Evaluated articles

eLife assessment

Satake and colleagues' important study elucidates somatic mutation processes in plants, demonstrating that in two tropical trees, mutation rates correlate with age, not growth rates. Their convincing evidence shows that many mutations do not align with cell divisions, suggesting many somatic mutations are generated in a replication-independent manner. This study represents a significant step towards advancing our understanding of plant development and the patterns and inheritance of mutations. This significant research is poised to engage a diverse array of scholars in plant evolution and development.

eLife assessment

The authors provide compelling evidence that MSP1 inhibition (leading to chromosomal instability or CIN in the cancer cells) increases phagocytosis and that tumors with CIN respond better to macrophage therapeutics. In this important study, they demonstrate particularly impressive survival rates for mouse models of CIN B16 tumors treated with adoptively transferred macrophages, CD47-SIRPα blockade, and anti-Tyrp1 IgG.

eLife assessment

The studies are important to the field of hepatic steatosis and inflammation. The data provided are convincing that treatment with I3A mitigated Western diet (WD)-induced hepatic steatosis, inflammation and reversed WD-induced alterations in liver bile acids and free fatty acids in mice.

eLife assessment

This study presents an important conceptual advance of how vitamin A and its derivatives contribute to atherosclerosis. There is solid evidence for the contributions of specialized populations of T cells in atherosclerosis resolution, including use of multiple in vivo models to validate the functional effects. A limitation is the insufficient analysis of lesions, but the manuscript has been improved from the original preprint version and the overarching conclusions have been refined.

eLife assessment

The authors expand the concept of a new layer to training immunity, which is currently being highlighted by several colleagues in the field. The work provides important hints to understand end-stage renal disease. Overall, the rational approach leads to experimental results that are solid.

eLife assessment

This paper investigates the impact of intranasal instillation of SARS CoV2 spike protein in mouse models of lung inflammation. The authors conclude that the spike protein can interact with macrophages through carbohydrate recognition and can induce recruitment and NETosis of neutrophils, contributing to lung inflammation. They also use the cremaster muscle model to investigate effect of the spike proteins on neutrophil dynamics and death using intravital microscopy. Given that mucosal vaccines using SARS CoV2 spike variants could be envisioned as desirable, the observation that spike can induce lung/mucosal inflammation even without an adjuvant is important. Despite limitations of some loose terminology and some weak controls, the key observations are solid and demand further attention given the importance of the antigen.

eLife Assessment

This important study examines heterochromatin domain dynamics using a model system that allows reversible transition from an embryonic stem cell to a 2-cell-like state. The authors present a solid resource to the research community that will further the understanding of changes in the chromatin-bound proteome during the 2C-to-ESC transition. However, conclusions related to the functional roles of the interaction between the SWI/SNF complex component SMARCAD1 and the DNA Topoisomerase II Binding protein (TOPBP1) remain incomplete.

eLife assessment

This study reports a new approach to determine the architecture of peptidoglycan (PG), the primary component of the bacterial cell wall, validating the pipeline through an architectural analysis of several members of the human gut microbiota. The technique is potentially valuable for this sub-field as it would enable researchers interested in peptidoglycan in a range of organisms to easily assess muropeptide composition in an easy, automated manner. However, there is some uncertainty about whether the pipeline was fully automated and it was noted that the pipeline requires prior knowledge of the peptidoglycan composition of an organism. Additionally, the use of the technique to investigate whether PG cross-bridge length is a determinant of cell wall stiffness produced evidence that would need more direct support and is therefore so far incomplete.

eLife assessment

This important and compelling study investigates the problem of intracellular acidification induced by commonly-used optogenetic stimulating opsins. The low proton permeability of two high-performance opsins is shown to reduce photostimulated acidification. The findings may be of broad interest in the fields of neuroscience research and optogenetic therapies.

