Evaluated articles

eLife Assessment

This valuable study provides convincing evidence that mutant hair cells with abnormal, reversed polarity of their hair bundles in mouse otolith organs retain wild-type localization, mechanoelectrical transduction and firing properties of their afferent innervation, leading to mild behavioral dysfunction. It thus demonstrates that the bimodal pattern of afferent nerve projections in this organ is not causally related to the bimodal distribution of hair-bundle orientations, as also confirmed in the zebrafish lateral line. The work will be of interest to scientists interested in the development and function of the vestibular system as well as in planar-cell polarity.

eLife Assessment

This valuable study is a detailed investigation of how chromatin structure influences replication origin function in yeast ribosomal DNA, with a focus on the role of the histone deacetylase Sir2 and the chromatin remodeler Fun30. The paper shows that Sir2 does not affect origin licensing but rather affects local transcription and nucleosome positioning which correlates with increased origin firing. Overall, the evidence is convincing and the model is plausible.

eLife Assessment

This valuable study presents the design of a new device for using high-density electrophysiological probes ('Neuropixels') in freely moving rodents. The evidence demonstrating the system's versatility and ability to record high-quality extracellular data in both mice and rats is compelling. This study will be of significant interest to neuroscientists performing chronic electrophysiological recordings.

eLife Assessment

This article describes a novel mechanism allows Drosophila to combat enteric pathogens while also preserving the beneficial indigenous microbiota. The authors provide compelling evidence that oral infection of Drosophila larvae by pathogenic bacteria activate a valve that traps the intruders in the anterior midgut, allowing them to be killed by antimicrobial peptides. This is an important finding revealing a new mechanism of host defense in the gut of insects.

eLife Assessment

This study represents valuable findings on the asymmetric connectivity pattern of two different types of CA3 pyramidal cell types showing that while athorny cells receive strong inputs from all other cell types, thorny cells receive weaker inputs from athorny neurons. Computational modeling is used to evaluate the impact of this connectivity scheme on the sequential activation of different cell types during sharp wave ripples. The evidence combining experimental and computational modelling approaches convincingly supports the authors' claims regarding the network mechanisms underlying the temporal sequences of neuronal activity during sharp-waves.

eLife Assessment

This computational modeling study builds on multiple previous lines of experimental and theoretical research to investigate how a single neuron can solve a nonlinear pattern classification task. The revised manuscript presents convincing evidence that the location of synapses on dendritic branches, as well as synaptic plasticity of excitatory and inhibitory synapses, influences the ability of a neuron to discriminate combinations of sensory stimuli. The ideas in this work are very interesting, presenting an important direction in the computational neuroscience field about how to harness the computational power of "active dendrites" for solving learning tasks.

eLife Assessment

The paper reports the important discovery that the mouse dorsal inferior colliculus, an auditory midbrain area, encodes sound location. The evidence supporting the claims is solid, being supported by both optical and electrophysiological recordings. The observations described should be of interest to auditory researchers studying the neural mechanisms of sound localization and the role of noise correlations in population coding.

eLife Assessment

This manuscript presents important finding regarding the regulation of a key stem cell population, namely muscle stem cells (or "satellite cells"). The evidence presented is convincing that Scx, a marker for tendon, is expressed in some myogenic cells and is essential for adult muscle regeneration.

eLife Assessment

This work identifies the molecular function of an orphan human transporter, SLC35G1, providing convincing evidence that this protein is involved in intestinal citrate absorption. This work provides important insight into transporter function and human physiology.

eLife assessment

This manuscript provides an important advance in our understanding of the molecular events that promote osteoclast fusion. Compelling data support the conclusion that an oxidized form of the ubiquitous protein La promotes osteoclast fusion following enrichment at the cell surface of osteoclast progenitors. These data improve our understanding of the processes that regulate bone resorption and will be of broad interest to researchers in the fields of cell biology and musculoskeletal physiology.

