bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the repertoire of human tandem repeat RNA-binding proteins
Authors: Ormazábal Agustín , Carletti Matías Sebastián , Saldaño Tadeo Enrique , Gonzalez-Buitron Martín , Marchetti Julia , Palopoli Nicolas , Bateman Alex 
Published: September 2022

AbstractProtein regions consisting of arrays of tandem repeats are known to bind other molecular partners, including nucleic acid molecules. Although the interactions between repeat proteins and DNA are already widely explored, studies characterising tandem repeat RNA-binding proteins are lacking. We performed a large-scale analysis of human proteins devoted to expanding the knowledge about tandem repeat proteins experimentally reported as RNA-binding molecules. This work is timely because of the release of a full set of accurate structural models for the human proteome amenable to repeat detection using structural methods. We identified 219 tandem repeat proteins that bind RNA molecules and characterised the overlap between repeat regions and RNA-binding regions as a first step towards assessing their functional relationship. Our results showed that the combination of sequence and structural methods finds more tandem repeat proteins than either method alone. We observed differences in the characteristics of regions predicted as repetitive by sequence-based or structure-based computational methods in terms of their sequence composition, their functions and their protein domains.
grandR: a comprehensive package for nucleotide conversion sequencing data analysis
Authors: Rummel Teresa , Sakellaridi Lygeri , Erhard Florian 
Published: September 2022

AbstractMetabolic labeling of RNA is a powerful technique for studying the temporal dynamics of gene expression. Nucleotide conversion approaches greatly facilitate the generation of data but introduce challenges for their analysis. We here present grandR, a comprehensive package for quality control, differential gene expression analysis, kinetic modeling, and visualization of such data. We compare several existing methods for inference of RNA synthesis rates and half-lives using progressive labeling time courses. We demonstrate the need for recalibration of effective labeling times and introduce a Bayesian approach to study the temporal dynamics of RNA using snapshot experiments.
Modulation effect of non-invasive transcranial ultrasound stimulation in an ADHD rat model
Authors: Wang Mengran , Wang Teng , Ji Hui , Yan Jiaqing , Wang Xingran , Zhang Xiangjian , Li Xin , Yuan Yi 
Published: September 2022

AbstractPrevious studies have demonstrated that transcranial ultrasound stimulation (TUS) with noninvasive high penetration and high spatial resolution has an effective neuromodulatory effect on neurological diseases. Attention deficit hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that severely affects child health. However, the neuromodulatory effects of TUS on ADHD have not been reported to date. To reveal the neuromodulatory effects, TUS was performed in ADHD model rats for 2 consecutive weeks, and the behavioral improvement of ADHD, neural activity of ADHD from neurons and neural oscillation levels, and the plasma membrane dopamine transporter (DAT) and brain-derived neurotrophic factor (BDNF) in the brains of ADHD rats were evaluated. The results showed that TUS can improve cognitive behavior in ADHD rats, and that TUS altered neuronal firing patterns and modulated the relative power and sample entropy of local field potentials in an ADHD rat model. In addition, TUS can also enhance BDNF expression in the brain tissue of the ADHD rat model. In conclusion, TUS has an effective neuromodulatory effect on ADHD and thus has the potential to clinically improve cognitive dysfunction in ADHD.
Pyro-Velocity: Probabilistic RNA Velocity inference from single-cell data
Authors: Qin Qian , Bingham Eli , La Manno Gioele , Langenau David M. , Pinello Luca 
Published: September 2022

AbstractSingle-cell RNA Velocity has dramatically advanced our ability to model cellular differentiation and cell fate decisions. However, current preprocessing choices and model assumptions often lead to errors in assigning developmental trajectories. Here, we develop, Pyro-Velocity, a Bayesian, generative, and multivariate RNA Velocity model to estimate the uncertainty of cell future states. This approach models raw sequencing counts with the synchronized cell time across all expressed genes to provide quantifiable and improved information on cell fate choices and developmental trajectory dynamics.
Negative regulation of C. elegans innate immunity by orphan nuclear receptor NHR-42
Authors: Goswamy Debanjan , Labed Sid A. , Gonzalez Xavier , Irazoqui Javier E. 
Published: September 2022

AbstractPositive and negative regulators of innate immunity work together to maintain immune homeostasis. We previously discovered that HLH-30/TFEB is a critical transcription factor that positively regulates host defense genes upon S. aureus infection in C. elegans. However, repression of host defense genes and negative regulation of immunity remain poorly understood. In this study, we identified nhr-42 as a negative regulator of host defense genes functioning downstream of HLH-30/TFEB, with major implications in host survival and metabolism after infection. nhr-42 expression is induced in an HLH-30/TFEB dependent manner mostly in the pharynx upon infection. We find that animals lacking nhr-42 have higher expression of host defense genes, which enables enhanced survival after infection. Antimicrobials expressed in the pharynx such as abf-2, function downstream of nhr-42 to confer resistance to infection by mitigating pathogen burden. Furthermore, nhr-42 deficient animals are defective in lipid mobilization, having higher lipid stores compared to wild type animals after infection. nhr-42 therefore enables C. elegans to limit the host defense response and reallocate energy resources through lipid mobilization after infection. To our knowledge, this is the first report of a transcription factor that represses host defense genes in C. elegans.
Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry
Authors: Vermij Lisa , Jobsen Jan J. , León-Castillo Alicia , Brinkhuis Mariel , Roothaan Suzan , Powell Melanie E. , de Boer Stephanie M. , Khaw Pearly , Mileshkin Linda R. , Fyles Anthony , Leary Alexandra , Genestie Catherine , Jürgenliemk-Schulz Ina M. , Crosbie Emma J. , Mackay Helen J. , Nijman Hans. W. , Nout Remi A. , Smit Vincent T.H.B.M. , Creutzberg Carien L. , Horeweg Nanda , Bosse Tjalling ,   TransPORTEC consortium
Published: September 2022

