Evaluated articles

eLife assessment

The work presented is fundamental to the field of negative-sense RNA viruses. It showcases a compelling set of ideas and approaches to study some physicochemical properties of organelles in live cells during a viral infection. However, the conclusions could benefit by adding a deeper theoretical approach and additional experimental support.

eLife assessment

This is an important survey of disulfide-rich peptides (DRPs), which comprise a large fraction of the most functionally important components of spider venom. While spider DRPs were thought to have evolved independently numerous times throughout the spider tree of life, the authors make a solid case for the idea that they all stem from a single common ancestral protein. The study makes a significant advance towards formalizing the diversity of spider venoms, which will be of interest both to scientists working on protein evolution and to those working on functional venomics.

eLife assessment

The present study presents the important finding that HIV infection activates the NLRP3, IFI16, and AIM 2 inflammasome pathways and that treatment with the anti-caspase 1 inhibitor VX-765 moderately reduces inflammasome activation and CD4 T cell depletion in a humanized NSG mouse model. The evidence supporting that inflammasome activation may play an important role in CD4 T cell depletion and that anti-caspase-1 inhibitors may reduce harmful inflammation is for the most part solid, although not always complete. The results will be of interest to scientists and physicians working on HIV immunology, pathogenesis and cure strategies.

eLife assessment

This important study provides evidence for CPC-3 mediating induction of the transcription factor CPC-1 in starved Neurospora cells, with CPC-1-mediated recruitment of Gcn5 and acetylation of the FRQ promoter counteracting the function of histone deacetylase HDA1, which in turn maintains high occupancy of the transcription factor WCC and attendant circadian rhythm of FRQ expression. The findings are significant in showing how the well-established pathways for circadian rhythm centered on FRQ gene expression and cross-pathway control centered on CPC-1 induction are integrated to maintain rhythmic cell growth in the face of amino acid limitation. However, the evidence for these claims is incomplete in certain respects and additional statistical analyses and experimental evidence are needed to better support the claims of rhythmic CPC-1 binding at FRQ, of the role of GCN-5 in rhythmic FRQ transcription in starvation conditions, and of rhythmic transcription of CPC-1-regulated amino acid biosynthetic genes.

eLife assessment

This work is of significant interest to those studying neurodegeneration, demonstrating key pathologies in PLA2G6-associated disease in both patient-derived neuronal models and a novel trans heterozygote mouse model. Moreover, it identifies a number of possible compounds that could potentially be re-purposed for therapeutic use in PLA2G6-associated neurodegeneration. Lastly, it shows a proof-of-principle in a mouse model that gene therapy with human PLA2G6 can rescue defects in PLA2G6 deficiency. Whilst the majority of the data are solid and convincing, there are a number of consolidatory experiments that would add greatly to the overall impact and novelty of the work.

eLife assessment

This important study presents insights into how conformational dynamics differentially influences drug specificity and affinity in myosin isoforms using computational approaches. The evidence supporting the conclusions is convincing, establishing a relationship between inhibition and protein dynamics using state of the art computational techniques followed by experimental validation. The work will be of broad interest to computational biophysicists and medicinal chemists.

eLife assessment

This study provides further detailed analysis of recently published Fly Atlas data supplemented with newly generated single cell RNA-seq data. Through characterizing these datasets, the authors define different germ cell and somatic cell clusters throughout the testis. This work confirms and extends previous observations regarding the changing gene expression programs these cells exhibit during their differentiation. This manuscript provides an important and detailed foundation for future studies of these lineages.

eLife assessment

This work provides an important pipeline for high-throughput screening platform to be used for drug discovery. The current data are incomplete. Further validation of human patients-derived iPSC clones and functional assays in mice will strengthen the conclusion.

eLife assessment

This paper is a first report of a human subject with an MCAT mutation showing reduced mitochondrial activity, but without defining the molecular mechanism connecting the loss of MCAT activity to mitochondrial dysfunction. It adds to the important field of mitochondrial disease genes and how they impact human physiology.

eLife assessment

This paper reports important findings on the mechanisms by which death pathways are activated by Shigella infection to impact the host response. The methods used provide compelling evidence for the involvement of multiple death cell pathways in the pathogenesis and host response to murine shigellosis. The results presented therein will be of interest to investigators in the field of bacterial pathogenesis, infectious disease and immunology.

