Evaluated articles

eLife assessment

This study presents a valuable finding on the heterogeneity of tumour metabolism using fluorescence lifetime imaging, measured across 4 cell lines, 4 tumour types of in vivo mouse models, and 29 patient samples. The indication is that the level of heterogeneity of cellular metabolism increases with model complexity and demonstrates high heterogeneity at a clinical level. The evidence supporting the claims of the authors is solid, and at the revision stage, the authors have included additional samples from 8 patients in the data pool, which is helpful for the conclusions that the authors are trying to draw. The work will be of interest to medical biologists developing methods for quantifying metabolic heterogeneity.

eLife Assessment

This study provides a valuable description of subtypes of V1 neurons, including birthdates and connections to motor neurons. V1 neurons are one of the main groups of inhibitory neurons in the spinal cord. The methods of data collection and analysis are convincing. This work will interest developmental biologists and neuroscientists working on spinal circuits.

eLife Assessment

This valuable study presents a machine learning model to recommend effective antimicrobial drugs from patients' samples analysed with mass spectrometry. The evidence supporting the claims of the authors is convincing. This work will be of interest to computational biologists, microbiologists, and clinicians.

eLife Assessment

This study presents a valuable finding on how the sensorimotor control system deals with redundancy within our body, based on a novel bimanual task. The evidence supporting the authors' claims is convincing, as demonstrated over four different experiments. The work will be of interest to researchers from the motor control community and related fields, and further investigation into the interpretation of the findings could increase the generalisation of the study to a broader audience.

eLife assessment

This is an important study describing a neuromuscular junction co-culture system using human cells that the authors use to study the synaptic consequences of ALS mutations. The data supporting the system are solid and show the value of using myotubes and motor neurons from the same donor. The study will be of interest to researchers who model neuromuscular junction disorders, however, the authors could more comprehensively compare and contrast their system with previous literature describing other similar models. There are also technical weaknesses that limit the interpretation of specific findings.

eLife Assessment

This fundamental, clearly written, and timely manuscript links the timing of ART with the kinetics of total and intact proviral HIV DNA. The conclusions are interesting and novel, and the importance of the work is high because the focus is on African women and clade C virus, both of which are understudied in the HIV reservoir field. The strength of the evidence is compelling. Overall, this work will be of very high interest to scientists and clinicians in the HIV cure/persistence fields.

eLife Assessment

This study presents valuable findings about daily rhythm changes of the Drosophila melanogaster adult gut metabolome, which is shown to be dependent on the circadian clock genotype, dietary regime and composition, and gut microbiota. The phenomena observed are supported by convincing experimental evidence. The general descriptive approach limits the power of the proposed conclusions. The work will be of interest to a broad range of physiology specialists

eLife Assessment

This valuable study advances our understanding of how Nipah virus fusion protein F (NiV-F) organizes into nanoclusters on cell and viral membranes using biochemical and super-resolution microscopy methods. The conclusions are supported by solid evidence and the revision has addressed most of the reviewers' concerns. The relationship between clustering and fusion is of high interest and an interesting hypothesis to continue investigating in future studies.

eLife Assessment

This valuable study suggests that capsaicin nanoparticle administration in rats activates the transcription factor Nrf2 by directly binding to its repressor, KEAP1, leading to the induction of cytoprotective genes and preventing alcohol-induced gastric damage, offering a potential avenue for treating alcoholism-related gastric disorders. The authors provide solid evidence through a wealth of biochemical experiments in vitro, in cultured cells as well as in a rat model. The work will be of great interest to researchers studying oxidative damage in a variety of different diseases and the exploitation of molecules for therapeutic approaches.

eLife Assessment

This study presents important new insights linking obesity to kidney disease using a Drosophila model. A series of compelling experiments demonstrate that a high-fat diet induces excretion of a leptin-like JAK-STAT ligand from fat body, driving the adipose-nephrocyte axis through activated JAK-STAT signaling and subsequently causing a functional defect in nephrocytes. The approach using combination of genetic tools and pharmacological intervention is solid and confirms the mechanistic link, together with phenotypic analysis that further supports the authors conclusions.

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.