Evaluated articles

eLife assessment

This valuable study combines in vitro and in vivo experiments designed to test if a deoxycytidine kinase inhibitor provides therapeutic benefit during infection with Staphylococcus aureus. The authors provide compelling evidence that this putative host-directed therapy has good potential to promote natural clearance of infection without targeting the bacterium. This paper would be of interest to bacteriologists, immunologists, and those studying host-microbe interactions.

eLife assessment

This important study advances our understanding of how landscape context affects the relationship between grassland plant diversity and biomass. This study used very well-designed approaches to analyze complex ecological relationships in real-world landscapes and thus provides compelling evidence to support its findings. The work will be of interest to landscape ecologists and community ecologists.

eLife assessment

This manuscript examines shared and divergent mechanisms of disruptions of five different mTOR pathway genes on embryonic mouse brain neuronal development. The significance of the manuscript is important, because it bridges several different genetic causes of focal malformations of cortical development. The strength of evidence is compelling, relying on both gain and loss of function, demonstrating differential impact on excitatory synaptic activity, conferring gene-specific mechanisms of hyperexcitability. The results have both theoretical and practical implications for the field of developmental neurobiology and clinical epilepsy.

eLife assessment

This paper presents an important discovery of the molecular basis of differential apterous expression during early Drosophila wing disc development. The evidence supporting these conclusions is compelling, ranging from classical genetic approaches to state-of-the-art genetic engineering techniques. By opening new questions, this paper is expected to be of broad interest to developmental biologists and geneticists working on transcriptional regulation.

eLife assessment

This study defines the roles for two different missense mutations observed in patients in the Trabid/ZRANB1 gene associated in children with a range of congenital disorders including reduced brain size. The study is important because the findings have theoretical or practical implications beyond a single subfield, as the study of DUB and cytoskeletal alterations have implications for neurodevelopment broadly. The methods are convincing as they utilize appropriate and validated methodology in line with current state-of-the-art by incorporating knock-in mice of the patient mutations. Many of the reviewer comments were focused on potential next experiments, rather than on evaluation of the data at hand, and the authors have considered these as future studies. The work as presented suggests critical roles for Trabid in the STRIPAK complex mediating APC deubiquitylation.

eLife assessment

This work reports a valuable finding on glucocorticoid signaling in male and female germ cells in mice, pointing out sexual dimorphism in transcriptomic responsiveness. The convincing evidence provided supports an inert GR signaling despite the presence of GR in the female germline and GR-mediated alternative splicing in response to dexamethasone treatment in the male germline. The work may interest basic researchers and physician-scientists working on reproduction and stress-related disease conditions.

eLife assessment

This study provides valuable insight into the role of miR-199a/b-5p in cartilage formation. The evidence supporting the significance of the identified miRNA and its target mRNA transcripts is convincing. This paper will likely primarily benefit scientists focused on diseases related to this biological process, such as osteoarthritis. Furthermore, researchers with a broader interest in miRNAs may find the computational model to identify novel RNA-RNA interactions particularly helpful.

eLife assessment

This is a valuable study that develops a new model of the way muscle responds to perturbations, synthesizing models of how it responds to small and large perturbations, both of which are used to predict how muscles function for stability but also how they can be injured, and which tend to be predicted poorly by classic Hill-type models. The evidence presented to support the model is solid, since it outperforms Hill-type models in a variety of conditions. Although the combination of phenomenological and mechanistic aspects of the model may sometimes make it challenging to interpret the output, the work will be of interest to those developing realistic models of the stability and control of movement in humans or other animals.

eLife assessment

This study provides useful insights into the subcellular localization, interaction with integrins, and functional importance of the cell surface receptor Piezo1 in migrating human T-cells. Whether Piezo1 is critically sensing mechano-physical cues during T-cell migration is however not well supported by direct experimental evidence. The data collected is solid otherwise.

eLife assessment

Guan and colleagues present solid arguments to address the question of how a single neural stem cell produces a defined number of progeny, and what influences its decommissioning. The focus of the experiments are two well-studied RNA-binding proteins: Imp and Syp. This is valuable work that will be of interest to the scientific community.

