Evaluated articles

Evaluation Summary:

This study describes an immunopeptidomic-based pipeline to discover new tumor antigens for the development of cancer vaccines. The pipeline is relatively straightforward and exploits molecular mimicry and tumor pathogen cross-reactive T-cells and would be interesting for cancer immunologists. If the utility of the pipeline were demonstrated in more diverse systems, including carcinogen-induced tumors and human settings, this work would provide an immediate impact to the immuno-oncology field and personalized cancer vaccine development.

(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 will be of interest to mechanobiologists and muscle scientists interested in how contraction of muscle may be linked to mechanical activation of a kinase domain in a large structural protein in a living animal. The study combines imaging of the moving live animal with FRET measurements to detect the structural (and presumably the activation) state of twitchin in C. elegans. The data convincingly shows that this activation is coupled to muscle contraction.

(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, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript will be of interest to insect neuroscientists and broadly to the neuroanatomy community. It presents a new web resource that collects and displays neuron, brain region and species data in user-friendly ways. If taken up by the community, it has the potential to become an important data hub.

(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:

Sharaf and colleagues present an elegant structural and functional analysis of the Neisseria meningitidis ABC transporters MetQ/MetNI illustrating that the substrate binding protein MetQ requires N-terminal lipidation and a substrate (e.g. L-Met and other Met analogs) to stimulate the ATPase, presumably in order to transport the substrate across the inner membrane. This paper will be of broad interest to microbiologists and membrane physiologists who study periplasmic substrate binding proteins and transporter interactions in bacteria.

(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 manuscript will be of interest to those interested in the regulation of DNA replication and those interested in how DNA damage impacts DNA replication. DNA replication must occur accurately to maintain genome integrity and also must be able to deal with DNA damage or metabolic conditions that induce replication fork stalling. Two key proteins involved in signaling such replication stress are Mrc1 and Rad53 kinase, and the authors use a powerful in vitro reconstitution system to make findings pertaining to these two proteins that are then supported by genetics.

(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 names with the authors.)

Evaluation Summary:

This work from Xu et al. uses state of the art viral tracing technologies in Cre-transgenic mouse lines to map the inputs and outputs of glutamatergic and GABAergic neuronal populations in the dorsal (DR) and median raphe (MR) nucleus. A large amount of high-quality anatomical dataset was collected with the advanced fMOST whole-brain imaging system. Data analysis was thorough with significant scientific insights. All figures are of high quality. Overall, this study nicely complements previously published work on whole-brain connectivity of the DR and MR which have chiefly focused on the main neuromodulatory neurons found in these nuclei, i.e. serotonin and dopamine neurons, and will be a valuable contribution to understanding neural circuits of the raphe system.

(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 describes the identification and characterization of the interaction between MLL fusion proteins with the HBO1 histone acetyltransferase complex and its role in leukemogenesis. This study adds mechanistic depth into the important recent discovery of HBO1 functions in MLL-fusion leukemias and opens possibilities for a new therapeutic approach.

(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:

The study is carefully performed and provides compelling evidence for a gene network involved in generating different sensory cell types from a common progenitor, showing how an enhancer can integrate a gene regulatory network and guide a cell-fate decision.

(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:

Severe COVID-19 is characterised by a high neutrophil to lymphocyte ratio and an underlying state of oxidative stress in blood has also been hypothesized. In the study presented here for the first time provide evidence that hydrogen peroxide generated by the neutrophil specific enzyme myeloperoxidase is not only accumulated in plasma but also perpetrates structural damage to the strong and weak lipid binding sites on albumin, a key antioxidant in blood plasma, using SLFAs and EPR spectroscopy. This study is timely and relevant in deciding treatment of severe COVID-19 patients with human serum albumin and possibly supplementation of FDA approved antioxidants like glutathione. The main strengths of the manuscript are the novelty. The main weak point is the need to study more patients.

(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 provides supportive sequencing data for the hypothesis of association between AITL and pre-existing clonal hematopoiesis. It will be of interest to researchers in both lymphoma and myeloid malignancies and raises new hypotheses about the potential smoking-related mechanisms (C>A signature) that may contribute to development of AITL in the background of clonal hematopoiesis. The hypotheses need further validation, as the authors used a small sample and make indirect inferences about the origin of the observed mutations.

