- Jul 2023
-
www.biorxiv.org www.biorxiv.org
-
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. The functional data supporting the role of the 15 amino acid insert are solid, although some clarifications and more data are needed to determine the molecular mechanism by which the insert changes the functional profile of the channel. Even so, these findings substantially advance our understanding of splice variants among glutamate receptors and will be of interest to neuro- and cell-biologists and biophysicists in the field.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study provides a comparative interactome analysis of α-arrestin in human and Drosophila. Using convincing methodology that includes affinity purification/mass spectrometry, bioinformatic tools and experimental data in human cells, the authors identify biological roles of protein-protein interactions (PPI) involving α-arrestin in the two species. This study will serve as a broadly relevant resource for understanding the PPI network of human and Drosophila α-arrestins.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.medrxiv.org www.medrxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.medrxiv.org www.medrxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
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 compelling, the electrophysiological data is high quality and the experimental design is rigorous.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In this useful 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.
-
-
www.biorxiv.org www.biorxiv.org
-
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 convincing 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.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study provides valuable insights into how the brain parses the syntactic structure of a spoken sentence. A unique contribution of the work is to use a large language model to quantify how the mental representation of syntactic structure updates as a sentence unfolds in time. Solid evidence is provided that distributive cortical networks are engaged for incremental parsing of a sentence, although the contribution could be further strengthened if the authors would further highlight the main results and clarify the benefit of using a large language model.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This paper describes important advances from the results of studies on atypical language lateralisation and how this might impact language behaviour, as well as its associations with reading skills and the prevalence of schizotypy and autistic traits. Despite most of the conclusions of this paper being supported by evidence, several aspects including the characteristics of participants tested, hypotheses/predictions, and data analysis, are incomplete and/or need some clarification. The work has implications for evolutionary hypotheses and our understanding of the effects of brain damage on distinct cognitive functions.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This valuable study provides a comprehensive assessment of cell-free DNA methylation to explore the ability of a newly-developed so-called "multimodal" predictive model in detecting malignancies and discriminating tumor of origin. The strength of evidence is solid and the logic beneath this study is well-organized. The study sheds insights into the early detection of malignancies with noninvasive methods using a large sample size with external validation cohort. This study will be of interest to cancer geneticists and oncologists for early diagnosis of cancer.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study advances our understanding of the ways in which different types of communication signals differentially affect mouse behaviors and amygdala cholinergic/dopaminergic neuromodulation. Researchers interested in the complex interaction between prior experience, sex, behavior, hormonal status, and neuromodulation should benefit from this study. Nevertheless, the data analysis is incomplete at this stage, requiring additional analysis and description, justification, and - potentially - power to support the conclusions fully. With the analytical part strengthened, this paper will be of interest to neuroscientists and ethologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study provides a valuable tool for predicting binding between immune cells receptors and antigens based on protein sequence data. Its improvement over existing methods is supported by solid analysis, though more details on data, architectures and benchmarking are needed to fully justify this claim. This study will be of interest to immunologists and computational biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In Drosophila melanogater, the Store-operated Ca2+ entry (SOCE) channel, Orai, is required for the development of flight-promoting dopaminergic neurons. Here, Mitra et al. determine that expression of a loss-of-function Orai1 mutant during the 72-96 hour window of pupal development impairs gene expression in dopaminergic flight neurons in part through the expression of Set2, a histone methyltransferase. The authors identify a large number of genes that are controlled by Set2, and show that Set2 is controlled by the trl transcription factor. Although the findings reported here are important, the evidence supporting some of the claims is incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
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 typical use of this term in the literature.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The work examines the effect of transcranial alternating current stimulation on the perception of specific features in sound: gaps in a frequency modulated noise. Several theories link the phase of brain oscillations to perception: the work is important in suggesting direct support for the link. The work is technically well executed on a good size cohort. Still one reviewer raised concerns that the effect seen might be an artifact of the analysis used, so the strength of evidence is incomplete at this stage . We encourage the authors to respond to this issue.
-
-
www.biorxiv.org www.biorxiv.org
-
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 non-human primates (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 incomplete (e.g., sample size constraints, potential and hard-to-quantify differences in attention allocation, motivation, and lived experience between species).
-
-
www.medrxiv.org www.medrxiv.org
-
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.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This paper provides a useful set of data examining the role of PTPMT1, a mitochondria-based phosphatase, in mitochondrial fuel selection. The data were collected and analyzed using solid methodology and can be used as a starting point for further studies that build on the findings here.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study provides solid evidence that the stability and function of the Eph-B2 receptor (EPHB2) are affected by interactions with the multifunctional MYCBP2 and Fbxo45 proteins, extending our knowledge of how members of this key family of receptors are regulated, in particular in regard to their forward signaling. The biochemical binding evidence is generally convincing, but the evidence from the C. elegans experiments is still incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents the valuable finding that a cleaved form of METTL3 (termed METTL3a) has an essential role in regulating the assembly of the METTL3-METTL14-WTAP complex. The evidence supporting the claims of the authors is solid, and the work will be of interest to medical biologists working on breast cancer.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study provides the community with a set of clearly interpretable computational methods to identify new pioneer transcription factors (PTFs) from which thirty two putative PTFs were predicted. The authors used multiple approaches to validate their predictions, and the evidence to support their claims is solid. This work will be of interest to computational and molecular biologists working on transcription factors.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study combines in vitro experiments with simulations to identify the mechanisms governing modulation of microtubule dynamics by GTP hydrolysis. The authors introduce a solid new approach by using a mixed GDP/GMPCPP lattice and varying GDP concentration to reveal that the nucleotide at the interface of two tubulin dimers determines the strength of the interaction between two dimers. Overall, the findings will be of interest to biophysicists and cell biologists, especially in the field of microtubule biology.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
The study presents patterns of cancer care disruption in southern Illinois and eastern Missouri in the summer of 2020. Survey results show factors that impact cancer care during the COVID-19 pandemic, including group differences by race. The important findings provide solid evidence about variation in cancer care disruptions and opportunities to improve return to care.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable work presents new results to characterize the relationship between electrical excitation and torque generation in stick insect joints. The evidence supporting this work is a series of torque-voltage measurements across individuals. The strength of evidence is solid in supporting the outcomes, but some details of the methodology, which could potentially shed light on the sources of this variation, are missing.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study reports selective CDKL5 inhibitors that may be of high interest to investigate the role of this kinase in disease (particularly, in CDKL5 deficiency disorder) and to address unsolved issues of inconsistency in the phenotypic characterization of CDKL5-deficient knockout mice. The evidence supporting the conclusions is convincing, with rigorous biochemical, in vitro and ex vivo assays. The work will be of interest to cell and medical biologists and epileptologists working in the fields of epilepsy and neural excitation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents a valuable finding on the combination treatment of ONC201/TIC10 with everolimus for metastatic ER+ breast cancer. The evidence supporting the claims of the authors is solid. The work will be of interest to medical biologists working on breast cancer.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study demonstrates an important method that drastically improves the precision of ultrasound localization in interacting mice. The authors present convincing evidence of the usefulness of the method for quantifying vocal behavior in various situations and demonstrate an interesting vocal dominance phenomenon between males. This tool will be of great interest to all scientists interested in vocal behavior in small animals.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study reports selective CDKL5 inhibitors that may be of high interest to investigate the role of this kinase in disease (particularly, in CDKL5 deficiency disorder) and to address unsolved issues of inconsistency in the phenotypic characterization of CDKL5-deficient knockout mice. The evidence supporting the conclusions is convincing, with rigorous biochemical, in vitro and ex vivo assays. The work will be of interest to cell and medical biologists and epileptologists working in the fields of epilepsy and neural excitation.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This study presents a valuable finding on the optimal prioritization in different malaria transmission settings for the distribution of insecticide-treated nets to reduce the malaria burden. The evidence supporting the claims of the authors is solid, although the authors have made various simplifications to enable the identification of optimal strategies. The work will be of interest from a global funder perspective, though somewhat less relevant for individual countries.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is important work analyzing the trial-by-trial progression of learning, and how the outcome of one trial influences cortex-wide neural responses on the next trial. However, the evidence for the central claims is incomplete because the potential confounds of slow hemodynamic effects and behavioral changes induced by the previous trial were not adequately addressed.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In this paper, the authors demonstrate an interesting link between mitofusin function (MFN2) and PARKIN recruitment and mitophagy, underlying cardiomyopathy. This is a valuable finding with broad implications for understanding the mitochondrial biology as well as mechanisms involved in heart pathologies. However, the analyses are incomplete and the main conclusions are only partially supported and need to be further evidenced.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This paper presents important findings on the hexametric structure of MCM8/9, which potentially explain its role as a DNA helicase in homologous recombination. This solid work will be of interest to biologists studying DNA transactions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents a valuable description of RNA in extracellular vesicles (EV-RNAs) and highlights the potential to develop biomarkers for the early detection of colorectal cancer (CRC) and precancerous adenoma (AA). The data were analysed using solid methodology and would benefit from further validation at each stage of CRC/AA to evaluate the potential application to early detection of CRC and AA.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This useful manuscript describes the TOR signaling pathway in the human and plant pathogen Aspergillus flavus. While the authors provide a large amount of descriptive and often confirmative data, the evidence for the new claims made here for the TOR pathway in this species is incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