eLife assessment

This important study demonstrates that disrupting a common protein-folding system restores sensitivity to antibiotics in drug-resistant clinical bacterial pathogens. Although some additional controls would be welcome, the work is overall convincing in showing that targeting protein folding can be used to combat multi-drug resistant pathogens, both by potentiating the efficacy of existing drugs and by therapeutic use of small-molecule inhibitors. This study is significant and timely as it furnishes a new strategy that is relevant to microbiologists and clinicians interested in combating antimicrobial resistance.

eLife assessment

This important study by Lu et al aimed to determine the key factors of T cell responses associated with durable antibody responses following the initial two shots of COVID-19 mRNA vaccinations. By comparing the SARS-CoV-2 spike protein (S)-specific T cell subsets between "Ab sustainers" and "Ab decliners" that were present post-vaccination, the authors concluded that S-specific CD4+ T cells in "Ab sustainers" were enriched with Tfh cells. There is solid evidence as the authors applied multiple methods and approaches to address the key questions, and the presented data are robust.

eLife assessment

This fundamental work quantifies the stochastic dynamics of neural population activity in the lateral intraparietal area (LIP) of the macaque monkey brain during single perceptual decisions. These single-trial dynamics have been subject to intense debate in neuroscience, and they have significant implications for modelling decision-making in various fields including neuroscience and psychology. Through a combination of state-of-the-art recordings from many LIP neurons and theory-driven data analyses, the authors provide convincing evidence for the notion that single-trial neural population dynamics in LIP encode the decision variable postulated by the drift-diffusion model of decision-making.

eLife assessment

This study combines molecular genetics and target validation to discover genes involved in obesity and determine their role. It was unanimously agreed that the work is important in terms of significance as it has conceptual and practical implications beyond metabolism, including embryonic and placental development. The strength of evidence is convincing from the use of their forward genetic screen in mice.

eLife assessment

This manuscript is an important advance in the study of Histone H1s, finding distinct distributions of various H1 variants in the genome. The controls presented by the authors provide convincing evidence to demonstrate a heterogenous distribution of H1 which might reflect functional regulation of chromatin accessibility by linker histones. This work will be of interest to the genome organization field, and could additionally provide a framework for understanding H1 mis-regulation observed in cancer cells.

eLife assessment

The present paper describes an important methodological development that combines light (confocal) microscopy with scanning and transmission EM and EM tomography. The method expands the level of structural detail accessible to large-volume EM studies and thus represents an approach to integrate analyses of cellular and sub-cellular structures in biological samples. The study, which provides a compelling proof-of-principle, will be of particular value to cell biologists interested in the in-depth interpretation of high-resolution ultrastructural information from sparsely distributed targets - at multiple scales and in diverse biological structures.

eLife assessment

This fundamental work substantially advances our structural understanding of S-layers in Archaea and how they are built to form formidable cell support structures able to stabilise the cytoplasmic membrane under harsh physicochemical conditions. The supporting evidence for the S-layer model is convincing, making excellent use of state-of-the-art 3D cryo-electron tomography reconstructions, although the proposed S-layer model would benefit from some additional validation.

eLife assessment

This manuscript reports important findings in the field of developmental neurobiology, particularly in our understanding of human cortical development. The methods, data, and analyses are solid yet, the lack of clonal resolution or timelapse imaging makes it hard to assess whether the inheritance of centrosomes occurs as the authors claim.

eLife assessment

This study transcriptomically profiles the developing zebrafish hindbrain from gastrulation through stages of rhombomere formation. The strength is that the transcriptomic data will be a valuable resource to the field. The paper would profit from a deeper analysis of functional aspects of hindbrain development during its segmentation into rhombomeres.

eLife assessment

This manuscript posits a novel role for the anterior cingulate cortex (ACC) in coding for sequential action strategies and the prevalence of each strategy. These findings provide important insight into ACC function and will therefore be of broad interest within the field of cognitive neuroscience. The evidence supporting the primary hypothesis is currently incomplete but could be rendered convincing with some further effort to rule out potential confounding factors.