Evaluated articles

eLife assessment

In this important study, the authors identify distinct roles for the calcium sensors Synaptotagmin 7 and Doc2alpha in the regulation of asynchronous release and calcium-dependent synaptic vesicle docking in hippocampal neurons. The current work adds to the field by placing the role of the two proteins in a new context, where Synaptotagmin 7 acts to promote synaptic vesicle docking and capture after a stimulus, while Doc2alpha has a role in specifically driving the asynchronous component of release as a calcium sensor. The methods, data, and analyses provide convincing support for the conclusions.

eLife assessment

The important work by Aballay et al. significantly advances our understanding of how G protein-coupled receptors (GPCRs) regulate immunity and pathogen avoidance. The authors provide convincing evidence for the GPCR NPR-15 to mediate immunity by altering the activity of several key transcription factors. This work will be of broad interest to immunologists.

eLife assessment

This is an important and interesting account of the ability of Ym1 crystals to promote type 2 immunity in vivo, in mice. The data presented are compelling, building on and significantly advancing evidence this group has previously published on the type 2 immunogenicity of other protein crystals. The work will be of relevant interest to immunologists and researchers working on type 2 inflammatory disease, in the lung and in others tissues.

eLife assessment

This important study introduces a novel AI method for the analysis of published data, with practical implications for early cancer diagnosis. The results are supported by compelling evidence.

eLife assessment

This study based on the use of Cancer Drug Resistance Accelerator (CDRA) chip is valuable as a platform technology to assess chemoresistance mechanisms. The strength is convincing from the technological point of view. However, the use of a single cell line model is a limitation. However we acknowledge the authors' plan to further validate their current findings across multiple TNBC cell lines.

eLife assessment

This article brings to bear a useful, extensive set of behavioral methods and neural data to report that activity in numerous cortical regions robustly covaries with the complexity of tone sequences encoded in memory. In its current state, the findings are solid but deserve further analysis to arrive at more convincing conclusions.

eLife assessment

This study reports a valuable finding on the discovery and evaluation of a potent small molecule inhibitor for CRM1 that may be important to treat extranodal NK/T cell lympohma (ENKTL). The evidence supporting the claims of the authors is solid that reflects an important finding for novel CRM1 inhibitors to treat ENKTL, although additional experimental evidence is needed. The work will be of interest to cancer biologists working on ENKTL.

eLife assessment

This study presents a valuable finding on the function of the gene Cst7 in sex-divergent pathological changes in microglia in a mouse model of AB-driven Alzheimer's disease. The evidence supporting the claims of the authors is solid, although the study would be strengthened by validation of some of the key differentially expressed genes identified in RNA-sequencing experiments, and the inclusion of key controls and additional timepoints to address whether Cst7 drives disease progression or is simply upregulated as a result. The work will be of interest to neuroimmunologists and neuroscientists working on microglia and neurodegenerative disease.

eLife assessment

This paper measures the neural activity in reach-to-grasp and reach-only tasks using intrinsic optical imaging. The paper describes these in the relationship to the Intra-cortical micro stimulation maps of the same animals. The dataset is unique and potentially highly important. However, the claim of "clustered neural activity" is not tested against any quantifiable alternative hypothesis of non-clustered activity, and support for this idea is therefore currently incomplete.

eLife assessment

This study uncovers a unique feature of the nucleotide binding domain interface in human CFTR, offering valuable insights into the effects of different non-hydrolytic mutations on CFTR gating. While the evidence presented is solid, a more thorough examination of the non-hydrolytic mutants of zebrafish CFTR for comparison would strengthen the authors' claims. In the current form, more cautious interpretations of some of the data are needed. This study will be of interest to researchers in the fields of cystic fibrosis and proteins in the ATP Binding Cassette (ABC) transporter family.

eLife assessment

This study provides important insights into the structural biology and molecular mechanism of the sensory proteins ToxR/S that are associated with survival and virulence of the cholera pathogen. The structural studies are solid and supported by a series of biophysical experiments revealing a split, periplasmic protein binding interface for bile acid. The results are of interest to both protein biochemistry and pharmacology, potentially opening new routes for intervention in cholera disease.

