Evaluated articles

eLife assessment

George et al. present a convincing new Python toolbox ("RatInABox") that allows researchers to generate synthetic behavior and neural data specifically focusing on hippocampal functional cell types (place cells, grid cells, boundary vector cells, head direction cells).

This is valuable for theory-driven research where synthetic benchmarks should be used. Beyond just navigation, it can be highly useful for novel tool development that requires jointly modeling behavior and neural data. The authors provide convincing evidence of its utility with well documented and easy to use code and the corresponding manuscript.

eLife assessment

This potentially valuable study provides some evidence that upregulation of sodium-activated potassium channels contributes to neuronal hyperexcitability and seizures following traumatic brain injury. However, the evidence supporting a direct link is incomplete. This work will be of interest to epilepsy and ion channel researchers.

eLife Assessment

These valuable studies explore the consequences of exposure to the toxin hydrogen sulfide (H2S) on the behavior and physiology of C. elegans. The work finds that behavioral changes evoked by H2S exposure are modulated by several regulatory pathways known to influence chemosensory-evoked locomotor behavior, but there is incomplete data to support the authors' claim of comprehensive mechanistic insight into the consequences of H2S exposure. Nevertheless, the findings may be informative for those studying organismal stress responses and the effects of mitochondrial ROS on behavior and physiology.

eLife assessment

In this important study, Guma and colleagues describe the use of structural neuroimaging to assess the cross-species convergence of sex differences in global and regional brain volumes in humans and mice. The goal of the work is to inform to what extent mouse studies of these aforementioned sex differences have relevance to humans. The authors suggest which aspects of brain anatomy (as measured by volume) are conserved or not, across species, which has theoretical and practical implications beyond a single sub-field. The evidence to support the findings is solid, it uses methods and data analysis that are appropriate and validated.

eLife assessment

This important work advances our understanding of how brains flexibly gate actions in different contexts, a topic of great interest to the broader field of systems neuroscience. Recording neural activity from several sensory and motor cortical areas along a sensorimotor pathway, the authors found that preparatory activity in motor cortical areas of the mouse depends on the context in which an action will be carried out, consistent with previous theoretical and experimental work. Furthermore, the authors provide causal evidence that these changes support flexible gating of actions. The carefully carried out experiments were analyzed using state-of-the-art methodology and provide convincing conclusions.

eLife assessment

This important work provides insight into the activity and spatial organization of synapses during early postnatal development in the mouse visual cortex, using state-of-the-art tools to show that synapses are distributed in co-active clusters well before eye opening. The evidence supporting the claims is convincing, and this revised version provides additional methodological details about the experimental paradigm and image analysis.. This work is of particular interest to the field of developmental neuroscience and can also be used by computational neuroscientists studying dendritic integration.

eLife Assessment

The contributions of ipsilateral cortical pathways to motor control are yet not fully understood. Here, the authors present important insights into their role in locomotion following unilateral spinal cord injury. Their data provide convincing evidence in rats that stimulation of ipsilateral motor cortex improves the injured side's ability to support weight and leads to improved locomotion, a result that may inspire new treatments for spinal or cerebral injuries.

eLife assessment

This study investigates BMP signaling mechanisms in the developing chick cerebellum to better understand germinal layer formation, cellular amplification and neuronal differentiation. The data from human tissue is compelling and lends support to the possible links of these processes to medulloblastoma, although this study does raise exciting questions regarding the generalized role of BMP signaling during normal development and malignant growth. Overall, this is an important study with beautifully presented findings.

eLife assessment

This is an important study that develops a method to fluorescently label peptide MHC complexes on live dendritic cells to enable detection of antigen specific T cells in polyclonal populations. Solid evidence that this can be used to effectively identify antigen specific T cells in vitro and in vivo is provided for one model antigen systems (Ova-OTII). The approach has exciting potential as prior single step methods with directly conjugated single peptides have generally failed due to high background. Thus, this approach potentially moves the state of the art forward, but further work is needed to realise and determine the limits and ultimate utility of the approach.

eLife assessment

This valuable study on the molecular and cellular mechanisms of ingestion avoidance of high salt in insects is focused in scope, but the authors present convincing evidence that a specific subset of gustatory receptors in a pair of pharyngeal taste neurons are necessary and sufficient for avoiding ingestion of high salt during feeding. This work will be of interest to Drosophila neuroscientists interested in taste coding and feeding behavior.

