Evaluated articles

eLife Assessment

Davies et al. present a valuable study proposing that Shot can act as a molecular linker between microtubules and actin during dendrite pruning, suggesting an intriguing role in non-centrosomal microtubule organization. However, the experimental evidence is incomplete and does not robustly support these claims, and the lack of a cohesive model connecting the findings weakens the overall impact. While the data suggest that Shot, actin, and microtubule nucleation contribute to dendritic pruning, their precise interplay remains unresolved.

eLife Assessment

In this useful study, the authors conducted a set of computational and experimental investigations of the mechanism of cholesterol transport in the smoothened (SMO) protein. The computational component integrated multiple state-of-the-art approaches such as adaptive sampling, free energy simulations, and Markov state modeling, providing support for the proposed mechanistic model, which is also consistent with the experimental mutagenesis data. However, substantial revisions are needed for the discussion of the computational results and interpretation of the literature to provide a more balanced and accurate perspective on cholesterol-mediated SMO regulation. In the current form, therefore, the strength of evidence of the study is considered incomplete.

eLife Assessment

This study is valuable for understanding how dysfunctional mitochondria contribute to vascular diseases by investigating the influence of Miro1 on smooth muscle cell proliferation and neointima development. The solid findings collectively indicate that Miro1 regulates mitochondrial cristae architecture and the efficiency of the respiratory chain. Nevertheless, the analysis would benefit from a more thorough assessment of the relationship between Miro1-dependent mitochondrial defects and vascular smooth muscle cell proliferation.

eLife Assessment

This study reports a dynamic association/dissociation between malate dehydrogenase (MDH1) and citrate synthase (CIT1) in Saccharomyces cerevisiae under different metabolic conditions that control TCA pathway flux rate. The research question is timely, the use of the NanoBiT split-luciferase system to monitor protein-protein interactions is innovative, and the significance of the findings is valuable. However, the strength of evidence needed to support the conclusions was found to be incomplete based on a lack of critical control and mechanistic experiments.

eLife Assessment

This paper presents an analysis of demography and selection from whole-genome sequencing of 40 Faroese, with data that are useful beyond the study region. Much of the analysis is solid, but a more fine-scale analysis of demographic history could have led to more interesting findings. In addition, there are concerns about the selection analyses, given the special nature of the studied population and sampling scheme. Finally, lack of data availability limits the broader value of the paper.

eLife Assessment

The authors investigate mechanisms of acquired resistance (AR) to KRAS-G12C inhibitors (sotorasib) in non-small cell lung cancer, proposing that resistance arises from signaling rewiring rather than additional mutations. While the study addresses a valuable clinical question, it is limited by several weaknesses in experimental rigor, data interpretation, and presentation, meaning the strength of evidence is incomplete

eLife Assessment

The study presents a valuable resource of proline hydroxylation proteins for molecular biology studies in oxygen-sensing and cell signaling with the characterization of Repo-man proline hydroxylation site. The evidence supporting the claim of the authors is solid, although further clarification of the overall efficiency of the HILIC analysis, the specificity/sensitivity of immonium ion analysis, as well as quantification of proline hydroxylation identifications will be helpful. The work will be of interest to researchers studying post-translational modification, oxygen sensing, and cell signaling.

eLife Assessment

This study provides fundamental insights into eukaryotic phosphate homeostasis by demonstrating how yeast vacuoles dynamically regulate cytosolic phosphate levels. The conclusions are convincing, supported by an elegant combination of in vitro assays and in vivo measurements. This study will be of interest to cell biologists, particularly for those who are working in the field of phosphate metabolism.

eLife Assessment

This manuscript offers valuable structural and mechanistic insights into the structure and assembly of the Type II internal ribosome entry site (IRES) from encephalomyocarditis virus (EMCV) and the translation initiation complex, revealing a direct interaction between the IRES and the 40S ribosomal subunit. While a solid cryo-EM method was used, enhancing the overall resolution or adding complementary biochemical data would further improve the clarity and impact of this study. This manuscript will attract researchers in cap-independent translation, host-pathogen interactions, and virology.

eLife Assessment

This study presents a valuable finding on the representational structure of task encoding in the prefrontal cortex. The evidence supporting the claims of the authors is solid, representing an impressive data collection effort and best-practice fMRI analyses. However, at least including visual regions as a control and controlling for behavioral differences in the task in representation analyses would have strengthened the study. The work will be of interest to cognitive neuroscientists interested in the neural basis of cognitive control.

