Evaluated articles

eLife assessment

This study aims to explore the diabetes-bone paradox using the Mendelian Randomization approach. That diabetes itself is not the direct cause, but rather the complications or associated risk factors increase the risk of fracture, constitutes a valuable insight. Mendelian randomization to explain the relationship of two complex conditions is solid and conducted properly; however, the efforts to reconcile the discrepancies between the Mendelian Randomization analysis and observational studies are incomplete.

eLife assessment

This fundamental study reports differential expression of key genes in full-term placenta between Tibetans and Han Chinese at high elevations, which are more pronounced in the placenta of male fetus than in female fetus. The gene expression data were collected and analyzed using solid and validated methodology, although there is limited support for hypoxia-specific responses due to a lack of low-altitude samples. Several of the placental genes found in this study have been previously reported to show signatures of positive selection in Tibetans, pointing to a potential mechanism of how human populations adapt to high elevation by mitigating the negative effects of low oxygen on fetal growth. The work will be of interest to evolutionary and population geneticists as well as researchers working on human hypoxic response.

eLife assessment

This study provides valuable insights into the specificity and promiscuity of toxic effector and immunity protein pairs. While the work is improved over a previous version, there are still some questions regarding the methodology used to draw certain conclusions, rendering the study somewhat incomplete. Nevertheless, this work will likely be of interest to microbiologists and biochemists working with toxin-antitoxin systems and effector-immunity proteins.

eLife assessment

This valuable study presents a screening pipeline (SPICE) for detecting DNA motif spacing preferences between TF partners. SPICE predicts previously known composite elements, but experiments to elucidate the nature of the predicted novel interaction between JUN and IKZF1 are incomplete. These experiments would benefit from more rigorous approaches using other databases to explore additional relevant data. The work will be of broad interest to those involved in dissecting the regulatory logic of mammalian enhancers and promoters.

eLife assessment

This manuscript uses genetic mouse modeling to delve deeper into a rare human disease of aging. The targeted approaches employed lend greater pathophysiologic insight and makes this paper valuable to the field art large. Additionally, the approaches used are rigorous and solid in supporting their conclusions. Some minor weaknesses were noted along with suggestions to add greater clarity.

eLife assessment

This study provides a comprehensive whole genome transcriptomic analysis of three small mammals, including Peromyscus leucopus, after exposure to endotoxin lipopolysaccharide. The authors find that the inflammatory response of the three species is complex and that P. leucopus responds differently compared to mice and rats. The data are convincing and constitute an important advance in our understanding of inflammatory responses in animals that serve as reservoirs for relevant pathogens.

eLife Assessment

This paper provides fundamental insights into the control of Salmonella within human macrophages, with convincing evidence that Salmonella can replicate in the macrophage cytosol in the absence of inflammasome signaling. This paper, which improves our understanding of how the immune system fights bacterial infections, will be of broad interest to cell biologists, immunologists and microbiologists.

eLife assessment

This study presents a valuable finding for the immunotherapy of cancer. The data support the role of PDLIM2 as a tumor suppressor, and more immediately, its relevance for strategies to improve the efficacy of immunotherapy. The evidence supporting the conclusions is compelling and the work will be of interest to biomedical scientists working on cancer immunology.

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.