Evaluated articles

eLife Assessment

This useful study investigates the impact of disrupting the interaction of RAS with the PI3K subunit p110α in macrophage function in vitro and inflammatory responses in vivo. Solid data overall supports a role for RAS-p110α signalling in regulating macrophage activity and so inflammation, however for many of the readouts presented the magnitude of the phenotype is not particularly pronounced. Further analysis would be required to substantiate the claims that RAS-p110α signalling plays a key role in macrophage function. Of note, the molecular mechanisms of how exactly p110α regulates the functions in macrophages have not yet been established.

eLife assessment

This paper presents a valuable automated method to track individual mammalian cells as they progress through the cell cycle using the FUCCI system. The authors have developed a technique for analyzing cells that grow in suspension and used their method to look at different tumor cell lines that grow in suspension and determine the effect of drugs that directly affect the cell cycle. They show solid evidence that the method can be applied to both adherent and non-adherent cell lines. This paper will be of interest to cell biologists investigating cell cycle effects.

eLife assessment

The study presents a potentially valuable approach by combining two measurements (pHLA binding and pHLA-TCR binding) to improve predictions of which mutations in colorectal cancer are likely to be presented to and recognised by the immune system. While this approach is promising, the evidence supporting the primary claim remains somewhat incomplete. The experimental validation of the computational predictions with actual immune responses is still limited, despite the increase in sample size from 4 to 8 in this revision.

eLife Assessment

This is an important study that investigates how neural networks can learn to stochastically replay presented sequences of activity according to learned transition probabilities. The authors use error-based excitatory plasticity to minimize the difference between internally predicted activity and stimulus-driven activity, and inhibitory plasticity to maintain E-I balance. The approach is solid but the choice of learning rules and parameters is not always always justified, with some unclear aspects to the formal derivation.

eLife Assessment

This valuable study delineates the cellular contributions of BMP signaling in liver development and function. The findings are convincing, and the study employs state-of-the-art molecular, genetic, and cellular approaches to demonstrate that hepatic stellate cells play a central role in liver health by mediating cell-to-cell crosstalk via the production of specific BMP proteins. This study will be of interest to scientists interested in developmental biology and organ physiology.

eLife assessment

This study assessed antibody levels, which are indicative of protection, resulting from both COVID-19 vaccination and natural infection in a representative sample of the Canadian population. The work provides solid evidence that Individuals who received a booster vaccination and had a prior infection had the highest antibody levels, particularly when either the vaccination or natural infection had occurred within the past six months. These findings are of fundamental importance in supporting the value of booster vaccination in populations vulnerable to severe COVID-19.

eLife assessment

This study presents an important finding that Obox4 and Dux act redundantly in regulating zygotic genome activation in mice. The evidence supporting the claims of the authors is solid. The work will be of interest to researchers interested in early embryo development and epigenetic reprogramming.

eLife assessment

This study is of potential interest to readers in human genetics and quantitative genetics, as it presents a new method for homozygosity mapping in population-scale datasets, based on an innovative computational algorithm that efficiently identifies runs-of-homozygosity (ROH) segments shared by many individuals. Although the method is innovative and has the potential to be broadly useful, its power and limitations have not yet been adequately evaluated. The application of this new method to the UK Biobank dataset identifies several interesting associations, but it remains currently unclear under what conditions the new approach can provide additional power over existing genome-wide association study methods.

eLife assessment

This study is focused on the question of how Nrp1 contributes to the regulation of vascular permeability and whether or why there are differences between different vascular beds. The scientific concept of this paper suggests a possible role of Nrp1 on perivascular cells as a participant in the regulation of vascular permeability. This concept is interesting and potentially useful. However, the methodology and quantitative analysis are currently inadequate to fully support the claims.

eLife assessment

This important study uses cellular automata and evolution algorithms to offer an alternative to long-range signalling models of developmental patterning. The computational evidence that local rules suffice to produce a robust and global pattern is convincing. With some additional insights that connect the theoretical findings back to real biological examples, this work could be of interest to the broad community of developmental and systems biologists.

eLife Assessment

This study provides valuable insights into the role of sensory stimulation in neurogenesis in the mammalian olfactory epithelium, where new olfactory sensory neurons are continually born throughout an animal's lifespan. The authors show that exposure to two different musk-related odors specifically increases the birth rates of those neurons that respond to these odors. This potentially results in adaptive changes in the subtype composition of the olfactory sensory neuron population. Solid evidence, well supported by control experiments, is presented to support these findings, though further work is needed to confirm that this phenomenon generalizes to olfactory sensory neurons expressing other types of odorant receptor and to explore the mechanisms underlying the stimulus specificity of neurogenesis.

