Evaluated articles

eLife Assessment

This study, which includes additional experiments in response to the reviewer comments, presents valuable findings illustrating the role of PI3Kα in heterotopic ossification in FOP model mice. The methods, data, and analyses are solid and generally support the claims although as noted by one of the reviewers, there is no data demonstrating the effect of BYL79 on cell growth, and it remains unclear whether BYL79 also inhibits the Smad2/3 pathway. While this study provides new insights into the role of the PI3Kα pathway as a therapeutic target for FOP, questions about the mechanism of BYL79 still exist.

eLife Assessment

African (or Salivarian) trypanosomes are significant pathogens of humans and domestic animals. For many decades is was accepted that only the "stumpy" non-proliferative form was capable of infecting the Tsetse-fly vector, but recent work challenged this, suggesting that the proliferative "slender" form is also infective. The current paper provides important and convincing laboratory evidence that the original concept is probably correct for most infections: the slender form was not infective for adult Tsetse, and was only able to infect young, less immunocompetent flies if N-acetyl glucosamine was added to the feed.

eLife assessment

This important study addresses the long-term effect of warming and precipitation on microbial growth, as a proxy for understanding the impact of global warming. The evidence that warming and altered precipitation exhibit antagonistic effects on bacterial growth is compelling and advances our understanding of microbial dynamics affected by environmental factors. This study will interest microbial ecologists, microbiologists, and scientists generally concerned with climate change.

eLife assessment

This paper presents a series of experiments investigating the role of cadherin-11 mediated interactions between cancer cells and fibroblasts in metastasis using updated 3D cell co-invasion assays. The primarily descriptive data are a valuable contribution to our understanding of the nature of cross cell-type interactions in metastasis, but are incomplete with respect to the far-reaching conclusions about the central role cadherin-11, especially given the complex nature of the phenotype and the need to better contextualize these observations in a complete picture of metastasis.

eLife assessment

This study presents valuable findings that examine both how Down syndrome (DS)-related physiological, behavioral, and phenotypic traits track across time, as well as how chronic treatment with green tea extracts 25 enriched in epigallocatechin-3-gallate (GTE-EGCG), administered in drinking water spanning prenatal through 5 months of age, impacts these measures in wild-type and Ts65Dn mice. The strength of the evidence is solid, due to high variability across measures, perhaps in part attributable to a failure to include sex as a factor for measures known to be sexually dimorphic. This study is of interest to scientists interested in Down Syndrome and its treatment, as well as scientists who study disorders that impact multiple organ systems.

eLife assessment

This valuable paper examines the Bithorax complex in several butterfly species, in which the complex is contiguous and not split, as it is in the well-studied fruit fly Drosophila. Based on genetic screens and genetic manipulations of a boundary element involved in segment-specific regulation of Ubx, the authors provide convincing evidence for their conclusions, which could be strengthened by additional data and analyses in the future. The data presented are relevant for those interested in the evolution and function of Hox genes and of gene regulation in general.

eLife Assessment

This paper explores the role of extracellular vesicles in providing extracellular matrix signals for migration of vascular smooth muscle cells. The evidence, based on cell culture experiments and supporting imaging of human samples, is mostly convincing. The paper will be valuable for researchers investigating cell migration during vessel repair and atherogenesis.

eLife assessment

This important study employs multiscale simulations to show that PIP2 lipids bind to DIV S4-S5 linkers within the inactivated state of a voltage-gated sodium channel, affecting the coupling of voltage sensors to the ion-conducting pore. The authors demonstrate that PIP2 prolongs inactivation by binding to the same site that binds the C-terminal during recovery from inactivation, and they suggest that binding to gating charges in the resting state may impede activation, both findings that contribute to our understanding of sodium channel modulation. The coarse-grained and atomistic molecular dynamics simulations are convincing, including state dependence and linker mutants to back up the claims.

