Evaluated articles

eLife Assessment

This valuable study presents findings on the mode of action of MOTS-c (mitochondrial open reading frame from the twelve S rRNA type-c), and its impact on monocyte-derived macrophages. The authors present solid evidence for its increased expression in stimulated monocytes/macrophages, its direct bactericidal functions, as well as its role in the modulation of monocyte differentiation into macrophages. Since most of the data were generated from a cell line (THP1), future work is required to validate observations in primary cells and to further support the claims of this work.

eLife assessment

This study develops a useful metric for quantifying codon usage adaptation - the Codon Adaptation Index of Species (CAIS). This metric permits direct comparisons of the strength of selection at the molecular level across species. The study is based on solid evidence, and the authors identify relationships between CAIS and the presence of disordered protein domains. Other correlations, such as the one between CAIS and body size, are weak and non-significant. In summary, the study introduces an interesting new approach to quantifying codon usage across species, which may be helpful in attempts to measure selection at the molecular level.

eLife assessment

This study describes important results from cardiac-specific overexpression of adenylyl cyclase type 8 (TGAC8) mice that was integrated with transcriptomic and proteomic evidence. The paper convincingly provides new insights into how one can interpret signals from visceral organs.

eLife Assessment

This important study shows that a splice variant of the kainate receptor Glu1-1a that inserts 15 amino acids in the extracellular N-terminal region substantially changes the channel's desensitization properties, the sensitivity to glutamate and kainate, and the effects of modulatory Neto proteins. In the revised paper the authors have clarified several points raised by reviewers but the structural portion of the study has not been improved and consequently, more data are needed to determine the molecular mechanism by which the insert changes the functional profile of the channel. Even so, these solid findings advance our understanding of splice variants among glutamate receptors and will be of interest to neuro- and cell-biologists and biophysicists in the field.

eLife assessment

This study provides a valuable resource that documents the protein-protein interactions (PPI) network for alpha-arrestins in both human and Drosophila based on affinity purification/mass spectrometry and the SAINTexpress method followed by a series of bioinformatic and functional assessments. Through these, the authors confirmed the roles of known and novel interactions, including proteins involved in RNA splicing and helicase, GTPase-activating proteins, and ATP synthase. This study represents a convincing example of how to adopt comparative molecular interactions and how to interpret the functional implications.

eLife assessment

This is an important contribution to the origins and translational consequences of the relatively low rate of translation elongation in the first ∼30-50 codons of genes in most organisms. The authors provide convincing evidence that the prevalence of rare codons in the first ~40 codons in yeast is due to the relatively recent evolution of these coding sequences, or of lower purifying selection operating on them, and that a preponderance of codons encoded by rare tRNAs near the N-terminus is not associated with higher translational efficiency in the manner proposed by the "translational ramp" hypothesis. The work is incomplete in that the results of reporter assays may have been confounded by alterations of mRNA sequence or structure that could have influenced their translation or mRNA stability; that the work cannot fully account for a greater enrichment of slowly translated codons in N-terminal vs. C-terminal regions; and that the work does not resolve whether translation elongation through N-terminal coding is truly slow.

eLife assessment

Using a newly developed C. elegans model of Alzheimer's disease that expresses Abeta aggregates extracellularly, the authors provide convincing evidence of a disintegrin and an ortholog of human ADAM9 that participate in removing these extracellular aggregates. The worm model presented in this important paper may be very useful to the Alzheimer Disease field.

eLife assessment

This important paper reveals distinct dynamics of two meiosis-specific cohesin complexes containing either REC-8 or CHO-3/4 in C. elegans: REC-8-cohesin is essential for sister chromatid cohesion in meiosis I and DNA double-strand break repair, while COH-3/4-cohesin, whose binding to meiotic chromosomes is stabilized by the cohesin accessory protein SCC-2, is necessary for loop-axis formation. The experimental evidence in the paper is solid based on cytological analysis using a conditional depletion of the gene. The work will be of interest to researchers working on meiosis and chromosome dynamics.

eLife assessment

This important manuscript, which describes the largest genetic association study to date, uses broadly compelling methods to address the genetic susceptibility to tuberculosis infection. A strength of the paper is that this multi-ancestry meta-analysis of genetic association studies than is more powerful than what has been done before. A weakness is that its main result is difficult to interpret due to the complexity of the genetic association signal.

