Evaluated articles

eLife assessment

This valuable work, of interest to ion channel physiologists, identifies regions involved in the desensitization of the proton-activated chloride channel (PAC), a widely expressed ion channel involved in organelle pH homeostasis and acid-induced cell death. At the present stage the data only incompletely support the interpretations, and further experiments will be required to consolidate some of the authors' claims.

eLife assessment

This manuscript follows the still unanswered concept of 'original antigenic sin' and shows the existence of a 24-year periodicity of the immune response against influenza H3N2. The valuable work suggests a long-term periodicity of individual antibody response to influenza A (H3N2) within a city. But, to substantiate their argument, the authors would need to to provide additional supporting data.

eLife assessment

This paper provides valuable new insight into the neural encoding and behavioral tracking of visual objects in the Drosophila. It provides solid evidence that a specific type of neuron in the fly visual system (T3 neuron) is involved in the tracking of moving objects during flight. With additional experimental evidence to resolve whether T3 neurons function as local object detectors, this paper would be of broad interest to visual neuroscientists.

eLife assessment

This work presents a framework for estimating missing data on cervical cancer epidemiology. If properly validated, it could help determine missing data in regions where data are scarce. The work will be of broad interest to researchers and policymakers evaluating cervical cancer prevention measures.

eLife assessment

Masschelin et al. investigate the role of Vitamin B2 (riboflavin), an essential cofactor for FAD and FMN coenzymes involved in the electron transport chain and TCA cycle, in fasting glucose metabolism. This study phenotypes B2-deficient mice liver and provides valuable data on genes and metabolites that are changed with B2 depletion +/- Fenofibrate administration. The work employs solid methodology and will be of interest to liver physiologists interested in fasting in the context of PPAR.

eLife assessment

This manuscript will be of interest to a wide range of neuroscientists and clinicians employing imaging methods. Using a combination of cutting edge high resolution magnetic resonance protocols, the authors investigate the structure-function relationship of specialised compartments in the human cortex in vivo. Their results indicate different patterns of myelination across the "stripes" of visual area V2, but will require further independent validation with myelin staining in the human brain.

eLife assessment

This manuscript reports the response by cortical interneurons from mice expressing genetically defined fluorescent markers to sensory stimulation performed in awake animals without anesthesia. The data show in some cases distinct responses in specific neuron types. This manuscript contains unique information that will be valuable to other researchers in the field and influence future research in the field of cortical GABAergic neurons.

eLife assessment

Combining electrophysiology, site-directed mutagenesis, lipid pharmacology, and single particle cryo-electron microscopy, this study provides solid evidence identifying a site on the extracellular half of the transmembrane domain of Proton-Activated Chloride (PAC) channels that could be occupied by PIP2 and related lipids to promote channel desensitization. These findings are important because pharmacological information for these biologically relevant ion channels is absent.

eLife assessment

Myostatin KO is known to increase muscle mass, but can transplanting the gut microbiome from these animals also increase muscle mass and strength? Based on the experiments performed in this paper, the answer is yes, and the positive impact of myostatin deletion on the gut-muscle axis may proceed through alteration of gut bacterial metabolism, including short-chain fatty acids. This is important work and will contribute to the expanding field of the gut-muscle axis.

eLife assessment

This paper is an important contribution to the biological aging field using eye image data to create an aging clock of the retina in data from eyePACS with validation in the UK Biobank. The authors provide compelling evidence that the clock correlates with chronological and phenotypic age, predicting mortality independently of chronological age. The work identifies novel genetic loci with a top site located in the ALKAL2 region, which is functionally validated in a Drosophila model.

eLife assessment

The study by Ben Yaakov et al. describes a single cell analysis of the mammalian ovary in young, adult and old mice. Based on gene expression profiles, the authors identified cell clusters corresponding to immune cell populations in mouse ovaries and compared their abundance in aged compared to adult animals. In comparison with previous studies that used single cell RNAseq to characterize the heterogeneity of cell types in the ovary, this study focuses only on immune cells resulting in much better coverage to characterize the changes that these cells undergo as a function of age. The combination of single-cell RNA sequencing and flow cytometry used by the authors is a robust and unbiased approach to characterize immune cell alterations in aging ovaries. Overall, the data and analyses presented in this study reveal profound modifications of the immune system in the aging reproductive system in mice. However, while both the data and biology presented are quite interesting, this study is perhaps too wide in breadth such that no individual result is extensively and rigorously explored.

eLife assessment

Single-particle tomography (SPT) is a useful method to determine the structure of proteins imaged in situ. This important work presents an easy-to-use tool for SPT that approximates the use of 2D tomographic projections using a "pseudo-subtomogram" data structure, chosen to facilitate implementation within the existing Relion codebase. The examples shown provide solid support for the claims about the efficacy of the approach.

eLife assessment

The authors address an important clinical entity and an important area of unmet clinical need. The authors use a combination of in vitro and in vivo experiments to learn how stromal cells surrounding vessels in venous malformations (VM) and angiomatosis of soft tissue (AST) contribute to the angiogenic activities driving the vascular lesions. They discovered that secretion of transforming growth factor-alpha (TGFa) from both endothelial cells and stromal cells, shows evidence for EGF-receptor phosphorylation. In addition, they show that afatinib, a pan-ErbB TKI inhibitor may have therapeutic benefits.

eLife assessment

The goal of this study is to identify allosteric modulators of a SLC-1 amino acid transporter, ASCT2, which has been implicated in cancer progression. By combining computational and docking methods with functional measurements, this study provides solid evidence for specific aspects of allosteric SLC-1 inhibition mechanisms. The findings are important to transporter mechanism and pharmacology.

eLife assessment

This solid study addresses the functionality of neurovascular coupling in response to somatosensory stimuli in premature neonates based on a compelling methodology combining recordings with fMRI and EEG (microstates approach). While the findings are important for the understanding of the emergence of brain sensory processing, more extended analyses of inter- and intra-subjects' variability are required to support the results interpretation and determine the influence of important factors impacting brain maturation and activity. With the theoretical and analytical parts strengthened, this study will be of interest to developmental neuroscientists and neuroimaging specialists and might have important clinical implications in the field of neonatology.

eLife assessment

This is an important paper that evaluates the roles of long descending propriospinal neurons in the recovery of walking ability after spinal cord injury. The data are convincing overall though some weaknesses in the evaluation of the completeness of the synaptic silencing strategy were identified. The data will be of interest to those who study spinal circuitry and its role in locomotor function after spinal cord injury.

eLife assessment

This fundamental study represents a significant advance in our understanding of the complex evolutionary history of the eggshell features in one of the main leaving bird lineages, Palaeognathae, with compelling and thoughtfully presented results. The work will be of interest to many biologists, paleontologists, and archaeologists.

eLife assessment

This important study combines rigorous behavior and single-unit recordings in nonhuman primates to investigate the role of three cortical areas in cross-modal sensory calibration, a form of neural plasticity that is important for perception and learning. The results convincingly demonstrate key similarities and striking differences across the three areas, and provide the first evidence for this form of calibration (in correspondence with behavior) at the level of single neurons. The work will be of broad interest to neuroscientists and psychologists studying multisensory perception, plasticity, and the role of sensory and association cortices in perceptual decisions.

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.