Evaluated articles

eLife assessment

This is an important study, that adds to the field a new understanding of exercise or mechanical loading, microRNAs, and secreted extracellular vessicles in the field of lung cancer (NSCLC), which may have relevance to other osteolytic cancers. The strength of the evidence was mixed: whereas in vitro microRNA experiments were convincing, other elements were incomplete (e.g., proving the roles of osteocytes, as opposed to other mechanosensitive cells, in vivo). This work would be of broad interest to those investigating osteolytic cancers, and the role of exercise in bone cancer, preclinically.

eLife assessment

This valuable study advances our understanding that YAP/TAZ, as well as their target genes, play a prominent role in the formation of processing bodies (P-bodies). The evidence supporting the conclusions is convincing. The article could be improved through further analysis to elucidate the mechanistic link between P-body formation and oncogenesis. The work will be of broad interest to scientists working in the field of Hippo signaling and cancer biology.

eLife Assessment

Genetic analysis of complex traits in Drosophila provides a resource for exploring the relationship between genetic and phenotypic variation. The web tool DGRPool presented in this paper makes data and results from the Drosophila Genetic Reference Panel accessible that will enable downstream analyses of genetic association. The findings of this paper are considered to be important, with practical implications beyond a single subfield, supported by convincing evidence using appropriate and validated methodology in line with current state of the art.

eLife assessment

This structural and biochemical study of the mouse homolog of acidic mammalian chitinase (AMCase) enhances our understanding of the pH-dependent activity and catalytic properties of mouse AMCase, and it sheds light on its adaptation to different physiological pH environments. The methods and analysis of data are solid, providing several lines of evidence to support the development of mechanistic hypotheses. While the findings and interpretation will be valuable to those studying AMCase in mice, the broader significance, including extension of the results to other species including human, remain less clear.

eLife assessment

The work is a valuable contribution to understanding the mechanism of nuclear export of tRNA in budding yeast. The authors present solid evidence that Dbp5 functions in parallel with Los1 and Msn5 in tRNA export, in a manner dependent on Gle1 for activation of its ATPase activity but independently of Mex67, Dbp5's partner in mRNA export. It further presents biochemical evidence that Dbp5 can bind tRNA but that Gle1 and InsP6 are required for activating ATP hydrolysis by the Dbp5-tRNA complex, suggesting a possible mechanism for tRNA export by Dbp5.

eLife assessment

This valuable study reports novel active learning batch selection methods that have been applied to optimization tasks related to ADMET and affinity properties relevant within the drug discovery field. While the evidence is solid, the paper could have benefited from a clearer and deeper description of methods as well as interpretation of the obtained models, and a wider comparison to existing methods. The article will be of general interest to scientist working in the field of drug discovery and, in general, to researchers within the fields of machine learning and data analysis.

eLife assessment

This fundamental study for the first time defines genetically the role of the Clock gene in basal metazoa, using the cnidarian Nematostella vectensis. With convincing evidence, the study provides insight into the early evolution of circadian clocks. Clock in this species is necessary for daily rhythms under constant conditions, but not under a rhythmic light/dark cycle, suggesting that the major role of the circadian oscillator in this species could be a stabilizing function under non-rhythmic environmental conditions.

eLife assessment

This important study extends existing sequentially Markovian coalescent approaches to include the combined use of SNPs and hypervariable loci such as epimutations. This is an intriguing addition to infer population size history in the recent past, and the authors provide solid validation of their methods via simulation and analysis of empirical data in Arabidopsis thaliana. Given the increasing availability of such data, this work is a timely contribution and represents a foundation for further developments to explore when and where these methods will be best used.

eLife assessment

This valuable study is focused on the requirement of the photoreceptor-specific tetraspanins, ROM1 and PRPH2, for the formation of light-sensitive membrane discs. The evidence supporting the claim that deficiency in one of the proteins can be compensated by the other is convincing, with both established and advanced techniques yielding results that will be of interest to those studying photoreceptor development and membrane curvature.

eLife assessment

This interesting and important manuscript combines in vitro and in vivo experiments to investigate the reciprocal regulation between mitochondria-associated membranes and Notch signaling in skeletal muscle atrophy, with implications beyond the single subfield of muscle atrophy. The methods, data, and analyses are solid and broadly support the claims.