eLife assessment:

This article reports the fundamental discovery that interfering with the function of the tyramine receptor causes a rapid decline in responses to olfactory stimuli in the honey bee. While tyramine signaling might specifically control the process of latent inhibition without affecting appetitive conditioning, the present analysis is incomplete in terms of ruling out the possibility that tyramine affects other functions of the antennal lobe. Nonetheless, compelling data highlight the role of one of the most highly expressed biogenic amine receptors in the insect olfactory system.

eLife assessment

This important study explores the question of "what gives rise to micro-diversity in ecological settings", and proposes a scenario of spatiotemporal chaos, in which interactions between strains drive large changes in the relative abundances of strains. The presented theoretical approach is compelling and goes beyond the current state of the art. This innovative theoretical work is of broad interest to the field of ecology and evolution.

eLife assessment

This is an important contribution to the field of dinosaur palaeontology. The authors provide convincing evidence for sexual dimorphism in dinosaurs, based on limb bones of ornithomimosaurs from the Cretaceous of France. The article makes several valuable and important contributions -- including the use of a large dataset and robust statistical approaches -- and will serve as a benchmark for future studies on dinosaurs and other fossil reptiles.

eLife assessment

This study presents a valuable finding of the role of under investigated pathway associated with development of placental oxygenation during pregnancy. The evidence supporting the claims of the authors is incomplete, although inclusion of a larger number of patient samples and an animal model have strengthened the study. The work will be of interest to developmental biologists working on placental function.

eLife assessment

This study demonstrates ultrafast real-time decoding of place fields in the hippocampus thanks to a head-mounted microscope for calcium imaging and to a novel data processing pipeline. This is a useful tool that aims at obtaining real-time capabilities that will enable closed-loop experiments that include decoding of a wide neuronal population, which could be applied in a variety of neuroscience fields. This will be of interest to anyone studying behaviors or functions that involve the hippocampus.

eLife assessment

In this important project, the authors used single-cell RNA-sequencing (scRNA-Seq) technology to profile the transcriptome of alveolar bone marrow single cells and demonstrated the protective role of mesenchymal stem cells (MSCs) during apical periodontitis. With comprehensive data, the authors identified new inflammatory biomarkers associated with the pathogenesis of oral inflammatory diseases. Their study suggests that certain MSC subsets may have a potential role in healing bone lesions.

eLife assessment

The primary goal of this paper is to characterize retinal dysfunction and retinal ganglion cell degeneration in the Wfs1exon8del murine model of Wolfram Syndrome 1. The study provides fundamental insight into the timelines of degeneration as well as valuable transcriptomic and proteomic datasets. The methodologies performed are generally rigorous and the conclusions reached are mostly well supported by the data, however, the interrogation of the mechanism is largely circumstantial and the relevance to disease is primarily speculative. The results of this study are highly relevant for molecular mechanisms in Wolfram Syndrome 1 and are of potential interest to scientists interested in oligodendrocyte and neuron communication.

eLife assessment

This study systematically integrates multi-omics data to identify the metabolic at-risk profiles within people living with HIV on antiretroviral therapy and presents findings that have focused importance and scope. The methods, data, and analyses as described now only partially support the primary claims.

eLife assessment

This manuscript starts from the hypothesis that a model of mitochondrial disease, the NDUFS4 knockout mouse, causes iron dysregulation, and that iron status may modify the neurological phenotypes that result in the mouse. This study has the potential to inform how body iron homeostasis can modify neurological phenotypes caused by mitochondrial disease. This study will be of interest to a broad audience of neuroscientists, particularly those with an interest in mitochondrial diseases.

eLife assessment

The study presents valuable findings on a gene called bero that affects the way larval Drosophila respond to nociceptive stimuli. This discovery is followed-up by the identification of neurons in which bero function is relevant for the modulation of nociceptive behavior, and by the additional identification of likely signaling molecules for conferring such modulation. The work will be of interest to neurobiologists working on genes, neural circuits, and behavior. While both interesting and methodologically elegant and diverse, important genetic controls for leaky expression of transgenes seem to be missing, as are alternative scenarios for results that, as the authors acknowledge, are unexpected or seemingly contradictory.