eLife assessment

This is an important study on learning strategy differences in autism vs typically developing controls. The study identifies similar learning rates but different learning strategies. The evidence provided by the authors is convincing, relying on well-done tasks and fMRI analyses.

eLife assessment

This important work provides evidence regarding the impact of the COVID-19 pandemic on cervical cancer screening and precancer treatments in the USA. As there are few screening registries, the study provides solid evidence using a survey of health providers' impressions to assess whether cervical cancer screening services declined during the pandemic. The work will be of interest to public health professionals working in cancer prevention.

eLife assessment

Salmonella invades and survives in host cells via SPI-1 and SPI-2 type III secretion system mechanisms, with the SPI-2 system allowing for intracellular survival in Salmonella-containing vacuoles, which have a low-pH environment. Transcription of SPI-2 genes at low pH is activated by the DNA-binding SsrB protein, which sits at the top of the SPI-2 regulatory hierarchy. This study provides important insights as to how SsrB is allosterically affected by pH resulting in acid-dependent DNA binding. However, there are concerns about some experiments, and the evidence presented is not fully conclusive.

eLife assessment

This paper reports the fundamental discovery of adrenergic modulation of spontaneous firing through the inhibition of the Na+ leak channel NALCN in cartwheel cells in the dorsal cochlear nucleus. This study provides unequivocal evidence that the activation of alpha-2 adrenergic or GABA-B receptors inhibit NALCN currents to reduce neuronal excitability. The evidence supporting the conclusions is exceptional, the electrophysiological data is high quality and the experimental design is rigorous.

eLife assessment

In this valuable study, the authors explore regulatory cascades governing mammalian cochlear hair cell development and survival. They confirm previous studies that the transcription factors Pou4f3 and Gfi1 are necessary for hair cell survival, and use compelling evidence to demonstrate that the RNA binding protein gene RBM24 is regulated by Pou4f3, but not Gfi1. These findings will be of interest to those working on hearing loss, and hold significance for viral gene delivery methods aiming to manipulate gene expression.

eLife assessment

In zebrafish, primary motor neurons (PMNs) control escape movements, and a more heterogeneous population of secondary motor neurons (SMNs) regulate the speed of rhythmic swimming. Using single cell RNA sequencing (scRNAseq), the authors have obtained compelling evidence that PMNs, and two types of interneurons innervating them, express a set of three genes encoding voltage-gated ion channels enabling rapid firing. The PMNs also express high transcript levels of proteins involved in exocytosis, which would be expected to support rapid neurotransmitter release. These results will be important for those working on spinal cord function and zebrafish genomics/transcriptomics.

eLife assessment

This article presents important results describing how the gathering, integration, and broadcasting of information in the brain changes when consciousness is lost either through anesthesia or injury. They provide convincing evidence to support their conclusions, although the paper relies on a single analysis tool (partial information decomposition) and could benefit from a clearer explication of its conceptual basis, methodology, and results. The work will be of interest to both neuroscientists and clinicians interested in basic and clinical aspects of consciousness.

eLife assessment

This valuable study provides insights into how the brain parses the syntactic structure of a spoken sentence. Convincing evidence is provided that distributive cortical networks are engaged for incremental parsing of a sentence, and neural activity recorded by MEG correlates with sentence structure measures extracted by a deep neural network language model, i.e., BERT. A contribution of the work is to use a deep neural network model to quantify how the mental representation of syntactic structure updates as a sentence unfolds in time.

eLife assessment

This study has important implications for theoretical proposals concerning how language lateralization affects the lateralization of other cognitive functions. The methods are solid, with an appropriate selection of cognitive control tasks that share homotopic regions of the brain with language, comparing participants with typical and atypical organization of language. The participants included in the study were mainly bilinguals, a population previously reported to have a more bilateral organization of cognitive control regions than monolinguals, limiting the generalizability of the results to the general population. Despite this limitation, the results will be of interest to researchers working of brain plasticity and development, in addition to those interested in language and cognitive control.

eLife assessment

This fundamental work substantially advances our understanding of retinol transport through the blood-brain barrier. The evidence supporting the conclusions is compelling, with rigorous biochemical assays. In general, the work is of broad interest to cell biologists, biochemists and neuroscientists.

eLife assessment

This study provides insights into the early detection of malignancies with noninvasive methods by developing a framework, which assesses methylation, CNA, and other genomic features. They established a solid model in discriminating malignancies from healthy controls, as well as the ability to distinguish tumor of origin. This important study will demonstrate its practical impacts in the clinic and other researchers of the field.