Evaluated articles

eLife Assessment

This valuable study describes the molecular mechanism of daptomycin insertion into bacterial membranes. The authors provide solid in vitro evidence for the early events of daptomycin interaction with phospholipid headgroups and stronger, specific interaction with phosphatidylglycerol. This work will be of interest to bacterial membrane biologists and biochemists working in the antimicrobial resistance field.

eLife assessment

The study makes a valuable empirical contribution to our understanding of visual processing in primates and deep neural networks, with a specific focus on the concept of factorization. The analyses provide convincing evidence that high factorization scores are correlated with neural predictivity. This work will be of interest to systems neuroscientists studying vision and could inspire further research that ultimately may lead to better models of or a better understanding of the brain.

eLife assessment

Based on analyses of retinae from genetically modified mice, and from wild-type ground squirrel and macaque, employing microscopic imaging, electrophysiology, and pharmacological manipulations, this valuable study on the role of Cav1.4 calcium channels in cone photoreceptor cells (i) shows that the expression of a Cav1.4 variant lacking calcium conductivity supports the development of cone synapses beyond what is observed in the complete absence of Cav1.4, and (ii) indicates that the cone pathway can partially operate even without calcium flux through Cav1.4 channels, thus preserving behavioral responses under bright light. The evidence for the function of Cav1.4 protein in synapse development is convincing and in agreement with a closely related earlier study by the same authors on rod photoreceptors. The mechanism of compensation of Cav1.4 loss by Cav3 remains unclear but appears to involve post-transcriptional processes. As congenital Cav1.4 dysfunction can cause stationary night blindness, this work relates to a wide range of neuroscience topics, from synapse biology to neuro-ophthalmology.

eLife assessment

This paper provides valuable insights into the neural substrates of human working memory. Through clever experimental design and rigorous analyses, the paper provides compelling evidence that the working memory representation of stimulus orientation is a reformatted version of the presented stimulus, though more work is needed to establish more generally that visual working memories are abstractions of percepts. This work will be of broad interest to cognitive neuroscientists working on the neural bases of visual perception and memory.

eLife assessment

This manuscript presents experiments that address the question of whether the lateral parafacial area (pFL) is active in controlling active expiration, which is particularly significant in patient populations that rely on active exhalation to maintain breathing (eg, COPD, ALS, muscular dystrophy). This study presents solid evidence for a valuable finding of pharmacological mapping of the core medullary region that contributes to active expiration and addresses the question of where these regions lie anatomically. Results from these experiments will be of value to those interested in the neural control of breathing and other neuroscientists as a framework for how to perform pharmacological mapping experiments in the future.

eLife assessment

This paper provides an important method that uses a computational model to predict photoreceptor currents in mammalian photoreceptors. By inverting the model, visual stimuli can be constructed to produce desired photoreceptor current responses. The authors provide compelling evidence that this approach can disentangle the effects of photoreceptor nonlinearities including light adaptation from downstream nonlinear processing, thus facilitating future studies of the higher visual system.

eLife Assessment

This study uses carefully designed experiments to generate a useful behavioural and neuroimaging dataset on visual cognition. The results provide solid evidence for the involvement of higher-order visual cortex in processing visual oddballs and asymmetry. However, the evidence provided for the very strong claims of homogeneity as a novel concept in vision science, separable from existing concepts such as target saliency, is incomplete. The authors and the reviewers do not agree on several points, which are explained in the reviews and author response.

eLife assessment

This study presents a valuable finding on a new role of Foxp3+ regulatory T cells in sensory perception, which may have an impact on our understanding of somatosensory perception. The authors identified a previously unappreciated action of enkephalins released by immune cells in the resolution of pain and several upstream signals that can regulate the expression of the proenkephalin gene PENK in Foxp3+ Tregs. The generation of transgenic mice with conditional deletion of PENK in Foxp3+ cells and PENK fate-mapping is novel and generates compelling data; they also show a comprehensive analysis of Tregs in control and transgenic mice, longitudinal data on heat sensitivity and co-localization of PENK+ Tregs with thermal sensory neurons in the skin further supporting their hypothesis. The study would be of interest to the biologists working in the field of neuroimmunology and inflammation.

