Evaluated articles

eLife assessment

In this paper, the authors demonstrate an interesting link between mitofusin function (MFN2) and PARKIN recruitment and mitophagy, underlying cardiomyopathy. This is a valuable finding with broad implications for understanding the mitochondrial biology as well as mechanisms involved in heart pathologies. However, the analyses are incomplete and the main conclusions are only partially supported and need to be further evidenced.

eLife assessment

This study presents a useful description of RNA in extracellular vesicles (EV-RNAs) and highlights the potential to develop biomarkers for the early detection of colorectal cancer (CRC) and precancerous adenoma (AA). The data were analysed using overall solid methodology and would benefit from further validation of predicted lncRNAs and biomarker validation at each stage of CRC/AA to evaluate the potential application to early detection of CRC and AA.

eLife assessment

This manuscript provides important information about the influence of TOR signaling pathway on development and aflatoxin production in the plant and human fungal pathogen Aspergillus flavus. Compared to an earlier version, the authors have addressed most of the concerns of the reviewers, including the convincing demonstration of the essential TOR pathway in this fungus by constructing a xylose promoter mutant strain.

eLife assessment

How the genome is folded three dimensionally is thought to control gene regulatory pathways during critical processes such as cellular differentiation. Using multiple assays, the authors of this important study probe topologically associated domains (TADs) and report involvement of a protein arginine methyltransferase 5 in chromatin organization and transcriptional regulation. The data gathered are generally solid and broadly support the role of this protein in organization of the adipocytic lineage, but additional control experiments would make the inferences stronger.

eLife Assessment

This is a fundamental cell biological study of host responses during symbiotic microbial infection of plants. Compelling imaging-based approaches using genetically encoded cell cycle markers show that in Medicago truncatula root cortex cells, early rhizobial infection events are associated with cell-cycle re-entry, but once the infection is established, host cells exit the cell cycle. The work will be of interest to a wide range of readers working in fields from development and cell biology to plant-microbe interactions.

eLife assessment

This useful study emphasizes some previously ignored aspects of synaptic communication between Purkinje neurons and their targets in the cerebellar nuclei. Reviewers felt that some aspects of the evidence were solid but that others were incomplete.

eLife assessment

This important study brings together a clear application of the digital twin approach to make predictions using patient specific models with different genotypes. The data are compelling and go beyond the current state-of-the-art to support proof-of-principle evidence. Given the low subject numbers, further studies will be required going forward to support the veracity of the data and its translational utility.

eLife assessment

This study by Chiu and colleagues is a valuable contribution to the study of the circuitry of aggressive behaviours and of mechanisms that generate persistent behavioural states. The authors find that activation of two interconnected sets of neurons results in an increase in female aggression. The data ruling out recurrent connectivity between these clusters underlying this persistent state are convincing.

eLife assessment

This valuable study examines the relationship between positional anchoring of grid cell activity and performance in spatial navigation tasks that requires path integration. The authors demonstrate that grid cells can either fire in relation to the position relative to task-relevant virtual stimuli or independently based on the distance covered. Their findings convincingly reveal that mice exhibited better performance in the path integration task when grid cell activity was anchored to their position on the virtual track rather than the distance traversed, highlighting the contribution of grid firing to spatial navigation behavior. The work will be of interest to experimental and computational neuroscientists interested in spatial navigation.

eLife Assessment

The authors tested the hypothesis that age-dependent factors in human sera affect the core circadian clock or its outputs in cultured fibroblasts, and they provide compelling evidence that genes involved in the cell cycle and transcription/translation remain rhythmic in both conditions, genes associated with oxidative phosphorylation and Alzheimer's Disease lose rhythmicity in the aged condition, while the expression of cycling genes associated with cholesterol biosynthesis increase in the cells entrained with old serum. Together, the findings suggest that yet to be identified age-dependent blood-borne factors affect circadian rhythms in the periphery. The paper provides fundamental insights and a possible explanation for previous observations showing that circadian gene expression in peripheral tissues tends to dampen or phase-shift with age.

