Evaluated articles

eLife assessment

This valuable study, of interest for students of the biology of genomes, uses simulations in combination with published data to examine how many TADs remain after cohesin depletion. The authors suggest that a significant subset of chromosome conformations do not require cohesin, and that knowledge of specific epigenetic states can be used to identify regions of the genome that still interact in the absence of cohesin. The theoretical approaches and quantitative analysis are state-of-the-art, and the data quality and strength of the conclusions are convincing, but it is unfortunately still unclear whether physical boundaries (of domains?) in the model appear to be a consequence of preserved TADs, or whether preserved TADs are caused by the physical boundaries.

eLife assessment

This study presents valuable findings on genetic risk factors for type 1 diabetes and celiac disease using a large cohort from the Environmental Determinants of Diabetes in the Young (TEDDY) study. The evidence supporting the claims of the authors is solid, although the inclusion of the genetic effect of this locus on individuals with different genetic backgrounds would have strengthened the study. The work will be of interest to population geneticists working on diabetes and celiac disease.

eLife assessment

This study presents a valuable finding on the association between DUX4 expression with features of immune evasion in human tissue and clinical outcomes in patients with advanced urothelial cancer. The evidence supporting the claims of the authors is convincing, using a range of corroborative statistical techniques. Compared to an earlier version, the quality of the manuscript has been enhanced, for example Figure 5 now illustrates the key features of survival probability estimates over time for patients assigned to with the test or training set.

eLife assessment

This study presents a valuable finding on the association between DUX4 expression with features of immune evasion in human tissue and clinical outcomes in patients with advanced urothelial cancer. The evidence supporting the claims of the authors is convincing, using a range of corroborative statistical techniques. Compared to an earlier version, the quality of the manuscript has been enhanced, for example Figure 5 now illustrates the key features of survival probability estimates over time for patients assigned to with the test or training set.

eLife assessment

The authors provide important insights into the pathogenesis of erectile dysfunction (ED) in patients with diabetes. The authors present compelling evidence, using single-cell transcriptomic analysis in both mouse and human cavernous tissues, to support their claims regarding the key roles of pericytes in diabetic ED. The identification of LBH as a potential pericyte-specific marker in both mouse and human tissues further strengthens their findings. This well-written manuscript offers novel and significant contributions to the field, identifying potential therapeutic targets for further investigation.

eLife assessment

The authors provide important insights into the pathogenesis of erectile dysfunction (ED) in patients with diabetes. The authors present compelling evidence, using single-cell transcriptomic analysis in both mouse and human cavernous tissues, to support their claims regarding the key roles of pericytes in diabetic ED. The identification of LBH as a potential pericyte-specific marker in both mouse and human tissues further strengthens their findings. This well-written manuscript offers novel and significant contributions to the field, identifying potential therapeutic targets for further investigation.

eLife assessment

This convincing study demonstrates a potentially important role for the factor Numb in skeletal muscle excitation-contraction coupling, since a Numb knockout reduced contractile force. The authors thus demonstrate a novel role for Numb in calcium release in skeletal muscle.

eLife assessment

This manuscript presents a useful method for a comprehensive numerical simulation to systematically characterise the effect of heterogeneity in either the initial conditions or the biophysical parameters on the dynamic behaviour of protein signalling networks. Nevertheless, the presentation and detail of their model appear incomplete to fully support the main claims of the manuscript.

eLife assessment

This paper reports a useful finding on the impact of choices of quality control and differential analysis methods on the discovery of disease-associated gene expression signatures. The study provides a solid comparison of the data process by re-analysis of a large-scale snRNA-seq dataset for Alzheimer's Disease. This paper would be of interest to the community as to rigorous analyses for large-scale single cell datasets.

eLife assessment

This valuable study illuminates molecular movements of acid-sensing ion channels by combining advanced chemical biology and biophysical techniques. The evidence for the main claim, lack of interaction of molecular termini, is compelling and challenges prior models. This work is expected to pique interest in the ion channel signaling field, providing a fresh perspective.