eLife assessment

This paper will be of considerable interest to population geneticists and other scholars in the field of paleogenomics. The study provides an impressive dataset containing 200+ novel human ancient genome sequences and a very creative, robust, and novel approach for studying human migration across time using ancient DNA. The authors find that the population structure in Europe has been remarkably stable over time. The conclusions are well supported by the data and the methods used are thoughtful and rigorous.

eLife assessment

This important study examines the existence of a fear memory engram in acetylcholine neurons of the basal forebrain and seeks to link this to modulation of amygdala for fear expression. Using a combination of techniques including genetic access to cFos expressing neurons, in-vivo chemogenetics, and optical detection of acetylcholine (ACh), the authors present solid evidence that posteriorly-located amygdala projecting basal forebrain cholinergic neurons participate in cue-specific threat learning and memory. This paper will be of interest to those studying circuit-level mechanisms of learning and emotion regulation.

eLife assessment

This is an important study of the mechanism of how binding of the fatty acid myristic acid (MYR) inhibits the activity of the kinase c-Abl, a critical regulator of many cellular processes. While the general aspects of this regulation are known from structure determination and biochemical studies, the exact molecular mechanism and the nature of the allosteric inhibition were not known. The authors use MD simulation to close this gap and provide a detailed mechanistic description of the inhibitory mechanism, although some of the evidence remains incomplete.

eLife assessment

This important multicenter study provides convincing evidence that the auditory noise emitted during online transcranial ultrasound stimulation (TUS) protocols can pose a considerable confound and is able to explain corticospinal excitability changes as measured with Motor Evoked Potentials (MEP). The findings lay the ground for future studies optimising protocols and control conditions to leverage TUS as a meaningful experimental and clinical tool. A clear strength of the study is the multitude of control conditions (i.e., control sites, acoustic masking, acoustic stimulation). These findings will be of interest to neuroscience researchers using brain stimulation approaches.

eLife assessment

This important paper addresses the process by which cryptic splice sites that occur randomly in exons are ignored by the splicing machinery. Integrating state-of- the-art genome-wide approaches such as CLIP-seq with the study of individual examples, this study convincingly implicates members of RBMX family of RNA binding proteins in such cryptic splice site suppression and showcases its importance for the fidelity of expression of genes with very large exons.

eLife assessment

This manuscript describes a deep mutational scanning study of the kinase domain of the MET receptor tyrosine kinase. The study yields an important catalog of essentially all possible deleterious mutations in this portion of the receptor., with convincing evidence. The manuscript will be of interest to researchers working in the field of receptor tyrosine kinases.

eLife assessment

This study presents useful findings for how sevoflurane anesthesia modulates the activity of corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus and how manipulation of such PVHCRH neurons influences anesthesia and post-anesthesia responses. The technical approaches are solid and the data presented is largely clear. Whether PVHCRH neurons are critical for the mechanisms of sevoflurane anesthesia is a direction for the future.

eLife assessment

This important study provides convincing evidence of the criticality of estradiol – estrogen receptor-mediated upregulation of kisspeptin within neurons of the preoptic area to generate an ovulation-inducing luteinizing hormone surge. The use of in vivo CRIPSR-Cas9 is novel in this system and provides a road map for future studies in reproductive neuroendocrinology. This paper will be of interest to reproductive neuroscientists and endocrinologists.

eLife assessment

This important manuscript focuses on the mechanisms by which food signals and food ingestion modulate animal foraging. The authors provide convincing support for the interesting idea that chemosensory and interoceptive signals converge on transcriptional regulation of the TGF-beta ligand DAF-7 in a single pair of C. elegans chemosensory neurons (ASJ) to regulate behavior. Their studies implicate a conserved signaling molecule, ALK, in this regulation, suggesting a conserved link between food cues and the neuroendocrine control of foraging behavior.