Evaluated articles

Evaluation Summary:

Mitra et al. developed an analysis framework using large-scale pan-cancer omics datasets to discover the roles of 30 long non-coding RNAs (lncRNAs) in cancer proliferation and growth. Direct function-testing experiments were also performed to validate the biological mechanisms of two lncRNAs. The analysis framework developed here can serve as a resource to study the functions of lncRNA in cancer, and the computational framework can also be further extended to study cancer-relevant transcriptional and post-transcriptional regulation.

(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 study explores autolysis regulation in the gram positive pathogen Streptococcus Pneumoniae and finds that the turnover of wall teichoic acids at the septum controls cell elongation. Specifically, a possible new enzyme WhyD regulates the level of wall teichoic acids (WTA) at the bacterial septum, limiting the number of WTA-associated autolysins such as LytA at division sites. The study provides new insights into the molecular interactions between enzymes that regulate PG-associated polymers and enzymes that hydrolyze to regulate cell morphogenesis. In principle, such regulation will also apply to other monoderm bacteria. This article will be of interest to microbiologists who are studying bacterial cell envelope dynamics. The experimental data support the conclusions drawn and the work provides tools, concepts and remaining questions to address that will be instrumental to understand the mechanism underpinning autolytic 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 agreed to share their name with the authors.)

Evaluation Summary:

This is a paper that will be of broad interest to cognitive scientists, cognitive neuroscientists and speech pathologists who study language disorders. They apply a new structural neuro-imaging technique - multi-parameter mapping (MPM) to a very large sample of children with and without developmental language disorders. MPM allows them to identify localized structural differences (particularly myelin) that cannot be observed with other techniques. It offers convincing evidence that differences in a range of neural structures--including theoretically motivated left hemisphere language areas, and procedural learning--can be linked to variation in language ability.

(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 name with the authors.)

Evaluation Summary:

The wrinkling of growing biofilms is considered in this paper experimentally in a clever set of experiments in a microfluidic setup that reveals aspects of the onset of the wrinkling instability and the formation of hollow channels within which bacteria move. Variations in the adhesive properties of the underlying surface are shown to affect the instability. While the results will surely be of interest to researchers in a range of areas, the connection with theoretical results needs further 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:

In this paper, the authors presented the joint efforts from nine modeling teams to provide six-month projection of the COVID-19 pandemic across the US, in view of the circulation of the more transmissible Delta variant. All of the nine models projected substantial Fall resurgences based on data as of 3 July 2021, but the actual resurgence scale as of 31 July 2021 had exceeded the projections of all of the nine models. This suggests that transmission may be even higher than expected given model assumptions, and that forecasts beyond more than a few weeks are likely to be highly uncertain. This paper will be of high interest to public health specialists, forecast modelers, and members of the general public interested in the evolution of the COVID-19 pandemic and the impact of public health interventions in the USA.

(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:

In this manuscript, the authors use zebrafish histological staining, lineage tracing, enhancer transgenes, and mutants to find evidence for the gill origin of the vertebrate jaws hypothesis. This study nicely integrates into the literature on the origins of the mandibular jaw including discussion of fossil evidence and work in chondrichthyans and tests the hypotheses that the pseudobranch is derived from the mandibular arch, and that the pseudobranch is a segmental homolog of the gills. This paper will be impactful to the field of developmental biology both because the fate mapping methods used are generally applicable to a range of other lineage questions and because evidence for a gill arch origin of the jaw is an important contribution to vertebrate evolutionary biology.

(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 is an interesting study addressing an overlooked feature of morphogen gradient interpretation. By studying transcriptional activation of early zygotic genes during early Drosophila development the authors' findings suggest that morphogens, which are known to pattern tissues in distinct domain of gene expression, can also induce a graded transcriptional response within these domains.

(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:

By theoretically analysing the energy of a confluent epithelial tissue, the authors unveil the reason for nearly universal shape fluctuations that have been reported earlier. With a better justification of some of the underlying approximations used by the authors, the manuscript would be relevant for all people with an interest in tissue structure and dynamics.

(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 leverage theory, simulations, and empirical population genomics to evaluate what are the consequences of differences in substitution rates in hybridizing species. This is a largely overlooked phenomenon. This study highlights the issue and demonstrates that two hybridizing species of Papilio have differences in their substitution rates. The work will be of interest to a large group of evolutionary biologists, especially those studying evolution at the whole-genome level.