eLife assessment

This study provides important new insights into the structural diversity of effectors – proteins secreted by pathogens and symbionts into host cells – from the plant-associated fungus Fusarium oxysporum f. sp. lycopersici. The study provides a convincing approach to elucidate how effectors navigate their host environment by exploiting both computational and experimental approaches to understand how their structure influences binding partners. The work will be of interest to those studying molecular host-microbe interactions and disease protection.

eLife assessment

The study presents valuable findings on how the hypoxia response pathway senses and responds to changes in the homeostasis of the amino acid cysteine and other sulfur-containing molecules. By providing a compelling, rigorous genetic analysis of the pathway, the study adds to a growing body of literature showing that prolyl hydroxylation is not the only mechanism by which the hypoxia response pathway can act. Although the paper does not reveal new biochemical insight into the mechanism, it opens up new areas of investigation that will be of interest to cell biologists and biomedical researchers studying the many pathologies involving hypoxia and/or cysteine metabolism.

eLife assessment

By developing a novel method for detecting genetic variants associated with germline mutation spectrum variation, this important study identifies a new "mutator" locus in a population of inbred mouse strains, although the causal gene(s) and allele(s) within this locus remain uncertain. The authors further demonstrate that this new mutator locus interacts epistatically with a previously identified mutator allele on C>A mutation rate, showcasing the complexity of the genetic basis underlying variation in mutation rate and spectrum. Evidence for major findings in this paper is convincing, and the new method has the potential to be applicable to a variety of experimental systems and natural populations.

eLife assessment

This study explores the activation mechanisms of members of the kinesin-3 family, demonstrating common and unique regulation modes with solid evidence. The findings make for valuable contributions to the field of kinesin activation and regulation.

eLife assessment

In this useful study, a solid machine learning approach based on a broad set of systems to predict the R2 relaxation rates of residues in intrinsically disordered proteins (IDPs) is described. The ability to predict the patterns of R2 will be helpful to guide experimental studies of IDPs. A potential weakness is that the predicted R2 values may include both fast and slow motions, thus the predictions provide only limited new physical insights into the nature of the underlying protein dynamics, such as the most relevant timescale.

eLife assessment

This study examines an important aspect of the development of the auditory system, the role of guanine nucleotide-binding protein subunits, GNAIs, in stereociliary bundle formation and orientation, by examining bundle phenotypes in multiple compound GNAI mutants. The experiments are highly rigorous and thorough and include detailed quantifications of bundle morphologies and changes. The depth and care of the study are impressive, with convincing results regarding the roles of GNAIs in stereociliary bundle development. Further, the reviewers believe this to be the definitive study of the role of GNAIs in bundle orientation and development.

eLife Assessment

This important study presents a methodologically rigorous framework for stability-guided fine-mapping, extending PICS and generalizing to methods such as SuSiE, supported by comprehensive simulations and functional enrichment analyses. The evidence is now convincing, demonstrating improved causal variant recovery and offering a robust alternative for cross-population fine-mapping. The approach will be of particular interest to statistical geneticists, computational biologists, and biomedical researchers who rely on fine-mapping to interpret genetic association signals.

eLife assessment

This study presents valuable findings on the symptoms and disease trajectories preceding a diagnosis of pancreatic cancer in Denmark. The evidence supporting the claims of the authors is solid, although an error analysis of the text mining evaluation results and a discussion on how the findings can be applied in practice would strengthen the study. The work will be of interest to public health researchers and clinicians working on pancreatic cancer.

eLife assessment

This article is of broad interest to public health researchers and to health policymakers in populations with national screening programs. It provides important knowledge on the impact of the COVID-19 pandemic on participation in mammography screening in Denmark by socio-economic indicators. The study provides convincing evidence for how the pandemic exacerbated disparities in breast cancer screening in Denmark.

eLife assessment

In this valuable report, the authors explore the connection between mTORC signaling and APA regulated by the CFIm complex. Using a combination of genetic and functional genomics approaches, the study reveals that a twin UGUA motif is a potent cis acting regulation of PAS usage that is recognized by CFIm. Overall, the evidence in general is convincing and supports the conclusions and provides the field with additional mechanistic insight of how signaling connects to APA regulatory machinery.