Evaluated articles

eLife Assessment

In this valuable study, Tutak and colleagues set out to identify factors that mediate Repeat Associated Non-AUG (RAN) translation of CGG repeats in the FMR1 mRNA which are implicated in toxic protein accumulation that underpins ensuing neurological pathologies. The authors provide solid evidence that RPS26 may be implicated in mediating the RAN translation of FMR1 mRNA. This article should be of broad interest to researchers in the variety of disciplines including post-transcriptional regulation of gene expression and neurobiology.

eLife assessment

Chang et al. have investigated the catalytic mechanism of I-PpoI nuclease, a one-metal-ion dependent nuclease, by time-resolved X-ray crystallography using soaking of crystals with metal ions under different pH conditions. This convincing study revealed that I-PpoI catalyzes the reaction process through a single divalent cation. The study uncovers important details of the roles of the metal ion and the active site histidine in catalysis.

eLife assessment

The study presents a valuable finding in advancing our understanding of the cellular and molecular mechanisms that regulate the switching of the migration mode from parallel to radial in cerebellar granule cell development. The evidence supporting the claims of the authors is solid and supports the main conclusion; the highlight was the imaging system's visualization of the cell-recognition event associated with neuronal migration, which established a new standard for the field. This study would be of interest to cell biologists and neurodevelopmental biologists working on cell-cell interaction and neuronal migration.

eLife Assessment

Wittkamp et al. investigated the spatiotemporal dynamics of expectation of pain using an original fMRI-EEG approach. The methods are solid and the evidence for a substantially different neural representation between the anticipatory and the actual pain period is convincing. These important findings are discussed within a general framework that encompasses their research questions, hypotheses, and analysis of results. Although the choice of conditions and their influence on the results might accept different interpretations, the manuscript is strong and contributes beneficial insights to the field.

eLife assessment

This important study introduces the MRAD database, an advancement in Alzheimer's disease research that provides a powerful tool for evaluating risk and protective factors through Mendelian randomization analysis. The evidence supporting the database's utility is solid, with findings backed by robust data, though addressing methodological concerns and ensuring more rigorous validation of associations would further strengthen its impact. This resource represents a significant leap forward in the field, offering unprecedented opportunities for researchers and clinicians to uncover key insights into Alzheimer's etiology, potentially revolutionizing how Alzheimer's research is approached and accelerating the discovery of new prevention strategies and treatments.

eLife Assessment

This interesting study explores whether tumor cells can manipulate their Hydra hosts, and includes important findings on the consequences for the fitness of the host Hydra. The evidence supporting these findings is convincing. The work will be of broad interest to many fields including development biology, evolutionary biology and tumor biology.

eLife assessment

Schafer et al. investigate the extremely interesting and important claim that the human hippocampus represents the interactions with multiple social interaction partners on two relatively abstract social dimensions – and that this ability correlates with the social network size of the participant. This research potentially demonstrates the intricate role of the hippocampus in navigating our social world. While some results are tantalizing, the empirical evidence for the main claims is currently incomplete and requires clarifications and substantial revisions.

eLife Assessment

The study follows up on previous work suggesting that lower glucose concentrations are protective from sepsis but put the patient at risk for hypoglycemia. In this paper, the authors identify that a slightly higher dose of glucose is still protective but no longer puts the patients at risk for hypoglycemia. The study is important, supported by convincing data, and will be of interest to a broad audience.

eLife assessment

This important study substantially advances our understanding of energy landscapes and their link to animal ontogeny. The evidence supporting the conclusions is compelling, with high-throughput telemetry data and advanced track segmentation methods used to develop and map energy landscapes. The work will be of broad interest to animal ecologists.

eLife assessment

This is an important and timely study that advances our understanding of the role of lateral hypothalamic orexin/hypocretin neurons in appetitive approach and consummatory behaviors. Specifically, using fiber photometry, the authors provide solid and convincing evidence that orexin neurons are primarily active during approach and not consummatory behavior, in a manner that is dependent on metabolic state. Further, using optogenetics and cell type-specific electrophysiology, they show that inputs from the ventral pallidum and lateral nucleus accumbens shell to orexin/hypocretin neurons in the lateral hypothalamus are predominantly inhibitory.