eLife assessment

This study reports that the timing of 'brain-to-gut' signaling influences the lifespan of the C. elegans model. The main finding, that modulating the same neurotransmitter, Acetylcholine, at different ages elicits lifespan shortening - or extending - effects utilizing different receptors, is important and of broad interest to the longevity field as recognized by all the reviewers. The data is largely consistent with the authors' model, but the strength of the evidence is incomplete. The study requires several rigorous experiments detailed by the reviewers to substantiate the main conclusions.

eLife Assessment

This study provides valuable scRNA-seq and scATAC-seq data for testicular tissues from patients with spermatogenesis disorders. By examining the transcriptomic and epigenetic changes in Sertoli cells, the authors uncovered key regulatory mechanisms underlying male infertility and identified potential therapeutic targets. While some of the cellular profiling results are convincing, the analyses for differential profiling of NOA cases and epigenomics data remain incomplete.

eLife assessment

The authors study how cells with lower levels of the conserved steroid hormone signaling component Taiman (tai) are out-competed by neighboring wild-type cells with higher fitness in Drosophila imaginal discs. The findings are useful since they uncover an unexpected link between tai and Wingless signaling in cell competition. The evidence however is incomplete, since the tai loss-of-clone phenotype is based on one allele and the mechanism involved in cell competition through Dlp and Wg lacks adequate supporting data.

eLife Assessment

This manuscript reports valuable findings on the role of the Srs2 protein in turning off the DNA damage signaling response initiated by Mec1 (human ATR) kinase. The data provide convincing evidence that Srs2 interaction with PCNA and ensuing SUMO modification is required for checkpoint downregulation. However, while the model that Srs2 acts at gaps after camptothecin-induced DNA damage is reasonable, direct experimental evidence for this is currently lacking. The work will be of interest to cell biologists studying genome integrity.

eLife Assessment

This study reports valuable findings that highlight the importance of data quality and data representation for ligand-based virtual screening experiments. The authors' claims are supported by solid evidence, although the conclusions have been inferred from only two datasets. The work would gain much impact if additional datasets were used. The main findings will be of interest to cheminformaticians and medicinal chemists working in QSAR modeling, and possibly in other areas related to machine learning.

eLife Assessment

Graca et al. reports a fundamental missing link in the ethanol metabolism of mycobacteria and illuminates the role of a flavoprotein dehydrogenase that acts as an electron shuttle between an uncommon redox cofactor and the electron transport chain. Overall, the data presented are compelling, supported by a range of well designed and meticulous experiments. The findings will be of broad interest to researchers investigating bacterial metabolism.

eLife assessment

This important study employs an innovative genetic selection-based approach to identify short peptide sequences that target bacterial proteins for degradation. Using random mutagenesis they identified 5 amino acid long "degrons" that target the toxin VapC for degradation permitting survival. They provide compelling data that degrons ending in Ala-Ala are selectively recognized by the ClpXP protease and identify the sequence FKLVA as a particularly significant target. As a whole, there is enthusiasm about the author's findings, although there are also some improvements that could be made to increase the clarity and impact, mostly in the form of revisions to the text.

eLife Assessment

This is a valuable study on the diffusion rates of drug molecules in human-derived cells, presenting convincing data indicating that their diffusion behavior depends on their charged state. It proposes that blocking drug protonation enhances diffusion and fractional recovery, suggesting improved intracellular availability of weakly basic drugs. The findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.

eLife assessment

The manuscript makes an important contribution to antimalarial drug discovery, utilizing diverse systems biology methodologies. It focuses on an improved M1 metalloprotease inhibitor and provides compelling evidence for the utility of chemoproteomics in pinpointing PfA-M1 targeting. Additionally, metabolomic analysis reveals specific alterations in the final steps of hemoglobin breakdown. These findings highlight the potential of the developed methodology not only for PfA-M1 targeting but also for other inhibitors targeting various malarial proteins or pathways.