eLife Assessment

The specific questions taken up for study by the authors-in mice of HDAC and Polycomb function in the context of vascular endothelial cell (EC) gene expression relevant to the blood-brain barrier, (BBB)-are potentially useful in the context of vascular diversification in understanding and remedying situations where BBB function is compromised. The strength of the evidence presented is incomplete, and to elaborate, it is known that the culturing of endothelial cells can have a strong effect on gene expression.

eLife assessment

This important paper addresses the challenging problem of dating the origin of several groups of marine microorganisms. However, while much of the analyses are solid, the lack of robustness analysis in molecular dating component such as using alternative time calibrations, clock models, and input gene sets makes the study incomplete. Despite some concerns, this work is a commendable attempt at an extremely difficult problem and will be of broad interest to microbiologists, geologists, and evolutionary biologists.

eLife assessment

This manuscript describes useful data on the mechanisms underlying the activation of the receptor tyrosine kinase FGFR1 and stimulation of intracellular signaling pathways in response to FGF4, FGF8, or FGF9 binding to the extracellular domain of FGFR1. Solid evidence for quantitative differences in the downstream responses induced by the three ligands is presented. This manuscript will be of interest to biochemists and cell biologists working on receptor tyrosine kinases and general cell signalling across membranes.

eLife assessment

This study describes a useful method to monitor the behavior of Drosophila larvae in a uniform environment over much longer time scales than was possible with previous methods. The authors provide a solid characterization of aspects of the method and show that the behavior of single larvae can be quantified over several hours. The experiments offer a proof-of-concept for a robotic device that will enable the investigation of behavior in long-term experiments in ways that were previously unimaginable.

eLife assessment

This manuscript provides a structural analysis of bushy cells in the mouse cochlear nucleus. These neurons receive a large synaptic contact from the auditory nerve termed an endbulb that preserves the temporal information present in the auditory nerve and are key elements of binaural sound localization circuits. The analysis combines volume electron microscopy techniques with computational models to predict heterogeneous bushy cell responses. The analysis takes morphological analysis of bushy cells to a new level, and the modeling is well done.

eLife assessment

This potentially important paper investigates the mechanisms that contribute to building inhibitory synapses through differential protein release from microtubules. The experiments are generally designed well, but the evidence supporting the conclusions is incomplete. This manuscript will be of interest to neuroscientists and cell biologists interested in intracellular trafficking and synapse maturation.

eLife assessment

These valuable findings presented by Wu et al. advance our understanding in novel cell signaling regulators of hepatic metabolism. The evidence supporting these conclusions are solid, utilizing in vivo and in vitro gain and loss of function studies. These work will be of interest to biologists working in the field of hepatic steatosis.

eLife assessment

The paper provides important insight into the function of FAM76B protein as a regulator of inflammation. The knockout/overexpression data are solid, however, the mechanism of regulation and the role of FAM76B in neurodegeneration is incomplete and requires additional experimentation. The work will be of interest to researchers studying inflammation, particularly neuroinflammation.

eLife assessment

This important study shows that exercise improves cerebrovascular function during aging using convincing methods, the authors show that aerobic exercise reverses aging-induced deficits in microvascular perfusion and oxygenation and potentially improves short-term memory. This work will be of broad interest to researchers and clinicians studying vascular function, age-related cognitive decline, and the effects of aerobic exercise on reversing age-related dysfunction.

eLife assessment

This valuable study identifies three independent patient mutations in MAD2L1BP (p31 comet) that cause infertility. Consistent with the known functions of p31 comet, solid experiments in mouse oocytes imply that infertility could be caused by a failure to silence the spindle assembly checkpoint, though the mechanism was not determined. Although the sample size is small, a rescue experiment in human oocytes promises the potential for therapy.

eLife assessment

This report is a useful demonstration of how to predict the mutational pathways to antimicrobial resistance (AMR) emergence, particularly in the enzyme DHFR (dihydrofolate reductase). The methodology is overall solid but some of the claims are only partially supported. The work will be of interest to microbiologists and evolutionary biologists interested in antimicrobial resistance and its population genetics dynamic.