Evaluated articles

eLife Assessment

This study offers valuable insights into the conformational dynamics of the nucleic acid recognition lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus. The authors investigate the influence of local dynamics and allosteric regulation on guide RNA binding affinity and DNA cleavage specificity through molecular dynamics simulations, advanced NMR techniques, RNA binding studies, and mutagenesis. While the mutations studied do not lead to significant changes in GeoCas9 cleavage activity, the study provides convincing evidence for the role of allosteric mechanisms and interdomain communication in Cas9 enzymes, and will be of great interest to biochemists and biophysicists exploring these complex systems.

eLife Assessment

In this valuable study, the authors integrate several datasets to describe how the genome interacts with nuclear bodies across distinct cell types and in Lamin A and LBR knockout cells. They provide convincing evidence to support their claims and particularly find that specific genomic regions segregate relative to the equatorial plane of the cell when considering their interaction with various nuclear bodies.

eLife Assessment

This valuable article represents a significant body of work that addresses some novel aspects of the biology of lung cancer, the overall influence of CHIP and its impacts on responses to therapy. While a high clonal hematopoiesis (CHIP) burden was previously linked with an inflammatory phenotype in other disease settings, the authors demonstrate with solid evidence that this is also true for lung cancer. CHIP is complex and more data will be required to substantiate more evidence with regard perhaps to specific mutations in certain situations and how this might influence therapy choices.

eLife Assessment

This study investigates the molecular mechanisms underlying chronic pain-related memory impairment by focusing on S1P/S1PR1 signaling in the dentate gyrus (DG) of the hippocampus. Through behavioral tests (Y-maze and Morris water maze) and RNA-seq analysis, the researchers discovered that S1P/S1PR1 signaling is crucial for determining susceptibility to memory impairment, with decreased S1PR1 expression linked to structural plasticity changes and memory deficits. This work has important significance and a convincing level of evidence, thus offering new insights into the mechanisms underlying chronic pain-related memory impairment.

eLife Assessment

This important study reports findings that Trpγ, a type of transient receptor potential (TRP) channel expressed in Dh44-releasing neuroendocrine cells, mediates starvation-dependent lipid catabolism. Overall, the claims of the authors are supported by solid evidence. The work should be of interest to both basic and medical biologists working on lipid metabolism.

eLife Assessment

Wang et al. presented visual (dot) motion and/or the sound of a walking person and found solid evidence that EEG activity tracks the step rhythm, as well as the gait (2-step cycle) rhythm, with some demonstration that the gait rhythm is tracked superadditively (power for A+V condition is higher than the sum of the A-only and V-only condition). The valuable findings will be of wide interest to those examining biological motion perception and oscillatory processes more broadly.

eLife Assessment

This important work uses an innovative approach to understand similarities between haemodynamic and electrophysiological activity of the human brain, and how the brain might carry out multiple functions concurrently across different brain regions by using multiple timescales. The study provides convincing evidence to indicate that while spatially similar functional brain networks are found in both modalities, there is a tendency for these to occur asynchronously. This work will be of interest to neurophysiological and brain imaging researchers.

eLife assessment

This important study combines prospective cohort, metabolomics and machine learning to identify a panel of nine circulating metabolites that improved the ability in risk prediction of progression from prediabetes to diabetes. The findings are convincing, and using current state-of-the-art methods the data and analyses support the claims. This paper provides insights into the integration of these metabolites into clinical and public health practice.

eLife assessment

This study provides important findings regarding the stability over time of the response properties of neurons in the auditory cortex, including their nonlinear sensitivity to sound context. The data obtained from chronic recordings combined with nonlinear stimulus-response estimation provide convincing evidence that auditory cortical representations are stable over a period of days to weeks. While this study should be of widespread interest to sensory neuroscientists, the paper would be strengthened by a more thorough assessment and discussion of the effects of context and of the stability of the responses, as well as by the inclusion of more information about the location and types of neurons that were sampled.

eLife Assessment

The study investigated the effects of the peptide galanin on brain Ca2+ activity in zebrafish, which provides a useful model organism for whole-brain imaging because of its transparency. They found that galanin has distinct effects on hyperactivity and expression of galanin changes after activity increases. The strength of evidence was incomplete particularly for some of the conclusions regarding the use of convulsants and relevance to epilepsy because of limitations to the methods and interpretations of results.

