Evaluated articles

eLife assessment

Hudson and colleagues provide a new link between oxygen sensing and cholesterol synthesis. In previous studies, this group had shown that the cholesterol synthetic enzyme squalene monooxygenase (SM) is subjected to partial proteasomal degradation, which leads to the production of a truncated, constitutively active enzyme. Here, the authors provide evidence for the physiological significance of SM truncation by showing that subjecting cells to hypoxia (oxygen deprivation) induces truncation of SM. The synthesis of cholesterol requires 11 molecules of oxygen and SM is the first oxygen-dependent enzyme in the cholesterol-committed branch of the pathway. It is possible that constitutive activation of SM under oxygen-deficient conditions could reduce the toxicity of squalene and other sterol intermediates.

eLife assessment

This valuable study examines a largely ignored brain structure (the thalamus) in functional brain imaging studies. In general, the study shows convincing evidence from the reanalysis of two task-based MRI studies that localized thalamic regions show hub properties in terms of their activation properties and connectivity to cortical regions. While the strength of the study is that converging evidence was shown across two large data sets, the empirical support for some of the claims in the current version remains incomplete.

eLife assessment

This is a fundamental study that demonstrates that ongoing neuronal activity plays a key role in the vulnerability of specific neuronal cell types in layer 2 of the entorhinal cortex that communicates with the hippocampus. The authors provide compelling evidence that chronic silencing of inhibitory but not excitatory neurons in the entorhinal cortex leads to their degeneration. Reelin-positive interneurons were the most vulnerable to silencing. The authors propose that developmental mechanisms associated with activity-dependent programmed cell death could be aberrantly reactivated in the context of Alzheimer's disease.

eLife assessment

This manuscript is of primary interest to immunologists with a focus on the effects of interleukin-2 and T cell receptor (TCR) signaling on effector T cell differentiation and function. Extensive and well-controlled experiments support a model where TCR and interleukin-2 signals promote a specific subset of effector CD8+ T cells - termed KILR cells - with superior target cell killing properties.

eLife assessment

This valuable study presents a new optimal control cost framework to predict features of walking bouts, adding a cost function term proportional to the duration of the walking bout in addition to the conventional energetic term. While predicted optimal trajectories from simulations qualitatively matched walking data from human subjects, the evidence supporting these claims is incomplete, as some methodological choices raise questions about the strength of the authors' claims.

eLife assessment

This is an important paper that proposes a novel evolutionary mechanism by which copy-number mutations can slow down the accumulation of point mutations in populations evolving in certain environments. The authors use an evolution experiment in bacteria equipped with a clever reporter system to provide solid evidence that this mechanism indeed operates. This paper will be of broad interest to readers in evolutionary biology and related fields.

eLife assessment

The C-type lectin receptor family recognise pathogens and self-components. Dectin-1 is known to recognize glucan on pathogens. In this fundamental study Dectin-1 and CLEC-2 another - C-type lectin receptor, expressed on platelets - interact through an O-glycosylated ligand presented in the stalk region of Dectin-1. This compelling study demonstrates a potential role for pattern recognition receptors in physiological processes.

eLife assessment

This study is of relevance to the field of collective animal behavior. The proposed crop-cue-based motion-switching rules provide a welcome alternative to other models that assume far more deliberative abilities of ants, and it will be valuable to add this example to the collective motion and collective decision-making literature. There were several major issues that need addressing, including: overly simplistic models, no connection to similar phenomena in motion ecology and statistical mechanics, potential deficiences in the stochastic modeling approach, as well as some confusing terms and curious citations of the literature.

eLife assessment

This paper presents findings from a novel experimental study of the dynamics of human overground running on naturalistically uneven terrain. The terrain used in the experiments has mildly stochastic undulating roughness, a condition that closely resembles many natural terrain conditions, such as trail running. The authors present evidence that humans use open-loop intrinsically stable strategies to run on this terrain, and do not visually guided foot placement. The findings make an important contribution toward understanding the context-dependent role of vision in navigating uneven terrain.

eLife assessment

This paper addresses the long-standing problem of color categorization and the forces that bring it about, which can be potentially interesting to researchers in cognition, visual neuroscience, society, and culture. In particular, the authors show that as a "model organism", a Convolutional Neural Network (CNN) trained with the human-labelled image dataset ImageNet for object recognition can represent color categories. The finding reveals important features of deep neural networks in color processing and can also guide future theoretical and empirical work in high-level color vision.

