Evaluated articles

eLife assessment

This manuscript describes a valuable method to study the mechanism of action of essential genes and novel putative drug targets. Evidence for the effectiveness of the system, which is based on engineering pre-validated targets for RNA-mediated knockdown into genes of interest, is compelling, and the method should find use as an orthogonal method for generating gene specific knockdowns.

eLife assessment

This study presents valuable findings from a study of identical twin pairs discordant and concordant for smoking to assess whether smoking has a direct effect on DNA methylation. The results are a valuable contribution as the study confirms the reported association between smoking and epigenetic profile is indeed due to the direct effects of constituents of tobacco smoke. The study design and methods applied by the authors are solid and provide a starting point for larger studies with rigorous laboratory approaches, as well as for assessing clinical impact. The work will be of broad interest to addiction researchers, genetic epidemiologists, and environmental scientists.

eLife assessment

This is an interesting and potentially significant study that adds important new information to our understanding of the mechanisms of lung epithelial repair after tissue injury. The authors have delineated a novel and non redundant role for the hippo pathway and the down stream regulators Yap/Taz in regulating repair of lung injury. These studies will inform future investigations into the mechanisms of repair of lung injury

eLife assessment

This study presents important results on the predicted impact of cancer screening disruptions in Australia during the COVID-19 pandemic based on consultation with public health stakeholders. The evidence presented is solid, as simulations were based on several previously validated breast, cervical, and bowel cancer screening decision models, though the scenarios were based on hypothetical disruptions that do not always match experienced disruptions. The work will be of interest to local policy-makers, public health specialists, and cancer epidemiologists.

eLife assessment

This work shows that higher socioeconomic status is associated with a higher risk of obesity, which should inform China's obesity public health programs and policies, and also be of interest to other countries and communities. The evidence supporting the conclusions is strong, but the data analysis is incomplete and would benefit from more rigorous approaches.

eLife assessment

This is important work that addresses a long-standing (but rarely acknowledged) question: given that multi-peaked tuning curves optimize Fisher information, why do early sensory areas typically have single-peaked tuning curves? This paper shows clearly, and convincingly, that multi-peaked tuning curves are likely to produce catastrophic errors at short times, so if speed is important, multi-peaked tuning curves should be avoided. This work should encourage neuroscientists to take into account the importance of stimulus encoding time in their formulations of models of neural coding.

eLife assessment

Endothelial cells mediate the growth of the vascular system, but they also need to prevent vascular leakage, which involves interactions with neighboring endothelial cells through junctional protein complexes. This important study provides a full mechanistic insight into how Sun1 is achieving its function, which supports the concept that nuclear anchoring is critical for proper mechanosensing and junctional organization. Although the evidence supporting the claims of the authors is solid and there are several merits and strengths in this study, a weakness is that some important controls are missing. The work will be of broad interest to cell biologists and vascular biologists.

eLife assessment

This manuscript presents a useful meta-analysis of genes with parent-specific expression from mouse published RNA-seq datasets, focusing on genes with weak allelic bias. A combination of systematic bioinformatic analysis and experimental validation convincingly shows that the number of parentally biased genes has been overestimated and the few novel ones lie at the periphery of known imprinted loci. The work will be of interest to genomicists with an interest in imprinting and its mechanisms.

eLife assessment

This study will be of interest to scientists within the field of hematopoiesis and ribosome biology. The paper provides evidence that haploinsufficiency of the mouse ribosomal protein gene Rps12 results in a number of phenotypes including defects in the production of specific blood cells and loss of hematopoietic stem cell quiescence. This work adds to the growing body of evidence that specific cell populations are particularly sensitive to disruption of mRNA translation machinery.

eLife assessment

This important paper advances our ability to understand feeding behavior in fruit flies and begins to address the challenging question of motivation. With innovative methods based on the detailed monitoring of interactions between foods of different qualities at different hunger states, they present compelling evidence for non-homeostatic feeding not driven by metabolic need.

