Evaluated articles

eLife assessment

In this important study, Baniulyte and Wade provide solid evidence that translation of a short ORF denoted toiL positioned upstream of the topAI-yjhQP operon is responsive to different ribosome-targeting antibiotics, consequently controlling translation of the TopAI toxin as well as Rho-dependent transcription termination. Strengths of the study include combining a genetic screen to identify 23S rRNA mutations that affect topA1 expression and a creative approach to map the different locations of ribosome stalling within toiL induced by different antibiotics, with ribosome profiling and RNA structure probing by SHAPE to examine consequences of different antibiotics on toiL-mediated regulation. The work could be improved by examining the physiological consequences of topAI-yjhQP activation on antibiotic exposure and by resolving discrepancies between the SHAPE data and the translation rate of toiL.

eLife assessment

How secretion is regulated during cell division and how membrane trafficking factors cooperate with the cytoskeleton during cell division remain poorly understood. In this work the authors find potential direct interactions between the polymeric septin cytoskeleton and the exocyst complex, using fission yeast as a model organism. The work provides a valuable body of new information that will be of great interest to the cell biology community. The evidence is strong and rigorous in many places but is incomplete in other respects.

eLife assessment

The study reports an important finding on the role of the global metabolic regulator Crp/cAMP in the formation of antibiotic persister Escherichia coli. The evidence supporting the claims is solid including metabolomic analysis and characterization of many mutant strains. However, batch culture-based methodologies are unreliable for studying the properties of persister cells that comprise only a fraction of the population and therefore leave the work incomplete.

eLife Assessment

This useful study examined the associations of a healthy lifestyle with comprehensive and organ-specific biological ages defined using common blood biomarkers and body measures. Its large sample size, longitudinal design, and robust statistical analysis provide solid support for the findings, which will be of interest to epidemiologists and clinicians.

eLife assessment

This study provides compelling data regarding the molecular characterization of a rare tumor type with few treatment options. This fundamental work significantly advances our mechanistic understanding of solitary fibrous tumours, a critical first step towards targeted precision medicine approaches. The results of this study will be of broad interest to cancer biologists and experimental oncologists.

eLife assessment

This manuscript presents a valuable machine-learning-based approach to the automated detection of urine and fecal deposits by rodents, key ethological behaviors that have traditionally been very poorly studied. The strength of evidence for their claim, however, that the method provides "easy, efficient, and unbiased spatiotemporal analysis of scent marking during behavioral experiments" is incomplete. In particular, there were concerns about the generalizability of the approach, the relatively limited detection capabilities of the method, and a lack of rationale for specific design choices. This manuscript could be of interest to researchers in animal behavior, neuroscience, and automated animal tracking.

eLife Assessment

This important paper introduces a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs), primarily based on single nucleotide variant (SNV) frequencies. A variety of solid approaches indicate that a mutation recurring three or more times is more likely to reflect selection rather than being the consequence of a mutation hotspot. The method is rigorously quantitative, though the requirement for larger datasets to fully identify all CDNs remains a noted limitation. The work will be of broad interest to cancer geneticists and evolutionary biologists.

eLife assessment

Glioblastoma is one of the most aggressive cancers without a cure. Glioblastoma cells are known to have high mitochondrial potential. This useful study demonstrates the critical role of the ribosome-associated quality control (RQC) pathway in regulating mitochondrial membrane potential and glioblastoma growth. Some assays are incomplete; further revision will improve the significance of this study.

eLife assessment

This study provides valuable information about the microbiome and metabolome, and their correlation with acute myocardial infarction. However, the relationship established between these variables is limited to a correlation, and therefore the strength of the evidence is incomplete.

eLife assessment

This study provides valuable insights, addressing the growing threat of multi-drug-resistant (MDR) pathogens by focusing on the enhanced efficacy of colistin when combined with artesunate and EDTA against colistin-resistant Salmonella strains. The evidence is solid, supported by comprehensive microbiological assays, molecular analyses, and in vivo experiments demonstrating the effectiveness of this synergic combination. However, the discussion on the clinical application challenges of this triple combination is incomplete, and it would benefit from addressing the high risk associated with using three potential nephrotoxic agents in vivo.

