Evaluated articles

eLife assessment

This paper presents H3-OPT, a deep learning method that effectively combines existing techniques for the prediction of antibody structure. This work, supported by convincing experiments for validation, is important because the method can aid in the design of antibodies, which are key tools in many research and industrial applications.

eLife assessment

This paper addresses a fundamental issue in the field of autophagy: how is a protein responsible for autophagosome-lysosome fusion recruited to mature autophagosomes but not immature ones? The work succeeds in its ambition to provide a new conceptual advance. The evidence supporting the conclusions is convincing, with fluorescence microscopy, biochemical assays, and molecular dynamics simulations. This work will be of broad interest to cell biologists and biochemists studying autophagy, and also those focusing on lipid/membrane biology.

eLife Assessment

The authors aim to elucidate the mechanism by which pyroptosis (through the formation of Gasdermin D (GSDMD) pores in the plasma membrane) contributes to increased release of procoagulant Tissue Factor-containing microvesicles. The data offers solid mechanistic insights as to the interplay between pyroptosis and microvesicle release with NINJ1. The study provides useful insights into the potential of targeting Ninj1 as a therapeutic strategy.

eLife Assessment

This work investigates ZC3H11A as a cause of high myopia through the analysis of human data and experiments with genetic knockout of Zc3h11a in mouse, providing a useful model of myopia. The evidence supporting the conclusion is still incomplete in the revised manuscript as the concerns raised in the previous review were not fully addressed. The article would benefit from a more robust genetic analysis and comprehensive presentation of human phenotypic data to clarify the modes of inheritance in the families, currently limited by loss of patient follow-up and addressing whether there is a reduction in bipolar cell number or decreased marker protein expression through cell counts or quantifiable, less saturated Western blots. The work will be of interest to ophthalmologists and researchers working on myopia

eLife Assessment

This manuscript aims to identify the pacemaker cells in the lymphatic collecting vessels - the cells that initiate the autonomous action potentials and contractions needed to drive lymphatic pumping. Through the exemplary use of existing approaches (genetic deletions and cytosolic calcium detection in multiple cell types), the authors convincingly determine that lymphatic muscle cells are the origin of the action potential that triggers lymphatic contraction. The inclusion of scRNAseq and membrane potential data enhances a tremendous study. This fundamental discovery establishes a new standard for the field of lymphatic physiology.

eLife assessment

This potentially important study employs advanced imaging techniques to directly visualize molecular dynamics and of the immune receptor kinase FLS2 in specific microenvironments. The evidence supporting the ligand-induced association with remorin and the requirement of a previously reported phosphosite as presented is solid, although support by independent methods would be welcome. The work will be of interest to plant biologists working on cell surface receptors.

eLife assessment

Tissue phenotyping is central to nearly all areas of biology. In this study, the authors use an advanced form of micro-CT (X-ray histotomography) in zebrafish to phenotype blood cells in the intact animal. These approaches build upon prior work from this group and others showing this is a scalable imaging method that could readily be applied to other cell types, and provide an excellent complement to histological analysis of tissues. This is important work, as it demonstrates that the method can provide an approach that is orthogonal to conventional histology. The strength of the presented data is compelling, with description of both the hardware and software needed to implement the protocol, which will make it accessible to other researchers in the field.

eLife assessment

This is a valuable contribution to our understanding of how some bacteria can transport sterols from the cytoplasm to the outer membrane. Though much remains to be tested and explored, the data and analyses presented here provide solid evidence for the genetic and physical interaction of BstA/B/C with bacterially-produced sterols. The manuscript will be of interest to scientists focusing on the characterization of novel bacterial proteins and those studying lipid transport and acquisition in bacterial pathogens.

eLife assessment

This study uses specific and robust genetic approaches to assess mechanisms of kainic acid-induced neurogenesis. This is a fundamental study that bridges several complementary methods and is a convincing use of existing approaches to explore roles for sonic hedgehog in activity-dependent and aging-associated hippocampal neurogenesis.

eLife assessment

This important paper reveals that one of the major roles of the WDR5 WIN site is to promote ribosome synthesis, and that by attacking the WIN site with inhibitors ribosome attrition occurs creating new vulnerabilities that can be therapeutically exploited. This deficiency of ribosomal proteins also provokes the p53 response. The data from a variety of approaches is generally very convincing, and together buttresses the authors' conclusions and interpretations quite nicely; overall, this paper will provide a justification for pre-clinical and translational studies of WDR5 interaction site inhibitors.

