Evaluated articles

Evaluation Summary:

This paper is of interest and relevance to clinicians and researchers in the field of muscular dystrophy, a condition that causes loss of muscle function and mobility primarily in older patients. The presented experiments suggest that at least part of the pathology of DM2, a certain form of muscular dystrophy, is caused by defects in a gene that is required for the production of small molecules, called polyamines which are known to support muscle health and function. Interestingly, in a Drosophila model of DM2, feeding with polyamines can restore muscle function. The paper gains broad interest by the demonstration that consistent with the findings in Drosophila, muscle biopsies from human DM2 patients show decreased ODC and polyamine levels, raising the possibility of using polyamines for therapy or prevention.

(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:

How the bacterium E.coli decides when to divide is an interesting, important, unsolved and highly controversial topic of interest to readers across disciplines, including microbiology, cell biology and statistical physics. Popular "single process" models invoke regulation at the step of replication initiation or at the step of cell division per se, whereas these authors have previously proposed a "concurrent cycles" model in which both processes are relevant, with different prominences in different situations. Consistent with the authors' motivating hypothesis, in the particular perturbed condition investigated in this work, a process different from DNA replication becomes increasingly important for division control as the degree of perturbation increases, which provides a new challenge to models for cell division control.

(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 #3 agreed to share their names with the authors.)

Evaluation Summary:

This paper addresses researchers interested in architecture and function of the insect central complex as it represents the first comprehensive projectome dataset of any central complex outside Drosophila. The authors use the bumblebee as representative for hymenopterans with their navigation skills. Further, they mine their data for conserved and diverged aspects compared to fly (Drosophila) knowledge and hypothesize how the differences may relate to diverged neural circuit function. Hence, they provide an excellent and comprehensive descriptive resource providing a point of reference for others and a starting point for comparative studies of neural circuits. In particular, this study is the first comprehensive description of columnar neurons in the bumblebee central complex, described through the lens of the recently published fruit fly connectome of the same, homologous neuropil. The comparative approach used here holds promise for describing neural circuits in bees and flies in shared frame of reference. The authors use an approach that reflects a compromise between quick collection of electron microscopy (EM) data and being able to fully reconstruct all neurons in the bumble bee's central complex. The authors are transparent about the method's limitations and draw appropriate conclusions.

(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:

In this rigorously conducted meta-analytic study, the authors investigated the functional and structural abnormalities associated with developmental dyslexia across languages. Convergent and divergent functional and structural changes as well as language-universal and language-specific brain alternations related to dyslexia are found. In general, the study has generated important results and the findings are of interest to readers in educational psychology/neuroscience fields, especially those focusing on reading development and dyslexia. The analytic approach used in this study is cutting-edge, the data support the main claims, and a detailed discussion is presented.

(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:

Bacterial ParB partition proteins have the novel property that they employ an unusual nucleotide cofactor for complex assembly at their specific DNA binding site, parS. The impact of this study is on our general understanding of this novel class of nucleotide-dependent processes, and the role that nucleotide-protein interactions play in DNA binding and bacterial physiology.

(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 interesting, timely and well-done study focuses on the mechanism underlying nevus growth arrest, which has received renewed attention as a result of recent studies that question the dogma that such arrest is mediated by oncogene-induced senescence. Through experiments involving both cultured primary human melanocytes and cells derived from clinical samples, the authors show that Braf-oncogene-induced nevus cell growth arrest results from microRNA-dependent suppression of the mitotic kinase Aurkb, which influences whether Braf activity is proliferative versus antiproliferative. While the conclusions made within the manuscript are justified, and there is sound acknowledgment of certain pitfalls that could be addressed in future research, more expansive sample sizes and further in vivo work would aid in providing more clinical relevance. This manuscript would appeal to researchers in the melanoma field, especially those studying the underlying mechanisms behind phenotypic plasticity and tumor heterogeneity.

(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 study provides an experimental and computational method for the identification and reconstruction of full-length circRNAs using nanopore sequencing,. With a better comparison to other existing methods in the field and a clearer demonstration of the advantages of the described methodology, the work would be of great interest to researchers in the circular RNA community.

(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 study describes reduced antibody cross-reactivity between the SARS-CoV-2 B.1.1.7 variant and the parental strain or the B.1.351 variant. Asymmetric antibody responses and reduced neutralizing antibodies against heterogeneous variants have been demonstrated in multiple studies. The current study reports reduction of B.1.1.7 COVID-19 sera against the SARS-CoV-2 parental strain and B.1.351. This observation is interesting and could be useful for future vaccine development. The work is of interest to virologists and infectious disease specialists.

(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 authors perform a tour-de-force study of classical conditioning in fly larvae. Experiments are original, findings are exciting, and we expect this paper to have a substantial impact. There is potentially an issue in the assay of larvae preference taking an hour of unrewarded presentation of CO2, while the training and extinction happen on much shorter scales, muddying the ability to interpret the results. A mathematical model of the conditioning process is also missing, which also makes interpretation harder.

(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 is of great interest for researchers working in the filed of cell adhesion and cell migration. The authors show for the first time that alpha5beta1 ligand spacing profoundly influences the collective migration behaviour of keratinocytes. They demonstrate that this parameter can outcompete the well-known and studied influence of substrate stiffness.

