Evaluated articles

eLife assessment

This paper addresses an important question within adaptive immunity, namely whether the T cell receptor (TCR) repertoire of negatively selected thymocytes shares common features. The authors analyze T cell receptor sequences from mice as they progress through positive selection, CD4/CD8 lineage commitment, and negative selection, to find small but consistent differences between the repertoires at these selection stages. They argue that their findings do not indicate any sequence-specific selection; however, some of the conclusions drawn are currently incompletely supported by the performed analyses.

eLife assessment

This is a very elegant study which clearly demonstrates the existence of CMV specific memory T cells in CMV+ pre-pandemic individuals that are capable of recognising epitopes from SARS-CoV-2. It provides new insights into the development of cross-reactive immune cells that was not anticipated. The study has been elegantly performed and presents important findings. In particular, the discovery of a public TCR which mediates the crossreactivity described is an important finding.

eLife assessment

This paper is of potential interest for skeletal biologist studying osteocytes and skeletal aging. Using a mouse model of partial osteocyte deletion, the authors provide new understanding on the role of osteocytes in regulating other lineage cells in bone, bone marrow, and skeletal muscle. This is an important and logically presented study that offers new insight into the biology of osteocytes. The set of data from the genetic mouse model, bone phenotypic analyses, and scRNA-seq analysis largely support the conclusion.

eLife assessment

Most birds today can lift the upper beak independently of the brain case, enabled by a series of mobile joints and bending zones in the skull. The computed tomography of the skull of a 120-million-year-old toothed bird produced by the authors shows for the first time that the joints were still absent, but also hints at how they may have evolved later. This compelling, important paper is of high interest to evolutionary biologists, vertebrate paleontologists (especially, but by no means only, those working on bird origins) and specialists in biomechanics.

eLife assessment

A commonly held hypothesis about how genetic variants predispose to common diseases and other human traits is that variants have phenotypic effects by altering transcript accumulation. The authors question this view by showing some evidence for shared genetic control of transcript abundance for genes believed to be involved in the traits, and for the traits themselves.

eLife assessment

Functional magnetic resonance imaging (fMRI) yields a notoriously noisy and autocorrelated signal, and the GLMsingle method presented here by Prince and colleagues demonstrably improves the estimation of responses evoked by single trials. This open source toolbox is implemented in a user-friendly manner and will be of interest to researchers using human neuroimaging to study neural responses in condition-rich designs, as is increasingly common in cognitive neuroscience experiments.

eLife assessment

Several mammal species, including dolphins, have evolved to be relatively "hairless". Kowalczyk and colleagues scan the genomes of multiple species to identify genomic regions that appear to have evolved at a faster or slower evolutionary rate along hairless lineages. They identify a number of protein-coding genes as well as noncoding regions that might explain how hairlessness evolved in mammals. This study is of interest to those investigating the development of the skin and its appendages as well as evolutionary biologists, especially those investigating instances of convergent evolution and those developing phylogenomic methods for genome comparisons.

eLife assessment

CRISPR-Cas systems are essential components of an adaptive immune system that protects bacteria and archaea from infection by foreign genetic elements like phages and plasmids. The work presented here demonstrates that some CRISPR systems (i.e., type III-A) rely on host nucleases (i.e., RNase R and PNPase) for faithful processing of CRISPR RNAs. Collectively, this work expands the fundamental understanding of how nucleases involved in RNA metabolism contribute to the adaptive immune response in bacteria.

eLife assessment

This is a valuable study performing elegant experiments making identification of a specific regulator in skeletal muscle regeneration. It will form a foundation for further mechanistic investigation. The work is of importance in the clinical field of muscle injury and regeneration.

eLife assessment

The authors provide a new method to target mouse CSF-cNs via intracerebroventricular injection of adeno-associated virus (AAV) with a neuron-specific promoter, which enabled them to introduce any genes into CSF-cNs. By doing so, they established the structure, connectivity, and function of mouse CSF-cNs in locomotion, recapitulating the findings obtained in zebrafish and lamprey, and extending the recent observations in mice. This study is very conclusive and important for the sensorimotor field.