(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 importance of extracellular matrix (ECM) in multicellular organization has been studied in many different contexts. This study investigates the role of the ECM in the formation of the very first cell types to form in a mammalian embryo. The authors find that it may help stabilize the cell fate of early inside cells and play a role in promoting the epithelial organization of the next cell type to form within the inner cell mass. With appropriate extended experimental analysis, this study could be of interest to the specialist mammalian development 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

The authors present an impressive view of introgression across the Drosophila clade. There is strong support for signals of introgression along numerous branches of the phylogeny. However, the placement of these introgression events on the phylogeny and their impact on genome-wide patterns of relatedness are less clear.

(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 is of interest to neuroscientists conducting reward learning and basal ganglia research. It combines optogenetics and dopamine recordings to demonstrate that dopamine release in the dorsal striatum is smaller following self-stimulation than unpredicted stimulation of dopamine neurons. These results build on similar findings recently shown for the ventral striatum. Further development of the underlying mechanism or the behavioral significance would broaden the scope of the paper.

(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:

Basic epidemiological parameters such as the force of infection (rate at which susceptible individuals acquire the infection) remain undetermined for human infection with the neglected food-borne zoonotic cestode Taenia solium, which may cause taeniasis and cysticercosis. Dixon and colleagues address this major gap by fitting simple mathematical models to datasets that describe the prevalence of taeniasis and cysticercosis in several countries. Importantly, they found that infection acquisition rates per year vary widely (up to two orders of magnitude) across endemic settings and provide an approach for mapping the global public health impact of taeniasis and cysticercosis.

(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 paper presents a Bayesian model framework for estimating individual perceptual uncertainty from continuous tracking data, taking into account motor variability, action cost, and possible misestimation of the generative dynamics. While the contribution is mostly technical, the analyses are well done and clearly explained. The paper provides therefore a didactic resource for students wishing to implement similar models on continuous action data.

(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 authors demonstrate that isoform-specific Dystonin-b (Dst-b) mutant mice show significant myopathy in skeletal and cardiac muscle at older ages without the peripheral neuropathy or post-natal lethality that are commonly observed by loss of function of the DST gene. The study provides novel information about the role of the Dst-b isoform in maintaining skeletal and cardiac muscle health. In addition, the study suggests that isoform-specific mutations in Dst-b gene may cause some hereditary skeletal and cardiac myopathies.

(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 is of broad interest to geneticists and bone biologists because it describes a method to filter candidate genes, identified from GWAS, and pinpoint the gene that affects bone biology. This method identified a gene with a previously unknown role in bone biology and the authors showed that its loss reduces bone mineral density, supporting the key claims in the paper.

(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:

Glioblastoma is a challenging disease with a high level of heterogeneity. Here the authors use global methylation profiling of tumor-initiating cells and matched iNSCs and identify a subgroup of hypomethylated tumors with an astrocytic phenotype. Understanding heterogeneity in glioblastoma is a major challenge, and the identification of alterations of functional and clinical impact is of importance to 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This manuscript is of interest to developmental and cell biologists exploring cilia dynamics and ciliopathies. The authors address the molecular mechanisms by which INPP5E, a phosphoinositide phosphatase essential for regulating cilia function, is targeted to the primary cilium of cultured mammalian cells. Using immunoprecipitation, ciliary localization, phosphatase activity assays in combination with structural modelling, the authors identify four motifs important for ciliary localization of INPP5E, and uncover several novel and important interactions with other ciliary proteins providing a likely mechanism for ciliary targeting. The claims are generally well supported by the data, but some additional data acquisition and analysis are required to fully support the authors' conclusions and provide a conceptual advance in 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 #3 agreed to share their names with the authors.)

Evaluation Summary:

Hair cell activity has been postulated to underlie their vulnerability to environmental insult including toxin exposure. Previous work has been confounded by the fact that reducing mechanotransduction also reduces entry of toxic chemicals. Here Lukasz and colleagues test these ideas by examining the vulnerability of zebrafish mutants with impaired synaptic activity, thought to be a major driver of neuronal metabolic load.

(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 manuscript presents data that high expression of Protein Phosphatase 1 (PP1) inhibitor in triple-negative breast cancer contributes to poor outcomes by downregulation of an important kinase, GSK3β. The study clearly demonstrates that changes in PPP1R14C expression alter the behaviour of the studied cancer cells and mouse models and proposes a mechanism linking PP1 inhibitor to GSK3β. If this mechanism were substantiated, this would enhance our understanding of the pathophysiology of this important disease and might suggest new treatment options.

(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.)