Evaluated articles

Evaluation Summary:

In a set of in vitro and in vivo experiments the investigators demonstrated that coating of urinary tract catheters with fibrinogen-degrading substances reduced adhesion and colonization with a broad range of bacteria relevant in the pathogenesis of CAUTI. This approach might, therefore, be interesting for prevention of CAUTI as an alternative to catheters coated with antibiotics.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript which links early markers of inflammation with residual abnormalities on chest CT following SARS-CoV-2 infection. Surprisingly, early surveyed symptoms do not predict long term radiologic outcomes (6 months after infection) while inflammatory markers have stronger predictive value. Residual symptoms are common at the 6 month time point.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

In this manuscript, a light-gated receptor system (LOV2) linked to T cell receptor signaling machinery is enhanced by addition of an adhesion system enabling robust operation over a larger range of kinetic parameters. This system enables an exploration of how kinetic proofreading processes executed in seconds relate to T cell activation program involving reactions taking minutes to hours.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

One hypothesis to explain recent worse-than-expected outcomes of universal test-and-treat HIV prevention trials is population mobility. The authors show phylogenetically that mobility could play a role in transmission events in a large trial in Botswana. This study is of public health interest, has a large sample size for a phylogenetic study in this setting, and overall precise analysis. A few methodological clarifications are still needed to ensure that the data supports the study's claims.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This paper will be of interest to neuroscientists studying visual processing and is also more broadly relevant to understanding how sensory systems process information. The paper reveals several new insights into how first-order interneurons in the fly visual system encode visual features that help guide behavior.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This paper will be of broad interest to neuroscientists, providing a rich resource for future research. Using available RNAseq data the authors build an easy-to-work-with web platform which will enable researchers to survey the expression patterns of palmitoylating and de-palmitoylating enzymes and their potential co-expressed substrates within the mouse nervous system. Using this map, the authors test hypotheses about the relationship between these enzymes and neurological diseases and generate hypotheses about enzyme/substrate relationships based on expression correlations.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper will be of interest to neuroscientists studying ingestive behavior and control of body weight. It reveals two distinct subsets of neurons within a little-studied brain area that are both activated by feeding, but only of them contributes to hormone-mediated suppression of feeding. The combination of molecular profiling and functional modulation of the neurons compellingly support the claims of the paper.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

Matityahu et al investigate the influence of nicotinic acetylcholine receptor signaling on striatal microcircuit function through a combination of slice electrophysiology, optogenetics, and pharmacology. They find that nicotinic signaling delays spiking of striatal projection neurons in response to excitatory input, likely through the tonic release of acetylcholine by cholinergic interneurons onto local GABAergic interneurons and their influence on striatal projection neurons. Understanding how acetylcholine shapes striatal circuits is important, as this neurotransmitter is implicated in multiple movement disorders as well as other basal ganglia-related diseases.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

Bitzenhofer and colleagues provide unprecedented details of odor response properties of layer 2 cells in LEC. The authors show that firing rates of LEC ensembles conveyed information about odor identify whereas timing of spikes odor intensity and that, on average, fan cells responded earlier than pyramidal neurons, and pyramidal neurons, but not fan cells, changed their peak timing in response to changes in concentrations, providing a basis for temporal coding of odor concentrations. The results provide important information about odor coding in LEC, an understudied area of the brain.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This study describes work measuring transcriptional changes through development and later aging. The authors broadly conclude that the transcriptomes of several tissues diverge during development, but re-converge during aging, a pattern that they term "divergence convergence", or DiCo. The trajectories the authors have identified could provide a powerful lens through which to improve our understanding of the basic biology of aging. This paper will be of interest to the aging community, especially to researchers interested in age-dependent gene expression changes and their consequences.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The oncogenic virus Human Papillomavirus encodes the E7 protein which is an important contributor to carcinogenesis. Here, the authors show that E7-mediated degradation of the cellular tumor suppressor PTPN14 leads to activation of YAP1 in basal cells of the stratified squamous epithelium. They show that the ability of E7 to extend the lifespan of keratinocytes and facilitate basal cell retention are both activities mediated by the basal-cell specific activation of YAP1 and conclude that this newly discovered function of HPV E7 contributes to its carcinogenic properties. This report will be of great interest for researchers in the HPV and epithelial differentiation fields.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper describes analysis and modeling of leading edge fluctuations in migrating cells driven by a branched Arp2/3 lamellipodial network. A stochastic model shows how branching contributes to shape stability, and reproduces the measured spectrum and dynamics of leading edge fluctuations. Analysis of the model as a function of branching angle suggests that the Arp2/3 branching angle might be selected to smooth lamellipodial shape. The authors provide new ideas to a big field of research, including Fourier analysis of leading edge fluctuations, which is a novel approach. The modeling methods and model design seem valid and the paper is well written.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

