Evaluated articles

eLife Assessment

This important study provides a novel approach for delineating subcortical-cortical white matter bundles. The authors provide convincing evidence by harnessing state-of-the-art methods and cross-species data. Together, this effort will be of interest to scientists across multiple subfields and accelerate progress in a biologically critical but methodologically challenging area.

eLife Assessment

This useful study attempts to place an ancient maize sample from Bolivia, dated to the end of the Incan empire, in genetic and geographical context. The analyses show that this sample is most closely related to ancient Peruvian maize, but the data remain inadequate to determine the direction of dispersal and the extent of Inca influence over the genetic make up of the analyzed sample. There are additional deficiencies in the statistical analyses and selection inferences. The topic of the study would appeal to researchers studying maize dispersal and adaptation.

eLife Assessment

This important study demonstrates the significance of incorporating biological constraints in training neural networks to develop models that make accurate predictions under novel conditions. By comparing standard sigmoid recurrent neural networks (RNNs) with biologically constrained RNNs, the manuscript offers compelling evidence that biologically grounded inductive biases enhance generalization to perturbed conditions. This manuscript will appeal to a wide audience in systems and computational neuroscience.

eLife Assessment

This important study reports that higher genetically predicted BMI is associated with a modestly increased risk of head and neck cancer. The convincing evidence is supported by rigorous Mendelian Randomization approaches, using multiple genetic instruments and models that reduce sensitivity to pleiotropy. However, results from pleiotropy-robust analyses were less consistent, which limits the strength of causal inference. The work will be of interest to researchers studying cancer risk factors and genetic epidemiology.

eLife Assessment

This study identifies novel approaches to improving transgene expression in the injured mammalian myocardium through a combination of a tissue regeneration enhancer element and engineered AAVs - specifically, a liver-detargeting capsid, AAV.cc84, and an in vivo library screen-selected AAV-IR41. The evidence is convincing, and the AAV vectors are of fundamental value to the field of cardiac gene therapy. Future research exploring how to combine the features of AAV.cc84 and AAV-IR41 could yield an even more promising vector for therapeutic use.

eLife Assessment

This valuable study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. A recent study questioned whether transgenerational inheritance in this paradigm lacks robustness. The authors of this study have worked independently of the group that reported the original phenomenon and also independently of the group that challenged the original report. With solid data, this study independently validates findings previously reported by the Murphy group, confirming that the paradigm is reproducible elsewhere. The reviewers also appreciated the information on reagent sources used by different groups. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.

eLife Assessment

This study presents a useful finding showing that the high susceptibility to sepsis of Kit-mutant mice is due to dysbiosis. However, the data provided is incomplete and would benefit from more rigorous approaches. With the mechanism part strengthened, this paper would be of interest to researchers on mast cell biology and mucosal immunology.

eLife Assessment

This work provides one of the first important attempts to look at Drosophila immune responses against bacterial, viral, and fungal pathogens in a way that combines the roles of four major arms in immunity (Imd signaling, Toll signaling, phagocytosis, and melanization) rather than studying them separately. The findings are compelling and the tools provided can be used as they are, or built upon, in various contexts.

eLife Assessment

This important study reports an advancement in the diagnosis of Animal African Trypanosomosis (AAT), which adapts a CRISPR-based diagnostic tool (SHERLOCK4AAT) to detect different trypanosome species responsible for AAT. The evidence supporting the conclusions is convincing and in line with the current state-of-the-art diagnostics. This study will be of interest to the fields of Epidemiology, Public Health, and Veterinary Medicine.

eLife Assessment

This important study presents a novel approach to enhance the therapeutic potential of mesenchymal stromal cells (MSCs) by genetically modifying their glycogen synthesis pathway, resulting in increased glycogen accumulation and improved cell survival under starvation conditions, particularly in the context of experimental pulmonary fibrosis. The methods and findings are generally solid and could be strengthened in the future by investigating the kinetics of persistence, the immunomodulatory effects, and the underlying improved mechanism of action of MSCs in this pulmonary fibrosis model. If confirmed, this approach could suggest potential methods to improve the therapeutic functionality of MSCs in cell therapy strategies.

eLife Assessment

This important study investigates frequency-dependent effects of transcutaneous tibial nerve stimulation (TTNS) on bladder function in healthy humans and, through a computational model, shows that low-frequency stimulation accelerates, and high-frequency delays, the urge to void. The integration of experimental and modeling approaches provides a solid foundation for clinical trials targeting urinary retention. However, concerns were raised about over-interpretation of modest effects and the limited physiological validity of the computational model, especially its mismatch with typical bladder behaviour and lack of quantitative validation.

