Evaluated articles

eLife assessment

This study provides a valuable contribution to the development of small molecules that inhibit the aggregation of tau, a protein involved in several neurodegenerative diseases. The authors present convincing evidence that analogs of the plant alkaloid tryptanthrin can prevent the formation of larger aggregates by targeting the early stages of tau oligomerization. Nevertheless, further studies are needed to elucidate the precise mechanisms of action and to provide a detailed kinetic analysis. This work will be of interest to biochemists and biophysicists focused on designing small molecules to inhibit fibril formation.

eLife Assessment

This paper reports important findings on giant organelle complexes containing endosomes and lysosomes (termed endosomal-lysosomal organelles form assembly structures [ELYSAs]) present in mouse oocytes and 1- to 2-cell embryos. The data showing the localization and dynamics of ELYSAs during oocyte/embryo maturation are convincing. This work will be of interest to general cell biologists and developmental biologists.

eLife assessment

A combination of molecular dynamics simulation and state-of-the-art statistical post-processing techniques provided valuable insight into GPCR-ligand dynamics. This manuscript provides solid evidence for differences in the binding/unbinding of classical cannabinoid drugs from new psychoactive substances. The results could aid in mitigating the public health threat these drugs pose.

eLife assessment

This study presents valuable findings on how the endocannabinoid system is involved in endometriosis progression using CNR1 and CNR2 knockout (KO) mouse models. The evidence supporting the authors' claims is incomplete; including bulk RNA-seq, flow cytometry, and imaging mass cytometry would have strengthened the study. This work might be of interest to medical scientists working on endometriosis.

eLife Assessment

This manuscript shows that chronic chemogenetic excitation of dopaminergic neurons in the mouse midbrain results in differential degeneration of axons and somas across distinct regions (SNc vs VTA). These findings are important for two reasons. This approach can be used as a mouse model for Parkinson's Disease without the need for the infusion of toxins (e.g. 6-OHDA or MPTP) — this mouse model also has the advantage of showing axon-first degeneration over a time course (2–4 weeks) that is suitable for experimental investigation. Also, the findings that direct excitation of dopaminergic neurons causes differential degeneration sheds light on the mechanisms of dopaminergic neuron selective vulnerability. The evidence that activation of dopaminergic neurons causes degeneration, alters motor behavior, and alters mRNA expression is convincing. This is an exciting paper that will have an impact on the Parkinson's Disease field.

eLife Assessment

This study presents useful albeit preliminary findings on transcriptome changes in cardiac lymphatic cells after myocardial infarction in mice. Despite revision, the conclusions of the authors remain uncertain as sample sizes in general are very low, and even sometimes too low to allow for valid statistical comparisons. Accordingly, there are concerns regarding statistical robustness, raised by both the editors and the reviewers. While the single-cell transcriptomic data were analyzed using solid advanced methodology, too few cells were included in the scRNA-seq data set and the spatial transcriptomics analyses. Thus, this study rather represents more a collection of preliminary transcriptomic data than a full scientific report that would definitively advance the field.

eLife Assessment

Through cellular, developmental, and physiological analysis, this valuable study identifies a gene that regulates the relative growth of roots and shoots under salt stress. The holistic approach taken provides convincing evidence that this member of a larger tandemly duplicated gene family together with an upstream regulator contributes to salt tolerance. The manuscript will be of interest to plant biologists studying mechanisms of abiotic stress tolerance and gene family evolution.

eLife assessment

This useful study presents a real-time transcriptomics analysis, with the aim of providing rapid access to sequenced data to reduce the costs associated with Oxford Nanopore long-read technology. Although the authors illustrate the compelling utility of this approach with three diverse experimental setups, issues with study design and analysis result in incomplete supporting evidence.

eLife assessment

This study provides a useful advance in generating mouse oligodendrocytes by direct lineage conversion from cortical astrocytes. The authors demonstrate that Sox10 converts astrocytes to MBP+ oligodendrocytes, whereas Olig2 expression converts astrocytes to PDFRalpha+ oligodendrocyte progenitor cells. The data supporting the conclusions are solid, but there are concerns regarding select figures and the experiments being limited to in vitro studies.

