Evaluated articles

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, the study remains limited, such that the biological conclusions do not extend greatly from those in the extant literature. This could be addressed with additional experimentation focused on cell cycle kinetic changes at early stages, as well as greater characterization of macrophage phenotypes (e.g., microglia vs circulating monocytes). 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 manuscript by Hensley and Yildez studies the mechanical behavior of kinesin under conditions where the z-component of the applied force is minimized. The important study shows that much of the mechanical information gleaned from the traditional "one bead" with attached kinesin approach was probably profoundly influenced by the direction of the applied force. The data are convincing, but in some cases the amount of data collected appears to be smaller than optimal.

eLife Assessment

This useful manuscript reports findings indicating that cell cycle progression and cytokinesis both play a role in the transition of early to late neural stem cell fates. The imaging data are solid and mostly support the conclusions. However, experimental details are missing, the method of quantitation could be improved, and orthogonal approaches are needed to confirm the findings, which are based on loss-of-function approaches and are not sufficient to support some of the authors' conclusions. Lastly, there is no investigation of the underlying mechanism linking the cell cycle or cytokinesis to the changes (or lack thereof) of early and late NSC fates.

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

This valuable work defines a "learning proteome" for a C. elegans gustatory associative learning paradigm. These results provide the field with a new set of genes to further explore their roles in learning and memory, provide new tools for other labs to employ in their investigations of behavior, and molecular pathways revelant for C. elegans learning and memory. The methodological evidence and the quality of the dataset are convincing. The results 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.

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 study presents important insights into the regulation of muscle hypertrophy, regulated by Muscle Ankyrin Repeat Proteins (MARPs) and mTOR. The methods are overall solid and complementary, with only minor limitations. Overall, the findings will be of interest for both muscle-biology specialists and the broader mechanobiology community.

eLife Assessment

This study is important as it demonstrates that 4-aminoquinoline antimalarials antagonize artemisinin activity under physiologically relevant conditions. Using isogenic parasite lines and a chemical probe, the authors provide mechanistic insight and compelling evidence implicating PfCRT in this antagonism. However, some weaknesses have been identified that limit full interpretation of the findings, which are based solely on in vitro assays, though the results have implications that will be of importance in optimizing future antimalarial combination strategies.

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, the inclusion of an arterial cell line and re-evaluation of the statistical tests used would strengthen the authors' conclusions.

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 lamella and whole cells. The method, which fits a B-spline model using cross-correlation-based local patch alignment of micrograph frames, represents a valuable tool for the cryo-EM community. The authors elegantly use 2D template matching to provide solid evidence that Unbend outperforms the previously reported method of Unblur by the same authors. The paper would benefit from the inclusion of a similar analysis for established alternative methods, such as MotionCor2.

eLife Assessment

This study identifies the Periportal Lamellar Complex (PLC), an important new structure revealed by a novel 3D imaging method. However, the evidence supporting its distinct cellular identity and functional role is currently incomplete, as it relies on transcriptomic re-analysis and correlation without direct experimental validation. Addressing the key issues of methodological rigor and providing functional evidence is essential to fully substantiate these significant claims.

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.

eLife Assessment

This is a valuable manuscript that reframes Gaucher's disease pathology through the analysis of renal health, using a Drosophila model mutant for glucocerebrosidase (GBA1). The authors provide physiological and cellular data showing that renal dysfunction may be a critical disease-modifying feature. This work broadens the field's focus beyond the nervous system to include systemic ionic regulation as a potential contributor to disease initiation and progression. The genetic and experimental approaches are solid and offer a rationale for investigating analogous dysfunction in human tissues; however, several claims extend beyond the presented evidence and would benefit from additional experimental support to fully support the conclusions.