eLife Assessment

The ratio of nuclei to cell volume is a well-controlled parameter in eukaryotic cells. This study now reports important findings that expand our understanding of the regulatory relationship between cell size and number of nuclei. The evidence supporting the conclusions is convincing obtained by applying appropriate and validated methodology in line with current state-of-the-art. The paper will be of broad interest for cell biologists and fungal biotechnologists seeking to understand mechanisms determining cell size and number of nuclei and why this knowledge might also be of importance for the production of enzymes and thus production strains not only of Aspergillus oryzae but also other industrially used fungi.

eLife Assessment

This study presents valuable findings regarding the basic molecular pathways leading to the cystogenesis of Autosomal Dominant Polycystic Kidney Disease, suggesting BICC1 functions as both a minor causative gene for PKD and a modifier of PKD severity. Solid data were supplied to show the functional and structural interactions between BICC-1 and PKD2 and their relevance to the pathogenesis of ADPKD, although the characterization of such interactions remains to be developed further and the clinical relevance is currently unclear.

eLife Assessment

The manuscript presents a valuable finding that CCDC32, beyond its reported role in AP2 assembly, follows AP2 to the plasma membrane and regulates clathrin-coated pit assembly and dynamics. The authors further identify an alpha-helical region within CCDC32 that is essential for its interaction with AP2 and its cellular function. While live-cell and ultrastructural imaging data are solid, future biochemical studies will be needed to confirm the proposed CCDC32-AP2 interaction.

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

eLife Assessment

This important study presents a pipeline for discovering cooperative transcription factor (TF) interactions that regulate development, and applies this pipeline in a systematic investigation of TF co-regulation in 11 human embryonic tissues. The authors provide overall solid bioinformatics and experimental support for their findings: although they make a convincing argument for the role of TEAD factors as co-repressors of regulatory activity with tissue-specific TFs, other aspects of the study would benefit from additional validation. This work would be of interest to cell biologists focused on development or on discovery of TF relationships.

eLife Assessment

This study provides valuable insights into the evolutionary conservation of sex determination mechanisms in ants by identifying a candidate sex-determining region in a parthenogenetic species. It uses solid, well-executed genomic analyses based on differences in heterozygosity between females and diploid males. While the candidate locus awaits functional validation in this species, the study provides convincing support for the ancient origin of a non-coding locus implicated in sex determination.

eLife Assessment

This useful manuscript addresses a stability issue for long-term chronically implanted array recordings and electrolytic lesioning, which is relevant to both basic science and translational research. The authors provide a systematic scanning electron microscopy (SEM) of explanted arrays, evaluating electrode damage and sharing extensive datasets accessible through interactive plots. The strength of the evidence is solid, but it can be improved by performing additional analyses on complementary neurophysiology, functional, or histological data.

eLife Assessment

This important study presents a compelling theoretical framework for understanding condensation or phase separation of membrane-bound proteins, with a focus on the organization of tight junction components. By incorporating non-dilute binding effects into thermodynamic models and validating the model's predictions with in vitro experiments on the tight junction protein ZO-1, the authors provide a quantitative tool that combines theory and experiments and will help researchers in the field quantitatively interpret their findings. Given that phase separation of membrane bound molecules is becoming key in signaling, spanning from immune signaling to cell-cell adhesion, this work will be of broad interest for cell biologists and biophysicists.

eLife Assessment

This paper provides a useful new theory of the hallucinatory effects of psychedelics. The authors present convincing evidence that a computational model trained with the Wake-Sleep algorithm can reproduce some features of hallucinations by varying the strength of top-down connections in the model, but discussion of the model's relationships to the psychedelics and sleep literatures is incomplete. The work will be of interest to researchers studying hallucinations or offline activity and learning more broadly.

eLife Assessment

This study proposes a potentially useful improvement on a popular fMRI method for quantifying representational similarity in brain measurements by focusing on representational strength at the single trial level and adding linear mixed effects modeling for group-level inference. The manuscript provides solid evidence of increased sensitivity with no loss of precision compared to more classic versions of the method. However, several assumptions are insufficiently motivated, and it is unclear to what extent the approach would generalize to other paradigms.