(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 names with the authors.)

Evaluation Summary:

This study reports that monocular inactivation of the fellow (good) eye with tetrodotoxin supports long-lasting recovery from the effects of monocular deprivation, as measured by visual evoked potentials in primary visual cortex. This work should be of interest to neuroscientists studying plasticity and clinicians treating amblyopia. The results are compelling, although the advance compared to previous work is incremental.

(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:

The precise, simple and non-interfering visualization of neuronal key structures is a major challenge and currently limiting the advancement of our understanding of brain function. This work presents intrabodies as selective and non-interfering tools for the visualization of PSD95 - a major scaffold of the neuronal excitatory postsynapse. This is an important and well executed work that provides an excellent new tool to study an important synaptic molecule.

(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:

In this work, the authors use independent public datasets to perform an unbiased investigation of the similarities and differences of mouse models to human malarial disease using comparative transcriptomics. Whilst the data cannot convincingly identify which mouse models are best suited for studying specific human malaria phenotypes, the comparative analyses do indicate that these models reflect the broad diversity of human 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 agreed to share their name with the authors.)

Evaluation Summary:

This paper focuses on the transcriptional regulation of the T cell receptor (TCR) signaling cascade and would be of interest to those studying T cell development and differentiation. The authors employ a conditional deletion of the Capicua (Cic) gene, a transcriptional repressor previously shown to be involved in regulating autoimmunity and follicular helper T (Tfh) cell differentiation, and now show that loss of CIC in hematopoietic cells leads to defects in TCR-beta selection as well as in positive and negative selection of developing thymocytes. The overall conclusions are well supported by the findings.

(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:

Single celled organisms are assumed to be smaller, simpler, and less complex than multicellular organisms like animals. However, there are many examples of large single-celled protists - especially amoeba - that can be up to centimeters in size, and it remains unclear how they are able to achieve these sizes and differentiated regions like tissues in animals. Here, the authors provide evidence for variation in gene expression in the syncytial (multinucleate) large amoeba Physarum polycephalum. While primarily descriptive work, the authors are claiming a provocative mechanistic interpretation of the single cell gene expression results, but not yet supported by the current data. This study is neverhteless elegant and interesting regarding heterogeneity of gene expression patterns and thus specialization of functions within a syncytial organism.

(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 on echolocation-mediated responses to prey movements will be of interest to a broad audience, including ethologists and neuroscientists as well as those more generally interested in the natural world. Its strengths come from the use of data from both wild and captive animals of different species of toothed whales, as well as trained harbour porpoises, enabling generalization of the findings and conclusions on sensory-motor feedback.

(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:

The authors studied the neural correlates of planning and execution of single finger presses in a 7T fMRI study focusing on primary somatosensory (S1) and motor (M1) cortices. BOLD patterns of activation/deactivation and finger-specific pattern discriminability indicate that M1 and S1 are involved not only during execution, but also during planning of single finger presses. These results contribute to a developing story that the role of primary somatosensory cortex goes beyond pure processing of tactile information and will be of interest for researchers in the field of motor control and of systems neuroscience.

(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 names with the authors.)

Evaluation Summary:

This manuscript will be of interest to scientists working on adult Drosophila behavior, especially as it relates to a region called subesophageal zone. This area is an important integration center for different nervous system functions, including taste information processing and motor control of mouth parts and body movements. Specifically, it provides genetic tools (sparse gal-4 lines) that target different cell types in the subesophageal zone for future functional analysis.

(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 manuscript develops a novel approach using the zebrafish to identify suitable drugs against the spread of cancer. With some stronger support of the methodology and conclusions, it will be of interest to cancer biologists, developmental biologists, and pharmacologists.

(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 addresses the intriguing hypothesis that different molecular chaperones may recognize and bind distinct tau species, and thus may use different mechanisms to prevent tau aggregation. The findings are very interesting and advance our understanding of how chaperones can counteract the deleterious effect of tau amyloidogenesis.

(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.)