Evaluated articles

Evaluation Summary:

The work supports the hypothesis that novel specific enymes evolved to modify metabolic pathways, allowing phototrophs to shift from growth under photoautotrophic and photomixotrophic growth conditions.

(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 name with the authors.)

Evaluation Summary:

The study by Kano et al. provides experimental evidence that specific features of the human eye, namely shape and sclera depigmentation, enhance the ability to detect gaze direction of individuals. The study is notable for being the first to adopt a comparative experimental approach, testing both humans and chimpanzees, to demonstrate that white sclera can enhance gaze discrimination in both species, particularly when visibility is poor.

(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:

This is a challenging study exploring the effects of a commonly used analgesic, remifentanil, on brain and spinal cord related pain processing in humans. It is of considerable interest to the pain research, neuroimaging and opioid neuroscience communities and are also relevant to clinicians who commonly use opioid infusions. The authors have used sophisticated methods for combined brain and spinal cord functional magnetic resonance imaging to examine the influence of an intravenous opioid on pain processing in the ascending and descending pain pathways in healthy subjects. The authors have conducted a comprehensive assessment in large numbers of subjects and have explored both changes in amplitude of activity as well as connectivity. Their detailed analysis strengthens findings from previous human and animal studies and extend to demonstrate novel changes in connectivity in the descending pathway to the spinal cord although these data are potentially compatible with alternative interpretations and may need to be reinforced by further 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:

Rutz et al. outline LOTUS, a new open-source database that links natural product structures with the organisms they are present in. It contains over 700,000 referenced structure-organism pairs and search tools that make mining the database intuitive and efficient. The LOTUS Initiative comprises an important data harmonization/integration effort over previous databases. The results are distributed to the public through Wikidata, which additionally supports future curation. This new resource is likely to be of great interest to natural product researchers as well as across fields of biology including ecology, evolution, and biochemistry.

(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:

Giove and colleagues demonstrate an intriguing dissociation of neurovascular (as measured with BOLD-fMRI) and neurometabolic (measured with fMRS) responses during perception. This is a thought-provoking study that makes one wonder about the signals we measure with human neuroimaging, especially fMRI. It will therefore be of great interest to the broad community of neuroimagers, as well as perception researchers.

(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 name with the authors.)

Evaluation Summary:

This paper uses an anatomically-constrained neural network model to investigate how looming visual stimuli - i.e. stimuli likely to collide with an organism - could be detected. The authors find one dominant solution to this problem reproduces both the computational properties and neural responses of known collision detecting neurons in the fruit fly, Drosophila melanogaster, without ever being trained on neural data. Their findings shed light on why biological collision detection circuits may have converged on particular solutions. A similar approach could reveal important computational features in other circuits.

(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:

Kidney organoid cultures derived from human induced pluripotent stem cells represent a new tool with which to study renal morphogenesis in both normal and pathological states. In the current study, the authors have combined morphological evaluation with proteomics to elucidate aspects of the temporal sequence of basement membrane composition during normal renal development and in the setting of a pathogenic collagen type IV alpha 5 chain variant associated with Alport syndrome, an inherited kidney disease. This model system may help us to better understand the pathogenesis of inherited diseases that affect renal basement membrane composition.

(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:

The work evaluates the production of P. falciparum sexual stage parasites in blood samples from asymptomatic parasite carriers through the dry season and symptomatic malaria patients in the wet season. Sexual stage parasites are required for malaria transmission via mosquito, but historically their low levels in peripheral blood have limited analysis. The work here monitored asexual and sexual stage parasitemia and found that the relative expression of early gametocyte genes, including ap2-g, is similar in samples from asymptomatic and asymptotic individuals. The data was used to model gametocyte availability from the initial symptomatic infection through the chronic phase and advances the understanding of factors that contribute to malaria transmission.

(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 potential mechanism of METTL3 N6-methyltransferase in the chemotherapeutic response is poorly defined. Herein, Li and colleagues describe a pathway where METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity. METTL3 knockdown results in DNA damage accumulation, which renders breast cancer cells sensitive to adriamycin treatment.

(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 investigates the role of role of the VEGFA signaling cascade, which is widely known to regulate formation of blood vessels, in muscle satellite cells and muscular diseases. on studying the relationship between muscle stem cells (MuSCs) and blood vessels. The authors identified the FLT1-AKT1 axis as an important effector of VEGFA on MuSC survival. They conducted a series of in silico, in vitro and in vivo experiments and showed that VEGFA-FLT1-AKT signaling promotes satellite cell survival both the physiologic and myopathy conditions. The paper will be interesting not only for muscle biologists, but also cell biologists and the general life science field.