(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 is an interesting study aiming to link the evolutionary effects of dietary mismatch in humans to increased inflammatory responses and risk of chronic diseases. To uncover more insights into the causal links, the study used a non-human primate (macaque) model to show that the dietary switch from a Mediterranean to a modern Western diet leads to the polarisation of monocyte cell populations toward a more pro-inflammatory state, which in addition to increasing the chronic health risk can also impose behavioural changes such as anxiety and social isolation. The results of this study are convincing, interesting, and have fundamental importance in evolutionary biology, immunology and psychology. The extent to which these findings can be extrapolated to human populations remains to be established.

(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:

Although the role of membrane potential in Cell Permeable Peptides (CPP) translocation has been consistently described in artificial systems, this multi scale study, combining cell biology, genetics and in silico approaches, further extends this topic to a live cell context where it shows that internalization stops when the membrane polarization is decreased by the removal of potassium channels. It proposes an original mechanism of CPP translocation based on water pore formation, which should be of interest for biophysicists, cell biologists and for applications such as drug delivery.

(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:

Glioblastomas, like many tumors, consist of a cohort of actively dividing cells and a substantially larger fraction of non-proliferating cells. The standard of care involves the administration of a chemotherapy drug (temozolomide (TMZ)) whose antitumor activity is thought to be dependent on a toxic intermediate produced during DNA replication. In this report, the authors show how this compound is also processed by the interaction of two DNA repair pathways which produce the same intermediate without the requirement for DNA replication. The paper will be of interest to those scientists concerned with the implications of DNA damage and repair for cancer chemotherapy, particularly for tumors as deadly as glioblastoma.

(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 study uses the approach of labeling neurons with distinct birthdates so they can be differentiated in experiments performed later in development. The authors then test morphological, functional and circuit inputs/outputs patterns of these neurons by using immunohistochemistry, slice electrophysiology, retrograde labelling, morphological reconstructions and behavioral assays. The manuscript is likely to make a strong impact in the field of developmental neuroscience and a good impact related to more general cellular and molecular 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 agreed to share their name with the authors.)

Evaluation Summary:

This study in the field of collective behavior addresses how naïve and experienced individuals (i.e., homing pigeons) pool information in order to navigate while flying back home. The authors show that the passage of information is largely democratic, meaning information passes both ways, and that, unexpectedly, exploration of the route is initiated both by naïve and experienced birds. The work provides a new perspective on information sharing during collective learning.

(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 study reports that calsyntenin-3, a synaptic adhesion molecule, is expressed in cerebellar Purkinje cells and that acute knockout of calsyntenin-3 increases excitatory synapse density and decreases inhibitory synapse density. The manuscript provides compelling evidence that elimination of calsyntenin-3 from cells in the cerebellar cortex alters the E/I balance for Purkinje cells by increasing the strength of excitatory parallel fiber inputs and decreasing the strength of inhibitory inputs. However, it would have been far better to selectively target Purkinje cells, but that was not done. This is the first study showing that a particular synaptic adhesion molecule regulates excitatory and inhibitory synapse in opposite directions.

(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 work will be of interest to anyone interested in signal transduction, and especially those studying GPCRs and membrane receptors. Dimerization and oligomerization of G protein-coupled membrane receptors (GPCRs) are expected to be critical for receptor function. This intriguing study helps understand the usually underestimated role of GPCR soluble domains. The authors discovered that oligomerization of a GPCR can be mediated by multiple weak interactions between soluble domains that are "tunable" by environmental factors, thus possibly modulating the function of this important class of membrane receptor proteins. What remains to be shown is how oligomerization alters receptor function.

(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 manuscript will be of interest to epidemiologists and population biologists interested in outbreak dynamics in populations with complex social structures, such as emergent viral infections of humans. The study offers a functional, differential-equation (DE)-based framework for capturing the transition from emergence to endemicity without the huge over-compensation cycles typically predicted by DE models but rarely seen in natural populations. The model framework currently offers insights into the drivers of epidemic dynamics and, after further testing and calibration, may be useful for assessing control strategies for emerging infectious diseases.

(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:

Drosophila species have long served as an important model system for genetics and genomics. The authors have developed an important community resource of high standard genomes for many species across the Drosophila clade. This resource will serve to empower the next generation of Drosophila research and provides an important road map for similar efforts in other groups of organisms.

(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 present the first digital adult zebrafish brain anatomy atlas that includes ten highly informative markers for different brain regions and cell types. The authors utilize new clearing techniques to enable staining of the whole fixed zebrafish adult brains, and light sheet microscopy fluorescent imaging to obtain high resolution three-dimensional data. Several individual dataset for each marker are registered and aligned to an anatomical model using fluorescent cell nuclei and autofluorescence patterns by state of the art volume registration algorithms. The results appear to be of high quality. The authors also provide a detailed and state-of-the-art anatomical annotation of brain regions. Using ten different antibodies to fluorescently label different neuron types, stem cells and glia, proliferation zones, and some specific anatomical regions, the authors demonstrate the utility of their database. This will be a valuable resource for neurobiology research in zebrafish.

(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.)