Evaluated articles

eLife Assessment

This important study allows for a better understanding of anthelmintic drug resistance in nematodes. The authors provide a detailed analysis of the role of UBR-1 and its underlying mechanism in ivermectin resistance using convincing behavioural and genetic experiments with C. elegans. Although the authors have addressed the concerns of the reviewers, it would be prudent for the authors to disclose the Dyf phenotype in ubr-1 mutants. The authors should at the very least report the Dyf phenotype and the experiment on which they base the argument that the Dyf phenotype does not affect their conclusions.

eLife Assessment

This useful study uses brain stimulation and electroencephalography to study speech-gesture integration. It investigates the role of frontotemporal regions in integrating linguistic and extra-linguistic information during communication, focusing on the inferior frontal gyrus and posterior middle temporal gyrus. Reliance on activation patterns of tightly-coupled brain regions over short timescales leads to incomplete support for the study's conclusions due to conceptual and methodological limitations.

eLife Assessment

This important study describes a first-in-human trial of autologous p63+ stem cells in patients with idiopathic pulmonary fibrosis, a lethal condition for which effective treatments are lacking. The authors provide convincing evidence that P63+ progenitor cell therapy can be safely delivered in patients with ILD, warranting movement to a Phase 2. However, given that this is a Phase 1 study with a small sample size, conclusions regarding efficacy should not yet be made.

eLife Assessment

This study addresses fundamental questions surrounding otitis media effusion in Down syndrome, identifying DYRK1A as a key gene involved in the condition. The findings are compelling, highlighting DYRK1A as a promising therapeutic target for addressing hearing loss in patients with Down syndrome.

eLife Assessment

This valuable study presents an interesting analysis of the role of the polyamine precursor putrescine in the pili-dependent surface motility of a laboratory strain of Escherichia coli. The overall data convincingly demonstrate a role in this case. This study presents interesting findings for those studying uropathogenic bacteria, and those studying bacterial polyamine function.

eLife Assessment

This useful study reports detailed molecular dynamics (MD) simulations of T-cell receptors (TCRs) in complex with a peptide/MHC complex, for a better understanding of the mechanism of T-cell activation. The MD simulations provide solid evidence supporting that different TCRs can respond mechanically in different ways upon binding to the same pMHC complex. The analyses are systematic and provide testable predictions that can be evaluated by future mutagenesis and force microscopy studies.

eLife Assessment

This valuable manuscript describes ATP5I, a subunit of F1Fo-ATP synthase, as a key target of medicinal biguanides. The knockout of ATP5I in pancreatic cancer cells mimics biguanide treatment, inducing a metabolic switch from OXPHOS to glycolysis due to a compromised expression of the Complex I protein NDUFB8. This results in a markedly decreased NAD/NADH ratio and decreased cell proliferation. These solid findings point out ATP5I as a promising mitochondrial target for cancer therapies and contribute to our understanding of metformin's mechanism of action since many of its molecular mechanisms remain poorly understood.

eLife Assessment

This manuscript describes an important study of the giant virus Jyvaskylavirus. The characterisation presented is compelling. The work will be of interest to virologists working on giant viruses as well as those working with other members of the PRD1/Adenoviridae lineage.

eLife Assessment

The study presents valuable findings on the role of Aff3ir, a gene implicated in flow-induced atherosclerosis and regulating the inflammation-associated transcription factor, IRF5. The in vivo data are solid in providing evidence on the role of Aff3ir in shear stress and formation of atheromatous plaques. The work will be of interest to clinical researchers and biologists focusing on inflammation and atherosclerosis in cardiovascular disease with a broad eLife readership.

eLife Assessment

This paper reports new data on the structure of the human CTF18-RFC clamp loader complex bound to the PCNA clamp. The new and convincing data complement previous reports of CTF-RFC-PCNA structures and as such, represents an important contribution.

