now extends to the divergence of early vertebrates.

eLife Assessment

This important study investigates how surface stickiness shapes whisker mechanics and peripheral neural responses during active touch. The biomechanical evidence that surface stickiness alters whisker mechanics and stick-slip dynamics is compelling, supported by a large and high-quality 3D dataset, while the electrophysiological evidence is solid but limited by a small sample size and insufficient validation of the sticky stimuli. The work will be of broad interest to sensory neuroscientists studying active touch.

eLife Assessment

This study presents a useful compendium of triangulated single-cell eQTLs, Mendelian randomisation and colocalization of genetic signals in prostate cancer datasets. Biological interpretation in the context of the aging prostate gland, the tumour microenvironment and immune cell specificity is incomplete, so this study is a starting point for further study, and would require validation of the resulting putative causal genes.

eLife Assessment

This useful study explores how macrophage cell-cycle state may influence endocytosis, Mycobacterium tuberculosis uptake, and the intracellular stress experienced by bacteria. While the question is interesting and the experimental approach has promise, the evidence for the central claim that endocytic capacity is specifically regulated by cell-cycle stage is incomplete. The main concern is that fluorescence-based sorting and total-fluorescence measurements likely covary with cell size, so the reported phenotypes could reflect biomass accumulation or other cell-cycle-associated changes rather than endocytic capacity as the causal determinant. As a result, whilst the study raises a hypothesis that is of importance, additional controls are required before the proposed mechanism can be considered well supported.

eLife Assessment

This important submission from Ambler and colleagues brings new insights into how torpor conditions may confer resilience in cases of cardioprotection. The study is backed by solid evidence and represents a unique interoceptive mechanism of interest.

eLife Assessment

This study addresses a recent discovery by others that electroconvulsive therapy (ECT) generates seizure activity and spreading depolarization (SD), reflected in large increases in calcium, which can be observed through imaging fluctuations in neuronal calcium. Revisions addressed some concerns of reviewers but not the main issues. Therefore, the consensus was that the work is useful but the evidence showing that SD, rather than seizures, confers the neuroplastic and other therapeutic effects of ECT is incomplete.

eLife Assessment

This valuable manuscript investigates how Drosophila larvae make foraging decisions in patchy environments with controlled resource density and valence; using movement tracking in bounded arenas, the authors show that larvae's patch residence time (PRT) differs depending on resource type, environmental context, and prior experience. A drift-diffusion model is used to describe patch-leaving behaviour, suggesting that an integration process may underlie stay-leave decisions during foraging. The strength of the evidence is mostly solid, but the interpretation and use of PRT needs further investigation, as PRT could be a direct effect of resource concentration on locomotion. Explicit reports of PRT statistical tests are needed for rigorous interpretation.

eLife Assessment

This useful study investigates noise-robust and energy-efficient circuit mechanisms for working memory by optimizing connectivity and reports that the resulting networks exhibit rotational dynamics and better match aspects of PFC population recording. However, the supporting evidence remains incomplete, given the restricted linear, task-specific training and analysis, and limited comparisons with other prominent models. The manuscript would be strengthened by extending the analysis to nonlinear dynamics, providing more rigorous comparisons with alternative models, and establishing a stronger link to prior theoretical and experimental work.

eLife Assessment

This important study advances our understanding of the biomechanics of seed processing in birds by providing a comprehensive 3D kinematic analysis of coordinated bill and tongue movements across two species with contrasting biting forces. The evidence is convincing, combining high-speed XROMM with Bayesian statistical modeling in a rigorous and technically innovative framework that advances the understanding of avian feeding kinematics. Strengthening the statistical validation of qualitative claims, particularly for tongue-seed velocity relationships, and improving the accessibility of the probabilistic modeling framework would further solidify the conclusions.

eLife Assessment

This valuable study investigates the mechanisms underlying inter-item biases in visual working memory. By experimentally manipulating the relative noise levels of target and non-target items, the authors report bias patterns that are broadly consistent with predictions of their previously proposed normative demixing theory. However, the supporting evidence remains incomplete, as the manuscript lacks a sufficient description of the underlying theory, key assumptions, and a quantitative link between the model and behavioral data. The manuscript would be substantially strengthened by clearer exposition and stronger tests, including analyses of the full error distributions and comparisons with alternative models, which would increase its potential interest to the cognitive neuroscience and computational cognitive science communities.

eLife Assessment

This valuable study investigates the neural basis for recovery of complex wheel running behaviour following a unilateral spinal cord injury in mice. By combining behavioural analyses, whole-brain mapping, and tracing techniques, the authors provide incomplete evidence that new cortico-medullary connections can drive effective motor recovery. The paper could be strengthened with manipulations to establish causality, a more fine-grained analysis of the behaviour, and some reorganisation of how the data are presented and discussed.

eLife Assessment

This study presents an important conceptual advance linking viral lifestyle (temperate versus lytic) to patterns of central carbon metabolism gene content across coral reef viromes, proposing that these associations may reinforce feedback loops influencing reef microbialization state. The revised manuscript better aligns its claims with the underlying data by separating observed metabolic gene associations from the hypothesized downstream effects on infection, host metabolism, and reef state, but the evidence for the central mechanistic claims remains incomplete, as no new analyses were added to establish that the identified metabolic genes are mechanistically linked to temperate viral genomes, to rule out compositional effects, or to validate key gene annotations. This work will be of interest to viral ecologists and to researchers studying coral reef microbial dynamics, providing a useful foundation for future studies testing these proposed relationships directly.