How the genome is folded three dimensionally is thought to control gene regulatory pathways during critical processes such as cellular differentiation. Using multiple assays, the authors of this important study probe topologically associated domains (TADs) and report involvement of a protein arginine methyltransferase 5 in chromatin organization and transcriptional regulation. The data gathered are generally solid and broadly support the role of this protein in organization of the adipocytic lineage, but additional control experiments would make the inferences stronger.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This useful study emphasizes some previously ignored aspects of synaptic communication between Purkinje neurons and their targets in the cerebellar nuclei. Reviewers felt that some aspects of the evidence were solid but that others were incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This manuscript compiles existing algorithms into an open-source software package that enables real-time motor unit decomposition from muscle activity collected via grids of surface electrodes and indwelling electrode arrays. The software package is valuable given that many motor neuroscience labs are using such algorithms and that there exist a host of potential real-time applications for such data. Validation of the software package is generally solid but incomplete in some significant areas: the primary data is narrow in scope and only from male participants, and there is a lack of ground truth tests on synthetic data. The impact of the software package could be strengthened by making it less tied to specific electrode hardware and by expanding it to easily permit offline analysis.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study presents a large experimental study to examine the effects of plant species richness, plant genotypic richness, and soil water availability on herbivory patterns on Piper species in several tropical sites. The authors find that water availability and both intra- and interspecific plant diversity influence herbivory and herbivore diversity, but that the effects differ in significant ways across sites. The major weakness lies in findings that can be better presented in a less complicated fashion. The major claims are currently supported by a combination of solid and incomplete evidence, and the manuscript would benefit from better organization.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
The authors have used a 'digital twin' strategy to recapitulate human pathophysiology of arrhythmia. These important findings have theoretical and practical implications beyond the single subfield of cardiovascular science for personalised medicine. The experimental design relies on state-of-the-art methodologies, with compelling results. The work will be of broad interest to colleagues in the general area of computational biology.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study by Chiu and colleagues is an important contribution to the study of the circuitry of aggressive behaviours and of mechanisms that generate persistent states. The data ruling out current ideas in the field are convincing.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study considers the relationship between performance in a path-integration-based navigation task and the degree to which medial entorhinal grid cells encode the animal's position. Using a virtual reality environment combined with neural recordings, the work presents solid evidence that the variability in the spatial firing of grid cells correlates with the behavioral performance of the mouse on the navigational task.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The authors tested the hypothesis that age-dependent factors in human sera affect the core circadian clock or its outputs in cultured fibroblasts. While the paper does not provide molecular mechanistic insight how sera from young versus old donors lead to differences in cyclic gene expression, it does provide fundamental insights and a possible explanation for previous observations showing that circadian gene expression in peripheral tissues tend to dampened or phase-shift with age. As presented, the strength of the evidence is, however, incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study provides important new insights into the structural diversity of effectors - proteins secreted by pathogens and symbionts into host cells - from the plant-associated fungus Fusarium oxysporum f. sp. lycopersici. The study provides a convincing approach to understand how effectors navigate their host environment using both computational and experimental approaches to understand how their structure influences binding partners. The work will be of interest to those studying molecular host-microbe interactions and disease protection.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study presents findings on how the hypoxia response pathway senses and responds to changes in the homeostasis of the amino acid cysteine and other sulfur-containing molecules, with compelling and rigorous genetic analyses. The works adds to a growing body of literature showing that prolyl hydroxylation is not the only mechanism by which the hypoxia response pathway can act. Although the paper does not reveal new biochemical insight into the mechanism, it opens up new areas of investigation that will be of interest to cell biologists and biomedical researchers studying the many pathologies involving hypoxia and/or cysteine metabolism.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
By developing a novel method for detecting genetic variants associated with germline mutation spectrum variation, this important study identifies a new "mutator" locus in a population of inbred mouse strains, although the causal gene(s) within this locus remains uncertain. The authors further demonstrate that this new mutator locus interacts epistatically with a previously identified mutator allele on C>A mutation rate, showcasing the complexity of the genetic basis underlying variation in mutation rate and spectrum. Evidence for major findings in this paper is convincing, but the power, statistical properties and limitations of the new method need to be further characterized to support its broader applicability to other systems.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In this useful study, a solid machine learning approach based on a broad set of systems to predict the R2 relaxation rates of residues in intrinsically disordered proteins (IDPs) is described. The ability to predict the patterns of R2 will be helpful to guide experimental studies of IDPs. A potential weakness is that the predicted R2 values may include both fast and slow motions, thus the predictions provide only limited new physical insights into the nature of the relevant protein dynamics.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study provides insights into the functions of different GNAI subunits, substantially advancing our understanding of their roles in the regulation of hair cell stereociliary bundle development. Convincing evidence is provided to support the findings and overall, the results of this study provide a thorough and careful examination of the roles of different GNAIs in the inner ear, with only minor weaknesses identified in review.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This work is a valuable exploration of a new stability-guided fine-mapping method, which aims to identify causal genetic variations, by extending the previously proposed PICS method. While the results are empirically validated using functional annotations, their evaluation is incomplete and lacks extensive simulations where true causal variants are known. The approach to improving fine-mapping of causal variants presented will be of interest to geneticists and biomedical researchers using genetic data to guide their investigations.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This study presents valuable findings on the symptoms and disease trajectories preceding a diagnosis of pancreatic cancer in Denmark. The evidence supporting the claims of the authors is solid, although an error analysis of the text mining evaluation results and a discussion on how the findings can be applied in practice would strengthen the study. The work will be of interest to public health researchers and clinicians working on pancreatic cancer.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This article is of broad interest to public health researchers and to health policymakers in populations with national screening programs. It provides important knowledge on the impact of the COVID-19 pandemic on participation in mammography screening in Denmark by socio-economic indicators. The study provides convincing evidence for how the pandemic exacerbated disparities in breast cancer screening in Denmark.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In this valuable report, the authors explore the connection between mTORC signaling and APA regulated by the CFIm complex. Using a combination of genetic and functional genomics approaches, the study reveals that a twin UGUA motif is a potent cis acting regulation of PAS usage that is recognized by CFIm. Overall, the evidence in general is convincing and supports the conclusions and provides the field with additional mechanistic insight of how signaling connects to APA regulatory machinery.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is an important study of the dimensionality and synchrony of calcium responses in Purkinje cells measured across a large region of the cerebellar cortex over the course of learning. This work has the potential to inform our understanding of the functional organization of the cerebellum and longstanding hypotheses about the role of cerebellar climbing fibers in the induction of learning and in the timing of movement, but the evidence provided for the many sweeping claims is incomplete. The paper would benefit from additional statistical analyses to more rigorously evaluate the central claims, with consideration of appropriate comparison groups and potential confounds.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study uses mathematical modelling to demonstrate that conformational autoinhibition of the RAF kinase is an important feature of its paradoxical activation by pharmacological inhibitors. This part of the theoretical analysis is highly compelling but its extension to the investigation of how the binding of 14-3-3 adaptors additionally contributes to the paradoxical activation phenomenon is incomplete and would benefit from more rigorous experimental validation. With the experimental part addressing 14-3-3-dependent regulation strengthened or the 14-3-3 part completely removed, this paper would be of considerable interest to cell biologists and cancer biologists, ultimately paving the way for improved RAF therapeutics.