eLife Assessment

This fundamental work provides evidence that glutamate and GABA are released from different synaptic vesicles at supramammillary axon terminals onto granule cells of the dentate gyrus. The study uses complementary electrophysiological and anatomical experimental approaches. Together, these provide convincing evidence that the co-release of glutamate and GABA from different vesicles within the same terminal could modulate granule cell firing in a frequency-dependent manner, although thorough elimination of alternative mechanisms would have strengthened the study. The work will be of interest to neuroscientists investigating co-release of neurotransmitters in various synapses in the brain and those interested in subcortical control of hippocampal function.

eLife assessment

This study describes the development and validation of an Automated Reproducible Mechano-stimulator (ARM), a valuable tool for standardizing and automating somatosensory behavior experiments. The data supporting the use of the ARM system are compelling, though the determination of whether that device emits any sounds, including in the ultrasonic range when in operation or when at rest, would add value to the study. Nevertheless, the ARM system is anticipated to be popular amongst somatosensory and pain researchers.

eLife Assessment

This important paper on measuring molecular connectivity using combined serotonin PET and resting-state fMRI provides both novel methods for studying the brain as well as insights into the effects of ecstasy administration. The methods are convincing, with the high anaesthetic dose used likely limiting network activity.

eLife assessment

This valuable paper investigates how fish avoid thermal disturbances that occur on fast timescales. The authors use a creative experimental approach that quickly creates a vertical thermal interface, which they combine with careful behavioral analyses. The evidence supporting their results is solid, but there is a potential confounding factor between temperature and vertical positioning, and characterization of the thermal interface would greatly assist in interpreting the results.

eLife Assessment

This valuable study uses zebrafish as a model to reveal a role for the cell cycle protein kinase CDK2 as a negative regulator of type I interferon signaling. The evidence supporting the authors' claims is convincing, including both in vivo and in vitro investigative approaches that corroborate a role for CDK2 in regulating TBK1 degradation. In this latest version, the authors included data addressing concerns raised by the reviewers at the first peer review round that strengthens the conclusions. This work will interest cell biologists, immunologists, and virologists.

eLife assessment

The manuscript presented by Moyse and colleagues provides valuable insight into the origin, morphology, dynamics, and behavior of several populations of mononuclear phagocytes in the zebrafish heart. The study presents solid evidence through the use of transgenic lines and live imaging, although some limitations related to lineage tracing and molecular profiles should be considered. This work exemplifies the use of zebrafish as a model to study the role of leukocytes in cardiac development and regeneration and potentially draw broader interest to biologists working in immunology fields.

eLife Assessment

In this manuscript, the authors present valuable findings on the apparent role of a salience-network anterior insula node in directing fronto-parietal and default-mode network activity within a tripartite network during control of memory, drawn from an impressive invasive human neurophysiological dataset. Overall, the authors have presented a convincing set of analyses. We also commend the use of a large intracranial EEG dataset to approach this question.

eLife Assessment

In this useful study, the authors tested the ability of bumblebees to use bird-view and ground-view for homing in cluttered landscapes using modeling and behavioral experiments, claiming that bumblebees rely most on ground-views for homing. However, due to a lack of analysis of the bees' behavior during training and a lack of information as to how the homing behavior of bees develops over time, the evidence supporting their claims is currently incomplete. Moreover, there was concern that the experimental environment was not representative of natural scenes, thus limiting the findings of the study.

eLife Assessment

This manuscript focuses on understanding if and how the glycosylation of SARS-CoV2 spike protein affects a putative allosteric network of interactions controlled by the binding of a fatty acid. The main conclusion is that glycans do not significantly affect the network of allosteric interactions. This valuable information - albeit mainly consisting of negative results - is based on convincing evidence. It will be of interest to scientists focusing on SARS CoV2 protein structure and dynamics.

eLife assessment

This study describes a useful antibody-free method to map both G-quadruplexes and R-loops in vertebrate cells independently of the BG4 and S9.6 antibodies. It also reveals that the helicase Dhx9 can affect the self-renewal and differentiation capacities of mESCs, perhaps by regulating co-localized G4s and R-loops. The datasets provided might constitute a good starting point for future functional studies, and although the strength of the evidence that DHX9 interferes with the ability of mESCs to differentiate by regulating directly the stability of either G4s or R-loops has been improved compared to a previous version, it is still incomplete.

eLife Assessment

This is a valuable study that tests the functional role of food-washing behavior in removing tooth-damaging sand and grit in long-tailed macaques and whether dominance rank predicts level of investment in the behavior. The evidence that food-washing is deliberate is compelling and the evidence that individual investment in the behavior varies is solid. Overall, the paper should be of interest to researchers interested in foraging behavior, cognition, and primate evolution.