Evaluated articles

eLife assessment

This valuable study presents the development of a single turnover stopped-flow fluorescence experiment to study the kinetics of substrate unfolding and translocation by the bacterial ClpB disaggregase. Using non-physiological nucleotides to bypass the physiological regulation mechanism of ClpB, the authors convincingly show that the ClpB disaggregase is a processive motor with a slow unfolding step preceding rapid translocation. The results of this analysis are of value for future mechanistic studies on energy-dependent unfolding, degradation, and disaggregation molecular machines.

eLife assessment

This study explores simple machine learning frameworks to distinguish between interacting and non-interacting protein pairs, offering solid computational results despite some concerns about dataset generation. The authors demonstrate a modest improvement in AlphaFold-multimers' ability to differentiate these pairs. Using a simple yet sound approach, this work is a valuable contribution to the challenging problem of reconstructing protein-protein interaction networks.

eLife Assessment

This study provides important insights into how the EBH domain of microtubule end-binding protein 1 (EB1) interacts with SxIP peptides derived from the MACF plus-end tracking protein. The revised manuscript includes convincing ITC and NMR experiments that clarify the role of flanking residues and address the influence of dimerization and cooperativity on binding. While some mechanistic aspects remain difficult to resolve experimentally, the data and analysis now more clearly justify the proposed "dock-and-lock" model and its interpretive value. This work will be of interest to structural biologists and biophysicists studying microtubule-associated protein interactions.

eLife assessment

Notario Manzano et al. offer a valuable first analysis of proteins within tunneling nanotubes (TNTs), membranous bridges connecting cells. This work distinguishes TNTs from extracellular vesicles, but further experimental and analytical tools are needed to refine the TNT proteome. Solid data supports a role for tetraspanins CD9 and CD81 in TNT function. The proposed model for CD9 and CD81 is over-interpreted and requires additional evidence for stronger support.

eLife Assessment

This important study reveals that the nucleolar protein Treacle undergoes liquid-liquid phase separation in vitro and in vivo. It provides convincing evidence that the ability of Treacle to form phase-separated condensates is necessary for the proper formation of the fibrillar center of the nucleolus, rRNA transcription, and rDNA repair. These findings will be of interest to the communities studying biomolecular condensates, nucleolar organization, and ribosome biogenesis.

eLife assessment

This paper presents useful findings on the dysmyelination phenotype of nervous system-specific Spns1 (a lysosomal lipid transporter) knockout mice. While the analysis of the phenotype is solid, the evidence for the underlying mechanisms, especially the molecular function for SPNS1, is incomplete. With more careful interpretation and/or additional experimental data, this work could have implications for understanding lipid transport and lysosomal storage diseases.

eLife Assessment

This fundamental work provides novel insights into the blood flow-dependent mechanisms of neuronal migration and the role of Gherlin signaling in the adult brain. The authors present convincing evidence that newborn rostral migratory stream (RMS) neurons are closely situated alongside blood vessels, preferentially along arterioles, and that migratory speed is correlated with blood flow. They also provide evidence (in vitro and some in vivo) that Ghrelin from blood is involved in augmenting RMS neuron migration speed.

eLife Assessment

Floeder and colleagues provide an important investigation that describes the experimental conditions that systematically produce "ramps" in dopamine signaling in the striatum. This somewhat nebulous feature of dopamine has been a significant part of recent theoretical and computational debates attempting to formally describe the different timescales on which dopamine functions. The current results are convincing and add context to that ongoing work.

eLife Assessment

This short manuscript uses mutation counts in phylogenies of millions of SARS-CoV-2 genomes to show that mutation rates systematically differ between regions that are paired or unpaired in the predicted RNA secondary structure of the viral genome. Such an effect of pairing state is not unexpected, but its systematic demonstration using millions of viral genomes is valuable and convincing.

eLife Assessment

This provocative manuscript presents important comparisons of the morphologies of Archaean bacterial microfossils to those of microbes transformed under environmental conditions that mimic those present on Earth during the same Eon. The evidence in support of the conclusions is solid. The authors' environmental condition selection for their experiment is justified.

