Evaluated articles

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.

eLife assessment

This is an important study of the dimensionality and synchrony of calcium responses in Purkinje cells measured across a large region of the cerebellar cortex over the course of learning. This work has the potential to inform our understanding of the functional organization of the cerebellum and longstanding hypotheses about the role of cerebellar climbing fibers in the induction of learning and in the timing of movement, but the evidence provided for the many sweeping claims is incomplete. The paper would benefit from additional statistical analyses to more rigorously evaluate the central claims, with consideration of appropriate comparison groups and potential confounds.

eLife assessment

This important study uses mathematical modelling to demonstrate that conformational autoinhibition of the RAF kinase is an important feature of its paradoxical activation by pharmacological inhibitors. This part of the theoretical analysis is highly compelling but its extension to the investigation of how the binding of 14-3-3 adaptors additionally contributes to the paradoxical activation phenomenon is incomplete and would benefit from more rigorous experimental validation. With the experimental part addressing 14-3-3-dependent regulation strengthened or the 14-3-3 part completely removed, this paper would be of considerable interest to cell biologists and cancer biologists, ultimately paving the way for improved RAF therapeutics.

eLife assessment

This is a descriptive paper in the field of metascience, which documents levels of accessibility and reproducible research practices in the field of cardiovascular science. As such, it does not make a theoretical contribution, but it argues, first, that there is a problem for this field, and second, it provides a baseline against which the impact of future initiatives to improve reproducibility can be assessed. The study was pre-registered and the methods and data are clearly documented. This kind of study is extremely labour-intensive and represents a great deal of work.

eLife assessment

This study presents important evidence of the impact of the covid pandemic on breast cancer screening globally but with important variations by healthcare setting. The data analysis is comprehensive, using solid systematic review methods. The results will be of interest to public health policymakers and health care and cancer control practitioners and researchers across the globe.

eLife assessment

TP73 is a member of the p53 family of tumor suppressors. The authors provide compelling evidence that a TAp73-alpha to TAp73-gamma switch could be a frequent phenomenon in human cancers and provide novel evidence that TAp73-gamma has oncogenic functions via Leptin. The authors provide a substantial amount of high-quality data and convincingly demonstrate a novel function of this specific isoform of p73 in lipid metabolism and tumorigenesis.

eLife assessment

This is a valuable contribution to the effort to provide genetic access to and characterization of the major classes of interneurons in the mammalian neocortex. The authors develop an improved strategy for intersectionally targeting a fourth (and final) major category of diverse interneurons in the mouse, including the previously studied neurogliaform cells. They provide a detailed characterization of these cells and show convincingly that their genetic strategy can be used to identify and manipulate these cells, both in vitro and in vivo.

eLife assessment

In this important study, the authors present evidence for the novel involvement of a scavenger receptor in tubular morphogenesis. Using a convincing set of data, the authors propose that the Drosophila scavenger receptor Emp (homologous to human CD36 ) couples endocytosis of luminal molecules and regulates tube length via controlling Crumbs and Src. This work will be of broad interest to cell and development biologists as well as cancer biologists.

eLife assessment

This manuscript is important as it showed an establishment of a method for looking a neuronal activity in embryos which can support the previously reported laterality in chick thalamofugal system. However, the evidence the author provided was incomplete as no actual data was provided.

eLife assessment

This important study provides a substantial advance with a method by which a protein target resistant to therapeutic approaches can be uniquely modulated by a cellular protein kinase ferried by nanobodies to a precise molecular site of recruitment. Evidence for this major claim is compelling, but evidence for some of the minor claims seems incomplete. The work will be of broad interest to cell biologists, cardiovascular researchers, and drug developers.

eLife assessment

This important study provides a state-of-the-art framework to explore the coupling of complementary cerebral measures (neural, hemodynamic, and metabolic) during development by providing an interesting roadmap for multimodal neuroimaging in infants. The methodological contribution is compelling with an original setup for simultaneous EEG and NIRS recording and solid data analyses. However, the claims about functional specialization and the role of the temporal-parietal junction in social processing are only partially supported by the results. This work will be of interest to a broad audience of scientists interested in multimodal neuroimaging and cognitive development.