eLife assessment

This is a binocular rivalry study that uses ECG to present visual stimuli pulsing in line with cardiac events, to examine whether systole-entrained stimuli (i.e. presented during the period where the heart has contracted) are suppressed within visual awareness. Arguably out of line with this idea, the dominance durations were increased for systole-entrained stimuli. The manuscript addresses an important, precisely defined, and theoretically well-motivated question using sophisticated experimental and statistical methods. The interpretation of these results is not straightforward, however, such that they currently only provide incomplete support for the claims.

eLife assessment

This important work unravels how female Drosophila can assess their social context via chemosensory cues and modulate the sperm storage process after copulation accordingly. A compelling set of rigorous experiments uncovers specific pheromones that influence the excitability of the female brain receptivity circuit and their propensity to discard inseminate from a mating. This insight into neuronal mechanisms of sexual behavior plasticity is of general interest to scientists working in the fields of animal behavior, neuroscience, evolution, and sexual selection, as well as insect chemosensation and reproduction.

eLife Assessment

In this work, the authors propose that astrocytic aquaporin 4 (AQP4) is the main pathway for tonic water efflux, without which astrocytes undergo cell swelling. These findings are important, because they shed light on key molecular mechanisms implicated with the regulation of brain water homeostasis. The authors use a broad set of experimental tools (e.g., acute brain slices, in vivo recording, and diffusion-weighted MRI) but the evidence remains incomplete without ruling out non-specific effects of TGN-020, and without evidence that changes in sulforhodamine B fluorescence can be used as reliable readouts of cell volume dynamics.

eLife Assessment

This valuable study presents findings on DNA methylation as an efficient epigenetic transcriptional regulating strategy in bacteria. The authors utilized single-molecule real-time sequencing to profile the DNA methylation landscape across three model pathovars of Pseudomonas syringae, identifying significant epigenetic mechanisms through the Type-I restriction-modification system, which includes a conserved sequence motif associated with N6-methyladenine. The evidence presented is solid and the study provides novel insights into the epigenetic mechanisms of P. syringae, expanding the understanding of bacterial pathogenicity and adaptation.

eLife Assessment

This important work attempts to understand observed variability in oral shedding of SARS-CoV-2 and suggests that routine clinical factors are not determinative. The evidence supporting the conclusion is solid though the limited clinical heterogeneity of the included cohorts, the lack of COVID vaccination, and the absence of comprehensive viral load data for model training, makes the results difficult to generalize to contemporaneous COVID-19 conditions. This study may be of interest to virologists, public health officials and clinicians.

eLife assessment

This study presents a valuable computational model for elaborating on the interpretation of chromosomal mosaicism in preimplantation embryos. The evidence supporting the claims of the authors is incomplete due to the assumption that is possible to quantify the cells in the embryo, oversimplification of mitotic errors, and the inclusion of the self-correction premise. The work will be of interest to embryologists, and geneticists working on reproductive medicine.

eLife assessment

In this useful study, the authors report the efficacy, hematological effects, and inflammatory response of the BPaL regimen (containing bedaquiline, pretomanid, and linezolid) compared to a variation in which Linezolid is replaced with the preclinical development candidate spectinamide 1599, administered by inhalation in tuberculosis-infected mice. The authors provide convincing evidence that supports the replacement of Linezolid in the current standard of care for drug-resistant tuberculosis. The work will be of interest to those studying tuberculosis treatment regimens.

eLife assessment

This study explores the role of calcyphosine-like (CAPSL) in Familial Exudative Vitreoretinopathy (FEVR) via the MYC pathway, offering valuable insights into disease mechanisms that are supported by a solid, multi-pronged approach. The manuscript, which presents the phenotype of an interesting new mouse model, provides convincing evidence that CAPSL variants cause disease.

eLife assessment

This study presents valuable findings on the mechanisms underlying a rare brain disease using an organoid system. In this revised version, there are remaining reviewers' comments that are not yet addressed and as such, while the data presented are solid, the evidence supporting some of the claims is deemed incomplete. The work will be of interest to neuroscientists and clinicians aiming to understand and combat similar neurodegenerative disorders.