eLife Assessment

This study presents experiments suggesting intriguing mesoscale reorganization of functional connectivity across distributed cortical and subcortical circuits during learning. The approach is technically impressive and the results are potentially of valuable significance. However, in its current form, the strength of evidence is incomplete. More in-depth analyses and the acquisition of data from additional animals in the primary experiment could bolster these findings.

eLife Assessment

In this valuable study, the authors developed long-term imaging tools to simultaneously monitor the temporal and spatial dynamics of excitatory and inhibitory synapses and reported that excitatory and inhibitory synapses need to develop synergistically during synaptogenesis to maintain balance. While the analysis and quantification of the imaging data are incomplete, there is convincing evidence that the developed tools are feasible. If these tools can function stably in vivo, their applications will be much broader.

eLife Assessment

This valuable study reports convincing evidence about associations between 35 polygenic indices (PGIs) for social, behavioral, and psychological traits, along with some non-fatal health conditions (e.g., BMI) and all-cause mortality in data from Finnish population-based surveys and a twin cohort linked with administrative registers. PGIs for education, depression, alcohol use, smoking, BMI, and self-rated health showed the strongest associations with all-cause mortality, on the order of ~10% increment in risk per PGI standard deviation. Effect sizes from twin-difference analyses tended to be slightly larger than the effect sizes from population cohorts, opposite the pattern generally observed when testing PGI associations with their target phenotypes and supporting robustness of findings to confounding by population stratification.

eLife Assessment

This valuable study reports evidence that items maintained in working memory can bias attention in an oscillatory manner, with the attentional capture effect fluctuating at theta frequency. The study provides incomplete evidence that this dynamic attentional bias is associated with oscillatory neural mechanisms, particularly in the alpha and theta bands, as measured by EEG. The study will be relevant for researchers studying attention, working memory, and neural oscillations, particularly those interested in how memory and perception interact over time.

eLife Assessment

This study presents valuable computational findings on the neural basis of learning new motor memories and the savings using recurrent neural networks. The evidence supporting the claims of the authors is solid, but it would benefit from more controls and from considering the role of explicit strategies and other brain regions. This work will be of interest to computational and experimental neuroscientists working in motor learning.

eLife Assessment

This useful study replicates a previous finding that information about peripherally presented visual stimuli is represented in the foveal visual cortex, and extends it by demonstrating that these representations are similar to those evoked by foveally presented stimuli. The authors' gaze-contingent fMRI design provides solid evidence for these findings. Some of the stronger theoretical claims, such as that the effects are due to predictive pre-saccadic remapping, are not fully supported by the current results.

eLife Assessment

This important work sets out to identify the neural substrates of associative fear responses in adult zebrafish. Through a compelling and innovative paradigm and analysis, the authors suggest brain regions associated with individual differences in fear memory. While several findings are well supported, aspects of the interpretation and presentation are partially incomplete, and the manuscript would benefit from adjusting key claims or including additional experiments. Nonetheless, this study showcases the strength of zebrafish for systems-level neuroscience and will be of broad interest to the neuroscience community.

eLife Assessment

This valuable study shows the impact of the metabolic state of bacteria on phage infection. The experimental results, based on various phages infecting E. coli, are solid and consistent with a two-step adsorption mathematical model, although the detailed evidence supporting this model is currently incomplete. This study should be of interest to the communities working on cell metabolism and on host-pathogen interactions.

eLife Assessment

Zandvoort and colleagues describe respiration-brain coupling in the context of apnoea in human newborns. The authors have addressed an important question and supported their claims with solid data. The rigor of the findings could perhaps be further strengthened with some relatively minor changes to the analysis methodology.

eLife Assessment

This study presents valuable and compelling evidence that β-glucan-induced trained immunity can protect against intestinal inflammation by reprogramming innate immune cells toward a reparative phenotype. The authors employ a convincing combination of functional assays, adoptive transfers, and single-cell transcriptomics to uncover mechanistic insights and demonstrate the therapeutic potential of innate immune memory in IBD. While the work is robust, addressing the underlying epigenetic mechanisms and including additional controls would further reinforce the trained immunity-specific interpretation.