eLife assessment

The authors collected and analyzed blood samples from >9,000 participants from two cross-sectional cohort studies in the UK, the ALSPAC cohort and the TwinsUK cohort. They measured anti-Nucleocapsid and anti-Spike antibodies using the collected blood samples. They investigated the variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination. They identify that following the third vaccination, risk factors associated with low antibody response after the first vaccination are less likely to lead to sub-protective levels. While this finding is of potential importance, the presentation of the data is diffuse and not focused at times, and more discussion is needed to highlight its relevance to the current stage of the pandemic.

eLife assessment

This valuable study combines phenotypic analysis, quantitative genetics and population genomics to propose that multiple genes underlie adaptive divergence in a marine midge system linked to tidal rhythm. Genes with a plausible role in perceiving and responding to lunar information are among the loci that most highly differentiate populations with distinct behaviors, but how much of this might be due to demography remains unclear. The evidence from quantitative trait locus is also deemed incomplete at this point.

eLife assessment

This manuscript is of interest to scientists studying the genetics of complex human diseases. The approach introduced here is potentially useful for the identification of tissues linked to complex disease heritability. Currently, the key claims of the paper are not entirely supported by the data. The claims may become well supported once the authors improve statistical rigor and perform a more comprehensive comparison with other methods.

eLife assessment

This manuscript provides valuable evidence for the role of magnesium homeostasis and relevant signaling pathway in Drosophila sleep regulation. It will be of interest to cellular biologists and neuroscientists interested in sleep:wake behavior and the potential role of magnesium in promoting sleep. Nevertheless, the evidence for the key claims of the manuscript is incomplete and is not fully supported by the data as reasonable alternative explanations exist.

eLife assessment

Tran-Van-Minh et al., attempt to develop a statistical approach which will allow consolidation of new, as well as previously-acquired datasets, to yield biologically significant insights into the logic underlying rabies vectors' expansion from single starter cells. While such work is called for, many of the premises presented here will need to be significantly adjusted, before the approach could be put into widespread use.

eLife assessment

This paper reports a fundamental set of new results describing replisome organization and dynamics in E. coli. Cellular sites of active DNA replication (forks) spatially co-localize into structures termed replication factories, but the biological rationale for this fork co-localization has remained unknown. In an elegant study, the authors provide strong evidence that these factories are necessary to both coordinate and promote the progression of colocalized forks, and to help prevent them from spontaneously and prematurely dissociating. Through these findings, it is shown, for the first time, that replisomes' association has a beneficial impact on the bacterium. This is important work that provides robust data in favor of the factory and splitting model.

eLife assessment

This study presents an important finding on the decoy effect in multiattribute economic choices in humans. It makes a compelling case for the conclusion that the distractor effect reported in previous articles was confounded with the additive utility difference between the available alternatives. Though the contribution is somewhat narrowly focused with respect to the phenomenon that it addresses - the distractor effect in risky choice, it is important for understanding this particular phenomenon. The main weakness is the complexity of the current manuscript.

eLife assessment

This manuscript provides the first cellular analysis of how neuronal activity in axons (in this case the optic nerve) regulates the diameter of nearby blood vessels and hence the energy supply to neuronal axons and their associated cells. This is an important subject because, in a variety of neurological disorders, there is damage to the white matter that may result from a lack of sufficient energy supply. This paper will stimulate work on this important subject.

eLife assessment

This study provides compelling structural evidence on regulation of cerebellar synapses by sleep-wake states. The authors used serial block face scanning electron microscopy to obtain 3D reconstruction of more than 7,000 spines and their parallel fiber synapses in the mouse posterior vermis. The analysis shows that sleep increases the fraction of the 'naked' spines that don't carry a presynaptic partner at Purkinje cells. The authors propose that sleep promotes the pruning of branched synapses to single spines. This is an elegant and thorough study and the observations are important in light of the circuit-specific mechanisms by which sleep modulate synaptic structure and function.

eLife assessment

This important study describes transcriptomic profiles of sensory and non-sensory cells of the zebrafish inner ear at single-cell resolution in embryonic through adult stages. These solid results catalogue transcriptomic data and show evidence that distinct cell subtypes exist between cells of the ear and the lateral line as well as within subcellular compartments in the inner ear. These findings provide information toward comparison studies of inner ear hair cell function in zebrafish and mammals.