Evaluated articles

eLife assessment

This paper reports a detailed functional analysis of the Rab1 effector Uso1, and it provides a fundamental advance in our understanding of how ER-derived vesicles deliver their cargo. The authors provide compelling evidence that the key function of Uso1 is promoting SNARE complex formation rather than tethering vesicles as generally assumed. These insights will be of interest to cell and structural biologists who study membrane traffic.

eLife assessment

This important study defines signaling mechanisms in tendinopathy development, which is significant as there is a clear need to identify therapeutic targets to prevent or reverse tendon pathology. The evidence supporting the conclusions are compelling combining an existing human tendinopathy transcriptomics dataset with ex-vivo assembloid model, and an in vivo injury model using genetic reporter mice. This work will be of interest to developmental and stem cell biologists.

eLife assessment

This paper describes valuable results from studies investigating circuits in the brain that underlie behavioral responses in fearful situations. The authors identified a role for a class of neurons that are sufficient to cause these stereotyped behaviors including freezing behaviors. These solid studies increase our understanding of brain pathways regulating these types of behaviors.

eLife Assessment

This study presents a valuable finding about the role of Perk (Protein kinase RNA-like endoplasmic reticulum kinase) and Atf4 (Activating Transcription Factor-4) in the integrated neurodegenerative and regenerative responses following the optic nerve injury. The authors present solid evidence, combining newly generated transcriptomic data with publicly available datasets to strengthen their findings. Despite some limitations in data quality and interpretation, the study is likely to be of interest to researchers studying optic neuropathies and axonal regeneration.

eLife assessment

This paper describes an important new marine reptile specimen. A solid ostelogical description of the saurosphargid Prosaurosphargis yingzishanensis, the earliest known member of this group, combined with a large-scale phylogenetic analysis enhances our understanding of the affinities of a wide range of Triassic reptiles. As such the relevance of this paper goes far beyond the immediate importance of this remarkable fossil - it also sheds light on the position of several important Triassic groups, including Testudinata and Archosauromorpha.

eLife assessment

Vocalizations are controlled by neural circuits connecting the amygdala and periaqueductal gray. This study presents valuable measures of the neurons that suppress vocalization in appropriate contexts using a rich variety of behavioural, imaging, optogenetic, and tracing methodologies. The evidence supporting the claims of the authors is solid, although their results only hint at the mechanisms that could underlie the hierarchical control of vocalization. The work will be of interest to neurobiologists working on motor control and vocalization.

eLife assessment

This study presents valuable findings on the risk factors of avascular osteonecrosis in patients with Gaucher disease. The evidence supporting the claims of the authors is convincing. The work will interest clinicians who treat patients with inborn errors of metabolism.

eLife assessment

This study presents valuable findings regarding the functional diversification of flavodoxins from diatoms, a protein initially described as an Fe-sparing substitute for ferredoxin in Fe-poor open ocean environments. The evidence supporting the claims of the authors is solid, although the study could be strengthened by using a wider gradient of oxidative stress in the experiments and using Fe limitation methodology, which allows more certain differentiation between a low Fe and oxidative stress response.

eLife assessment

This valuable study combines population genetic theory and deep learning approaches to estimate the extent of assortative mating and sex bias in modern admixed populations in the Americas. The new approach provides solid evidence for their main conclusions that socially constructed hierarchies have influenced mating behaviors, though certain results would benefit from further consideration. This paper would be of interest to human population geneticists and social scientists, particularly those studying demographic processes.

eLife assessment

This compelling study brings together two earlier observations: that Ca2+ influx can trigger exosome release from multivesicular bodies, and that plasma membrane repair after wounding requires Ca2+ and involves Ca2+-binding annexin proteins. This important work takes these earlier findings in an interesting new direction by showing that exosome release from MVBs is also triggered by Ca2+ influx during plasma membrane wounding and requires the annexin isoform ANX6. The study suggests a few possible mechanisms (such as Ca2+-dependent tethering of MVBs to the plasma membrane by ANX6) and raises the interesting possibility that cell injury and repair may contribute to the release of exosomes into biological fluids.

