Evaluated articles

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.

eLife assessment

This study demonstrates that neurons receiving inputs from auditory cortex in the inferior colliculus widely encode the outcome of a sound detection task independant of the presence of auditory cortex. This valuable study based on imaging of transynaptically labelled neurons provides convincing evidence that auditory cortex is necessary neither for sound detection, nor to channel information related to behavioral outcome to the subcortical auditory system. This study will be of wide interest for sensory neuroscientists.

eLife assessment

This manuscript describes a potentially important theoretical framework to link predictive coding, error-based learning, and neuronal dynamics. The provided evidence is solid, but some details would benefit from additional clarification. The exposition of the manuscript is targeted for a specialist audience.

eLife assessment

This fundamental study presents a method to restore muscle innervations in ALS mouse models using optogenetics. It is convincing that embryonic stem cell derived motor neurons can be transplanted into and applied to reinnervate the muscles in an ALS mouse model. The work will be of broad interest to researchers and medical biologists to develop new strategies for the treatment of neurodegenerative disorders resulting from denervated skeletal muscles.

eLife assessment

This valuable study examines the evolution of the pillars in the shell architecture of organo-phosphatic brachiopods. The phylogenetic implications of this shell structure in relation to other early Cambrian brachiopod families are interpreted based on solid evidence. As such, this paper with interesting ideas regarding the evolution of brachiopod shell structure contributes to our understanding of the ecology and evolution of brachiopods as a whole.