Evaluated articles

eLife Assessment

This useful study presents a genetically encoded barcoding system that could advance transcriptomic studies and that has the potential for further applications, such as in high-throughput population-scale behavioral measurements. The evidence supporting the claims of the authors is solid and highlights both the usefulness and the limitations of the approach.

eLife assessment

The manuscript looks at how dysregulated purine metabolism in mutants for the Aprt gene impacts survival, motor and sleep behavior in the fruit fly. Interestingly, although several deficits arise from dopaminergic neurons, dopamine levels are increased in Aprt mutants. Instead the biochemical change responsible for Aprt mutant neurobehavioural phenotypes appears to be a reduction in levels of adenosine. This valuable study suggests that Drosophila Aprt mutants may serve as a model for understanding Lesch-Nyhan Disease (LND), caused by mutations in the human HPRT1 gene, and may also potentially serve as a model to screen for drugs for the neurobehavioural deficits observed in LND. The strength of evidence is solid.

eLife assessment

This study makes a valuable contribution to spatial transcriptomics by rigorously benchmarking cell-type deconvolution methods, assessing their performance across diverse datasets with a focus on biologically relevant, previously unconsidered aspects. The authors demonstrate the strengths of RCTD, cell2location, and SpatialDWLS for their performance, while also revealing the limitations of many methods when compared to simpler baselines. By implementing a full Nextflow pipeline, Docker containers, and a rigorous assessment of the simulator, this work offers robust insights that elevate the standards for future evaluations and provides a resource for those seeking to improve or develop new deconvolution methods. The thorough comparison and analysis of methods, coupled with a strong emphasis on reproducibility, provide solid support for the findings.

eLife assessment

This study presents a convincing analysis of the effects of covariates, such as age, sex, socio-economic status, or biomarker levels, on the predictive accuracy of polygenic scores for body mass index; The work is further supported by important approaches for improving prediction accuracy by accounting for such covariates across a variety of association studies. The authors did a commendable job addressing reviewer suggestions and comments. The work will be of interest to colleagues using and developing methods for phenotypic prediction based on polygenic scores.

eLife assessment

In this important study, the authors describe a novel function for RAPSYN in bcr-abl fusion associated leukemia, presenting convincing evidence that RAPSYN stabilizes the oncogenic BCR-ABL fusion protein. Compared to an earlier version of the manuscript, the authors have added data using primary samples that strengthen the conclusions.

eLife Assessment

This manuscript addresses infections of the parasite Taenia solium, which causes neurocysticercosis (NCC). NCC is a common parasitic infection that leads to severe neurological problems. It is a major cause of epilepsy, but little is known about how the infection causes epilepsy. The authors used neuronal recordings, imaging of calcium transients in neurons, and glutamate-sensing fluorescent reporters. A strength of the paper is the use of both rodent and human preparations. The results provide convincing evidence that the larvae secrete glutamate and this depolarizes neurons. Although it is still uncertain exactly how epilepsy is triggered, the results suggest that glutamate release contributes. Therefore, the paper is a fundamental step towards understanding how Taenia solium infection leads to epilepsy.

eLife assessment

This important study reports how swallowtail butterflies pattern structures composed of chitin at the nanometer scale to produce structural colors. The work uses state-of-the-art microscopy techniques to convincingly show that F-actin is utilized in these butterflies in a novel way to produce structure, paving the way for further studies on growth regulation leading to precise ultrastructures and structural colors.

eLife assessment

This study, based on a large-scale data set and established behavioural tasks, has the potential to provide a valuable contribution to the literature if the authors could combine and correlate their behavioural evaluations with neural data and/or clinical assessments. As a standalone dataset, however, the current study appears incomplete because it does not go beyond merely replicating existing findings in a large cohort of children. In order to elevate their study, the authors are encouraged to publish their full dataset and explore the relationship between behavioural and neural or clinical data.

eLife assessment

This important study poses a provocative mechanism of channel activation of the mechanically activated ion channel TREK-1. The data provide solid evidence that the application of shear to cells causes a redistribution of both TREK-1 and an associated enzyme, PhospholipaseD2 in the membrane that increases the enzyme activity. The work offers a new mechanism, but note that this is only one possible method of channel activation, and mechanisms independent of PLD2 are also probable.

eLife Assessment

The aim of this important study is to identify novel genes involved in sleep regulation and memory consolidation. It combines transcriptomic approaches following memory induction with measurements of sleep and memory to discover molecular pathways underlying these interlinked behaviors. The authors explore transcriptional changes in specific mushroom body neurons and suggest roles for two genes involved in RNA processing, Polr1F and Regnase-1, in the regulation of sleep and memory. Their findings offer convincing evidence that the expression of RNA processing genes is modulated during sleep-dependent memory, with Polr1F potentially contributing to increased sleep.

