Evaluated articles

eLife assessment

This paper investigates how the EWS::FLI1 fusion protein organizes chromatin topology and regulates gene expression in an aggressive pediatric bone cancer known as Ewing sarcoma. The authors used the most recent genomics methodologies to provide solid-based evidence for the role of a short alpha helix in the DNA binding domain of FLI1 in modulating binding to GGAA microsatellites and promoting enhancer activity. The study provides valuable insight into the underlying oncogenic mechanisms in Ewing sarcoma, despite the inherent limitations of the some of the techniques used.

eLife assessment

In this interesting study, Drożdżyk and colleagues analyze the ability of placental CALHM orthologs to form stable complexes, identifying that CALHM2 and CALHM4 form heterooligomeric channels. The authors then determine cryo-EM structures of heterooligomeric CALHM2 and CALHM4 that reveal a distinct arrangement in which the two orthologs can interact, but preferentially segregate in the channel. This is an important study; the data provide compelling support for the interpretations and overall, the work is clearly described.

eLife Assessment

This manuscript presents solid evidence suggesting that the loss of ZNRF3 and RNF43, two E3 ubiquitin ligases, leads to dysregulation of EGFR signaling in cancer. The authors propose that EGFR is a direct substrate of ZNRF3/RNF43. While the authors provide immunoprecipitation data showing increased detection of ubiquitinated species, this evidence does not definitively establish that EGFR itself is ubiquitinated by RNF43/ZNRF3. The absence of direct evidence for EGFR ubiquitination is a major limitation, although the findings are useful as they may provide novel insights into the mechanisms underlying EGFR-driven cancers and open new therapeutic avenues.

eLife Assessment

In this revised manuscript, Dong et al. investigate the role of the small Ras-like GTPase Rab10 in the exocytosis of DCVs in mouse hippocampal neurons, showing that Rab10 depletion hinders DCV exocytosis independently of its effects on neurite outgrowth. Upon revising their work, these findings provide compelling evidence that Rab10 depletion leads to altered ER morphology, impaired ER-based calcium buffering, and decreased ribosomal protein expression, which collectively contributes to defective DCV secretion. The study comes to the fundamental conclusion that Rab10 is critical for DCV release by ensuring ER calcium homeostasis.

eLife assessment

This fundamental study reports the most comprehensive neurotransmitter atlas of any organism to date, using fluorescent knock-in reporter lines. The work is comprehensive, rigorous, and compelling. The tool will be used by broad audience of scientists interested in neuronal cell type differentiation and function, and could be a seminal reference in the field.

eLife Assessment

The manuscript reports on an important comparison of a range of approved clinical inhibitors for BTK used for the treatment of chronic lymphocytic leukemia (CLL). The authors provide compelling evidence for their claims, using a combination of HDX-MS and NMR spectroscopy. The novelty is that this study also seeks to evaluate resistance mutation bias. The manuscript will be of high interest to scientists working on protein drug interactions.

eLife assessment

This study presents valuable findings on the ligand- and ion-dependent structural dynamics of a transcriptional riboswitch. The single-molecule data presented are solid and prompts intriguing hypotheses and models, which will undoubtedly stimulate future structural analyses. These findings are of considerable interest to biochemists and biophysicists engaged in the study of RNA structure and riboswitch mechanisms.

eLife assessment

Sisigano et al. report findings about the role of sphingolipids using lipidomics with machine learning in paclitaxel-induced peripheral neuropathy and preliminary translation of the impact of SA1P in cultured neuronal cells. This study presents a valuable finding on the increased activity of two well-studied signal transduction pathways in a subtype of breast cancer. The significance is limited by incomplete evidence which can be addressed in larger clinical cohorts in the future and with more robust biological validation approaches.

eLife Assessment

Morphological characteristics and phenotypes of mutations in key developmental genes suggest that head, trunk, and tail development are regulated by discernible modules. Gdf11 signalling plays a crucial role in orchestrating the transition from trunk to tail tissues in vertebrate embryos. This important study presents convincing evidence that Tgfbr1 acts upstream of Isl1 (a pivotal effector of Gdf11 signalling) and regulates blood vessels, the lateral plate mesoderm, and the endoderm associated with the trunk-to-tail transition. Together with the previous studies, this work identifies a key signal that acts as the pivot of the trunk-to-tail transition.