eLife assessment

This important study by Lee et al. investigates the heterogeneous response of non-growing bacteria to the antimicrobial peptide (AMP) tachyplesin. In this response, a subpopulation of bacteria limits the accumulation of a fluorescent analog of the AMP, avoiding lethal damage. The study provides compelling data showing the differential accumulation of AMP in subpopulations and its correlation with antimicrobial efficacy. However, the evidence for increased efflux as the main survival mechanism remains incomplete.

eLife assessment

This manuscript describes an unexpected role of cellular caspases in cleaving Drp1, a protein involved in mitochondrial fission, in virus-infected cells. Drp1 cleavage augments mitochondrial fission, reinforcing MAVS-dependent type-1 IFN response against multiple viruses. The findings presented in this manuscript are important and the strength of evidence is solid. Additional studies may allow for more robust mechanistic substantiation of the proposed model.

eLife assessment

This study presents valuable findings on how mitochondrial transplantation affects post-cardiac arrest myocardial dysfunction (PAMD). The authors demonstrate that mitochondrial transplantation enhances cardiac function, increases survival rates after the return of spontaneous circulation (ROSC). While the findings are promising, the organization of the paper, along with the analysis and interpretation of the results, are inadequate and need revision.

eLife assessment

Feeding, the circadian rhythm, and the gut microbiota are all intimately linked, motivating new approaches to identify causal relationships while minimizing confounding factors. The authors employ an innovative combination of the stool softener lactulose and a defined 3-member gut microbiota to acutely induce gut bacterial metabolism in mice during the daytime, resulting in changes in the ileal expression of clock genes and altered feeding behavior. Together, this study utilizes solid methods to provide important new insights into the role of gut microbiota in the circadian rhythm, setting the stage for follow-on studies aimed at better understanding the mechanisms responsible.

eLife assessment

This study provides novel insights into COVID-19 immune responses by using the delta of the normalised accessible surface area (DASA) to map IgM responses to the SARS-CoV-2 Membrane protein M1-subtype across multiple European cohorts. The evidence supporting the findings is solid, with thorough validation and comprehensive analysis, although additional clarity on T-independent B cell reactions and the impact of comorbidities would further strengthen the conclusions. The methods and data presented are valuable for advancing diagnostic and prognostic tools for COVID-19, particularly in the context of long COVID.

eLife assessment

This important work identifies a non-autophagic role for ATG5 in lysosomal repair and the trafficking of the glucose transporter GLUT1 to the cell surface, mediated through the retromer complex. The evidence supporting the conclusions is solid.

eLife assessment

This important work substantially advances our understanding of the molecular mechanisms underlying the timing of the initiation of metamorphosis of the Ciona ascidian tadpole larva. Through the combination of gene knockdown experiments and fluorescent molecular reporters the authors provide compelling evidence about a crosstalk between different G protein mediated signalling pathways and are able to place different signalling molecules within a signalling network. The work will be of interest to molecular, developmental and marine biologists and to scientists working on animal metamorphosis.

eLife assessment

This valuable study provides integrated analyses of RNA sequencing and mapping data of the m6A RNA modification in the context of unbalanced genomes, using aneuploid Drosophila as a model, and suggests that the dosage compensation complex and m6A act in a feedback loop. The evidence is incomplete due to technical concerns, as quantitative assessments are being made using non-quantitative methods, and the study would be improved by further functional studies. If strengthened, the study will be of interest to RNA and developmental biologists.

eLife Assessment

The paper will be of broad interest to fungal biologists and fungal immunologists seeking to understand the biosynthesis of the fungal cell wall, in particular of ß-1,6-glucan synthesis and the importance of this so far understudied constituent of the cell wall for cell wall integrity and immune response. The study is of fundamental significance and adds structural clarity to the genetic, and biochemical basis of this difficult-to-analyze carbohydrate. It opens the potential for understanding its role in immune recognition and potentially as a drug target. Overall, the data is compelling, properly controlled and analyzed.