eLife assessment

This carefully executed study provides a comparison of the chemical composition of mouse urine across strain and sex with the responses of vomeronasal sensory neurons, which are responsible for detecting chemical social cues. While the authors did not examine all molecular classes found in mouse urine or directly test whether the urinary volatile chemicals that vary with sex and strain are effective vomeronasal neuron ligands, solid data are provided that will be of significant interest to those studying chemical communication in rodents. This work should provide a valuable foundation for future research that will determine which molecules drive sex- and strain-specific vomeronasal responses.

eLife Assessment

This intracranial EEG study presents important and convincing neural evidence supporting the high spatial specificity (receptive field) of visually driven alpha-band oscillation in human brains and its potential role in exogenous cuing attention. The work challenges the predominant view about the role of alpha-band oscillation in visual attention and advocates that stimulus-driven alpha suppression is precisely tuned and might contribute to exogenous spatial attention.

eLife assessment

In this valuable study, the authors use a computational model to investigate how recurrent connections influence the firing patterns of grid cells, which are thought to play a role in encoding an animal's position in space. The work suggests that a one-dimensional network architecture may be sufficient to generate the hexagonal firing patterns of grid cells, a possible alternative to attractor models based on recurrent connectivity between grid cells. However, the support for this proposal was incomplete, as some conclusions for how well the model dynamics are necessary to generate features of grid cell organization were not well supported.

eLife assessment

This study reports valuable findings on the correlation between the positions of dendritic mitochondria and the orientation preference of calcium responses of individual spines. The conclusion about the biased localization of dendritic mitochondria near functional diverse spines is informative to understand the functions of dendritic mitochondria. The experimental evidence supporting the conclusion is compelling.

eLife assessment

The manuscript offers useful descriptive insights into the potential influence of whole-brain lactate and pH levels on the manifestation of behavioral phenotypes seen in diverse animal models of neuropsychiatric disorders. However, reviewers have raised concerns about the potential loss of specificity in capturing regional and cell-type-specific effects when relying solely on whole-brain analysis methods. While the evidence supporting the conclusions is largely solid, the robustness of these conclusions could be enhanced by the inclusion of additional data and further analysis.

eLife assessment

This important study uses a range of technical approaches to investigate the responses of zona incerta neurons to movement and sensory stimuli. The majority of neurons exhibited movement related activity but only a small proportion were modulated by whisker deflections. The major conclusion of the study is that the zona incerta distributes a general motor signal. The evidence supporting this claim is solid, although the study would be improved by greater transparency and discussion of experimental methods and histological verification of recording sites, viral spread, and which territories of the zona incerta were investigated. The work will be of interest to behavioral and physiological neuroscientists.

eLife assessment

This work advances on two Aso et al 2014 eLife papers to describe further resources that are valuable for the field. This paper identified and contributes additional MBON split-Gal4s, convincingly describing their anatomy, connectivity and function.

eLife Assessment

This important manuscript by Genzoni et al. reports the striking discovery of a regulatory role for trophic eggs in ant caste determination. Prior to this study, trophic eggs were widely assumed to play only a nutritional role in the colony, but this compelling study shows that trophic eggs can suppress queen development, and therefore regulate caste determination in specific social contexts.

eLife Assessment

The study is considered important with solid evidence that demonstrates the impact of plasma membrane nano-domains and protein interactions in the plant defence response to viruses. It includes a molecular understanding of the role of a calcium dependent kinase (CPK3) and a remorin protein in the cell-to-cell spread of viruses and cytoskeletal dynamics demonstrating, conclusively, the role of CPK3 with multiple lines of evidence. The work opens avenues to investigate different viruses and other plasma membrane proteins to gain a fuller picture of the involvement of plasmodesmata and other nanodomains in virus spreading.