Tags
Annotators
URL
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is a descriptive paper in the field of metascience, which documents levels of accessibility and reproducible research practices in the field of cardiovascular science. As such, it does not make a theoretical contribution, but it argues, first, that there is a problem for this field, and second, it provides a baseline against which the impact of future initiatives to improve reproducibility can be assessed. The study was pre-registered and the methods and data are clearly documented. This kind of study is extremely labour-intensive and represents a great deal of work.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This study presents important evidence of the impact of the covid pandemic on breast cancer screening globally but with important variations by healthcare setting. The data analysis is comprehensive, using solid systematic review methods. The results will be of interest to public health policymakers and health care and cancer control practitioners and researchers across the globe.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
TP73 is a member of the p53 family of tumor suppressors. The authors provide compelling evidence that a TAp73-alpha to TAp73-gamma switch could be a frequent phenomenon in human cancers and provide novel evidence that TAp73-gamma has oncogenic functions via Leptin. The authors provide a substantial amount of high-quality data and convincingly demonstrate a novel function of this specific isoform of p73 in lipid metabolism and tumorigenesis.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is a valuable contribution to the effort to provide genetic access to and characterization of the major classes of interneurons in the mammalian neocortex. The authors develop an improved strategy for intersectionally targeting a fourth (and final) major category of diverse interneurons in the mouse, including the previously studied neurogliaform cells. They provide a detailed characterization of these cells and show convincingly that their genetic strategy can be used to identify and manipulate these cells, both in vitro and in vivo.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In this important study, the authors present evidence for the novel involvement of a scavenger receptor in tubular morphogenesis. Using a convincing set of data, the authors propose that the Drosophila scavenger receptor Emp (homologous to human CD36 ) couples endocytosis of luminal molecules and regulates tube length via controlling Crumbs and Src. This work will be of broad interest to cell and development biologists as well as cancer biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This manuscript is important as it showed an establishment of a method for looking a neuronal activity in embryos which can support the previously reported laterality in chick thalamofugal system. However, the evidence the author provided was incomplete as no actual data was provided.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study provides a substantial advance with a method by which a protein target resistant to therapeutic approaches can be uniquely modulated by a cellular protein kinase ferried by nanobodies to a precise molecular site of recruitment. Evidence for this major claim is compelling, but evidence for some of the minor claims seems incomplete. The work will be of broad interest to cell biologists, cardiovascular researchers, and drug developers.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study provides a state-of-the-art framework to explore the coupling of complementary cerebral measures (neural, hemodynamic, and metabolic) during development by providing an interesting roadmap for multimodal neuroimaging in infants. The methodological contribution is compelling with an original setup for simultaneous EEG and NIRS recording and solid data analyses. However, the claims about functional specialization and the role of the temporal-parietal junction in social processing are only partially supported by the results. This work will be of interest to a broad audience of scientists interested in multimodal neuroimaging and cognitive development.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
Overall, this is an important study that characterizes human oral lichen planus via single-cell analysis. Although the work is descriptive, it can represent an important resource for future studies and highlights potentially relevant biology. However, the claims are a bit overstated and some of the analyses that lead to interpretations remain incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study is a valuable contribution to our understanding of vocal variation in acoustic displays of male baleen whales, part of a developing story about cultural change in songs in species other than the relatively well studied humpback whales. The authors present solid evidence of changes at various timescales in 20-Hz song note intervals and call center frequency over decadal time scales and large spatial scales.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is an important study demonstrating distinct roles for the nuclear receptor genes COUP-TFI and COUP-TFII in hippocampal development. The strength of evidence is compelling, using rigorous state-of-the-art methods to demonstrate functional redundancy of these genes in regulating the Lhx2/Lhx5 axis. The major strengths of the study are the dramatic morphogenic phenotypes, and the resultant altered gene networks. These findings have theoretical or practical implications beyond a single field, and will be of interest to geneticists, developmental neurobiologists and chromatin biologists among others.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment:
This study offers new fundamental information on a role for the sodium/potassium pump in sleep regulation. Elegant methods were used to provide compelling evidence supporting the claim. The work will be of interest to sleep researchers in zebrafish as well as in other species for future investigation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study provides a framework bearing on the role of Eph-Ephrin signaling mechanisms in the clinically condition of amyotropic lateral sclerosis. It provides compelling evidence for the roles of glial cells in this condition. This novel astrocyte-mediated mechanism may help identify future therapeutic targets.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is an important study that revealed a new noncoding RNA regulatory circuit involved in T cell function. The authors provide compelling evidence, that is more rigorous than the state-of-the-art, using genetically engineered mice and cell-based experiments. The interpretation of the results should be tempered due to the small effect size observed.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study aims to discover the mechanisms governing the switch between conventional DNA replication and the specialized mechanism of telomere end replication. Solid genetic and biochemical assays suggest an interplay between sumoylated PCNA and chromosome terminal capping proteins. The questions addressed have implications for several fields, such as genome stability.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable Tools and Resources paper presents new tools for investigating GLP-1 signaling: a genetically-encoded sensor constructed from a mutated GLP1R receptor as well as a caged agonist peptide. The evidence for these tools working as advertised is largely convincing and they may be helpful for screening compounds that bind to GLP1R. On the other hand, their overall utility is limited by their very weak apparent affinity relative to the likely biological concentration and response. Incomplete characterization of the properties of the tools makes it difficult to anticipate which applications are most likely to succeed.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable Tools and Resources paper presents new tools for investigating GLP-1 signaling: a genetically-encoded sensor constructed from a mutated GLP1R receptor as well as a caged agonist peptide. The evidence for these tools working as advertised is solid and they may be helpful for screening compounds that bind to GLP1R.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study examines the role of the locus coeruleus in the extinction of instrumental behaviors. The work is valuable to highlight the function of this part of the brain. Evidence is incomplete as spontaneous recovery is not demonstrated in control subjects. Further analyses on the effect of the manipulations on baseline lever pressing, magazine entries, and the coupling of lever-presses and magazine entries help capture the function of the locus coeruleus.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study aggregates across five fMRI datasets and reports that a network of brain areas previously associated with response inhibition processes, including several in the basal ganglia, are more active on failed stop than successful stop trials. This study is valuable as a well-powered investigation of fMRI measures of stopping. However, evidence for the authors' conclusions regarding the role of subcortical nodes in stopping is incomplete, due to the limitations of fMRI and a lack of theoretical synthesis.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Based on a technological advance which couples onboard calcium imaging with in vivo electrophysiology in freely behaving mice, this work presents important insights about the brain circuits through which the cerebellum could participate to social interactions. In particular, correlative measurements provide interesting but incomplete evidence that connections between cerebellum and cingulate cortex connections specifically contribute to the complex sensory-motor computations underlying social contacts. This study is of interest for a broad range of neurophysiologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study reveals the use of an allocentric spatial reference frame in how the perception of the location of a dimly lit target is updated during locomotion. The evidence supporting this claim is convincing, based on a series of cleverly and carefully designed behavioral experiments. The results will be of interest not only to scientists who study perception, action and cognition, but also to engineers who work on developing visually guided robots and self-driving vehicles.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important work advances our understanding of the differences in locomotion-induced modulation in primate and rodent visual cortexes. The evidence in support of these differences across species is convincing, although greater use of the primate dataset with some additional analyses would have strengthened the claims. This work will be of broad interest to neuroscientists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The study provides valuable insights into allosteric regulation of BTK, a non-receptor protein kinase, challenging previous models. Using a variety of biophysical and functional techniques, the paper presents evidence that the N-terminal PH-TH domain of BTK exists in a conformational ensemble surrounding a compact SH3-SH2-kinase core, that the BTK kinase domain can form partially active dimers, and that the PH domain can form a novel inhibitory interface after SH2/SH3 disengagement. Overall the presented evidence is solid, but the EM results may be over-interpreted and the work would benefit from additional functional validation.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The manuscript describes a valuable theoretical calculation focusing on the structural changes in the photosynthetic reaction center postulated by others based on time-resolved crystallography using X-ray free-electron laser (XFEL) (Dods et al., Nature, 2021). The authors argue that calculated changes in redox potential Em and deformations using the XEFL structures may reflect experimental errors rather than real structural changes. The study is still incomplete in the sense that it focuses on explaining why the proposed structural changes do not match the theoretical calculations, but it does not yet provide an alternative model.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is a valuable study of the molecular basis of summer-to-winter transition in Cacopsylla chinensis. Despite the convincing molecular and organism-level experiments, evidence of cold sensitivity in the protein of interest is incomplete, with a lack of methodological detail. The results of this study will be of interest to entomologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study and associated data is compelling, novel, important, and well-carried out. The study demonstrates a novel finding that different chemotherapeutic agents can induce nucleolar stress, which manifests with varying cellular and molecular characteristics. The study also proposes a mechanism for how a novel type of nucleolar stress driven by CDK inhibitors may be regulated. The study sheds light on the importance of nucleolar stress in defining the on-target and off-target effects of chemotherapy in normal and cancer cells.