eLife assessment

This useful study compares gene expression patterns among different autonomic ganglia and will be of interest to developmental neuroscientists and neurophysiologists. The study expands the database of genes expressed by subpopulations of autonomic neurons in ganglia, a key step in decoding their developmental origins and physiological functions. The evidence supporting the alternative view that the pelvic ganglionic neurons are actually modified sympathetic neurons is incomplete and may cause confusion, given the enrichment of cholinergic neurons, as well as the large number of molecular and functional differences known to be present between cranial and sacral neurons.

eLife assessment

Bladder dysfunction following spinal cord injury (SCI) represents a severe and disabling complication without effective therapies. Following evidence that AMPA receptors play a key role in bladder function the authors show convincingly that AMPA allosteric activators can ameliorate many of the subacute defects in bladder and sphincter function following SCI, including prolonged voiding intervals and high bladder pressure thresholds for voiding. These valuable results in rodents may help in the development of these agents as therapeutics for humans with SCI-induced bladder dysfunction.

eLife assessment

This study presents an important finding that implicates a rhodopsin gene duplication in the progression of autosomal dominant retinitis pigmentosa in patients. The authors utilize a retinal organoid model to demonstrate a similar disease phenotype and suggest defects can be ameliorated by using photoregulin. The data supporting the conclusions are solid, but there are some concerns regarding the strength of the phenotype in retinal organoids. This work will be of broad interest to vision researchers.

eLife assessment

This study presents a valuable finding on relationship between high protein diet and resistance exercise on fat accumulation and glucose homeostasis. The evidence supporting the claims of the authors is solid, although inclusion of mechanistic insight would have strengthened the study. The work will be of interest to dietician and exercise biologists working to understand the synergy between diet and physical activity.

eLife assessment

The report presents the cryo-EM structure of human vesicular monoamine transporter 2 (VMAT2) bound to tetrabenazine, a clinical drug. VMAT2 is critical for neurotransmission, and the study constitutes an important milestone in neurotransmitter transport research. The evidence presented in the report is convincing and provides new opportunities for developing improved therapeutic interventions and furthering our understanding of this vital protein's function.

eLife assessment

This study presents a valuable finding that pathways associated with ribosome biogenesis (RiBi) are activated during transition cell states and targeting ribosome biogenesis could be a viable approach to overcome EMT-related chemoresistance in BCs. The evidence supporting the claims of the authors is quite solid, although inclusion of additional experimental support that blocking of EMT/MET is necessary for the synergistic effect of standard chemotherapy together with RiBi blockage would have strengthened the study. The work will be of interest to scientists working on breast cancer.

eLife Assessment

What makes one member of the species behave differently from another? This is a core problem in behavioral neuroscience. This valuable study seeks an answer for the specific case of the fruit fly expressing preferences for one odor over another. By a combination of behavioral measurements, neurophysiology, and network modeling, the authors find solid evidence for at least one locus of individuality in the peripheral olfactory system.

eLife assessment

This prospective study advances our understanding of the predictive role of circulating tumor DNA (ctDNA) in the prognosis and of patients with mTNBC as well as other cancers. The evidence supporting the conclusions is convincing with rigorous analysis of the association between ctDNA (ctDNA-positive or not) with the progression-free survival (PFS) of patients. However, there are a few areas in which the article may be improved through further analysis of the clinical outcome and elaboration of the prospective study (i.e., the inclusion and exclusion criteria of the patients). The work will be of broad interest to clinicians, medical researchers and scientists working in cancers.

eLife assessment:

Interoceptive signals from internal organs activate neurons in the nucleus tractus solitarius (NTS) to help maintain homeostasis. The authors of this paper use gain-of-function and loss-of-function experiments to examine three distinct NTS neuronal populations, individually and in combination, and find that activating (or inhibiting) combinations of these neurons have more robust effects on food intake and body weight than activating (or inhibiting) them individually. The results of this paper are convincing and solid but do not provide mechanistic insights.

eLife assessment

Retinal ganglion cells which are intrinsically photosensitive play important and emerging physiological roles. The mechanisms of phototransduction are still not well known and there exists a controversy regarding the ion channels responsible for the photocurrent. The authors of this manuscript present data that can contribute to understanding the actual ionic mechanisms in two of these cell types. This manuscript will be of general interest to biologists and neuroscientists and should help resolve a major issue in retinal physiology.