eLife assessment

This report details the creation and wide-scale utilization of "Repix", a new technique for chronic neurophysiological recordings using and re-using Neuropixels probes in freely behaving mice and rats. The authors include data and feedback from a variety of labs and researchers who have used this technique, setting an example for open science and reproducibility, and providing convincing evidence that this approach can be employed for chronic Neuropixels recordings. However, evidence is currently incomplete for claims about the advantages of this design over previous approaches and for cell yield and stability claims. This important work will have an impact on a broad range of neuroscientists seeking a straightforward methodology for chronic Neuropixels recordings and will facilitate ethologically relevant experimental designs.

eLife Assessment

This study presents the cryo-EM structures of two human biotin-dependent mitochondria carboxylases involved in various biological pathways, including the metabolism of certain amino acids, cholesterol, and odd chain fatty acids. The cryo-EM structures offer a valuable addition to the structural description of biotin-dependent carboxylases and provide solid evidence to support the major conclusions of this study. This paper would be of interest to biochemists and structural biologists working on biotin-dependent carboxylases.

eLife Assessment

With compelling electrophysiological and behavioural evidence, this work establishes that the activity of insulin-producing cells (IPCs) depends on the nutritional state in Drosophila and that, like in mammals, there is also an incretin-like effect with IPCs responding to glucose feeding but not to glucose perfusion. Moreover, the authors demonstrate that DH44 neurons respond to glucose perfusion and, together with IPCs, modulate locomotor activity. This important study on the neuronal regulation of metabolic homeostasis will be of interest to both neuroscience and to medical research in diabetes.

eLife assessment

This study presents an important contribution to cardiac arrhythmia research by demonstrating long noncoding RNA Dachshund homolog 1 (lncDACH1) tunes sodium channel functional expression and affects cardiac action potential conduction and rhythms. The evidence supporting the major claims are convincing. The work will be of broad interest to cell biologists and cardiac electrophysiologists.

eLife Assessment

This important paper addresses the role of fluid flows in nutrient uptake by microorganisms propelled by the action of cilia or flagella. Using a range of mathematical models for the flows created by such appendages, the authors provide convincing evidence that the two strategies of swimming and sessile motion can be competitive. These results will have significant implications for our understanding of the evolution of multicellularity in its various forms.

eLife Assessment

This is an important study showing that age-related gut microbiota modulate uric acid metabolism through the NLRP3 inflammasome pathway and thereby regulate susceptibility to age-related gout. Several experimental approaches (mechanistic insights) and methods (data quality) remain incomplete. This paper should be of interest to researchers working on gout and microbiota.

eLife Assessment

This study reports valuable insights into the interactome of the RNA-binding protein SERBP1 and possible links through PARylation to diverse processes, including splicing, cell division, and ribosome biogenesis. The diversity of processes SERBP1 may regulate means this work would be of very broad interest to the cell biology community. The proteomics data are solid, but the functional connection to downstream processes and the link to Alzheimer's disease, while compelling, still require further examination. These latter data currently rely on a very limited set of experiments and patient samples with questionable quality of preservation and methodology.

eLife Assessment

In this valuable study, Tutak and colleagues set out to identify factors that mediate Repeat Associated Non-AUG (RAN) translation of CGG repeats in the FMR1 mRNA which are implicated in toxic protein accumulation that underpins ensuing neurological pathologies. The authors provide solid evidence that RPS26 may be implicated in mediating the RAN translation of FMR1 mRNA. This article should be of broad interest to researchers in the variety of disciplines including post-transcriptional regulation of gene expression and neurobiology.

eLife assessment

Chang et al. have investigated the catalytic mechanism of I-PpoI nuclease, a one-metal-ion dependent nuclease, by time-resolved X-ray crystallography using soaking of crystals with metal ions under different pH conditions. This convincing study revealed that I-PpoI catalyzes the reaction process through a single divalent cation. The study uncovers important details of the roles of the metal ion and the active site histidine in catalysis.