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This interesting study describes the development of a three-dimensional cell culture system to investigate muscle tissue development and homeostasis. It is a solid study that could be valuable in the study of human as opposed to animal cells in studying muscular disorders.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents useful findings regarding the impact of forest cover and fragmentation on the prevalence of malaria in non-human primates. The evidence supporting the claims of the authors is, however, incomplete, as the sampling design cannot adequately address the geospatial issues that this study focuses on.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study by Verdikt et al. provided solid evidence demonstrating the potential impacts of Δ9-tetrahydrocannabinol (Δ9-THC) on early embryonic development using mouse embryonic stem cells (mESCs) and in vitro differentiation. Their results revealed that Δ9-THC enhanced mESCs proliferation and metabolic adaptation, possibly persisting through differentiation to Primordial Germ Cell-Like Cells (PGCLCs), though the evidence supporting this persistence was incomplete. Although the study is important, it was limited by being conducted solely in vitro and lacking parallel human model experiments.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This manuscript describes useful information on in vitro binding and hydrogen exchange (HDX) mass spectrometry experiments using various bacterial-expressed BRAF N-terminal fragments, to tease out domain-specific interactions with RAS proteins or wildtype and oncogenic mutant BRAF kinase fragments. The characterization of the auto-inhibitory mechanism of the regulation of BRAF is solid but several concerns remain. The data will be of interest for researchers in the RAS/RAF and general kinase regulation fields.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The study by Gu et al. presents direct evidence on the role of microglia morphological dynamics during sleep/wake cycles and the modulatory effect of sleep deprivation, making it a valuable contribution to the ongoing investigation of microglial function. The use of a novel miniature two-photon microscope technique adds strength to the evidence supporting the conclusions. However, concerns remain about certain methodological and experimental aspects of the study, indicating that further validation is necessary and that the evidence presented is currently incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The discovery of Homo naledi-associated evidence for intentional burial and engravings would undoubtedly have important implications for our understanding of the evolution of complex cognition and behavior. Based on claims made in two related preprints by Berger et al., this study discusses the potential implications of the purported mortuary practice and symbolic behaviors claimed to be associated with the small-brained H. naledi remains. Unfortunately, the evidence presented in the two related submissions that the current paper entirely relies on is incomplete at this stage.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This paper presents important information about potentially Homo naledi-associated markings discovered on the walls of the Hill Antechamber of the Rising Star Cave system, South Africa. If confirmed, the antiquity, intentionality, and authorship of the reported markings will have profound archaeological implications, as such behaviors are otherwise widely considered to be unique to our species, Homo sapiens. As it stands, the study is incomplete, and the evidence presented does not support the claims about the anthropogenic nature, age, and author of the engravings. While it is appreciated that this report concerns preliminary findings, all reviewers agree that: a) the initial nature of the reported results must be more clearly indicated, b) the anthropogenic nature of the engravings must be adequately demonstrated, c) ideally the chronology of the claimed engravings has to be established for any age estimate to be reliable, and d) the claim about H. naledi being the author of the reported engravings requires robust association.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The authors study the context of the skeletal remains of three individuals and associated sediment samples to conclude that the hominin species Homo naledi intentionally buried their dead. Demonstration of the earliest known instance of intentional funerary practice – with a relatively small-brained hominin engaging in a highly complex behavior that has otherwise been observed from Homo sapiens and Homo neanderthalensis – would be a landmark finding. However, the evidence for these claims is considered inadequate in the current version of the study. The four reviewers were in strong consensus that the methods, data, and analyses do not support the primary conclusions. Without full excavations, the study is missing crucial geoarchaeology (especially micromorphology) and taphonomic components, among other limitations, that make premature the conclusion that H. naledi intentionally buried their dead. The null hypothesis must be that these skeletons accumulated naturally and the research must then reject the null hypothesis and robustly exclude equifinality in order to justifiably draw the remarkable conclusions made in the present version of the paper.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Brain inflammation is a hallmark of multiple sclerosis. Using novel spatial transcriptomics methods, the authors provide convincing evidence for a gradient of immune genes and inflammatory markers from the meninges toward the adjacent brain parenchyma in a mouse model. This important study advances our understanding of the mechanisms of brain damage in this autoimmune disease.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This research advance article describes a valuable image analysis method to identify individual cells (neurons) within a population of fluorescently labeled cells in the nematode C. elegans. The findings are solid and the method succeeds to identify cells with high precision. The method will be valuable to the C. elegans research community.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study characterises the involvement of condensin complexes in the segregation of telomeres in fission yeast. The authors present solid evidence in support of their claims, employing a diverse range of complementary techniques. This research will be of interest for cell biologists working on chromosome biology and cell division.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study describes engineered dengue virus variants that can be used to dissect epitope specificities in polyclonal sera, and to design candidate vaccine antigens that dampen antibody responses against undesirable epitopes. The evidence supporting the major claims is solid, although experiments to distinguish the impact on antibody binding versus neutralizing activities would have strengthened the study. This work will be of interest to virologists and structural biologists working on antibody responses to flaviviruses.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important article provides insights into the neural centres in the Japanese quail brain that are associated with photoperiod-induced life-history states. The physiological and transcriptomic analyses of the mediobasal hypothalamus and pituitary gland offer evidence for a coincidence timing mechanism for measuring day length, which is relevant for the field of circannual biology. Despite some shortcomings in data analysis, the study's convincing experiments and findings have the potential to captivate the attention of molecular and organismal endocrinologists.
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
eLife assessment:
This important study describes spatial RNA processing events by combining methods for single-cell transcriptomics data with spatial transcriptomics data. The evidence supporting the claims of the authors is solid, although the analysis could be further strengthened by including a broader range of samples as well as orthogonal validation either by experimental methods or simulated data. The work will be of general interest to researchers in the spatial transcriptomics field as well as researchers investigating alternative pre-mRNA processing across diverse tissues.
Tags
Annotators
URL
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment:
Trypanosoma brucei evades mammalian humoral immunity through the expression of different variant surface glycoprotein genes. In this fundamental paper, the authors extend previous observations that TbRAP1 both interacts with PIP5Pase and binds PI(3,4,5)P3, indicating a role for PI(3,4,5)P3 binding and suggesting that antigen switching is signal dependent. While much of the evidence is compelling, one reviewer suggested that the work would benefit from further controls.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This paper describes an important, well-organized study into an under-exploited area of spatial transcriptomics. The limitations of the approach are generally made clear, but there is insufficient orthogonal validation to demonstrate the biological significance of the results, which leads to the evidence for the claims being currently incomplete. Nevertheless, the tools presented will provide a resource to researchers wishing to characterise spatial patterning of mRNAs, and the paper will be of interest to researchers studying cell biology, RNA biology, and method development for spatial transcriptomics/proteomics.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important paper reports a novel, compelling method, based on barcoding viral genes and next-generation sequencing, to quantify both viral transcription levels and progeny virus production in influenza virus-infected cells at the single-cell level. The authors show that viral transcription and progeny virus production are unexpectedly poorly correlated, and that cells in which viral RNAs are transcribed at high levels are not necessarily those producing the most progeny virions. Because of its novelty, the study will be of interest to the broader virology community.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is an important study that reports the discovery of a new pathway of miRNA sorting to exosomes, involving a mitochondrially-localized protein. The evidence provided by some of the biochemical data is convincing. However, the major body of evidence is still incomplete.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Overall, this is an interesting topic of study, and the conclusions could be of relevance more broadly. However, mechanistic support, limited TTF frequencies/timing, and visual support of the quantitative data would be critical in order to provide convincing and rigorous support for this interesting concept.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study explores the regulatory function of O-GlcNAcylation on DNA methyltransferase 1 and identifies serine 878 as the main target. This study is of interest to those in epigenetics and metabolism. The significance is important and the strength of the evidence is convincing.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This US study presents findings from an online survey and in-person interviews of healthcare providers in areas associated with cervical screening provision during the post-acute phase of the pandemic. The findings are valuable as they provide insights into a range of areas, from healthcare characteristics to screening barriers and HPV self-sampling. The evidence supporting the claims of the authors is solid, although the inclusion of a nationally-representative sample of healthcare providers and a greater gender/ethnicity/racial mix of interviewees would have strengthened the study. The work will be of interest to public health scientists and a cancer prevention and control audience.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This manuscript suggests a novel mechanism of purifying selection by which programmed cell death contributes to the selective removal of mtDNA deletion mutations in C. elegans. The evidence for this mechanism of removal is strong although questions remain regarding the underlying mechanism and the role of canonical ageing pathways. Because of the likely central role of mtDNA deletions in ageing and age-dependent diseases, this work will be of interest to scientists in the field of mitochondrial biology as well as ageing.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This work provides a valuable structural and functional characterization of the neurotransmitter's spatial distribution heterogeneity in cortical and subcortical regions. The authors report a systematic description and annotation of a new "layer" of brain organization that has been relatively poorly integrated with the wider neuroimaging literature to date. In sum, this paper has the potential to be of great interest to a wide audience in neurosciences.