eLife assessment

This manuscript provides a description of an approach for efficiently integrating diverse libraries into the C. elegans genome and tools that enable researchers to use the method. It is a valuable contribution for researchers carrying out experiments that would benefit from easy generation of such libraries, and the data for the effectiveness of the method is solid. The advantages of this approach in terms of ease and effectiveness relative to others with similar aims will emerge as they are put to more general use in addressing biological problems.

eLife assessment

The study has some significance for the field of dementia research and neurodegenerative diseases more broadly. Using the brain-age paradigm, the main findings are that having an older-appearing brain is associated with more advanced stages of amyloid and tau pathology, higher white matter hyperintensities, higher plasma NfL and carrying the APOE 34 allele. Findings were broadly similar in cognitively normal people and people with mild cognitive impairment and the evidence for these findings is convincing. Although sex differences are emphasized, the evidence for this is generally incomplete.

eLife assessment

This study presents important new findings regarding prenatal thalamocortical development. The authors present convincing evidence to overcome substantial methodological challenges in charting prenatal brain development in vivo. This work will be of interest to pediatric and developmental neuroscientists and neuroradiologists.

eLife assessment

The authors present valuable findings regarding the mechanism of high mannose induced cellular toxicity in cancer cells. The evidence supporting genomic instability as the anti-cancer activity of mannose is convincing with multiple orthogonal approaches showing consistent results, but the conclusions related to metabolic remodeling could be further strengthened by additional metabolomics data. While the findings are limited to genetically modified cancer cell lines cultured in vitro, this work will be of interest to cell biologists working on cancer metabolism.

eLife assessment

This potentially important study examines brain age based on resting state functional connectivity (RSFC) following an 18-month lifestyle intervention. The design of the intervention study is generally solid; the randomized controlled trial includes three intervention groups and assessments at two-time points of numerous health markers, however, the methodology for brain age prediction appears somewhat incomplete and would benefit from more rigorous approaches. The lack of control groups also prevents firm conclusions about the extent to which the observed RSFC changes are linked to the intervention. With these parts strengthened, the paper would be of broad interest to neuroscientists and biologists working on obesity, lifestyle interventions, and brain health.

eLife assessment

This paper reports a valuable new method for creating localized damage to candidate brain regions for functional and behavioral studies. The authors present solid support for their ability to create long-term local lesions with mm spatial resolution. The paper is likely to be of broad interest to brain researchers working to establish causal links between neural circuits and behavior.

eLife assessment

This valuable work proposes a framework inspired by chemotaxis for understanding how the brain might implement behaviours related to navigating toward a goal. The evidence supporting the conceptual claim is convincing. The manuscript proposes a hypothesis that would be of interest to the broad systems neuroscience community, although it was noted the relationship to existing similar hypotheses could be clarified.

eLife assessment

This important paper reports recent improvements and extensions to stdpopsim, a community-driven resource that is built on top of powerful software for performing simulations of population genomic data and provides a catalog of species with curated genomic parameters and demographic models. In addition to describing the new features and species in stdpopsim, the authors provide a set of practical guidelines for implementing realistic simulations. Overall, this convincing manuscript serves as an excellent overview of the utility, challenges, common pitfalls, and best practices of population genomic simulations. It will be of broad interest to population, evolutionary, and ecological geneticists studying humans, model organisms, or non-model organisms.

eLife assessment

This study presents valuable structural data for the bacterial adhesin PrgB, an atypical microbial cell surface-anchored polypeptide that binds DNA. There is convincing support for the claims regarding the overall function and importance of individual domains, which integrate a wide range of new and previously published experimental data. The structure-based model of PrgB molecular activity will be impactful in the field of bacterial adhesins, conjugation, and biofilm formation, especially because it focuses on a clinically relevant Gram-positive pathogen, whereas most work in the field has been focused on Gram-negative model systems.

eLife assessment

This valuable paper informs on the role of type I PRMTs in programming muscle stem cell identification. The evidence presented is mostly solid, with some weaknesses in the evidence regarding the proposed mechanism. The paper will be of particular interest to those who study skeletal muscle satellite cell biology.