TRPV4 is an ion channel protein and mutations in TRPV4 gene resulted in different types of skeletal defects. In this study, the authors created two types of TRPV4 mutations (mild V620I and lethal T89I mutations) in human iPS cells through CRISPR-Cas9 gene editing. They identified key molecules potentially involved in TRPV4 mutation-induced changes in chondrocyte activities and concluded that the inhibition of chondrocyte hypertrophy induced by the mutations may cause the bone diseases.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This work is of clinical relevance to those interested in the etiology and pathology of hereditary gingival fibromatosis (HGF). The paper discusses two novel findings: identification of a causative role of a missense mutation in the gene encoding the zinc finger protein 862 (ZNF862) that leads to hereditary gingival fibromatosis (HGF), a rare disease characterized by overgrowth of gingivae, in an examined family, and a suggestion of the molecular consequences of that mutation that leads to the disease.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript is of broad interest to readers in the fields of drug addiction and relapse, reinforcement learning and punishment, and those interested in cortical function, particularly the insular cortex. The authors extend a context and punishment-based relapse model to the widely-used drug nicotine and use a number of complementary approaches to support the conclusion that the insular cortex plays a role in nicotine relapse. The experiments were carefully designed and implemented.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper will be of great interest to researchers interested in the brain mechanisms of pain. It shows how the connectivity of brain networks associated with sustained pain change over time. These findings are conclusively supported by state-of-the-art fMRI analyses of a tonic pain paradigm in two cohorts of healthy human participants. These insights are important for the understanding of the brain mechanisms of sustained pain which is the hallmark of chronic pain as a major health care problem.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

FGF2 moves directly from the cytoplasm through the plasma membrane in a reaction driven by its subsequent high affinity binding to cell surface heparan sulfate proteoglycans. This study concludes that Glypican-1 is the principal proteoglycan involved, possibly involving a unique tri-sulfated disaccharide binding site in close proximity to the cell surface. While the role of Glypican-1 appears unique to FGF2 rather than part of a generalized direct secretion mechanism, the observations highlight the complexity and significance of proteoglycan variation. The work is well done and generally convincing, but additional support for the authors' conclusion that a specific glycan structure in GPC1 is a specific ligand for FGF2 is required.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Padoa-Schioppa and colleagues describe possible neuronal correlates of behavioral biases observed in monkeys making value-based choices when options are presented simultaneously versus sequentially. Building on the lab's previous work detailing functional roles of different neurons in the orbitofrontal cortex, the authors relate different choice biases to different groups of OFC neurons. They propose that these relationships indicate that different biases are likely to arise from specific stages of decision computation. The study results are convincing and represent a significant advance in understanding circuit-level computations underlying decision-making.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This paper is of interest for cell biologists and biophysicists that work on eukaryotic cell motility and the dynamics of the actin cytoskeleton. The authors combine a series of clever biological approaches to fuse small Dictyostelium cells together into 'giant cells' that make it much easier to spatially resolve actin wave dynamics with and without electrical stimulation when cultured on smooth or nano-textured surfaces. Sophisticated and methodical computational approaches are used to analyze these images and relate the data to actin polymerization and wave dynamics parameters using optic flow and associated techniques. This study is mostly descriptive, a full mechanistic explanation of the results remains open, but this compelling experimental system opens up possibilities for the field to analyze the molecular subtleties involved in these cytoskeletal reorganizations.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This study adds to the considerable, but often conflicting, work on how neurotransmitter systems contribute to auditory processing dysfunction. The paper details a thorough and careful analysis of an important hypothesis from the point of view of schizophrenia research: do muscarinic and dopaminergic receptors contribute to mismatch negativity effects? The answers could be useful for future treatment allocation in psychosis. The analysis was pre-registered and departures from the planned analysis were well-motivated and clearly described.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)