Evaluated articles

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 an important advance by extending an intuitive visualization tool that enables assessment of how dendritic and synaptic currents potentially shape neuronal output. The evidence supporting the tool's capabilities is convincing, with well-documented code, algorithmic innovation, and application to hippocampal pyramidal neurons. 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 the mechanics of the body, which are altered through a tendon transfer surgery affecting finger extensor and flexor muscles. By measuring task performance, joint kinematics, and muscle activity for several weeks post surgery, the authors provide convincing evidence that monkeys undergo a two-phase adaptation process. First, they adopt a maladaptive strategy to overcome the functional challenges imposed by the surgery, and then revert to a strategy that uses the same patterns of muscle coactivation observed pre-tendon transfer.

eLife Assessment

The authors have performed a potentially valuable new kind of analysis in connectomics, mapping to an interesting developmental problem of synaptic input to sensory neurons. While the analysis itself is solid, the authors have drawn broader conclusions than are directly supported by the presented data. With more measured claims and greater clarity and explanations for the analysis, the study could potentially become stronger.

eLife Assessment

The work by van der Pijl presents important findings on the role of titin-associated muscle ankyrin repeat proteins (MARPs) on hypertrophy via mTOR signalling. The study presents rigourous data using in vivo loss-of-function and pharmacological approaches to investigate effects on hypertrophy. While the evidence supporting the role of MARPs on hypertrophy is solid, there are limitations. For example, the use of Rapamycin only inhibits some aspects of mTORC1 signalling and the study is limited to analysis of the diaphragm and thus it is not clear if the mechanisms are conserved across other muscle types.

eLife Assessment

This is an important study with direct implications for the rational selection of antimalarial drug combinations. The authors present data demonstrating antagonism between 4-aminoquinoline antimalarials and peroxide drugs under physiologically relevant conditions, including robust effects at the trophozoite stage and for chloroquine at the ring stage. While the conclusions are based on in vitro assays and further work will be needed to fully resolve the underlying mechanism, the findings are convincing and provide a strong rationale for evaluating drug combinations in relevant preclinical models prior to clinical testing.

eLife Assessment

This study presents vassi, a Python package that streamlines the preparation of training data for machine-learning-based classification of social behaviors in animal groups. This package is a valuable resource for researchers with computational expertise, implementing a framework for the detection of directed social interactions within a group and an interactive tool for reviewing and correcting behavior detections. However, the strength of evidence that the method is widely applicable remains incomplete, performance on benchmark dyadic datasets is comparable to existing approaches, and performance scores on collective behavioral datasets are low. While the package can analyze behavior in large groups of animals, it only outputs dyadic interactions within these groups and does not account for behaviors where more than two animals may be interacting.

eLife Assessment

This study presents valuable findings on the role of KLF6 in in vitro endothelial cells exposed to altered (high or low) shear stress with a customized microfluidic device to investigate mechanisms of atherosclerosis. The finding that altered shear stress results in endothelial cell ferroptosis through reduced expression of KLF6 is compelling and adds a new layer of complexity to the pathogenesis of atherosclerotic plaques. However, more detailed characterization of ferroptosis is needed.

eLife Assessment

This paper describes Unbend - a new method for measuring and correcting motions in cryo-EM images, with a particular emphasis on more challenging in situ samples such as lamellae and whole cells. The method, which fits a B-spline model using cross-correlation-based local patch alignment of micrograph frames, represents an important tool for the cryo-EM community. The authors elegantly use 2D template matching to provide convincing evidence that Unbend outperforms the previously reported method of Unblur by the same authors. Comparison to alternative programs for motion correction shows smaller gains, but with interesting differences between data sets.

eLife Assessment

This study presents an important methodological advance-Liver-CUBIC combined with multicolor metallic nanoparticle perfusion-that enables high-resolution 3D visualization of the liver's complex multi-ductal architecture. The identification of the Periportal Lamellar Complex (PLC) as a novel perivascular structure with distinct cellular composition and low-permeability characteristics is convincing, supported by rigorous imaging data. The observed scaffolding role during fibrosis offers intriguing biological insights, though the functional claims would benefit from direct experimental validation.

eLife Assessment

This study investigates how sleep loss and circadian disruption affect whole-organ metabolism in flies (Drosophila melanogaster) and reports that wild-type flies align metabolism in anticipation of diurnal rhythm, while mutant flies with impaired sleep or circadian function shift to reactive or misaligned metabolism. The integration of chamber-based flow-through respirometry with LC-MS metabolomics is innovative, and the significance of the findings is valuable. However, the strength of evidence needed to support the conclusions is incomplete based on concerns regarding the inappropriate use of constant darkness to disrupt circadian rhythms and the lack of details justifying the methods used to correlate respirometry data with whole-body metabolomics.

eLife Assessment

This important study examines the potential role of ARHGAP36 transcriptional regulation by FOXC1 in controlling sonic hedgehog signaling in human neuroblastoma. While there are many solid findings that strongly support this signaling pathway, there are some aspects of the study that are underdeveloped, particularly the generalizability in the context of cancer cells.