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This important paper describes a valuable systematic review and meta-analysis of mental health problems in polycystic ovary syndrome (PCOS) that drive the excess economic burden associated with this common endocrine disorder. Interestingly, the cost of the diagnostic evaluation is only a relatively minor part of the total costs, but mental health disorders were identified as a significant component of the economic burden. These solid findings could not have been anticipated intuitively and are of considerable value for public health prioritization of PCOS.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents a valuable and elegant kinetic analysis of the GSKbeta activity as a function of phosphorylation and Axin binding - providing insights into critical steps of Wnt pathway signaling. The results will be of big use to the broader signaling community, however, the incomplete dissection of the mechanism by which Axin binding inhibits GSKbeta inhibitory phosphorylation remains a weakness of this study. The work will be of broad interest to cell biologists and biochemists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study used high-resolution brain imaging methods to visualize and index non-invasively auditory and language pathways of young children born with inner ear malformations or cochlear nerve dysfunction resulting in profound hearing loss. Nerve fiber impairments were compellingly demonstrated in subcortical auditory and cortical language pathways relative to typically-hearing controls. The results suggested novel approaches for clinical assessment of central auditory and language pathways that may influence different intervention strategies, pending further evidence linking these structural findings with functional outcomes.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Rodberg et al. show systemic β adrenergic antagonism reduces engagement in decision-making, particularly in female rats, and reduces task-related encoding in neural activity. This is a valuable finding that addresses a gap in the field, however, the understanding of the direct contribution of β adrenergic receptors to the observed effects is incomplete. Further, the theoretical grounds, data analyses, and results could be improved in several ways.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This work provides fundamental new insight into fine axonal morphologies based solely on extracellular action potential recordings. They provide compelling evidence of fine resolution in mapping functional connections between neurons. The work may have broad use in neurobiology, bioengineering, stem cell biology, as well as tissue engineering in functional characterization.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The tool developed and implemented in this study has valuable significance for the combined analysis of large, diverse omics datasets, but some of the methodology is incomplete. Regarding the strength of evidence, there are some more significant concerns regarding potentially inadequate controls for false discovery and multiple testing corrections.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The manuscript represents a valuable contribution to an ongoing discussion about the substrate binding site and mechanism of the Bile Acid Sodium Symporter (BASS) family of transporters. Structural and biochemical analysis of a bacterial homolog, ASTBnm, in complex with its native substrate (not bile acids, but a vitamin A precursor, pantoate) show a new binding site that is consistent with classical proposals for elevator-type transport mechanisms. Molecular simulations highlight the improved stability for the substrate in the active site when ions are present, suggesting a binding order during the transport cycle. The structural studies, binding assays, and MD simulations are convincing, although support for the transport mechanism is incomplete without a pantoate transport assay.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study advances our knowledge of how parasites evade the host complement immune system. The new cryo-EM structure of the the trypanosome receptor ISG65 bound to complement component C3b is highly compelling and well-supported by biochemical experiments. This work will be of broad interest to parasitologists, immunologist, and structural biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study identifies two new transporters of the apicoplast, a non-photosynthetic organelle of apicomplexan parasites. In its current state, evidence is incomplete, as it only partially reveals how important those transporters are and as it does not address the metabolic function for the parasite. The results should be of interest to parasitologists and eukaryotic cell biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study includes important findings on protein evolution, namely that changes in function are largely attributable to pairwise rather than higher-order interactions, and that epistasis potentiates rather than constrains evolutionary paths. Compelling evidence supporting the conclusions is provided by applying a new model to a previously generated experimental dataset on deep mutational scanning of the DNA-binding domain (DBD) of steroid hormone receptor. The implications of this work are of considerable interest to protein biochemistry, evolutionary biology, and numerous other fields.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This fundamental study identifies the components of the N6-methyladenosine methyltransferase complexes in yeasts, with major differences with the same complexes in mammals and flies. The evidence supporting the conclusions is convincing, with rigorous high-throughput sequencing approaches and detailed functional analysis. This work will be of broad interest to colleagues in the RNA modification and meiosis fields.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study examined the use of dantrolene, a Ryanodine Receptor stabilizer, in slowing pathological progression of pressure-overload heart failure in a guinea pig model and reducing arrhythmias. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for future studies of dantrolene in Ca2+ handling in ROS production and further deterioration of cardiac function in chronic heart failure.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The paper provides a useful and novel application of recursion theory to the long call vocalisations of orangutans to demonstrate repetitive, rhythmic sub-structuring. However the evidence provided to support the major claims of the paper is currently incomplete. Specifically, it is not yet clear how the rhythmic structuring found in these long calls is more similar to human language recursion per se rather than isochrony as a broader, more common phenomenon.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study describes a combination of in vitro and in vivo results implicating Dyrk1a in the regulation of mTOR. Strengths include the combination of cell and whole-animal (Drosophila) based studies. However, the evidence supporting the conclusions is incomplete and additional experimentation (which could include IPs, more confirmation of the T1462 phosphorylation, and more information about Akt) would strengthen the main conclusions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study reports important findings about new locomotory dynamics of crawling Drosophila larva based on imaging the reaction forces during larval crawling. The new high-resolution microscopy method is compelling, as it significantly improves the spatial, temporal, and force resolution compared to previous methods for studying Drosophila larva and could be applied to other crawling organisms. The manuscript would nevertheless benefit from more details explaining the new technology, limitations, and justifications for the choice of technology and certain experimental details. The work will be of interest to the broad neuroscience community interested in the mechanisms of locomotion in a highly tractable model.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study reports the important finding that there appears to be a timer that monitors the repair of DNA after damage and regulates whether cells are subsequently able to enter mitosis. The authors identify proteins important for this decision and propose a mechanism supported by solid but not conclusive data. This study will be of interest to researchers in the fields of DNA damage repair and cell cycle control.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In this important study, the human membrane receptor guanyl cyclase GC-C was expressed in hamster cells, co-purified in complex with endogenous HSP90 and CDC37 proteins, and the structure of the complex was determined by cryo-EM. The study shows that the pseudo-kinase domain of GC-C associates with CDC37 and HSP90, similarly to how the bona fide protein kinases CDK4, CRAF and BRAF have been shown to interact. The methodology used is state of the art and the evidence presented is compelling.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study is useful to scientists studying cell polarity, epithelial morphogenesis, cancer, and primary cilia. The authors confirm the need for CRB3A/B in regulating ciliogenesis by using a combination of a mammary epithelial cell-specific conditional Crb3 knockout mouse model, and cellular, molecular and biochemical approaches. The results are solid, supporting and extending previous findings; the results also indicate that CRB3 affects ciliogenesis by a still incompletely understood mechanism involving Rab11 and gamma-TuRC.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study represents an important contribution to the field by supporting the utility of functional ultrasound imaging for evaluating cerebral hemodynamics in rat models of brain injury. Solid evidence is presented supporting the possibility of imaging the effect of thrombolysis during stroke in awake rats. This work will be of interest to researchers working in functional neuroimaging and more precisely with preclinical models of stroke in rodents.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important paper reports technical advances for in vivo intramuscular electrical recording from multiple motor units in behaving animals. This new muscle recording method has the potential to provide new insight into a range of questions in motor neuroscience. The paper includes compelling demonstrations of the efficacy of this new technique in multiple animal species, although further evidence is needed to support the claim that electromyogram "spike sorting" can reliably disambiguate individual motor units.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study documents valuable findings on three variants in SNAP25 that are associated with developmental and epileptic encephalopathy. The thorough characterization of synaptic release and in vitro vesicle fusion phenotypes provides interesting information about the nature of the SNAP25 variants. The evidence supporting the claims is compelling, and this work will be of interest to neuroscientists working on SNAP25, SNAP25-associated encephalopathy, and synaptic vesicle exocytosis.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important work examines the potential utility of socio-emotional and socio-cognitive mental training on hippocampal subfield structure and function, and cortisol levels. The evidence provided here is solid, but additional methodological considerations are needed to strengthen the evidence in support of their claims. The work will be of broad interest to neuroscience researchers including those in cognitive, social, and clinical neuroscience.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study examines how self-citations in the neuroscience literature differ according to geography, gender, seniority, and subfield within neuroscience. The evidence supporting the claims is mostly solid, but aspects of the analysis - notably concerning estimates of uncertainty, and the exact interpretation of the results - would benefit from further work. Overall, the article is a valuable addition to the literature on self-citations
-
-
www.biorxiv.org www.biorxiv.org
-
Editor’s Assessment
This work has generated metabolic models for the human pathogens Mycobacterium leprae and Mycobacteroides abscessus, alongside a new computational tool that can be used to identify potential drug targets. The standardised genomic scale metabolic models have been developed using the systems biology community standards for quality control and evaluation of models. After providing more detail on reproducibility, comparative performance of the models, and reuse, these resources are now published and are available for reuse by the global scientific community via the GigaDB, Biomodels, and PatMeDB repositories.