eLife Assessment

This fundamental study advances substantially our understanding of sound encoding at synapses between single inner hair cells of the mouse cochlea and spiral ganglion neurons. Dual patch-clamp recordings-a technical tour-de force-and careful data analysis provide compelling evidence that the functional heterogeneity of these synapses contributes to the diversity of spontaneous and sound-evoked firing by the neurons. The work will be of broad interest to scientists in the field of auditory neuroscience.

eLife assessment

The study presents valuable findings on sexually dimorphic patterns of osteocytic transcriptomes and low calcium diet-induced osteocytic osteolysis in FNDC5-deficient mice. The authors present solid evidence for sex-specific changes in osteocyte morphology and gene expression under a calcium-demanding setting in this particular strain of mice, although the protective role of FNDC5-deficiency in lactation and low-calcium diet in female mice remains unclear due to lack of mechanistic studies. The study also lacks evidence that irisin, a proteolytically cleaved product of FNDC5, is responsible for the observed phenotypes, as irisin was not directly measured.

eLife assessment

This study presents a valuable finding on the process of brown to white adipogenic transdifferentiation within the perirenal adipose depot. The evidence supporting the claims is convincing, although limited sequencing depth of single nuclei and lack of regulatory insights somewhat lessens the impact of these findings. The work will be of interested to adipose tissue biologists.

eLife assessment

This is a potentially useful study that shows changes in the chromatin landscape of GABAergic neurons in induced pluripotent stem cells (iPSCs) derived from both Dravet Syndrome (DS) patients and healthy donors. The strength of the evidence is currently incomplete because the authors compared iPSCs from different individuals, rather than isogenic controls. A strategy for minimizing variability across cell lines is used, but the explanation is not complete. The revised manuscript adds RNAseq and qPCR measurements of the expression of the gene SCN1A, however these do not appear to agree, perhaps because of the way the qPCR measurements are normalized, and there is no measurement of Nav1.1, the gene product thought to be responsible for the majority of DS cases. Hence the evidence that there is reduced expression of SCN1A or its gene product is not complete and therefore it is difficult to evaluate whether or not the observed epigenetic changes are causal. The work would potentially be of interest to scientists who study development, developmental disorders, and epigenetic contributions to disease.

eLife Assessment

This comprehensive and compelling study presents a robust, cost-effective method for expanding pluripotent stem cells. The authors have identified a media condition that maintains iPSCs in suspension cultures by inhibiting the PKCβ and Wnt signaling pathways. The manuscript is important for the pluripotent stem cell field as it seeks robust and economical approaches to expand iPSCs at scale for high throughput screens and preclinical studies. While the authors have tested their media and protocol on a few lines, given the variability of iPSCs, further testing across more cell lines and in different laboratory settings will be crucial to evaluate its reproducibility.

eLife assessment

Varadharajan et al. explore the mechanistic basis of MBOAT7 SNP association with steatotic liver disease and link its function in LPI acylation to altered lipidomics of endosomal/lysosomal system and impaired TFEB mediated lysosomal biogenesis. The findings are important with theoretical and practical implications in MAFLD, alcohol-induced hepatic steatosis, and lysosomal diseases. The strength of evidence is convincing using methodology in line with current state-of-the-art.

eLife assessment

This work presents an important technological advance, in the form of a high throughput platform for Single Particle Tracking allowing us to measure millions of cells and thousands of compounds per day. Analysis of the diffusional behaviour of fluorescently-tagged targets permits the identification of, and differentiation between, small molecules that bind directly or affect the target indirectly. The methodology and metrics employed are compelling, leading to the identification of multiple compounds that effectively change the diffusive state of the estrogen receptor, the POC target of the study.

eLife Assessment

This important work presents data showing that all non-proneural phenotypes of the Inhibitor of DNA binding (Id) protein Emc are mediated through inappropriate nonapoptotic caspase activity. Using the developing Drosophila retina as a model the authors show that Emc acts by transcriptionally regulating the Death-Associated Inhibitor of Apoptosis 1 (diap1) gene, which impacts on Notch signaling by caspase-dependent increase of Delta protein. These are compelling findings, interesting for the caspase/apoptosis field as they add more non-apoptotic functions of caspases to the list, as well as for the Id field, which examines how Id proteins inhibit cell differentiation.

eLife assessment

The findings are fundamental for understanding IgM signaling in myeloid cells. The work is compelling in its ability to manipulate and harness myeloid cells to further anti-tumor immunity.

eLife assessment

Through a theoretical approach, this study makes important contributions to our understanding of the evolutionary causes of the ageing process. Using a simple individual-based model and computational simulations, the authors provide convincing evidence that ageing can be a trait under natural selection, opening the door for further discussion in the context of lifespan extension research.