Evaluated articles

eLife Assessment

This important study advances our understanding of the mechanisms controlling lipid flux and ion permeation in the TMEM16 and OSCA/TMEM63 family channels. The study provides compelling new evidence indicating that side chains along the TM4/6 interface play a key role in gating lipid and ion fluxes in these channels. The authors suggest that the transmembrane channel/scramblase family proteins may have originally functioned as scramblases but lost this capacity over evolution.

eLife assessment

This important study builds on a previous publication, demonstrating that T. brucei has a continuous endomembrane system, which probably facilitates high rates of endocytosis. Using a range of cutting-edge approaches, the authors present compelling evidence that an actomyosin system, with the myosin TbMyo1 as an active molecular motor, is localized close to and can associate with the endosomal system in the bloodstream form of Trypanosoma brucei. It shows convincingly that both actin and Myo I play a role in the organization and integrity of the endosomal system: both RNAi-mediated depletion of Myo1, and treatment of the cells with latrunculin A resulted in endomembrane disruption. This work should be of interest to cell biologists and microbiologists working on the cytoskeleton, and unicellular eukaryotes.

eLife assessment

This is a solid study that follows a well-established canvas for variant-to-gene prioritisation using 3D genomics, applying it to activated T cells. The authors go some way in validating the lists of candidate genes, as well as exploring the regulatory architecture of a candidate GWAS locus. Jointly with data from previous studies performing variant-to-gene assignment in activated CD4 T cells (and other immune cells), this work provides a useful additional resource for interpreting autoimmune disease-associated genetic variation.

eLife assessment

This is a useful manuscript describing the competitive binding between Parkin domains to define the importance of dimerization in the mechanism of Parkin regulation and catalytic activity. The evidence supporting the importance of Parkin dimerization for an 'in trans' model of Parkin activity described in this manuscript is solid, but lacks more stringent and biochemical characterization of competitive binding that could provide more direct evidence to support the author's conclusions. This work will be of interest to those focused on defining the molecular mechanisms involved in ubiquitin ligase interactions, PINK-Parkin-mediated mitophagy, and mitochondrial organellar quality control.

eLife Assessment

This study presents an important finding on the molecular mechanism for transduction of environmentally induced polyphenism. The evidence supporting the claims of the author is solid. This paper would be of interest to those studying aphids wing dimorphism.

eLife Assessment

This valuable study contributes to the understanding of phase separation in Dishevelled (DVL) proteins, by investigating the endogenous complexes of DVL2 using ultracentrifugation and contrasting them with DVL1 and DVL3 behaviour and the functional validation of the DVL2 intrinsically disordered regions mediating the protein condensate. The study includes a solid characterisation of several overexpression constructs, including in KO cells. However, investigations of the roles of the described DVL2 regions at the endogenous level remain to be carried out.

eLife Assessment

This valuable study reports the critical role of two cyclin-dependent kinases, CDK8 and CDK19, in spermatogenesis. The data presented are generally supportive of the main conclusion and are considered solid. This work may be of interest to reproductive biologists and physicians working on male fertility.

eLife Assessment

The authors present an important theoretical framework that describes the interplay between liquid-liquid phase separation and protein aggregation within a mean-field model. This work will be of high interest to the biophysics and molecular biology communities, as it will help understand and analyse assembly within biomolecular condensates in cells or in-vitro. Major strengths of this convincing work are the consideration of aggregates with various dimensionality and the possibility for protein gelation.

eLife Assessment

This valuable work presents the latest version of CTFFIND, which is the most popular software for determination of the contrast transfer function (CTF) in cryo-electron microscopy. CTFFIND5 estimates and considers acquisition geometry and sample thickness, which leads to improved CTF determination. The paper describes compelling evidence that CTFFIND5 finds better CTF parameters than previous methods, in particular for tilted samples (e.g. for cryo-electron tomography) or where thickness is an issue (e.g. cellular samples, or electron microscopy at low voltages).

eLife Assessment

This work is of fundamental significance and has an exceptional level of evidence for a new population that protects against obesity-induced hypothalamic inflammation. This topic will attract attention from a broad base of readers, from hypothalamic neuroscientists to immunologists with an interest in metabolism.

eLife Assessment

This paper addresses an important topic (normative trajectory modelling), seeking to provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on a pre-trained population normative model. The evidence provided for the new methods is solid.

eLife Assessment

The manuscript presents valuable findings of bone remodeling under chronic unpredictable mild stress (CUMS). This is an interesting work on mental stress on bone health and osteoporosis, and the authors offer solid evidence of decreased bone mass mediated by miR-335-3p/Fos signaling in osteoclasts that are involved in the induction of bone loss caused by CUMS. This revised version provided new data that improved the quality of the manuscript and addressed the reviewers' concerns.

eLife Assessment

This study provides valuable insights into our understanding of the development of the enteric nervous system. The authors use genetically engineered mice to study the behavior of stem cells in organizing the enteric nervous system and the secreted signals that regulate these cells. The study rests on a degree of incomplete evidence since the characterization of some of the mouse resources is not complete in the current version.

eLife Assessment

This study provides valuable information on a novel gene that regulates meiotic progression in both male and female meiosis. The evidence supporting the conclusions of the authors is solid. This study will be of interest to developmental and reproductive biologists.

eLife assessment

In this small study involving patients with a history of myocardial infarction, Fawaz et al. found no significant contribution of clonal hematopoiesis and mosaic loss of the Y chromosome to the incidence of myocardial infarction and atherosclerosis. Although the evidence provided by the study is incomplete due to its small sample size, the findings are valuable for guiding future larger studies that will further investigate this significant and controversial subject.

eLife Assessment

This study presents useful findings to inform and improve the in vitro differentiation of hematopoietic progenitor cells from human induced pluripotent stem cells. Relying on a well-characterised technical approach, the data analysis is overall solid and reasonably supports the main conclusions.

eLife assessment

This valuable study investigates how a predicted - but not presented - stimulus within a sequence is represented in the brain using time-resolved EEG decoding. The results demonstrate that when the predicted stimulus is omitted, it is still represented at the expected space and time, although at present they provide only incomplete support given some alternative explanations. The findings will have implications for researchers across domains who are interested in learning and perception.

eLife Assessment

This important work presents a consolidated overview of the NeuroML2 open community standard and provides convincing evidence for its central role within a broader software ecosystem for the development of neuronal models that are open, shareable, reproducible, and interoperable. A major strength of the work is the continued development over more than two decades to establish, maintain, and adapt this standard to meet the evolving needs of the field. This work is of broad interest to the sub-cellular, cellular, computational, and systems neuroscience communities undertaking studies involving theory, modeling, and simulation.

eLife assessment

This study presents valuable findings as it shows that sleep rhythm formation and memory capabilities depend on a balanced and rich diet in fly larvae. The evidence supporting the claims of the authors is convincing with rigorous behavioral assays and state-of-the-art genetic manipulations. The work will be of interest to researchers working on sleep and memory.

eLife Assessment

This important work explores the modulation of pain by intense stress. The authors employed a series of cutting-edge techniques and provided convincing evidence suggesting that the dorsal lateral septum-> lateral hypothalamus-> rostral ventromedial medulla circuit is responsible for mediating stress-induced analgesia. This work will be of interest to neuroscientists interested in the neural circuits of behavior, and scientists interested in stress or pain.