(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 #4 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript reports a surprising discovery in C. elegans: upon losing its normal sensory properties, the ADL nociceptive/pheromone sensing neuron relays and thereby enhances oxygen behavioral responses via neuropeptide signaling. This effect could be interpreted as cross-modal sensory plasticity or more general a cross-modulation between sensory circuits, a still open question that should be addressed in a revision. The study is relevant to scientists working on sensory neurobiology and neuronal plasticity.

(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:

In this paper, Sahinyan and colleagues developed a method for analyzing chromatin accessibility in single murine myofibers. This goal was achieved by adapting the previously published OMNI-ATAC protocol to the specific properties of the myofiber environment. To demonstrate the validity of this method, they isolated myofibers from uninjured and regenerating murine EDL muscles dissected from wild type animals. In a second experiment, this method was applied to isolate myofibers from mdx mice, a model of Duchenne Muscular Dystrophy. The resulting datasets were further compared to the one generated from purified muscle stem cells.

(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:

The study by Cantero-Recasens et al. aims to investigate if mucus secreted by colorectal cancers would impact the effect of the frequently used chemotherapy treatment, FOLFIRI as it has been reported that mucinous carcinomas are more treatment resistant. They further investigate the role of some mucus secretion regulatory genes in this context. The conclusions made on the effect of the mucus secretion regulatory genes are well supported, though the link to the function of mucus in reducing treatment availability needs some further clarifications.

(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:

In their manuscript, Lu et al. use a combination of experimental approaches to determine how cellular components are transported from nurse cells into the growing oocyte during Drosophila egg development. The authors demonstrate that the minus-end directed microtubule motor, dynein, generates cortical flow by gliding microtubules along the cell cortex. This flow is capable of propelling cargoes through the ring canals into the growing oocyte via a bulk cytoplasmic transport mechanism. This action is distinct from dynein's cargo transport functions, as the authors are able to replace dynein with a minus-end directed kinesin linked to the cortex and observe the same phenomenon. Overall, this work had broad significance to cell biologists and developmental biologists interested in intracellular transport functions and oocyte 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This manuscript will be of interest to readers in the field of immunology and especially in the induction of immune tolerance in the thymus. The work uses several mouse models to substantially broaden the current understanding of MHCII/TCR -mediated cell-cell crosstalk in the thymus and suggests a novel mechanism that contributes to the generation of functional and self-tolerant T-cells.

(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 presents a mathematical model for prioritizing drugs for prostate cancer patients based on signal network database. The manuscript is of broad interest to the field of oncology and precision medicine. The methodology developed is sophisticated and relevant to real patient prostate cancer data. The predictions from the model are validated in an experimental setting and provide suggestions for the personalisation of prostate cancer treatment. The study can serve as a roadmap for future development of predictive, personalized models.

(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 provides strong evidence that adaptation in cone photoreceptors of the primate retina can subtly change the balance of excitatory and inhibitory inputs to On parasol ganglion cells and thereby fundamentally affect how these cells integrate visual information. This study provides important mechanistic insight into the previous observation that On parasol cells display nonlinear spatial stimulus integration under standard reversing gratings but linearly integrate signals in the context of natural scenes. The findings will be of great interest to visual neuroscientists.

(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:

Using computational modeling and dynamic clamp recordings, this work supports the concept that hyperexcitability of cortical circuits in a familial mouse model of Alzheimer's disease is caused by impairments of biophysical properties of Kv3 channels in parvalbumin-positive cortical interneurons. Overall, the work is clear and interesting but some further analysis is required to provide compelling support to the central 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This study demonstrates that differences in areas outside the regions that encode the TCR genes can affect the properties of TCRs that get made. This paper will be of interest to a broad swathe of immunologists who study such variable lymphocyte receptors. It combines several large datasets in an extremely statistically rigorous analysis, producing results consistent with but substantially expanding upon the prior knowledge of the field.

(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 work elegantly fuses cryo-EM, x-ray crystallography, and in vitro transport experiments to describe the structural basis for functional diversity in the SLC11/NRAMP family of membrane transporters. This work identifies factors responsible for selectivity of classical NRAMPS for transition metal ions (Fe, Mn) and the NRMT clade for alkali metal ion (Mg). Although selectivity is much discussed in transport of divalent metal ions, this is an outstanding example of a study that gets to the bottom of the structural determinants governing this 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 and Reviewer #2 agreed to share their names with the authors.)