Evaluated articles

eLife assessment

Opioid-induced respiratory depression is one of the side effects of opioid drugs. Although opioid overdose deaths are highly prevalent, our knowledge of the neural circuits underlying respiratory depression in the brainstem is far from complete. The present study used a variety of sophisticated experimental techniques to convincingly reveal the identity of brainstem components that are part of the neural circuits involved in the mediation of opioid respiratory effects, together with defining potential synaptic underlying mechanisms. They focused on two regions of the brainstem, namely the Kolliker-Fuse and the preBötzinger Complex, and proposed a combination of three complementary processes at pre- and post-synaptic sites in both KF and preBötC regions to explain respiratory depression linked to opioid exposure. This study provides very important findings on the circuitry involved in opioid-induced respiratory depression, and the present results are of broad interest to the respiratory control research community, as well as medically relevant.

eLife assessment

Candida morphogenesis is important for virulence. This study provides important new information as to how C. albicans regulates the switch from budding to hyphal morphology. Their results identify transcription factors involved in the process of hyphal morphogenesis in the host. The results are convincing and will be interesting to scientists in the fields of medical mycology and cell biology.

eLife assessment

This manuscript analyzes large-scale Neuropixels recordings from visual areas and hippocampus of mice passively viewing repeated clips of a movie and reports that neurons respond with elevated firing activities to specific, continuous sequences of movie frames. The important results support a role of rodent hippocampal neurons in general episode encoding and advance understanding of visual information processing across different brain regions. The strength of evidence for the primary conclusion was found to be convincing.

eLife assessment

This work critically evaluates several widely-used assays of transcriptional responses to water limitation in Arabidopsis grown on defined agar-solidified media and, finding inconsistent responses in root transcriptome responses, introduces a new 'hard agar' assay with more consistent responses. The work is valuable as a simple and alternative experimental system that would enable high-throughput genetic screening (and GWAS) to assess the impacts of environmental perturbations on transcriptional responses in various genetic backgrounds. Within this scope, the work is solid, though the debate about whether field-level physiological inferences can be made from such assays remains.

eLife assessment

This study makes valuable observations about the representation of "value" in the mouse brain, by using a nice task design and recording from an impressive number of brain regions. The combination of state-of-the-art imaging and electrophysiology data offer solid support for the authors' conclusions. The paper will be of interest to a broad audience of neuroscientists interested in reward processing in the brain.

eLife assessment

This study examines the inflammatory and immune response to live E. coli bacterial infection in neonatal and juvenile mice. Important information is described on the roles of Class II MHC and interferon responsive genes in regulating the host response to infection. This study will inform future efforts to further elucidate the impact of bacterial infections on lung development.

eLife assessment

This is a valuable study showing that fast, but transient, modifications of the synaptic efficacies, alone, can support the integration of information over time. Convincing supportive evidence is provided by showing that feed-forward networks, when equipped with such short-term synaptic modulations, can successfully perform a variety of temporal integration tasks at a performance level comparable with that of recurrent networks. These results will be of interest to both neuroscientists and researchers in machine learning.

eLife assessment:

Bone marrow stromal cells (BMSCs) can differentiate into a variety of cell types such as osteoblasts, chondrocytes, and adipocytes. The authors of this important study provide compelling and strong evidence that ablating O-GlcNAc transferase (OGT) in BMSCs impairs bone formation but promotes marrow adiposity. The results show that the balance of osteogenic and adipogenic differentiation of BMSCs is controlled by reciprocal O-GlcNAc regulation of lineage-specifying transcription factors, and highlights the importance of an intracellular glycosylation process of specific proteins in bone formation and bone marrow adipocytes.

eLife assessment

This theoretical work deals with the problem of homeostasis of protein density within cells, relying on the Pump and Leak model. The model makes predictions both for growing and senescent cells, which they compare to experimental data on budding yeast. The work extends previous works and makes biologically-relevant predictions, which will be of interest to both theorists and experimentalists interested in cell physiology.

eLife assessment

The analysis of 89,000 independent somatic mtDNA mutations provides compelling evidence that allows the authors to refute the idea that reactive oxygen species (ROS) are a main driver of mtDNA mutagenesis, although ROS effects may still be tissue-dependent. These are fundamental results with convincing evidence, and they should appeal to a broad audience. The discovery of transversion mutations (C>A/G>T and C>G/G>C), which previously were assumed to be almost nonexistent, will nevertheless require additional validation.

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.