eLife Assessment

This is an important and convincing dataset shedding new light on a role for Malat1 in osteoblast physiology. The work is of value to areas other than the bone field because it supports a role and mechanism for beta-catenin that is novel and unusual. The findings are significant in that they support the presence of another anabolic pathway in bone that can be productively targeted for therapeutic goals. Revisions further improved the paper and addressed the reviewers' concerns.

eLife assessment

This study provides an important advance in the molecular understanding of the lipopolysaccharide export mechanism and machinery in bacteria. By using advanced spectroscopy approaches, the experiments provide convincing biophysical support for the dynamic behavior of the multisubunit Lpt transport system. This work has implications for understanding bacterial cell envelope biogenesis and developing drugs that target Gram negative pathogens.

eLife Assessment

The study by Pudlowski et al. shows that a previously-identified protein complex, composed of delta- and epsilon-tubulin together with TEDC1 and TEDC2, functions in generating centriolar triplet microtubules, and that this is crucial for the proper formation of centriolar subdomains and the stability of centrioles throughout the cell cycle. This is an important study that advances our understanding of centriole biogenesis and structure and is supported by convincing evidence based on knockout cell lines, immunoprecipitation, and ultrastructure expansion microscopy. The work is of interest to cell biologists, in particular researchers with interest in centrosome biology.

eLife Assessment

This important study explores the relationship between the sequence of prokaryotic promoter elements and their activity using mutagenesis to generate thousands of mutant sequences. The evidence supporting these findings is convincing. This work will appeal to those interested in bacterial genetics, genome evolution, and gene regulation.

eLife Assessment

This is a valuable study describing how rhabdomyosarcoma fusion-oncogenes, VGLL2-NCOA2 and TEAD1-NCOA2, function at the genomic, transcriptional, and proteomic levels in multiple systems. The experimental data is convincing, supporting a model in which these fusion-oncogenes leverage TEAD transcriptional signatures independent of YAP/TAZ. This work offers new mechanistic insights into oncogenic gene fusion events and reveals potential therapeutic strategies for the treatment of rhabdomyosarcomas.

eLife Assessment

This important work provides another layer of regulatory mechanism for TGF-beta signaling activity. The evidence convincingly supports the involvement of microtubules as a reservoir of Smad2/3, and association of Rudhira with microtubules is critical for this process. The work will be of board interest to developmental biologists in general and molecular biologists in the field of growth factor signaling.

eLife assessment

This useful work provides a risk-prediction tool, in the form of a nomogram, for practitioners and elderly patients with non-metastatic colon cancer using data from the SEER registry. The unique contribution of this work is the focus on conditional survival. However, the underlying statistical approach is suboptimal and therefore incomplete, which substantially lessens the potential impact of this work. The analysis could use a more rigorous consideration of competing risks.

eLife assessment

This study provides a novel and promising NPRL2 gene therapy for enhanced immunotherapy response in a KRAS/STK11 mutant anti-PD1 resistant metastatic NSCLC humanized mouse model. Overall, the authors presented a large amount of convincing in vivo data to demonstrate that NPRL2 gene therapy induces antitumor activity through DC-mediated antigen presentation and cytotoxic immune cell activation. This work will be of interest and useful to medical biologists and oncologists in the research field of KRAS-mutant NSCLC.

eLife assessment

This important study provides new insight into the dynamics that underlie the development of therapy resistance in prostate cancer by revealing that divergent tumor evolutionary paths occur in response to different treatment timing and that these converge on common resistance mechanisms. The use of barcoded lineage tracing and characterization of isolated tumor clonal populations provides compelling evidence supporting the importance of clonal dynamics in a tumor ecosystem for treatment resistance. Several open questions remain, however, raising the possibility of alternative interpretations of the data set in its current form. Overall, the findings deepen our understanding of prostate cancer evolution and hold promising implications for how drug resistance can be addressed or prevented.

eLife Assessment

The authors propose that positive biodiversity-ecosystem functioning relationships found in experiments have been exaggerated because commonly used statistical analyses are flawed. To remedy this, a new type of analysis based on a concept of "partial density monoculture yield" is proposed. However, the presented concept and analysis methods are not reproducibly described (how can partial density monoculture yield experimentally be assessed?), do not appear to be complete, and are inadequate for hypothesis testing. The reviewers found that the authors misinterpret current research in the field and made limited efforts to understand or address the reviewer comments about this study.