eLife Assessment

This work introduces an important new method for depleting ribosomal RNA from bacterial single-cell RNA sequencing libraries, demonstrating its applicability for studying heterogeneity in microbial biofilms. The findings provide convincing evidence for a distinct subpopulation of cells at the biofilm base that upregulates PdeI expression. Future studies exploring the functional relationship between PdeI and c-di-GMP levels, along with the roles of co-expressed genes within the same cluster, could further enhance the depth and impact of these conclusions.

eLife Assessment

This important study provides interesting insights into the mechanisms of action of adjuvants. It shows that adjuvants, MPLA and CpG especially, modulate the peptide repertoires presented on the surface of antigen presenting cells, and surprisingly, adjuvant favored the presentation of low-stability peptides rather than high-stability peptides by antigen presenting cells. As a result, the low stability peptide presented in adjuvant groups elicits T cell response effectively. Evidence in support of these conclusions is solid, and this paper would be of interest to vaccinologists and immunologists.

eLife Assessment

This study makes a valuable contribution by elucidating the genetic determinants of growth and fitness across multiple clinical strains of Mycobacterium intracellulare, an understudied non-tuberculous mycobacterium. Using transposon sequencing (Tn-seq), the authors identify a core set of 131 genes essential for bacterial adaptation to hypoxia, providing a convincing foundation for anti-mycobacterial drug discovery.

eLife Assessment

This important study shows the effect of gut dysbiosis on the colonization of mycobacteria in the lung. The data with comprehensive analysis of gene expression profiles in the lung with dysbiotic mice is compelling and goes beyond the current state of the art. However, the mechanistic insight, where the lung epithelial cell line was used, and the experiments with Mtb infection are currently incomplete.

eLife assessment

The manuscript by Carbo et al. reports a novel role for the MltG homolog AgmT in gliding motility in M. xanthus. The authors provide convincing data to demonstrate that AgmT is a cell wall lytic enzyme (likely a lytic transglycosylase), its lytic activity is required for gliding motility, and that its activity is required for proper binding of a component of the motility apparatus to the cell wall. The findings are valuable as they contribute to our understanding of the molecular mechanisms underlying the interaction between gliding motility and the bacterial cell wall.

eLife Assessment

This study provides important insights into how IL-1 cytokines protect cells against SARS-CoV-2 infection. By inducing a non-canonical RhoA/ROCK signaling pathway, IL-1beta inhibits the ability of SARS-CoV-2 infected cells to fuse with uninfected cells and produce syncytia. Convincing evidence underlies the identification of the key signaling components required for this inhibitory phenotype, and suggests that this process may also function to inhibit SARS-CoV-2 infection in vivo.

eLife Assessment

In this valuable study, the authors propose a model wherein the bacterial redox state plays a crucial role in the differentiation of Chlamydia trachomatis into elementary and reticulate bodies. They provide solid evidence to argue that a highly oxidising environment favours the formation of elementary bodies while a reducing condition slows down development. Overall, the study convincingly demonstrates that Chlamydial redox states play a role in differentiation, an observation that may have implications for the study of other bacterial systems.

eLife Assessment

This important study examines the role of TNF in modulating energy metabolism during parasite infection. The authors perform an elegant set of studies, however the evidence supporting the major claims of the manuscript is incomplete, particularly in highlighting a direct role for GLUT1 in monocytes. This work integrates an interesting set of observations that will be of interest to the Plasmodium and pathogenesis communities with an expanded set of experiments.

eLife Assessment

This study offers a valuable assessment of the impact of antibiotics on the human gut microbiota across diverse observational cohorts. The findings presented are convincing, despite the observational design and residual confounding that may still contribute to discrepancies between the cross-sectional and longitudinal data. The work is relevant for researchers and clinicians interested in antimicrobial resistance and the impact of antibiotics on the host.

eLife Assessment

This valuable study reports the link between a disruption in testicular mineral (phosphate) homeostasis, FGF23 expression, and Sertoli cell dysfunction. The data supporting the conclusion are solid. This work will be of interest to biomedical researchers working on testis biology and male infertility. The assessment is based on the editors' critical evaluation of the authors' responses.