Evaluated articles

eLife assessment

This paper investigates how isoform II of transcription factor RUNX2 promotes cell survival and proliferation in oral squamous cell carcinoma cell lines. The authors used gain and loss of function techniques to provide incomplete evidence showing that RUNX2 isoform silencing led to cell death via several mechanisms including ferroptosis that was partially suppressed through RUNX2 regulation of PRDX2 expression. The study provides useful insight into the underlying mechanism by which RUNX2 acts in oral squamous cell carcinoma, but the conclusions of the authors should be revised to acknowledge that ferroptosis is not the only cause of cell death.

eLife assessment

This valuable study, which implicates a specific Wolbachia gene in driving the male-killing phenotype in a moth, contributes to a growing body of literature from the authors in which they have nicely teased apart the loci responsible for male killing across diverse insects. Solid evidence supports the conclusions, though improvements to the statistical analysis for certain assays would strengthen the inferences further.

eLife assessment

This valuable study provides new insight into the disassembly of vimentin filaments and the dependence of this mechanism on net charge, albeit with incomplete evidence. In particular, the experimental replicates are limited (in most cases n=1), there is a lack of quantitative analysis to substantiate claims, inconsistency of the proposed mechanisms with previously published work, and lack of biochemical evidence supporting the observations in cells. Addressing these concerns would strengthen the manuscript and help support the proposed hypothesis on vimentin disassembly.

eLife assessment

In this important study, the authors have partially revealed the mechanism behind lip thickening in cichlid fishes, which has evolved independently across three lakes in Africa. To explore this phenomenon, the authors utilized histological comparison, proteomics, and transcriptomics, all of which are well suited for their objectives. With convincing evidence, this contribution holds significant value for the field.

eLife assessment

Mark and colleagues developed and validated a valuable method for examining subspace generalization in fMRI data and applied it to understand whether the entorhinal cortex uses abstract representations that generalize across different environments with the same structure. Evidence supporting the empirical findings - which show abstract entorhinal representations of hexagonal associative structures across different stimulus sets - is solid but could be further supported through additional analyses, discussion, and clarifications.

eLife assessment

This study presents an interesting mechanism for the regulation of RNA levels, establishing an important regulatory connection between protein arginine methyltransferase 1 and the splicing factor SFPQ. While these findings have theoretical implications beyond a single field, the evidence is incomplete, with only partial support for the main claims.

eLife Assessment

This valuable study investigates the oscillatory activity of gonadotropin-releasing hormone (GnRH) neurones in mice using GCaMP fiber photometry. It demonstrates three distinct patterns of oscillatory activity that occur in GnRH neurons comprising low-level rapid baseline activity, abrupt short-duration oscillations that drive pulsatile gonadotropin secretion, and, in females, a gradual and prolonged oscillating increase in activity responsible for the relatively short-lived preovulatory LH surge. The evidence presented in the study is solid, offering theoretical implications for understanding the behaviour of GnRH neurones in the context of reproductive physiology, and will be of interest to researchers in neuroendocrinology and reproductive biology.

eLife assessment

This important work advances our understanding of factors influencing efficacy assessments and biomarker viability for complement-directed gene therapy against age-related macular degeneration. The data presented is convincing and offers insights and teachings for the design of gene therapy and complement-targeted therapeutics in the eye and more broadly for future ocular biomarker studies.

eLife assessment

The authors combined neurophysiological (electroencephalography [EEG]) and neurochemical (magnetic resonance spectroscopy [MRS]) measures to empirically evaluate the neural noise hypothesis of developmental dyslexia. Their results are solid, supported by consistent findings from the two complementary methodologies and Bayesian statistics. Additional analyses, particularly on the neurochemical measures, are necessary to further substantiate the results. This study is useful for understanding the neural mechanisms of dyslexia and neural development in general.

eLife assessment

Somatostatin-expressing neurons of the entopeduncular nucleus (EPNSst+) co-release GABA and glutamate in their projection to the lateral habenula, a structure that is key for reward-based learning. Combining fiber photometry and computational modeling, the authors provide compelling evidence that EPNSst+ neural activity represents movement, choice direction, and reward outcomes in a probabilistic switching task but, surprisingly, neither chronic genetic silencing of these neurons nor selective elimination glutamate release affected behavioral performance in well-trained animals. This valuable study shows that despite its representation of key task variables, EPNSst+ neurons are dispensable for ongoing performance in a task requiring outcome monitoring to optimize reward. This study will be of interest to those interested in reward learning and/or reward-related behavior and systems or behavioral neuroscience more broadly.

eLife assessment

This study presents a useful approach for revealing large-scale brain attractor dynamics during resting states, task processing, and disease conditions using insights from Hopfield neural networks. The evidence supporting the findings is solid across the many datasets analysed. The work will be of broad interest to neuroscientists using neuroimaging data with interest in computational modelling of brain activity.

eLife Assessment

This valuable study is a companion to a paper introducing a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs). The evidence that recurrent SNVs or CDNs are common in true cancer driver genes is convincing, with more limited evidence that many more undiscovered cancer driver mutations will have CDNs, and that this approach could identify these undiscovered driver genes with about 100,000 samples.

eLife assessment

This important study examined neuronal activity in the dentate nucleus of the cerebellum when monkeys performed a difficult perceptual decision-making task. The authors provide convincing evidence that the cerebellum represents sensory, motor, and behavioral outcome signals that are sent to the attentional system, but further analysis focusing on the disparity of performance between animals would improve the quality of the paper. This paper is of great general interest in that it shows the involvement of the cerebellum in cognitive processes at the neuronal level.

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.