Evaluated articles

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.

eLife assessment

This important study advances our understanding of how distinct types of communication signals differentially affect mouse behaviors and amygdala cholinergic/dopaminergic neuromodulation. The evidence supporting the authors' claims is solid. Researchers interested in the complex interaction between prior experience, sex, behavior, hormonal status, and neuromodulation should benefit from this study.

eLife assessment

This study provides an important tool for predicting binding between immune cells receptors and antigens based on protein sequence data. The analysis convincingly showed the tool's effectiveness in both supervised TCR binding prediction and unsupervised clustering, surpassing existing methods in accuracy and reducing annotation costs. This study will be of interest to immunologists and computational biologists.

eLife assessment

In Drosophila melanogaster, the SOCE channel Orai is required for the development of flight promoting dopaminergic neurons. The Hasan laboratory has previously shown that disabling Orai function impairs Drosophila flight due to aberrant neuronal development at the pupal stage. In this fundamental study, Mitra et al show that SOCE drives a transcriptional feedback loop via the homeobox transcription factor, 'Trithorax-like' (Trl), and histone modifiers, Set2 and E(z), to regulate the expression of key genes required for the function of dopaminergic flight neurons, including the muscarinic acetylcholine receptor and the inositol 1,4,5-trisphosphate receptor. This solid study is carefully performed with validated methodology and most of the analyses are rigorous.

eLife assessment

This manuscript supports the intriguing idea that some aspects of novel learning can occur during sleep and outside of awareness. The authors provide solid evidence that presenting participants with novel words and their translations during sleep, especially during slow oscillation troughs, leads to the ability to categorize the semantic meaning of those words during awake testing 36 hours later. These findings represent a valuable contribution to the literature on unconscious processing and learning during sleep, although the claim that the results reflect episodic memory formation, in particular, deviates from the typical use of this term in the literature.

eLife assessment

In this manuscript, Chakraborty et al address the role of IP3R1 in regulating store-operated calcium entry in neurons and neural progenitors. Long-standing observations in non-neuronal cells have shown that IP3Rs are not required for SOCE. In contrast to those findings, this manuscript determines that in neuronal cells, knockdown of IP3R1 suppresses SOCE by disrupting ER-plasma membrane contact sites. The paper supports a novel role for IP3R1 as a tether in promoting membrane contact sites which would have broad implications for a range of physiological processes including SOCE and lipid metabolism.

eLife assessment

This study reports valuable behavioral and computational observations regarding how passive exposure to auditory stimuli can facilitate auditory categorization. The combination of behavioral results in mice with a study of artificial neural network models provides solid evidence for the authors' conclusions. This paper will likely be of broad interest to the general neuroscience community.

eLife assessment

This is an important study on the role of the Ras/MEK/Erk signaling cascade in brain development, with both theoretical and practical implications in multiple fields. The authors reveal functional redundancy and shared function for Erk1 and Erk2 in determining medial ganglionic eminence derived glial number, and exclude a role for Erk1 and Erk2 in the regulation of GABAergic neuron number or initial specification of GABAergic identity. They combine multiple methods including Ribotags, electrophysiology, and chemogenetic stimulation using DREADDs towards comprehensive conclusions. Reviewers expressed concerns about the coherence of the findings, and about the selection of controls mouse lines. Heterozygous ERK1/2 mice are used as 'het controls' throughout the manuscript, however, reviewers felt that there was not sufficient evidence that ERK levels in heterozygous mice are similar to wildtype mice. Nevertheless, these compelling findings will be of interest to a broad readership, and especially readers interested in kinase function and neurodevelopmental syndromes.

eLife assessment

This detailed and well powered manuscript explores auditory perception of modulated noise in the presence of transcranial alternating-current stimulation (tACS) and shows valuable results suggesting that there are subject-specific effects when the phase of 2-Hz tACS varies relative to the phase of the noise modulation. The strength of the evidence is mixed. There is convincing evidence that tACS alters perception significantly in individuals; however, the effects are inconsistent across subjects and even across sessions, frustrating attempts to draw conclusions about the underlying mechanisms of the idiosyncratic effects. Despite these limitations, the paper will be of great interest to researchers interested in determining when and how tACS influences neural processes, especially those interested in neural entrainment and its relationship to perception.

eLife assessment

fMRI was used to address an important aspect of human cognition - the capacity for structured representations and symbolic processing - in a cross-species comparison with macaques; the experimental design probed implicit symbolic processing through reversal of learned stimulus pairs. The authors present solid evidence in humans that helps elucidate the role of brain networks in symbolic processing, however the evidence from macaques was necessarily incomplete (e.g., hard-to-quantify differences in learning trajectories and lived experience between species).

eLife assessment

The manuscript by Bull et al provides valuable information on the relationship between metabolic features, in particular different lipoproteins and fatty acids, and colorectal cancer. They use solid methods and combine different data sources to analyze forward and reverse Mendelian Randomizations that support their claims.