eLife Assessment

In their important manuscript, Chen et al. investigate the phospho-regulation of the C. elegans kinesin-2 motor protein OSM-3, revealing that the kinase, NEKL-3, phosphorylates a serine/threonine patch at the hinge region of the motor to mediate autoinhibition until it reaches the ciliary middle segment. The findings are supported by robust genetic data, in vivo imaging, and motility assays with wild-type and mutant motors. Overall, the study provides a compelling contribution to understanding the regulation of OSM-3 kinesin activity both on the molecular and cellular levels.

eLife Assessment

This important study demonstrates that screening by artificial intelligence can identify relevant novel compounds for interacting with KATP channels. The experimental work is compelling. The broader significance of this work relates to the possibility that KATP channel mutations linked to congenital hyperinsulinism may be effectively rescued to the cell surface with a drug, which could normalize insulin secretion or enhance the effectiveness of existing KATP channel activators such as diazoxide.

eLife Assessment

This study provides an important set of analyses and theoretical derivations to understand the mechanisms used by recurrent neural networks (RNNs) to perform context-dependent accumulation of evidence. The results regarding the dimensionality and neural dynamical signatures of RNNs are convincing and provide new avenues to study the mechanisms underlying context-dependent computations. This manuscript will be of interest to a broad audience in systems and computational neuroscience.

eLife Assessment

This study presents DeepTX, a valuable methodological tool that integrates mechanistic stochastic models with single-cell RNA sequencing data to infer transcriptional burst kinetics at genome scale. The approach is broadly applicable and of interest to subfields such as systems biology, bioinformatics, and gene regulation. The evidence supporting the findings is solid, with appropriate validation on synthetic data and thoughtful discussion of limitations related to identifiability and model assumptions.

eLife Assessment

This is an important study that provides compelling data from a diverse set of approaches from single cell transcriptome data and network analysis from genetically diverse mouse cells to identify novel driver genes underlying human GWAS associations. The authors present evidence that network analysis of scRNA-seq data from genetically diverse mouse bone-marrow derived stromal cells can be informative for identifying human BMD GWAS driver genes. Their approach should be broadly used and applicable to other GWAS studies.

eLife Assessment

This valuable study combines experiments and theory to investigate the putative role of spontaneous correlated activity in establishing aligned topographic maps of neural activity in higher-order sensory areas, and will be of interest to researchers studying multisensory integration and brain development. However, the evidence presented is incomplete, as there are notable disconnects between the experimental data and the modeling setup, and there are methodological details that are either unclear or missing, limiting the strength of the claims.

eLife Assessment

This study presents an important contribution to the understanding of neural speech tracking, demonstrating how minimal background noise can enhance the neural tracking of the amplitude-onset envelope. The evidence, through a well-designed series of EEG experiments, is convincing. This work will be of interest to auditory scientists, particularly those investigating biological markers of speech processing.

eLife Assessment

This study presents important findings on the role of pyramidal cells driving vasoconstriction in brain arteries through a COX-2/PGE2 pathway, with additional contributions from NPY (interneurons) and 20-HETE (astrocytes). Optogenetic stimulation of cortical pyramidal neurons induces vasoconstriction, potentially leading to oxygen and nutrient undersupply in regions with sustained activation - a mechanism potentially relevant under pathological conditions. The authors provide convincing evidence from brain slice experiments and some in vivo data from anesthetized animals, carefully discussing the strengths and limitations of both approaches.

eLife Assessment

The present study described GEARBOCS, an adeno-associated virus tool for in vivo gene editing in astrocytes, which is both timely and of importance for glial biologists, who often are troubled by efficient gene targeting in astrocytes. Overall, the finding is valuable, and the strength of the evidence is solid. Presumably, there will be great potential associated with GEARBOCS applications in the future.

eLife Assessment

This is an important study that describes the development of optical biosensors for various Rab GTPases and explores the contributions of Rab10 and Rab4 to structural and functional plasticity at hippocampal synapses during glutamate uncaging. The evidence supporting the conclusions of the paper is solid, and several improvements were noted by the reviewers upon revision, although some persisting inconsistencies would benefit from further clarification.