eLife assessment

This paper on the regulation of microtubule dynamics during C. elegans meiosis will be of interest to scientists in the broad field of microtubule function in both mitosis and meiosis. The experiments are beautifully conducted and presented and generally support the conclusions of the paper. The results are interesting and add to our understanding of the control of microtubule dynamics at the kinetochore and its functional consequences for meiosis.

eLife assessment

This paper addresses an important question: the relationship between the cell wall and other, primarily lipid, based components of the cell envelope. Building on previous work, the authors provide data suggesting that the activity of a PonA2, non-essential peptidoglycan synthase, promotes membrane partitioning through its role in cell wall synthesis. While the data are consistent with this model, the reviewers felt additional experiments are necessary to fully support the authors' conclusions.

eLife assessment

This paper is of potential interest to any neuroscientist, given it asks how the brain compensates for its own neural transmission delays. This is a problem that runs across neuroscientific disciplines. The authors use a clever and simple design where they study this question in the context of decoding from EEG signals during visual motion processing. They robustly show evidence that the brain can indeed compensate for these delays, although all compensation appears to be afforded by early processing. The manuscript is well-written but can be strengthened by outlining its significance for the broader community as well as some further analyses.

eLife assessment

This fundamental study demonstrates that the two isoforms of the ARPC5 subunit (ARPC5 and ARPC5L) of the Arp2/3 complex have specific functions in regulating cytoplasmic and nuclear actin filament assembly in response to DNA replication stress and T cell receptor signaling in T lymphocytes. The data presented in the manuscript are convincing and of good technical quality, and the study provides interesting new insights into specific cellular roles of different Arp2/3 isoforms in T lymphocytes.

eLife assessment

This work examines the evolutionary origins of acid-sensing ion channels (ASICs), a class of pH-sensing receptors expressed throughout the brain and body. By combining analysis of sequences, functional measurements, and measures of tissue distribution, the authors provide solid evidence that ASICs existed far earlier than previously believed. The present data indicate that ASICs emerged after the split between bilaterians (organisms with two-fold symmetry) and Cnidaria (jellyfish, anemones, corals, etc.), approximately 680 million years ago. This evolutionary and functional analysis of ASIC channels across bilaterian lineages provides relevant information about the evolution of nervous and sensory systems.

eLife assessment

This manuscript reports an association between TCR convergence and involvement in an antigen-specific response. TCR convergence is assessed as a potential biomarker of response to immune checkpoint blockade (ICB). From jointly analyzing TCR-seq data, single-cell RNA-seq data, and antigen-specific TCR information, the authors provided evidence that convergence is a potential indicator for ongoing T cell antigen-specific response. Overall, the analyses are sound the manuscript is well-written, and the study provides the first evidence that TCRseq alone could be used to predict clinical outcomes.

eLife assessment

The authors present a rich investigation of the evolution of social-movement rules in animal societies under pathogen pressure. The study should be of interest to a broad readership.

eLife assessment

This research focuses on the role of a long noncoding RNA VPS9D1-AS1(VPS) in colorectal cancer (CRC) immune evasion and provides evidence on how it is responsible for escape from cytotoxic T cells killing via amplifying intra-tumoral TGF-β signaling. The findings are of considerable translational significance since VPS9D1-AS1 was validated targetable in this work, and it is of broad interest to readers in cancer biology and immunotherapy.

eLife assessment

Harkin and colleagues explore functional properties of dorsal raphe serotonin neurons using the approach called a generalized integrate-and-fire [aGIF] model, which incorporates a relatively small number of salient biophysical properties of a specific neuron type, and whose parameters are optimized based on voltage dynamics obtained experimentally. The authors make an interesting finding that after-hyperpolarization and A-type potassium currents, in combination with heterogeneous feedforward inhibition from local GABA neurons, give rise to a derivative-like input-output relationship in serotonin neurons.

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.