Evaluated articles

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 investigates the potential role of extracellular vesicles in providing extracellular matrix signals for migration of vascular smooth muscle cells. The findings could be useful for researchers interested in cell migration, but the evidence supporting the conclusions is presently incomplete.

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.

eLife assessment

This valuable study combines electrophysiology and neuroanatomy with pharmacological and optogenetic manipulation in the Drosophila genetic model system to pinpoint the neural substrate that is influenced by altered activity during a critical period (CP) of larval locomotor circuit development. Increasing activity during the CP causes permanent network changes, manifesting in increased recovery times from seizures and altered intersegmental coordination during locomotion, thus indicating that a setpoint of network excitability is determined during the CP. Next, compelling experiments demonstrate that this goes along with increased excitation/inhibition ratios to single identified motoneurons and most importantly, for excitability setpoint determination during the CP excitatory and inhibitory inputs are integrated such that the effect of CP hyperexcitation is rescued by the stimulation of endogenous inhibitory inputs to the motoneurons. This provides novel insight into how developing neural network excitability is tuned and how it can be entrained during the CP.

eLife assessment

Picard et al. propose a Facial Expression Pain Signature (FEPS) derived from functional magnetic resonance imaging (fMRI) data to predict facial expressions associated with painful heat stimulation. This important work advances our understanding of the brain mechanisms associated with facial expressions of pain. It provides solid evidence that facial expressions of pain contain information that is complementary to other pain-related brain processes. The work will be of broad interest to researchers from varied fields ranging from neurosciences to psychology and affective sciences.

eLife assessment

In this manuscript, Jain and colleagues explore whether increasing adult-born neurons is protective against status epilepticus and the development of spontaneous recurrent seizures (chronic epilepsy) in a mouse pilocarpine model of temporal lobe epilepsy. This is an important work that provides solid data, contradicting previous studies on suppressing chronic seizures by reduction in adult-born neurons.

eLife assessment

Antibodies are some of the most critical tools in biomedical research. However, their quality and specificity vary significantly. This fundamental study provides guidelines for how the quality of an antibody should be assessed and recorded and provides compelling data on the selected antibodies. This paper will be of interest to researchers working in experimental cell biology.

eLife assessment

This study presents an important methodology to increase the efficiency and precision of gene editing in human hematopoietic stem and progenitor cells. The evidence supporting the claims is convincing in that primitive LTC-ICs were minimally affected as a result of the editing procedure and the lack of edits at predicted off-target sites. The work will be of interest to biologists studying hematopoietic stem and progenitor cells and genome editing for potential clinical applications.

eLife assessment

This study presents a valuable insight into a computational mechanism of pain perception. The evidence supporting the authors' claims is compelling. The work will be of interest to pain researchers working on computational models and cognitive mechanisms of pain in a Bayesian framework.