This assessment refers to version 1 of this preprint.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study demonstrates that vitamin D-bound VDR increased the expression of SIRT1 and that vitamin D-bound VDR interacts with SIRT1 to cause auto-deacetylation on Lys610 and activation of SIRT1 catalytic activity. This is an important finding that is relevant to the actions of VDR on colorectal cancer. The data presented to support the presented conclusion are convincing.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study provides solid evidence that acute experimental pain induces changes in cortical excitability and GABAergic neurotransmission. The findings will be of interest to researchers interested in the brain mechanisms of pain and may lay the ground for future studies on acute pain-related excitability changes as probed by TMS and EEG.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This manuscript addresses an important question, that in countries endemic for P. vivax the need to administer a primaquine (PQ) course adequate to prevent relapse in G6PD deficient persons poses a real dilemma. On one hand PQ will cause haemolysis; on the other hand, without PQ the chance of relapse is very high. As a result, out of fear of severe haemolysis, PQ has been under-used. This manuscript is convincing that regimen (1) can be used successfully to deliver within 3 weeks, under hospital conditions, the dose of PQ required to prevent P. vivax relapse.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study tested the hypothesis that liver-derived but not serum-derived antibodies that are cross-reactive to E.coli and to host proteins can play a role in the hepatic damage found in severe alcoholic hepatitis (SAH). Using a solid methodology that includes state-of-the-art microscopy, proteome arrays, and gene ontology assays, it provides strong evidence that liver-derived IgG and IgA with cytotoxic properties and reactivity to both gut-derived E.coli and autoantigens accumulated in hepatocytes of SAH patients but not of healthy controls. The study would benefit from a broader analysis of gut microbiota proteome and further characterization of B cells infiltrating the liver tissue including their numbers/field and their origin (infiltrating versus resident cells). The work opens new avenues of understanding for the pathogenesis of severe alcoholic hepatitis and is of great interest to researchers and clinicians in the field.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This paper presents a useful study regarding the meiotic functions of ARID1A, the DNA-binding component of the SWI/SNF chromatin remodeler BAF. Whereas this work suggests that ARID1A regulates chromatin composition of the sex body relative to the autosomes, the reviewers raised substantial issues with the data and interpretation. The efficiency of the conditional deletion allele seems low and the CUT&RUN experiments are inadequate.
-
-
arxiv.org arxiv.org
-
eLife assessment
The OpenApePose dataset presented in this manuscript represents an important contribution to the field of primate behaviour and computer-vision science with methodological applications that are sure to be applicable for a wide variety of taxa. The analysis supporting the utility of this database is solid and compelling but would benefit from some additional clarity, particularly with regards to the landmark annotations, model parameters and division of the dataset for training, validation and testing.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents a valuable finding on the role of fragile X messenger ribonucleoprotein (FMRP) and its target the microtubule associated protein 18 (MAP1B) in postnatal tangential migration of neuroblasts. The study combined molecular genetics (FMRP knock-out mice) with acute inactivation of FRMP and MAP1B to conclusively support the notion that FMRP-dependent regulation of MAP1B is necessary for proper neuronal migration toward the olfactory bulb using the rostral migratory stream. The evidence supporting the claims of the authors is solid, although inclusion of additional controls for experiments and/or more rigorous description of the finding and conclusions would have strengthened the study. The work improves our knowledge of the molecular mechanisms that control how neurons migrate in the brain to reach their final destinations and confirms that cytoskeleton regulators are key players in this process. will be of interest to developmental neurobiologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study unravels the interaction between effort cost, pupil-indexed brain state, and movement (saccadic) vigor during foraging decisions in marmoset monkeys. Based on a computational model, the authors derive the prediction that anticipated effort should affect both decisions and movement vigor during foraging; and then provide solid behavioural and pupillometric evidence for this prediction in a foraging task. This paper will be of interest to decision and motor neuroscience as well as to all researchers studying animal behavior.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is an important paper that links distinctive stinging behavior of two related anemones occupying different ecological niches to varying inactivation properties of voltage-gated calcium channels conferred by auxiliary Cavβ subunits. Further convincing evidence is provided that these differences are mediated by alternative splicing of Cavβ subunit of the calcium channel. The study will be of interest to scientists studying Ca2+ signaling, ion channel biophysicists, and marine biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Gap junctions, formed from connexins, are important in cell communication, allowing ions and small molecules to move directly between cells. By determining the Cryo EM structure of the structure of connexin 43 in a putative closed state involving lipids, the study makes an important contribution to the development of a mechanistic model for connexin activation. The connexin 43 structure is solid and its presentation will appeal to the channel and membrane protein communities.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important paper uses a genome-wide, massively parallel reporter assay to determine how CpG methylation affects regulatory sequences that control the expression of human genes. The authors provide compelling evidence that methylation not only influences baseline activity of regulatory sequences but also the magnitude of acute responses to environmental stimuli. The findings are of broad interest, and the extensive data set will likely become a key resource for the community.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study describes important findings on how a core component of the circadian clock impacts the effect of dietary restriction (DR) on longevity and fecundity in Drosophila, which lead the authors to postulate rhythmic control of proteostasis in the fat body as a critical aspect of DR effects. The evidence presented is still incomplete, not fully supporting the conclusions of the study, as alternative hypotheses/explanations have not yet been systematically explored. The work will nevertheless be of substantial interest to researchers working in circadian and cell biology, metabolism, and aging, with an interesting hypothesis to be explored further.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study provides insights into mechanisms of placental aging and its relationship to labor initiation. The authors provide solid evidence and have thoroughly investigated the molecular characteristics of normal placental aging using in vivo and in vitro model systems and human placental tissue analysis to corroborate their findings. This work contributes to existing work in placental aging and preterm birth and will be of interest to reproductive scientists.
-
-
www.biorxiv.org www.biorxiv.org
-
Editor’s Assessment
Like other mollusc species, the freshwater pearl mussel (Margaritifera margaritifera) has a challenging genome to assemble owing to the large size of their genomes, heterozygosity, and repetitive sequence. The first published M. margaritifera genome was highly fragmented, but here an improved reference genome assembly was generated using PacBio CLR long reads to reduce fragmentation levels, missing and truncated genes, and chimerically assembled regions. The number of gene models predicted is a bit higher compared than other molluscan genomes, but after clarification and double checking these seem in line with some Mollusca and Bivalvia with similar and higher numbers of gene predictions. This new genome represents a new resource to start exploring the many biological, ecological, and evolutionary features of this threatened and commercially important group of organisms.
This assessment refers to version 1 of this preprint.
-
-
www.biorxiv.org www.biorxiv.org
-
Editor’s Assessment
Hybrid genomes are tricky to assemble, and few genomic resources are available for hybrid grapevines such as ‘Chambourcin’, a French-American interspecific hybrid grape grown in the eastern and midwestern United States. Here is an attempt to assemble Chambourcin’ using a combination of PacBio HiFi long-reads, Bionano optical maps, and Illumina short-read sequencing technologies. Producing an assembly with 26 scaffolds, an N50 length 23.3 Mb and an estimated BUSCO completeness of 97.9% that can be used for genome comparisons, functional genomic analyses, and genome-assisted breeding research. Error correction and pilon polishing was a challenge with this hybrid assembly, but after trying a few different approaches in the review process have improved it, and as they have documented what they did and are clear about the final metrics, users can assess the quality themselves.
