Evaluated articles

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.

eLife Assessment

This fundamental work reveals that the accessibility of the unstructured C-terminal tails of α- and β-tubulins differs with the state of the microtubule lattice. Their accessibility increases with the expansion of the lattice induced by GTP and certain MAPs, which can then dictate the subsequent interactions between MAPs and microtubules, and post-translational modifications of tubulin tails. The evidence supporting the conclusion is compelling, although the characterisation of the probes does not answer whether they directly affect the lattice or expose the C-terminal tails of tubulin. This work will be of great interest to the cytoskeleton field.

eLife Assessment

This valuable study presents EM structures of new conformational states of the LONP1 AAA+ protease in conjunction with the mitochondrial protein substrates (StAR, TFAM), along with biochemical functional assays. The EM structures revealed new conformational states in a closed configuration. The structures and associated functional results are solid. However, a notable weakness is the absence of substrates found threaded through the ATPase pores.

eLife Assessment

In this valuable study, the authors present traces of bone modification on ~1.8 million-year-old proboscidean remains from Tanzania, which they infer to be the earliest evidence for stone-tool-assisted megafaunal consumption by hominins. Challenging published claims, the authors argue that persistent megafaunal exploitation roughly coincided with the earliest Achulean tools. Notwithstanding the rich descriptive and spatial data, the behavioral inferences about hominin agency rely on traces (such as bone fracture patterns and spatial overlap) that are not unequivocal; the evidence presented to support the inferences thus remains incomplete. Given the implications of the timing and extent of hominin consumption of nutritious and energy-dense food resources, as well as of bone toolmaking, the findings of this study will be of interest to paleoanthropologists and other evolutionary biologists.

eLife Assessment

This study presents a valuable finding on mutations in ZNF217, ZNF703, and ZNF750 through 23 breast cancer samples alongside matched normal tissues in Kenyan breast cancer patients. The evidence supporting the claims of the authors is solid, yet the analysis of the manuscript lacks methodological transparency, statistical detail, and sufficient comparison with existing large-scale datasets. The work will be of interest to medical biologists and scientists working in the field of breast cancer.

eLife Assessment

The manuscript concerns a fundamental and controversial question in Trypanosoma brucei biology and the parasite life cycle, providing further evidence that slender bloodstream forms can indeed infect Tsetse flies. The study is solid in design and execution, and addresses several criticisms made of the authors' earlier work. Nevertheless, some of the main conclusions are only partially supported: one issue is how, precisely, a "slender" bloodstream form is defined, and discrepancies with some results from other laboratories remain unexplained.

eLife Assessment

This important study presents a thoughtful design and characterization of chimeric influenza hemagglutinin (HA) head domains combining elements of distinct receptor-binding sites. The results provide convincing evidence that polyclonal cross-group responses to influenza A virus can be elicited by a single immunization. While the mechanistic basis of heterotrimer formation and immunodominance differences remains unclear, the authors provide new insights for protein design, vaccinology, and computational vaccine design.

eLife Assessment

Clonal hematopoiesis of indeterminate potential (CHIP) is a known risk factor for coronary artery disease, though its precise role in disease progression continues to emerge. This study leverages valuable single-cell RNA data from patients with CHIP mutations and controls to predict key interactions between endothelial cells and monocytes. Using an AI prediction model, the authors identify druggable targets that mediate immune cell interactions in CHIP and provide solid evidence to support their findings.

eLife Assessment

This important and compelling study establishes a robust computational and experimental framework for the large-scale identification of metallophore biosynthetic clusters. The work advances beyond current standards, providing theoretical and practical value across microbiology, bioinformatics, and evolutionary biology.

eLife Assessment

This study by Roseby and colleagues shows that region-specific mechanosensation - especially anterior-dorsal inputs - controls larval self-righting, and links this to Hox gene function in sensory neurons. The work is important for understanding how body plan cues shape sensorimotor behaviour, and the experimental toolkit will be of use to others. The strength of evidence is solid with respect to the assays developed and the involvement of the anterior region; it is incomplete with respect to dorso-ventral involvement in that region and the role of Hox genes in the process. These findings will be of broad interest to researchers studying neural circuits, developmental genetics, and the evolution of behaviour.