eLife assessment

This manuscript reports an important finding that spermatogenic defects in Parl KO mice, a genetic model for Leigh syndrome, may result from mitochondrial defects leading to ferroptosis. The finding, if confirmed, would be of great significance because male germ cell ferroptosis has not been well characterized. However, the criteria for determining male germ cell ferroptosis were vague, and the supporting data were inadequate.

eLife assessment

This study presents important findings on the decision-making capacities of honey bees in controlled conditions. The evidence supporting the study is solid, however, the explanation of the methods, importance, and novelty of the study requires further clarification. With a deeper development of the relevance of this study, the reader will have a clear idea of how this study contributes to the field.

eLife assessment

This paper will be of broad interest to immunologists that study T cell responses and formation of the peripheral T cell compartment. Using elegant live imaging approaches, the authors provide convincing evidence in support of a revised model for how positive-selected thymocytes are called to the thymus medulla to interact with distinct antigen-presenting cells. The work makes an important contribution to the field by identifying previously unappreciated complexities related to cellular movement during T cell generation.

eLife assessment

This study presents valuable findings on how gender-neutral vaccination against human papillomavirus can help improve program resilience in the case of vaccination disruptions. The evidence supporting the claims of the authors is convincing, although the results are only applicable to India and other countries with a similar HPV context; researchers can adapt the model for their local context and use it as a starting point for future research.

eLife assessment

This paper reports on the role of RIF1 during early stages of zebrafish embryonic development, with the important finding that Rif1 seems to be required predominantly to establish the correct embryonic transcriptional program first, followed by a switch to a more replication-timing centered later function. The evidence is convincing, with the major strength being the elegant system and the possibility to also address the problem of the maternal pool of Rif1. A weakness is that the study remains descriptive and the presentation slightly disconnected, with limited mechanistic insight. The work will be of interest for researchers both in the transcription and the replication field, especially for scientists investigating the interplay between the two processes.

eLife assessment

This important study reports a novel mechanism linking DHODH inhibition and subsequent pyrimidine nucleotide depletion with upregulation of cell surface MHC I in cancer cells. The in vitro mechanistic data are compelling, with rigorous methodology and validation across multiple cell lines. The authors also provide in vivo evidence for additive effects of DHODH inhibitors and immune checkpoint blockade. However, the in vivo assessments of the functional relevance of this mechanism remain incomplete, requiring additional analyses to fully substantiate the conclusions made.

eLife assessment

Gap junctions, formed from connexins, are important in cell communication, allowing ions and small molecules to move directly between cells. By determining the Cryo EM structure of the structure of connexin 43 in a putative closed state involving lipids, the study makes an important contribution to the development of a mechanistic model for connexin activation. The connexin 43 structure is solid and its presentation will appeal to the channel and membrane protein communities.

eLife assessment

This study presents fundamental new insight into the regulatory apparatus of PI3Kγ, a kinase in signaling pathways that control the immune response and cancer. A suite of biophysical and biochemical approaches provide convincing evidence for new sites of allosteric control over enzyme activity. The rigorous findings provide structure and dynamic information that may be exploited in efforts to control PI3Kγ activity in a therapeutic setting.

eLife assessment

This important study provides an unprecedented overview of the subcellular organization of proliferative blood stage malaria parasites using expansion microscopy. The localization of multiple parasite organelles is comprehensively probed using three-dimensional super-resolution microscopy throughout the entire intraerythrocytic development cycle. This work provides a compelling framework to investigate in future more deeply the unconventional cell biology of malaria-causing parasites.

eLife assessment

This paper reports the development of SCA-seq, a new method derived from PORE-C for simultaneously measuring chromatin accessibility, genome 3D and CpG DNA methylation. Most of the conclusions are supported by convincing data. SCA-seq has the potential to become a useful tool to the scientific communities to interrogate genome structure-function relationships.