Evaluated articles

eLife Assessment

This study extends prior work on head bristle mechanosensation by delivering a synaptic-resolution map of second-order partners that preserves somatotopy and highlights a cholinergic pathway linking sensory input to grooming circuits, providing a valuable resource for the field. The reconstructions and quantitative connectivity analyses provide solid support the main anatomical claims, while causal sufficiency for the behavioral sequence remains inferential and could be strengthened by a simple rank-order test relating wiring to the known grooming hierarchy.

eLife Assessment

This timely and fundamental study introduces a human iPSC-based co-culture system that models Kupffer cell-hepatocyte interactions and aims to recapitulate liver-specific immune-parenchymal dynamics. Direct contact between iMacs and iHeps promotes mutual tissue-specific maturation, with iHeps downregulating fetal genes while iMacs acquire a Kupffer cell-like profile. This convincing in vitro model holds significant promise and is a leap forward; future experimental understanding will enhance its translational impact.

eLife Assessment

The results in this study are useful because they begin to establish a causal link between physical activity and the cellular mechanisms of regeneration. The evidence presented is largely solid, supporting the conclusion that exercise-induced changes in the extracellular matrix disrupt regeneration; however, some claims are incomplete, requiring additional controls and a clearer distinction between the effects of mechanical loading and mechanical injury to the blastema. The work will be of interest to researchers in regenerative medicine.

eLife Assessment

This study provides valuable insights into aged muscle stem cell biology by revealing phenotypic and functional heterogeneity within the geriatric MuSC pool and proposing a VCam-low/negative subpopulation that may account for the reported decline in MuSC numbers with age. These findings have implications for understanding aging-related changes in stem cell maintenance and for improving strategies to isolate or rejuvenate aged MuSCs. However, the evidence supporting the main claims is incomplete, key analyses such as absolute MuSC quantification, fate assessment of VCam-low/negative cells, inclusion of standard aged cohorts, and validation of proposed surface markers are still needed to confirm that overall MuSC abundance is maintained and that a distinct subpopulation has been identified.

eLife Assessment

This study reports important findings regarding the role of the NF-kB signaling pathway in the development and long-term survival of gamma delta T cells. The authors report disparate roles of IKK-dependent NF-kB activation in the development and long-term survival of gamma delta T cell subsets. The approach and methodology employed is convincing. This work will be of great interest to immunologists interested in innate-like T cell biology and in T cell development.

eLife Assessment

This study provides a valuable insight into how the medial and lateral entorhinal cortices interact through distinct excitatory and inhibitory pathways. Using anatomical tracing, optogenetics, and electrophysiology, the authors show that glutamatergic medial entorhinal neurons provide broad excitatory input to lateral entorhinal, while long-range SST+ interneurons deliver selective inhibition to layer I. These findings reveal a novel layer- and cell-type-specific organization of medial to lateral entorhinal connectivity with implications for spatial and episodic memory. The work is solid, but validation of injection specificity and viral spread is needed to fully confirm the anatomical interpretations; with these clarifications, this will be a significant contribution to understanding entorhinal-hippocampal circuit organization.

eLife Assessment

The authors use a convincing methodology to investigate the detachment and reattachment kinetics of kinesin-1, 2, and 3 motors against loads oriented parallel to the microtubule. The findings are useful to the field in providing a clearer view of kinesin function under load. However, as the manuscript stands, the conclusions drawn from the experiments, as well as the overall interpretation of the results, are only partially supported by the presented data, and the novelty relative to previous reports appears less clear.

eLife Assessment

The mechanistic basis for the potential health benefits of NAD⁺ precursors remains incompletely understood. This manuscript provides a useful assessment of the role of SIRT1 in mediating the effects of NMN in mice fed a high-fat diet. The study addresses a key question, though some of the conclusions appear only partially supported by the presented data.

eLife Assessment

This work identifies a novel, conserved link between glycolysis and sulfur metabolism that governs fungal morphogenesis and virulence. The compelling evidence, integrating multiple approaches, provides an important conceptual advance. A future mechanistic dissection of how sulfur metabolites interface with known pathways is encouraged.

eLife Assessment

The important study uses genome-wide CRISPR/Cas9 screenings to identify a novel target B4GALTZ1 that is implicated in modulating CD8+ T cell function in the context of anti-tumor immunity. The strength of evidence is solid but could benefit from more detail, particularly to verify the efficiency of knockout in their single gene KO lines and identification of N-glycosylation sites of TCR and CD8s. This work highlights the role of protein N-glycosylation, particularly B4GALT1 deficiency, in regulating CD8 function and anti-tumor immunity.