This assessment refers to version 2 of this preprint.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
In this valuable study, advanced simulation methodologies are used to extract the mechanisms of inactivation for the potassium ion channel KcsA. The string method approach provides solid evidence that reveal features associated with the interplay between gate size and collapse of the selectivity filter, as well as remarkable differences between different force fields. While this manuscript does not address recent discoveries in K channel inactivation involving dilated selectivity filter structures obtained by Xray and cryo-EM, it does help us understand the KcsA constriction process. With added descriptions and analysis of collective variables, improved reproducibility of results, consistency between string method free energies and unbiased simulations, and improved transition rate calculation, this manuscript will be of interest to the ion channel field.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The primary goal of this paper is to examine microtubule detyrosination as a potential therapeutic target for axon regeneration. The valuable findings of this study provide convincing evidence for mechanistic links between microtubule detyrosination and neurite outgrowth in vitro and some evidence for axon regeneration in vivo.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This fundamental study provides a framework for leveraging systems genetics data to dissect mechanisms of gut physiology. The authors provide compelling analyses to highlight diverse modes of interrogating intestinal inflammation, dietary response, and consequent impacts on inflammatory bowel disease. As a resource, it will have great utility for linking genetic variation and diet to gut-related pathophysiologies.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents an important description on the dynamics of histone variant exchange controlling the organization of the chromatin state of the Arabidopsis genome, combining the analysis of histone variants, histone modification, and chromatin states. The evidence supporting the claims of the authors is compelling. This work will be of great interest to those in the field of epigenetics and chromatin biology.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study uses machine learning-based network analysis on transcriptomic data from different tissue cell types to identify a small set of conserved (pan-tissue) genes associated with changes in cell mechanics. The new method is compelling and, together with rigorous in silico and experimental validation, provides convincing evidence for the claims. The study would be strengthened with an expanded set of validation (e.g. testing genes with hitherto unknown roles and different perturbation techniques), but will nonetheless be of broad interest to cell biologists, biophysicists, and bioengineers.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study combines virology experiments and mathematical modeling to determine the nuclear export rate of each of the eight RNA segments of the influenza A virus, leading to the proposal that a specific retention of mRNA within the nucleus delays the expression of antigenic viral proteins. The proposed model for explaining the differential rate of export is compelling, going beyond the state of the art, but the experimental setup is incomplete and would benefit from additional approaches. The insight so far is interesting, but because in the end it is left as an observation, the overall advance remains limited.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents the valuable finding that sustained calcium signaling in induced-Treg (iTreg) cells can lead to the loss of Foxp3 expression and iTreg identity by altering the chromatin landscape. The evidence supporting the claims of the authors is solid, but alternative interpretations of the data should be considered and tested. The work will be of interest to immunologists working on Treg cell therapy.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study provides useful findings regarding the capacity for mental state attribution on the Frith-Happé task in a highly social non-human primate species, the marmoset. The methods are solid, integrating validated brain imaging and eye-tracking techniques, however, the theoretical analysis is incomplete due to the omission of a "goal-directed condition." The inclusion of the goal-directed condition would enable a stronger interpretation of the findings and would be of broad interest to neuroscientists working in social and affective sciences.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study provides important new insights into how learning affects behavior in the Drosophila model. Using a combination of connectomics, neurophysiology, and behavioral analysis, a small group of neurons in the Drosophila brain that integrates learned odor valences and promotes odor tracking by driving upwind orientation and movement is described. The study's conclusion is supported by convincing evidence and rigorous quantitative analysis. Insights from the neural circuit mechanism that translates learning-induced plasticity into appropriate behavioral actions will be of broad interest to neuroscientists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This simulation work with open source code will be of interest to those developing visual prostheses and demonstrates useful improvements over past visual prosthesis simulations. While the authors provide compelling evidence to support the generation of individual phosphenes and integration into deep-learning algorithms, the assumptions beyond individual phosphenes and the overall validation process are inadequate to support the claim of fitting the needs of cortical neuroprosthetic vision development.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This study provides useful information on the impact of the pandemic on the quantity of healthcare delivered to patients with pancreatic cancer in England. The authors showed that there was no difference in the number of diagnoses of pancreatic cancer during the pandemic compared to the preceding 5-year period, but a reduction in surgical resections by nearly 25%. They reported no difference in deaths between the two periods. They show no differences in rates of diagnosis, but the clinical relevance is incomplete as they have not compared survival from cancer between those time periods.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is an important study reanalysing previously published datasets to understand methylation changes during aging. The evidence supporting the conclusions is solid and sheds new light on features of aging in cells, highlighting the concept of cell-specific methylation changes and their relationship to other physiological changes such as inflammation that may impact methylation patterns. This work will be of broad interest to cell and molecular biologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study reveals the genetic regulation of changes in cuticular hydrocarbon profiles in a Hymenopteran insect and links these changes with courtship behaviour and sexual attractiveness. It provides convincing empirical evidence, spanning genetic, chemical, and behavioural data. It adds valuable new perspectives on the mechanisms that underlie chemical recognition and communication systems in nature.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The significance of this manuscript is that is provides useful information for the field of hepatology and endocrinology on the regulatory mechanisms of cholesterol homeostasis by melanocortin. The authors provide solid evidence utilizing both in vivo and in vitro molecular, cellular, and biochemical approaches to support their claims.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important work advances our understanding of the import of clonal heterogeneity in cancers in immune response to individual antigens. The evidence supporting the conclusions is convincing, and uses interesting tools, although the mechanistic basis of the observations is unclear. The work will be of broad interest to immunologists including cancer immunologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is an important study describing the mechanism of Spermidine modulation of Src kinase, identifying the interacting amino acids and the effect on indoleamine 2,3-dioxygenase 1 (IDO1) activation based on solid evidence. Considering the important role of IDO1 in the immune response this study could provide important information for the design of allosteric modulators capable of turning SRC on/off.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This work examines a role for altered splicing in pancreatic tumorigenesis by interrogating effects of a specific mutation in the Sf3b splicing factor in pancreatic organoid and cell line growth primarily, with some in vivo work also performed. There is significant potential in the study but there is a concern about the lack of in vivo validation of claims that are most relevant to metastatic progression and the focus on one specific mechanism at the expense of other possible effects on splicing of factors important for disease progression.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment:
This fundamental study provides compelling evidence that long-range resection is important for recombination between distal, but not proximal, homologous sequences. It is thus proposed that a major role of long resection of a double-strand break mediated by Sgs1 and Exo1 is to activate the DNA damage checkpoint to allow the chromosomal mobility needed for the DNA ends to find a distant homologous sequence with which repair via homologous recombination, adding a new biological meaning to the role of long DNA resection in homologous recombination.
-
- Jun 2023
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The mechanisms underlying mirror neurons are a topic of wide interest for all who study the workings of the brain. The authors use an elegant decoding approach to test whether mirror neurons encode action categories in the same framework regardless of whether actions are executed in the dark or observed in the light. This new approach identifies only a small subset of mirror neurons with fully matched coding among a larger set showing partial matches. The thought-provoking study opens up new principled avenues to probe the mechanics of matching action and perception.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Using C. elegans as a model organism, the study hones in on the role of ether lipid biosynthesis as an effector of metformin--a process previously implicated in extending lifespan in response to diet--, TOR signalling, and mitochondrial interventions. The data in this paper are compelling, and a better understanding of biguanide impact on metabolism is highly important in the field.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents valuable insights into the circuits that are common for innate and learned threat. The evidence supporting the author's conclusions is solid, but the specificity of the circuit targeting methods requires further histological assessment and clarification. Deeper interpretation of novel mechanistic insights that are gained would benefit the study.
-
-
psyarxiv.com psyarxiv.com
-
eLife assessment
This valuable study advances our knowledge of the effects of anxiety/depression treatment on metacognition, demonstrating that treatment increases metacognitive confidence alongside improving symptoms. The authors provide convincing evidence for the state-dependency of metacognitive confidence, based on a large longitudinal treatment dataset. However, it is unclear to what extent this effect is truly specific to treatment, as changes in metacognitive confidence in the group receiving online therapy were not statistically different from those in the control group.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This fundamental study substantially advances our physical understanding of the sharp increase and saturation of the viscosity of non-confluent tissues with increasing cell density. Through the analysis of a simplified model this study provides compelling evidence that polydispersity in cell size and the softness of cells together can lead to this phenomenon. The work will be of general interest to biologists and biophysicists working on development.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents a valuable finding on the impact of metformin-induced shifts in gut microbial community structure and metabolite levels for drug efficacy in a mouse model of liver injury. The current evidence supporting the claims of the authors is incomplete, although inclusion of additional controls and a revision to clarify the reviewer's methodological concerns could strengthen the study. This paper could be of broad interest to researchers across multiple disciplines, including the study of the microbiome, liver disease, and pharmacology.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