eLife assessment

This study is a potentially important contribution to the field of protein biosynthesis pathways and their link to aging, especially regarding the thorough analysis of variation in measures expected to correlate with elongation rate in old and new daughter cells derived from old and new mother cells. However, the imaging results, analysis, and methodologies are incomplete, as in its current form several key questions remain unanswered.

eLife assessment

This study presents a valuable new approach for efficient computation of statistics on correlations between genetic variants (linkage disequilibrium, or LD), which the authors apply to quantify the extent of LD across chromosomes. The method appears solid, although the presentation of equations needs clarification and improvement. The authors document that cross-chromosome LD can be substantial, which has implications for geneticists who are interested in population structure and its impact on genetic association studies.

eLife assessment

This valuable study substantially advances our understanding of molecular mechanisms driving the phase separation behavior of HP1 paralogs. The evidence supporting the conclusions is convincing, with rigorous and well-designed computational simulations. The work will be of broad interest to biophysicists and biochemists.

eLife assessment

P-glycoprotein is a major ABC-transporter that exports drugs used in chemotherpay and effects the pharmacokinetics of other drugs. Here the authors have determined cryo-EM structures of drug complexes in previously unforeseen outward-facing conformations. These convincing findings are mechanistically important and reveal potential regions to be exploited by rational-based drug design.

eLife assessment

This important study will provide evidence about a novel screen-triage-treat strategy for cervical cancer prevention. The trial will generate convincing evidence regarding the efficacy, effectiveness, cost-effectiveness, feasibility and acceptability in a range of geographically spread low-resource settings. The strategy should contribute to improving access to cervical cancer prevention to vulnerable women with low access to health care, and, therefore, at the highest risk of cervical cancer.

eLife assessment

This important study advances our understanding of the biological significance of the DNA sequence adjacent to telomeres. The data presented convincingly demonstrate that subtelomeric repeats are non-essential and have a minimal, if any, role in maintaining telomere integrity of budding yeast. The work will be of interest to the telomere community specifically and the genome integrity community more broadly.

eLife assessment

This study provides valuable findings showing the production of IL-22 from intestinal ILC3 during intermittent fasting promotes beigeing of white adipose tissue. The authors provided solid data and mechanistic insight by which IL-22-derived from ILC3 directly induces beigeing.

eLife assessment

This valuable study provides molecular-level insights into the functional mechanism of bacterial ice-nucleating proteins, detailing electrostatic interactions in the domain architecture of multimeric assemblies. The evidence supporting the claims of the authors is solid, with results from protein engineering experiments, functional assays, and cryo-electron tomography, while the proposed structural model of protein self-assembly remains hypothetical. The work is of broad interest to researchers in the fields of protein structural biology, biochemistry, and biophysics, with implications in microbial ecology and atmospheric glaciation.

eLife assessment

Little is known about the role of the microbiome alterations in epithelial ovarian cancer. This important and rigorous study carefully examined the microbiome composition of 1001 samples from close to 200 ovarian cancer cases and controls, and presents compelling evidence that the fallopian tube microbiota are perturbed in ovarian cancer patients. These insights are expected to fuel further exploration into translational opportunities stemming from these findings.

eLife assessment

The authors' findings have theoretical or practical deep implications, which makes them important. The methods, data, and analyzes support the authors' arguments with only minor weaknesses, and overall they are solid. In vitro culture experiments could provide evidence to strengthen the evidence for the functional significance of Th1-mediated cytokines in the observed B cell responses.

eLife assessment

Gain-of-function mutations and amplifications of PPM1D are found across several human cancers and are associated with advanced tumor stage and worse prognosis. Thus far, the clinical translation has not been possible due to the lack of PPM1D inhibitors with favorable pharmacokinetic properties. This useful study leverages CRISPR/Cas9 screening to determine that loss of SOD1 and is synthetic lethal with PPM1D mutation in leukemia. The mechanistic analyses are still incomplete.