eLife assessment

This manuscript describes a model to estimate what fraction of DNA from specific human tissues becomes cell-free DNA in plasma. This fundamental study, supported by convincing evidence, will be of great interest to the community, as the amount of DNA from a certain tissue (for example, a tumor) that becomes available for detection in the blood has significant implications for disease detection.

eLife assessment

The effect of Vitamin D supplementation in reducing asthma via anti-inflammatory mechanisms is a topic of wide interest, with somewhat conflicting published data. Here, bioinformatic approaches help to identify a role of VDR in inducing the expression of the key regulator Ikzf3, which possibly suppresses the IL-2/STAT5 axis, consequently blunting the Th2 response and mitigating allergic airway inflammation. These are important findings based on convincing evidence.

eLife assessment

This study provides valuable findings on a causative relationship between LRRC23 mutations and male infertility due to asthenozoospermia. The evidence supporting the conclusions is solid. This work will be of interest to biomedical researchers who work on sperm biology and non-hormonal male contraceptive development.

eLife assessment

The authors provide the first investigation of the role of the lateral habenula in vocal learning in the songbird. This study provides important insights into the conserved connectivity of the lateral habenula with dopaminergic reinforcement circuits and presents a potential role of this circuit in zebra finch song learning. The results stem from a careful anatomical and functional mapping and from a rigorous behavior analysis that, together, implicate a previously undescribed analog between mammals and songbirds. Although many aspects of the manuscript - like the analysis of song behavior - are exceptional, the evidence linking behavior to selective lesions of the lateral habenula is, at this point, incomplete, leaving the interpretation of key results difficult.

eLife assessment

This important study sheds light on several apparent discrepancies observed across animal studies examining neuroimaging biomarkers of functional recovery following focal ischemia. Using 2-photon imaging of calcium activity in awake mice, the authors show compelling evidence that deficits in neuronal activity and functional connectivity after photothrombosis occur within a very small distance from the infarct (<750 microns) whereas these measures were relatively unaltered more distally, even those typically implicated with functional remapping of the forelimb representation in anaesthetized animals. These findings reveal a complex spatiotemporal relationship between perilesional neuronal network function and behavioral recovery that is more nuanced than previously reported, and motivates the need for better criteria for what is considered remapping.

eLife assessment

In this work, the authors make a valuable contribution based on convincing evidence that children 6-to-7-years-old improve in 2 years of development towards utilising more optimal value-based decision-making strategies while performing a reinforcement learning task. They found that delayed feedback learning was associated with volume in the hippocampus while immediate feedback learning was not. Striatal volume was associated with both forms of learning, in contrast to prior research funding in adults. Brain-behaviour correlations were stable across the 2-year period, despite the hippocampus increasing in volume and striatal volume remaining stable.

eLife Assessment

This valuable study advances understanding of how corticotrophin releasing factor in the bed nucleus of the stria terminalis regulates sustained and phasic fear and how this differs between sexes. The evidence is convincing and based on state-of-the-art techniques. The work will be of interest to neuroscientists studying the biological basis of fear processing.

eLife assessment

The authors have improved a method to differentiate human iPSC-derived microglial cells with immune responses and phagocytic abilities; and through transplantation into the adult mouse retina, the authors further demonstrated their integration and occupation of native microglial cell space, and functional response to retinal injuries. The study is important and the data are convincing for potential microglial replacement therapy to treat retinal and CNS diseases.

eLife assessment

This valuable study informs whether diminishing BDNF expression or alterations in the activity of BDNF-containing neurons in the paraventricular nucleus of the hypothalamus contributes to metabolic alterations in individuals with reduced RAI1 function, including those afflicted with Smith-Magenis syndrome (SMS). The evidence supporting the conclusions is compelling in that RAI1 deficits in BDNF-containing neurons partly contribute, with prominent effects on glycemic control and modest effects on feeding and body weight regulation. This study would be of interest to neuroscientists and medical biologists working on metabolic disorders such as obesity and diabetes, as the findings in this study further links SMS-associated obesity with reduced Bdnf gene expression in the PVH and shed light on the role of the Rai1 gene in the PVH Bdnf neurons and offer a basis for future therapeutic strategies for managing obesity in SMS.