This manuscript provides important evidence on the association between sleep regularity and mortality in the UK Biobank, which is a popular topic in recent sleep and circadian research in population-based studies. The study is based on a large accelerometer study with validated follow-up of incident diseases and deaths, and the data quality and large sample size strengthen the credibility of the conclusion. Overall, the analyses are appropriately done, the manuscript is clearly written, and the strength of the evidence is convincing.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents valuable findings describing how two brain regions, the midbrain periaqueductal gray matter and basolateral amygdala, communicate when a robotic predator threat is detected. While the experimental design and data collection methods are solid, the main claims are only partially supported by the data and would benefit from more rigorous anatomical approaches as well as functional validation of the role of the paraventricular nucleus of the thalamus as the critical connection between the periaqueductal gray and basolateral amygdala. The study will appeal to a broad audience, including basic scientists interested in neural circuits, basic and clinical researchers interested in fear, and behavioral ecologists interested in foraging.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This potentially important study used single-cell whole-brain imaging of the immediate early gene Fos to identify the brain areas recruited by two anesthetics, ketamine and isoflurane. The results suggest these anesthetics might induce anesthesia via different brain regions and pathways. However, the support for the primary conclusions is incomplete owing to differences in route of administration between the drugs, lack of a dose response curve and behavioral/physiological measures of the depth of anesthesia, and statistical analysis that does not correct for multiple comparisons. With these issues addressed, this paper would be of interest to preclinical and clinical scientists working with anesthetic and dissociative drugs.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study provides an important investigation of the role that alpha-band activity modulations play in the generation of the P300. The data offer solid evidence in favour of such a role although further analyses may be required to determine whether the observed relationships may be driven by inter-individual differences in factors that may modulate both signals in tandem such as skull thickness.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study dissects the interplay between internal energy homeostasis, food intake and food-related memories, focusing on the role played in Drosophila by Octopamine, a monoamine functionally related to noradrenalin. This work will help interpret previously published work on the function of Octopamine, and should be of interest to the growing community of biologists interested in how internal state shapes behavior, including decision making processes, learning and memory. The experimental evidence is solid, but additional evidence using, for instance, tissue-specific and effector-specific manipulation, and a unifying model would strengthen the present study.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study provides useful information on the evolution of gene expression levels and plasticity in tissues impacted by hypoxia during colonization of a high-altitude environment. Unfortunately, the evidence for the conclusions is incomplete because of the low sample size available.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This fundamental study advances our understanding of seabird responses to environmental conditions, with implications for movement ecology, flight biomechanics, animal foraging and bio-energetics. Animal-borne data-loggers are used to generate a compelling high quality dataset on animal movement and environmental conditions. The study will interest ornithologists, comparative bio-mechanists, ocean ecologists and those interested in technological advances in animal sensors.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This work presents valuable findings on the non-breeding itinerant behavior of a migratory raptor. With its extensive dataset and solid analytical framework, this work will be of broad interest to researchers investigating the ecological drivers of bird migration. However, the main claim on a novel migration pattern (so-called 'fox-trot migration') is incomplete in light of current knowledge on bird migratory behavior.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Wang et al present a useful manuscript that builds modestly on the group's previous publication on KLF1 (EKLF) K47R mice focused on understanding how Eklf mutation confers anticancer and longevity advantages in vivo (Shyu et al., Adv Sci (Weinh). 2022). The data demonstrates that Eklf (K74R) imparts these advantages in a background, age, and gender independent manner, not the consequence of the specific amino acid substitution, and transferable by BMT. However, the authors overstate the meaning of these results and the strength of evidence is incomplete, since only a melanoma model of cancer is used, it is unclear why only homozygous mutation is needed when only a small fraction of cells during BMT confer benefit, they do not show EKLF expression in any cells analyzed, and the PD-1 and PDL-1 experiments are not conclusive. The definitive mechanism relative to the prior publication from this group on this topic remains unclear.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
The authors analyze a comprehensive cohort of human plasma samples to identify an extracellular vesicles protein signature for earlier diagnosis of pancreatic cancer. Application of liquid biopsies is valuable, and it addresses a significant clinical problem as pancreas cancer is often diagnosed in late stage with standard biopsies often nondiagnostic. The strength of evidence is largely solid; however, certain aspects of the data were deemed incomplete, given the broad manuscript claims. This work supports the use of extracellular vesicles in clinical settings, with potential interest to scientists and clinicians.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study reports that a long non-coding RNA disrupts the activity of the tumor suppressor p53 to contribute to the growth and therapeutic response of glioblastoma. Most evidence supporting the claims of the authors is solid, but the conclusions would benefit from more rigorous approaches. The work will be of interest to biologists working on the non-coding RNA and brain tumors.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This represents an important study that demonstrates a high degree of heterogeneity within trailblazer cells in clusters that participate in collective migration. Solid methods highlight this heterogeneity and show that in TNBC cancers, trailblazer cells are defined by vimentin (and not Keratin 14) and are dependent on both TGFbeta and EGFR signaling.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important manuscript presents several structures of the Kv1.2 voltage-gated potassium channel, based on state-of-the-art cryoEM techniques and algorithms. The authors present solid evidence for structures of DTX-bound Kv1.2 and of Kv1.2 in potassium-free solution (with presumably sodium ions bound within the selectivity filter). These structures advance our knowledge of the molecular basis of the channel inactivation process.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This valuable study adds to our understanding of the DNA replication origin selection process in budding yeast. The authors provide convincing evidence that the number of possible origins of replication is much higher than previously appreciated, although many of the newly identified origins probably direct replication initiation only very rarely. This work will be of interest to those studying DNA replication and investigating protein-DNA interactions across the genome.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important work substantially advances our understanding of the interplay between genetic variation, chromatin, and genes within topologically associated domains and how this interplay regulates gene expression. The evidence supporting the conclusions is convincing, with appropriate and validated methodology in line with current state-of-the-art genomic and epigenomic techniques. The work will be of broad interest to geneticists and those working to understand the basic mechanisms of gene expression.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study presents valuable findings regarding the role of the transcription factor BATF and its target PD1 in lipid metabolism including a model of nonalcoholic fatty liver disease (NAFLD). Overall, the evidence supporting the conclusions is convincing. The work will be of interest to medical biologists working on NAFLD.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The mechanisms that determine when neural stem cells should stop dividing after having generated their full repertoire of progeny remain not completely understood. The authors present useful findings on how Notch activity regulates the termination of neurogenesis in central brain of Drosophila. The evidence supporting the claims of the author is solid, although other complementary approaches could have been used to probe more deeply into the underlying molecular mechanisms. This work will be of interest to developmental neurobiologists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This is a useful investigation of the changes in gene expression and some of the physiological consequences of sublethal exposures to the neonicotinoid insecticide imidacloprid in honeybee larvae. While the study adds to our understanding of how this insecticide impacts development and growth of honeybees, the evidence supporting the major claims is incomplete. The study would benefit from a more thorough mechanistic characterization of the phenotypes to substantiate the conclusions.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
The manuscript by Eyraud and colleagues examines the role of interactions between fibrocytes and CD8 cells as drivers of disease progression in COPD (chronic obstructive pulmonary disease). The findings that there exist bidirectional interactions between CD8 cells and fibrocytes are supported by solid evidence that combines histology of clinical lung samples, in vitro studies obtained from circulating blood fibrocytes and CD8 cells, as well as a computational model that predicts how bidirectional interactions could promote disease progression over the course of 20 years. The study, which is based on patient samples, thus provides fundamental insights on COPD progression.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study uses the brain endocast of a ~1.9-million-year-old hominin fossil from Kenya, attributed to genus Homo, to show that the organization of the Broca's area in members of early Homo was primitive. Specifically, the prefrontal sulcal pattern in this early Homo specimen more closely resembles that of chimpanzees than of modern humans. Because Broca's area is associated with speech function, the compelling evidence from this study has relevant for understanding the timing and trajectory of evolution of speech related traits in our genus. Coupled with its potential implications for taxonomic classification, this study will be of interest to paleoanthropologists, paleontologists, archaeologists, and neuroscientists.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study reports that Foxc2+ cells in the testis represent the quiescent spermatogonial stem cells (SSCs). The data supporting this claim are solid. The finding is of great significance to reproductive and stem-cell biology as male fertility depends on the fine balance between self-renewal and differentiation activities of the male germline stem cells, i.e., SSCs.
-
-
www.medrxiv.org www.medrxiv.org
-
eLife assessment
In this valuable study, patients homozygous for both minor frequency alleles of the APOL1 gene are shown to be at significant risk for progression into sepsis after infection. The study has enrolled a significant number of subjects and provides solid results. The study addresses to infectious diseases and critical care experts and one major weakness is the lack of inclusion of non-Black patients.
-
-
-
eLife assessment
This study presents a valuable finding on the putative molecular patterns underlying characteristic morphological regions observed in colorectal cancer (CRC) and the extent to which morphotype heterogeneity impedes prognostic and predictive expression-based classifiers. The evidence supporting the claims of the authors is solid, although clarity in terms of patient selection and subtype definition would have strengthened the study. The work will be of interest to medical biologists working on colorectal cancer (CRC).
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This study follows the career trajectories of the winners of an early-career funding award in the United States, and finds that researchers with greater mobility, men, and those hired at well-funded institutions experience greater subsequent funding success. Using data on K99/R00 awards from the National Institutes of Health's grants management database, the authors provide convincing evidence documenting the inequalities that shape faculty funding opportunities and career pathways, and show that these inequalities disproportionately impact women and faculty working at particular institutions, including historically black colleges and universities. Overall, the article is an important addition to the literature examining inequality in biomedical research in the United States.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This paper contributes to the field of hippocampal registration by introducing a novel surface-based approach that utilizes the topological and morphological features of the hippocampus for anatomical registration across individuals, rather than volumetric-based methods commonly used in the literature. The study provides compelling evidence for the efficacy of this approach using histological samples from three different datasets and offers validation of the method through comparison with traditional volumetric registration. This is important work given the large number of studies that examine hippocampal shape, thickness, and function in large cohorts, providing strong support for the use of hippocampal unfolding methods in future studies.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
This important study provides a panoramic view of the spectrum of natural variation in C. elegans egglaying behavior, begins to illuminate molecular and genetic influences underlying this variation, and reveals how distinct egglaying behaviors might impact maternal and offspring fitness in diverse environmental conditions. The evidence supporting the authors' conclusions is convincing. This work establishes intraspecific variation in C. elegans egglaying behavior as a model for elucidating the genetic basis for evolutionary transitions between oviparity and viviparity. As such, it will be of interest to evolutionary biologists studying molecular mechanisms underlying fitness tradeoffs between parent and offspring that influence adaptation to changing environments.
-
-
www.biorxiv.org www.biorxiv.org
-
eLife assessment
Scheer and Bargmann provide an important behavioral genetics study on how behavioral context affects decision making of C. elegans. The results and interpretations are overall convincing; the behavioral analysis at multiple time scales combined with genetic and neuronal manipulations revealed how arousal states affect decision making. However, alternative interpretations should be considered and statistical methods should be justified. This work will be of interest to both neuroscientists and ecologists.
-