eLife assessment

This valuable paper compares blood gene signature responses between small cohorts of individuals with mild and severe COVID-19. The authors provide solid evidence for distinct transcriptional profiles during early COVID-19 infections that may be predictive of severity, within the limitations of studying human patients displaying heterogeneity in infection timelines and limited cohort size.

eLife assessment

This valuable study demonstrates that there is significant variation in the susceptibility of isoniazid-resistant Mycobacterium tuberculosis clinical isolates to killing by rifampicin, in some cases at the same tolerance levels as bona fide resistant strains. The evidence provided is solid, with no clear genetic marker for increased tolerance, suggesting that there may be multiple routes to achieving this phenotype. The work will be of interest to infectious disease researchers.

eLife assessment

The fundamental study by Galicia C. et al. captured the GTP-bound active structure of CtRoco, a homolog of human LRRK2, using conformation-specific nanobodies. This convincing body of work reports the first structure of a GTP-bound ROCO protein, illustrating how GTP facilitates the dimer-to-monomer transition of CtRoco and functional activation.

eLife assessment

This important study, using three bioactive compounds as a model, demonstrates that estimating the intake of food components based on food composition databases and self-reported dietary data is highly unreliable. The authors present convincing data showing the differences in the estimated quantile of intake of three bioactive compounds between biomarker and 24-hour dietary recall with food-composition database. The work will be of broad interest to the clinical nutrition research community.

eLife assessment

This study presents a predictive scoring system in DLBCL based on the expression of three tumour microenvironment-related genes. Such a scoring system seems useful for predicting tumour purity levels in DLBCL. The provided evidence showing an association between worse DLBLC prognosis and high-risk score is solid, but it is incomplete to draw a clear conclusion about the links between risk score and drug sensitivity.

eLife assessment

Supported by convincing data, this valuable study demonstrates that the Chitinase 3-like protein 1 (Chi3l1) interacts with gut microbiota and protects animals from intestinal injury in laboratory colitis model. The revised manuscript sufficiently addressed the reviewers' comments. The work will be of interest to scientists studying crosstalk between gut microbiota and inflammatory diseases.

eLife assessment

Overall, the reviewers found the significance of the work valuable to the field of visual neuroscience, particularly given the large data set and strength of the method used that allowed for spatial analysis of neuronal responses in macaque V1. The evidence was deemed compelling, owing in part to the consistency of responses across animals and the fitness of modeling. The authors have addressed the major comments from reviewers and improved the manuscript through relation to prior literature and addressing specific limitations of the method used.

eLife assessment

This valuable manuscript reports alterations in autophagy present in dopaminergic neurons differentiated from iPSCs of patients with WDR45 mutations. The authors identified compounds that improved the defects present in mutant cells by generating isogenic iPSC without the mutation and performing an automated drug screening. The methodological approaches are solid, but the claims still need to be completed; showing the effects of the identified compounds on iron-related alterations is crucial. The effects of these drugs in vivo would be a great addition to the study.

eLife assessment

These are important findings that support a link between low-dimensional brain network organisation, patterns of ongoing thought, and trait-level personality factors, making it relevant for researchers in the field of spontaneous cognition, personality, and neuropsychiatry. While this link is not entirely new, the paper brings to bear a rich dataset and a well-conducted study, to approach this question in a novel way. The evidence in support of the findings is convincing.

eLife Assessment

This important study describes two findings: first, that TEAD is subject to turnover by the ubiquitin-proteasome system involving RNF146 and Parylation, and second, the development of a pan-TEAD heterobifunctional degrader that is used to inhibit growth of a YAP-dependent cancer cell line and to characterize TEAD binding sites in the genome. Convincing evidence supports the development and specificity of the degrader. This article will be of relevance to cancer biologists and scientists interested in proteostasis, cellular signaling, and post-translation modification of proteins.

eLife assessment

This study focuses on nuclear pore complex dysfunction in a mouse model of Alzheimer's disease related Aβ pathology. If future revisions can adequately respond to the reviewer comments, the findings may eventually be useful in supporting the idea that nuclear cytoplasmic transport defects occur prior to plaque deposition in this disease model and may be caused by Alzheimer's disease pathology. However, even after revision, the work suffers from overinterpretation of some of the data and remains incomplete in several respects.