Evaluated articles

eLife assessment

This manuscript is of interest to readers in the field of bone biology. It identifies a novel role for the vacuolar ATPase accessory protein ATP6AP2 within the osteoblast lineage and shows that loss of ATP6AP2 in the mature osteoblast results in disorganized bone formation. A similar, but milder, bone disorganization phenotype is also observed when this gene is knocked out in osteocytes. The authors show that this bone phenotype is partially rescued via restoration of MMP14 action.

eLife assessment

This paper reports on the development of an impressive microfluidic platform for the study of motility, and motility transitions, exhibited by single algal cells in circular confinement. Building on previous work that showed a three-state motility repertoire for certain green algae, the present work uses extremely long time series and a variety of physical perturbations to show how those dynamics can be altered by environmental conditions. The work will be of interest to a wide range of scientists studying motility and nonequilibrium dynamics, but its impact would be improved by a more insightful analysis of the voluminous data, with connections to physical principles.

eLife assessment

This paper asks whether a risk score integrating the impact of common genetic variants across the genome (polygenic risk score) on Type II Diabetes is also to any degree predictive of diabetes in pregnancy (Gestational diabetes or GDM).The study population comprises women of South Asian ancestry, who are particularly susceptible to GDM. Strong evidence is presented in favour of the hypothesis of the hypothesis in two sizeable cohorts, one from Canada and the other from the UK. The paper will be useful to those studying women's health in pregnancy, and in particular GDM, which is associated with a number of adverse pregnancy outcomes.

eLife assessment

We admired the study by Krehenwinkel and colleagues for its novelty, depth, and ecological breadth, but have questions regarding the laboratory, bioinformatic and statistical methodologies that require clarification. It is likely to make a substantial impact in the field of plant-based arthropod metabarcoding, revealing ecological insights that can be derived from existing bio-banked material. The work, which creatively exploits herbarium material to track arthropod communities, will be interesting to a general audience in addition to ecologists, foresters, phytopathologists, and industry.

eLife assessment

This manuscript will be of interest to cardiovascular clinicians, medical geneticists, pharmaceutical companies, and the general cardiovascular disease research community. The study adds evidence for the causal role of triglyceride to several atherosclerotic cardiovascular diseases. Their use of Mendelian Randomization method is appropriate and provides convincing support to their findings, which may provide insights on the mechanism of TG biology and drug repurposing of TG-lowering agents.

Evaluation Summary:

The authors leverage genotyping data from the islands of Cabo Verde to study its admixture history and to gain insights into the onset of the Trans-Atlantic Slave Trade. They find that patterns of ancestry between the islands are not the same, suggesting diversity in the founding populations of these islands. These results provide a nice example of how ancestry patterns vary across admixed populations due in part to their unique local history and social practices of that time.

(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.)

eLife Assessment:

The authors aim to predict bacterial enzymes responsible for drug biotransformation, and the work showcases the potential of this approach as a hypothesis generator for characterizing and validating novel bacterial enzymes in vitro. The authors describe the relevance of an accurate input (in terms of reaction completeness, including cofactors and reaction products) as paramount for the quality of the prediction. The conclusions, however, require additional experimental and non-experimental validations.

(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.)

eLife Assessment:

This manuscript uses a genetically-encoded calcium indicator to assess neural activity across a population of axons connecting the fly's brain to its ventral nerve cord while the tethered fly behaves on a floating ball. Changes in fluorescence signal correlate better with states such as walking, resting, and grooming than with particular limb movements or joint angles, suggesting that specific descending neurons represent the larger behavioral subdivisions. The preparation and large-scale analysis represent a significant step forward in determining how the brain compresses sensory and state information to convey commands to the ventral nervous system for behavior execution by motor 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. The reviewers remained anonymous to the authors.)

eLife Assessment

This report describes evidence that the main driving force for stimulation of glycolysis in dentate granule cell neurons in acute hippocampal slices from mouse by electrical activity comes from influx of Na+ including Na+ exchanging into the cell for Ca2+. The findings are presented very clearly and the authors' interpretations seem reasonable. This is important and impactful because it identifies the major energy demand in excited neurons that stimulates glycolysis to supply more ATP.

eLife Assessment:

This paper should be of high interest to scientists within the field of developmental neuroscience. The authors characterize the earliest spontaneous waves of the retina - a topic that is poorly understood. The ability to monitor waves over the entire retina at high resolution is a strength of the work. Weaknesses include reliance on pharmacology and some missing details in the 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 #1 and Reviewer #3 agreed to share their name with the authors.)

eLife Assessment:

A comprehensive single-cell transcriptomic study was performed in this study to gain insight into the development of endothelial cells and other co-developing mural cells derived from human induced pluripotent stem cells (hiPSCs) in 3D environment. This study gave us important information about signature genes, trajectories, and cell-cell interactions at various stages of vessel formation. Accordingly, the results of this study could potentially be of valuable interest to scientists working in the fields of stem cells, regenerative medicine, and tissue engineering.