eLife assessment

This study presents a valuable finding and developed ME3BP-7 as a novel microencapsulated formulation of 3BP, which specifically targets MCT1-overexpressing PDAC cells. It demonstrates its specificity and efficacy in vitro and in PDAC mouse models, with significant anti-tumor effects and improved serum stability. Overall, the evidence supporting the authors' claims is solid.

eLife Assessment

The formation of the Z-ring at the time of bacterial cell division interests researchers working towards understanding cell division across all domains of life. The manuscript by Jasnin et al reports the cryoET structure of toroid assembly formation of FtsZ filaments driven by ZapD as the cross linker. The findings are important and have the potential to open a new dimension in the field, and the evidence to support these exciting claims is solid.

eLife assessment

This is an important study that demonstrates that RNA intermediates arising from improper splicing are exported out of the nucleus via the canonical mRNA export machinery and the nuclear pore basket. The authors provide convincing evidence that the role of the nuclear basket rather than retaining the transcripts is stimulating their export, putting into question the current model of the role of the basket. The conclusions are in line with recent studies in mammalian cells that suggest that the basket's role in mRNA export and quality control has to be revised.

eLife assessment

The Hippo signaling pathway plays a crucial role in controlling organ size, cell proliferation, and apoptosis, though its role in endocrine pancreas development has remained unclear. In this useful work, the authors study the function of the Tead1 transcription factor, a Hippo effector, specifically in pancreatic beta cells. They provide solid evidence, using multiple different conditional knockout models to reveal Tead1's regulatory functions in insulin secretion and beta cell proliferation. However, deeper exploration of their data and incorporating findings from existing literature on this topic would provide a clearer understanding of Tead1's role in β-cell function, within or beyond the Hippo pathway.

eLife assessment

The work provides valuable genomic resources to address the endocrine control of a life cycle transition in the Malabar grouper fish. The revised manuscript is more solid and the resources and experimental data help to build up a meaningful biological understanding of thyroid signaling in grouper fish.

eLife assessment

This work provides a valuable characterization of neural activity in the anterior insular cortex during fear. Using behavior, single unit recording, and optogenetic control of neural activity, the paper provides convincing data on the role of anterior insular circuits in bidirectionally controlling fear. The study is a great starting point on the path to testing hypotheses about bidirectional control of behavior via neural activity in anatomically defined output populations.

eLife assessment

This study investigates plant-microbe interactions for an invasive plant, Ageratina adenophora. The findings are valuable in advancing our understanding of how leaf and soil microbes separately affect its performance, with solid experimental evidence revealing the importance of litter microbes in shaping A. adenophora populations. The work will be of interest to invasion biologists.

eLife Assessment

This important study details changes in the brain functional connectivity in a longitudinal cohort of Gambian children assessed outside a lab setup with functional near-infrared spectroscopy (fNIRS) from age 5 to 24 months, in relation to early physical growth and cognitive flexibility capacities at preschool age. While evidence supporting conclusions on the evolution of brain connectivity are solid, the statistical power was insufficient to perform proper analyses of longitudinal data and link the connectivity trajectories with early adverse conditions such as undernutrition and later cognitive development. This study will be of significant interest to neuroscientists, psychologists and neuroimaging researchers working on infant development in relation to environmental factors.

eLife Assessment

This study presents a valuable finding on a potential signaling pathway responsible for the direct effects of nicotine on intestinal stem cell growth and tumorigenesis. The evidence supporting the claims of the authors is solid. This research will be of interest to medical biologists specializing in intestinal tumors.

eLife Assessment

This paper describes the structure and connectivity of brain neurons that send descending connections to motor neurons and muscle in the fruit fly nerve cord, using a synapse-resolution connectome. This important work provides a wealth of hypotheses and predictions for future experimentation and modelling. Using state-of-the-art methods, the authors provide solid evidence for their conclusions.