eLife Assessment

This valuable study provides insights into the role of Pten mutations in SHH-medulloblastoma, by using mouse models to resolve the effects of heterozygous vs homozygous mutations on proliferation and cell death throughout tumorigenesis. The experiments presented are convincing, with rigorous quantifications and orthogonal experimentation provided throughout, and the models employing sporadic oncogene induction, rather than EGL-wide genetic modifications, represent an advancement in experimental design. However, additional experimentation focused on a greater characterization of macrophage phenotypes (e.g., microglia vs circulating monocytes) would enhance this study. The work will be of interest to medical biologists studying general cancer mechanisms, as the function of Pten may be similar across tumor types.

eLife Assessment

The study provides important mechanistic insight into the transcriptional control of γδT17 development, elegantly demonstrating how HEB and Id3 act sequentially and cooperatively to regulate γδT17 cell specification and maturation. The study provides compelling evidence that advances the understanding of E-Id protein dynamics in thymic T cell specification. The work is comprehensive, technically rigorous, and conceptually clear, and will be of interest to immunologists, developmental biologists, and those studying the molecular underpinnings of physiological outcomes.

eLife Assessment

The current work uses DNA-tethered motor trapping to reduce vertical forces and improve datasets for kinesin-1 motility under load. The evidence is compelling and the significance is important to the kinesin field. Kinesin-1 is more robust and less prone to premature detachment than previously indicated. This represents a significant advancement in the field and is generally applicable to work with optical tweezers.

eLife Assessment

This manuscript reports important findings indicating that cell cycle progression and cytokinesis both contribute to the transition from early to late neural stem cell fates. Loss-of-function experimental evidence convincingly shows that disrupting the cell cycle or cytokinesis can alter cell fate. This work sets the stage for future investigations into the underlying mechanisms linking the cell cycle to the expression of temporal factors controlling cell fate.

eLife Assessment

This study provides a valuable genome-centric characterization of microbial communities across deep sediment cores from a Spartina patens salt marsh. The study provides claims on the metabolic capabilities of the deep sediment microbiome as well as on a burial microbial assembly process and functional complementarity at depth. However, some of these claims remain incomplete and would benefit from further supporting evidence. Overall, this work will be of interest to microbial ecologists working on wetlands.

eLife Assessment

The authors used a Bayesian modeling framework to fit behavior and serotonin neuron activity to reward history across multiple timescales. A key goal was to distinguish value coding from other influences, particularly thirst, by comparing model fits across neurons. Although the question and approach are valuable, several limitations of the current manuscript mean that support for the conclusions is incomplete.

eLife Assessment

In reporting on a valuable "learning proteome" for a C. elegans gustatory associative learning paradigm, this work identifies a new set of genes to be tested for roles in learning and memory, describes molecular pathways involving these genes and relevant for learning and memory in C. elegans, and deliver a new set of tools for prodding worm behavior. The methods and results convincingly support the findings, which will be of interest to neuroscientists and developmental biologists seeking to understand the self-assembly and operation of neural circuits for learning and memory.

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

eLife Assessment

This study presents valuable findings from a spatiotemporal analysis of arbovirus case notification data from 2013 to 2020 in Brazil, reporting associations between covariates representing potential drivers of arbovirus transmission and recorded incidence. The work is methodologically solid, though it is unclear how much explanatory power inclusion of the covariates adds. The findings will be of interest to researchers working on the epidemiology of arboviruses.

eLife Assessment

This study offers a valuable advance for neuroscience by extending a visualization tool that enables intuitive assessment of how dendritic and synaptic currents shape the output of neurons. The evidence supporting the tool's capabilities is convincing and solid, with well-documented code, algorithmic innovation, and application to hippocampal pyramidal neurons - although experimental confirmation of the predictions is not provided. The work will be of interest to computational and systems neuroscientists seeking accessible methods to examine dendritic computations.

eLife Assessment

This important study investigates how the nervous system adapts to changes in body mechanics using a tendon transfer surgery that imposes a mismatch between muscle contraction and mechanical action. Using electromyography (EMG) to track muscle activity in two macaque monkeys, the authors conclude that there is a two-phase recovery process that reflects different underlying strategies. However, neither monkey's data includes a full set of EMG and kinematic measurements, and the two datasets are not sufficiently aligned with each other from a behavioural point of view; as a result, the evidence supporting the conclusions is solid but could be improved.