(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.)

eLife Assessment:

This is a rigorous evaluation of whether the compression of time cells in the hippocampus follows the Weber-Fechner Law, using a hierarchical Bayesian model that simultaneously accounts for the firing pattern at the trial, cell, and population levels. The two key results are that the time field width increases linearly with delay, even after taking into account the across trial response variability, and that the time cell population is distributed evenly on a logarithmic time scale. Overall, the paper is well written, the experiment and data analysis are technically sound, and the conclusions are mostly well supported.

(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.)

eLife Assessment:

This manuscript sheds light on the biology of embryonal rhabdomyosarcoma, a common pediatric muscle tumor, by exploiting an established zebrafish model. Specifically, new knowledge is revealed of how the p53 tumor suppressor contributes to progression and extent of disease. This paper will be of interest not only to pediatric oncologists but also the broader cancer research community given the frequency of TP53 mutations as secondary lesions in human cancer.

(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.)

eLife Assessment:

The authors perform a Transposon-Sequencing screen to determine bacterial factors (including receptors) important for infection by two phages in the model bacterium Corynebacterium glutamicum. Using their established high-density transposon library, they identify genes required for infection with the phages Cog and CL31. They also identified a spontaneous phage-resistant mutant that led to the discovery of a gene involved in mycolic acid synthesis. Overall, the work is of broad interest to scientists in the field of cell wall biogenesis, phage infection, and bacterial cell 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 #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

eLife Assessment:

In this manuscript, the authors perform an extensive systematic analysis of membrane contacts sites to uncover novel proteins required for tethering organelles and modulation of membrane contacts. The authors identify over 100 new potential contact site proteins and effectors including proteins associated with the recently discovered plasma membrane-LD (pClip) and Golgi-peroxisome (GoPo) contact sites. Further, the authors identify and characterize novel lipid transport proteins associated with the pClip as well as Lec1, an ER-Lipid droplet contact site associated protein which contains a novel putative lipid binding domain and may facilitate ergosterol transport between the plasma membrane and lipid droplets.

(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.)

eLife Assessment:

This manuscript presents a biophysical study of the nature of the mechanosensitivity of voltage-gated sodium channels. The identification of a voltage-independent mechanosensitive step is well founded, the proposal that this step is the intracellular gate is plausible speculation. It is expected to be of interest to scientists studying the physical basis of mechanosensitivity in electrophysiology.

(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.)

eLife Assessment:

This manuscript presents the cryo-EM structure of the Yta7 chromatin remodeler, which provides new mechanistic insight into how this AAA+ protein unfolds histone H3 in yeast for DNA replication. The study details the putative role of the C-terminal bromodomains, as well as an N-terminal bromo-interaction motif, in engaging nucleosomes for subsequent capture of the H3 tail for ATP-driven translocation by the upper AAA1 ring. The accompanying functional work helps establish the proposed nucleosome recognition mechanism, providing a structural framework that may be generally used by AAA+ nucleosome remodelers. The work will be of interest to colleagues in chromatin biology as well as all who study the very large family of AAA-ATPases.

(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.)

eLife Assessment:

This paper demonstrates an integrated labeling and block face fluorescence imaging method that enables the rapid evaluation of biological specimens as large as an E18 mouse embryo with single cell resolution. Such capabilities will likely be of great interest to developmental biologists and pathologists. While the approach can be considered a major step forward, additional experimental support is necessary to gauge how quantitative the method is.

(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.)

eLife Assessment:

Replogle et al. present their design of a compact and functionally validated dual sgRNA libary and dCas9-effector protein that will enable new forms of CRISPRi-based screening in mammalian cells. Quantitative comparisons to previously published standards demonstrate strengths and weaknesses, which, along with the protocols and design strategies outlined, should enable end users to rapidly adopt their 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.)

eLife Assessment:

This paper presents a new mathematical model describing biologically plausible feedback that glial cells might use to properly modify the conduction velocity in axons and promote optimal timing of neural impulses through changes in myelination. This problem is of great importance in the field of neuronal plasticity. The mathematical model is solid and predicts that individual oligodendrocytes are able to modify their myelination pattern in response to correlated action potentials. This work provides an important step forward by providing the theory for myelin-mediated neuronal plasticity. The study will benefit from adapting physiological parameters for oligodendrocytes that are guided by experimental 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 #2 agreed to share their name with the authors.)