Evaluated articles

eLife assessment

The study presents analyses linking cell-types to monogenic disorders using over-expression of known disease-associated genes in single-cell data to identify 110 disease-affected cell types for 714 Mendelian diseases. Overall this important study combines multiple data analyses to quantify the connection between cell types and human disorders. While some of the analyses are compelling, updates to the method are needed to ensure that statistical inference is appropriately stringent and rigorous.

eLife assessment

This important study demonstrates that the human FUS protein, which is implicated in ALS and related conditions, interacts with RNAs containing GGGGCC repeats and can regulate their translation by altering three-dimensional structures caused by these repeats. The study is carefully executed and the data provide convincing evidence for its major claims. This work will likely be of interest to researchers studying RNA binding proteins, and to those working on ALS and related diseases.

eLife assessment

This paper presents a valuable advance in the ability to manipulate the integrity of the barrier between endothelial cells. A wide range of data are presented, offering convincing support for the effectiveness of the method. This work is likely to attract a diverse audience of both cell biologists and researchers developing tools to manipulate cell and tissue function.

eLife assessment

This important study investigates the dynamic activation mechanism of a key mitotic kinase complex, Aurora B/INCENP. The method of generating specifically phosphorylated forms of the complex is elegant, supporting a compelling biochemical analysis of how these sites synergistically activate Aurora B. However, the limitations of the molecular dynamics approach and how these models compare to previous structural studies are incompletely addressed. This work will be of interest to cell biologists and biochemists studying cell division and kinase regulation.

eLife assessment

This important study advances our understanding of the composition and circuit organization of the preBötzinger complex (preBötC)-the brainstem region that generates the respiratory rhythm and coordinates breathing with different motor and physiological behaviors in mammals. The reviewers agreed that the evidence supporting the conclusion that the preBötC is composed of a segregated subgroup of output neurons that modulates orofacial muscle activity is compelling and based on technically elegant, state-of-the-art combinatorial dual viral transgenic and optogenetic approaches in rats. After the cytoarchitectonic analyses are strengthened, the work will be of interest to neuroscientists and physiologists working on the neural control of breathing and other motor systems.

eLife assessment

This study on snapping shrimp morphological weaponry presents important findings on trade-offs in investment in costly weaponry traits as related to body size and reproduction. Convincing evidence is based on the collection of an exceptional number of fields samples, the inclusion of three shrimp species, and the measurement of numerous morphological and behavioral traits. The evidence shows that there are size-dependent trade-offs, where males and females differ in weapon investment, as weapons are beneficial to males but expensive for females. The findings will be of broad interest to evolutionary biologists and researchers working in the field of animal behavior.

eLife assessment

This valuable study carried out a genetic screening of Drosophila lines expressing wild-type or ALS/FTD mutations of ubiquilin 2, and identified several suppressors and enhancers of ubiquilin 2 phenotypes. The study particularly focused on two genes involved in axon guidance pathways, unc5 and beat-1b. The evidence supporting the conclusions is solid, although some of the presented data are unrelated to the main findings, which detracts from the focus of the work. This work will be of interest to a broad audience studying ALS/FTD and neurodegenerative diseases.

eLife assessment

This fundamental study describes the structure-based design of novel hybrid inhibitors targeting a human sodium channel which is a pain target. Exceptionally strong evidence for key claims was produced with a structural biological pipeline for iterative structural determination of drugs complexed with an engineered sodium channel. This work is expected to be of interest to biophysicists, drug developers, neurobiologist, and pain researchers.

eLife assessment

This valuable study provides a synthesis of sector models for cellular resource partitioning in microbes, and shows how a simple flux balance model can quantitatively explain growth phenomena from numerous published experimental datasets. The study is overall convincing, although there are a few incomplete points regarding parameter values (justification and discussion of robustness). This work should be of interest to the microbial physiology community.

eLife assessment

In this useful and potentially important manuscript, Mazanek and colleagues combine computational analysis and in vitro experiments to develop a comprehensive analysis of the ability of pyrin-only proteins (POPs) to inhibit inflammasome assembly. The results lead the authors to propose that a mixture of favorable and unfavorable interaction surfaces is required for a POP to inhibit a given inflammasome component. The results presented are solid, but additional experimentation is required to fully justify the authors' model.