eLife assessment

This is an important report that has implications for both the brain stimulation field and beyond. The strength of evidence provided is quite convincing. The major strength of this work is the recognize the importance of participant expectation in brain stimulation studies.

eLife assessment

This paper provides a fundamental expansion of vestibular compensation into transient and partial dysfunction, as well as insights into the adaptation of visual reflexes in this process. The conclusions are convincingly supported with paired histological and behavioral measurements, which are additionally modeled for further interpretation. This work would be of interest to neuroscientists working in multisensory integration and recovery mechanisms.

eLife assessment

This paper provides valuable information regarding visuospatial working memory performance in patients with MS compared to healthy controls, using a relatively novel continuous measure of visual working memory. There are some weaknesses with the way the clinical groups were matched, but those limitations are acknowledged and the strength of evidence for the claims is otherwise convincing. The paper will be of interest to those working in the field of clinical neuroscience.

eLife assessment

This article provides a review and test of image-analysis methods for bacteria growing in the 'mother-machine' microfluidic device, introducing also a new graphical user interface for the computational analysis of mother-machine movies based on the 'Napari' environment. The tool allows users to segment cells based on two previously published methods (classical image transformation and thresholding as well as UNet-based analysis), with solid evidence for their robust performance based on comparison with other methods and use of datasets from other labs. While it was difficult to assess the user-friendliness of the new GUI, it appears to be valuable and promising for the field.

eLife assessment

The authors describe the dynamics underlying allostery of the adenosine A1 receptor, providing valuable insights into the receptor's activation pathway. The enhanced sampling molecular dynamics simulations of available structural data, followed by network analysis, reveal transient conformational states and communication between functional regions. The authors carefully state the limitations of their work, including the restricted convergence of the free energy landscape and missing water-mediated hydrogen bond coordination. Collectively, they provide a convincing framework for advancing rational design strategies of specific modulators with desired modes of action.

[Editors' note: this was originally reviewed and assessed by Biophysics Colab]

Evaluation statement (16 June 2023)

Maria-Solano and Choi present the dynamics underlying allostery of the adenosine A1 receptor, providing valuable insights into the receptor's activation pathway. The enhanced sampling molecular dynamics simulations of available structural data, followed by network analysis, reveal transient conformational states and communication between functional regions. The authors carefully state the limitations of their work, including the restricted convergence of the free energy landscape and missing water-mediated hydrogen bond coordination. Collectively, the findings provide a convincing framework to advance rational design strategies of specific modulators with desired modes of action.

Biophysics Colab considers this to be a convincing study and recommends it to scientists interested in the structural dynamics, allosteric pathway activations, and free energy landscapes of GPCRs.

(This evaluation by Biophysics Colab refers to version 5 of this preprint, which has been revised in response to peer review of versions 3 and 4.)

eLife assessment

This manuscript presents valuable findings that contribute to our understanding of how sphingolipids and membrane contact sites, formed by the tethering protein family tricalbins, are involved in regulating vacuolar morphology in S. cerevisiae. The evidence supporting the authors' claims is largely solid. While the reported correlation between sphingolipid levels and vacuole homeostasis is interesting and intriguing, more work is needed to thoroughly substantiate the proposed mechanism. This study will be of interest to cell biologists focusing on intracellular organization and lipid metabolism.

eLife assessment

In this important study, the rabbit was used as a non-rodent mammalian model to show that DMRT1 has a testicular promoting function as it does in humans. The experiments are meticulous and compelling, and the arguments are clear and convincing. These results may explain the gonadal dysgenesis associated with mutations in human DMRT1 and highlight the need for mammalian models other than mice to better understand the process of gonadal sex determination in humans.

eLife Assessment

This valuable study uses tools of population and functional genomics to examine long non-coding RNAs (lncRNAs) in the context of human evolution. Analyses of computationally predicted human-specific lncRNAs and their genomic targets lead to the development of hypotheses regarding the potential roles of these genetic elements in human biology. Compared to previous versions, the conclusions regarding evolutionary acceleration and adaptation have become more solid by more fully taking data and literature on human/chimpanzee genetics and functional genomics into account.

eLife assessment

This paper reports important findings on a potent activator of the YAP pathway, demonstrating its mechanism through alternative splicing changes. The authors provide convincing evidence to support their claims. This research is of interest to biologists studying alternative splicing or the Hippo pathway, with significant implications for medical research.

eLife assessment

This important study outlines how the agr quorum sensing system in Staphylococcus aureus confers long-lived protection against oxidative stress, thereby linking bacterial metabolism to virulence in this pathogen. While the findings, which are supported by solid data, seem at first glance to contradict earlier findings that show increased fitness of agr mutants under oxidative stress, the core conclusions of the study are well-substantiated. The topic of the paper holds broad relevance to microbiologists, especially those focusing on host-pathogen interactions and bacterial responses to ROS.