eLife assessment

Mutations in mitochondrial genes can lead to deafness but the mitochondrial biology of sensory hair cells is not well understood. In this study, high-resolution imaging of mitochondrial development in sensory hair cells of normal and mutant zebrafish lateral line systems was described. The authors provide evidence that the formation of the mitochondrial architecture requires normal hair cell activity. This paper is of potential interest to researchers interested in metabolic homeostasis and sensory hair cell biology.

eLife assessment

This important work presented is of interest to the electron microscopy community, which expanding to more and more cell biologists. The field has long searched for a suitable method to combine the pristine preservation of vitrified samples with a volumetric imaging modality that reveals subcellular architecture at sufficient contrast for ultrastructural analyses, and the authors describe here the use of novel ion beams for imaging cellular samples in three dimensions, concluding that one of the four plasma sources tested produces the highest quality images. This allows them to provide several recommendations for imaging along with software for improving collected images. This approach should be very useful for addressing many biological questions.

eLife assessment

This manuscript reports important and valuable new data about the intriguing role of the lncRNA Charme during cardiac development. Whilst the majority of claims are convincingly supported by the data, the evidence for the cardiac phenotype and the mechanism by which Charme/MATR3 interacts is currently incomplete and requires additional experimental support. This paper is of general interest to cardiac developmental biologists as well as to anyone studying non-coding RNAs.

eLife assessment

This valuable work provides insight into how Plasmodium falciparum optimises the balance between infection of the human host and investment in onward transmission to the mosquito. Based on the appropriate and validated methodology most of the results are convincing, nonetheless, some conclusions are incomplete and require further support.

eLife assessment

A small proportion of the genomes of humans whose ancestors lived outside Africa traces back to an interbreeding event with Neanderthals. While we know that selection has generally acted to remove Neanderthal ancestry, intense interest has focused on understanding the contribution to current human phenotypic variation. This paper uses a new set of approaches to carefully quantify this contribution, taking into account various complicating factors. The work will be of interest to colleagues in human evolution and evolutionary biology more generally.

eLife assessment

This manuscript will be of interest to centrosome and cilia cell biologists. It evaluates the in vivo and in vitro role of PCM1, and by extension, centriole satellites in ciliogenesis. The major strength of this study is the detailed characterisation of Pcm1-/- mutant mice, which reveals a role for PCM1 in biogenesis of specific types of cilia, such as motile cilia on ependymal cells. The claims are generally well supported by the data, but the mechanistic basis for the cell-type specific requirement for PCM1 in ciliogenesis remains to be fully clarified.

eLife assessment

In the present study, the authors discovered the inhibitory neurons that are potentiated during the repetitive visual stimuli and control neurons that transmit looming information to evoke escape responses. Thus, the study elucidated a principle of habituation using a model vertebrate zebrafish.

eLife assessment

The RNA-binding protein Tristetraprolin (TPP) regulates the abundance of mRNAs encoding proinflammatory cytokines. The study by Scinicariello and collaborators examined mechanisms regulating the turnover of TTP in cultured cells and identified the ubiquitin E3 ligase HUWE1 as a regulator of TPP degradation. The conclusions are largely supported by the cellular and biochemical experiments. This paper thus implicates the HUWE1-TPP axis in regulating macrophage inflammatory responses at the post-transcriptional steps.

eLife assessment

This manuscript reports valuable findings regarding the evolution of nitrogenases through ancestral sequence reconstruction and resurrection. The results are solid and support the conclusions of the study, and highlight the historical constraints that have been acting on this enzyme. The findings will be of interest for people interested in enzyme evolution in general and particularly for those interested in the evolution of nitrogenases.

eLife assessment

This is an important paper that combines comparative analysis and experimental assays to investigate the role of protein-coding and regulatory changes at TRNP1 in mammalian brain evolution. The evidence supporting a contribution of TRNP1 is convincing, although the link between protein-coding changes and trait evolution is stronger and more readily interpretable than the data on gene regulation. The work will be of interest to researchers in the areas of mammalian evolution, brain evolution, and evolutionary genetics.