AbstractBackgroundRisk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement.MethodsParaffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n=424), and a Dutch prospective clinical cohort called MST (n=256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan-Meier method, log-rank tests and Cox’s proportional hazard models were used for survival analysis.ResultsIn total, 649 HR-EC were included. No independent prognostic value of ER, PR, L1CAM and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15-0.75).ConclusionsER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. ER-positive NSMP EC may be regarded as a novel fifth molecular subgroup. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.
Excess mortality in the general population versus Veterans Healthcare System during the first year of the COVID-19 pandemic in the United States
Authors: Weinberger Daniel M. , Rose Liam , Rentsch Christopher , Asch Steven M. , Columbo Jesse , King Joseph , Korves Caroline , Lucas Brian P. , Taub Cynthia , Young-Xu Yinong , Vashi Anita , Davies Louise , Justice Amy C. 
Published: September 2022

ABSTRACTImportanceThe COVID-19 pandemic had a substantial impact on the overall rate of death in the United States during the first year. It is unclear whether access to comprehensive medical care, such as through the VA healthcare system, altered death rates compared to the US population.ObjectiveQuantify the increase in death rates during the first year of the COVID-19 pandemic in the general US population and among individuals who receive comprehensive medical care through the Department of Veterans Affairs (VA).DesignAnalysis of changes in all-cause death rates by quarter, stratified by age, sex race/ethnicity, and region, based on individual-level data. Hierarchical regression models were fit in a Bayesian setting. Standardized rates were used for comparison between populations.Setting and participantsGeneral population of the United States, enrollees in the VA, and active users of VA healthcare.Exposure and main outcomeChanges in rates of death from any cause during the COVID-19 pandemic in 2020 compared to previous years.ResultsSharp increases were apparent across all of the adult age groups (25 years and older) in both the general US population and the VA populations. Across all of 2020, the relative increase in death rates was similar in the general US population (RR: 1.20 (95% CI: 1.17, 1.22)), VA enrollees (RR: 1.20 (95% CI: 1.14, 1.29)), and VA active users (RR: 1.19 (95% CI: 1.14, 1.26)). Because the pre-pandemic standardized mortality rates were higher in the VA populations prior to the pandemic, the absolute rates of excess mortality were higher in the VA populations.Conclusions and RelevanceDespite access to comprehensive medical care, active users of the VA had similar relative mortality increases from all causes compared with the general US population. Factors that influenced baseline rates of death and that mitigated viral transmission in the community are more likely to have influenced the impact of the pandemic.
Sexual risk-taking behavior amongst emerging adults in Africa: a systematic review and meta-analysis
Authors: Chea Stevenson K. , Kagonya Vincent A. , Abdullahi Osman , Abubakar Amina A. , Abbeddou Souheila , Michielsen Kristien , Hassan Amin S. 
Published: September 2022

AbstractBackgroundIncidence of HIV and other sexually transmitted infections (STIs) among emerging adults (EmA) is high in some African settings. Estimates on sexual risk-taking behavior (SRTB) among EmA is varied in literature, which presents a challenge when designing targeted interventions. We aimed to review and summarize literature on prevalence and risk factors of SRTB among EmA in Africa.MethodsA search for studies published in PubMed, Embase and Psych Info involving EmA (18 – 25 years), conducted in Africa and reporting one or more SRTB was done. Pooled prevalence estimates were summarized using forest plots. Heterogeneity in SRTB was explored by sex, geographic region, year of publication and outcome definition. Risk factors were synthesized using a modified socio-ecological model.ResultsOverall, 117 studies were analyzed. Non-condom use had the highest pooled prevalence (46.0% [95% CI: 14.0-51.0]), followed by study-defined SRTB (37.0% [95% CI: 23.0 -51.0]), concurrency (35.0% [95% CI: 19.0-53.0]), multiple sex partnerships (30.0% [95% CI: 24.0-37.0]), younger age at sexual debut (25.0% [95% CI: 19.0-31.0]), age disparate relationships (24.0% [95% CI: 17.0-32.0]) and transactional sex (17.0% [95% CI: 11.0-24.0]). In four of the seven outcomes, heterogeneity was partially explained by sex, with female participants having higher pooled prevalence estimates compared to their male counterparts. In four of the seven outcomes, alcohol/drug use was the most common risk factor.ConclusionsSRTB was common among EmA and differentially higher in emerging female adults. Non-condom use had the highest pooled prevalence, which may contribute to the propagation of HIV and other STIs in this population. Interventions targeting emerging female adults and alcohol/drug use may reduce SRTB, which may in-turn mitigate propagation of HIV and other STIs among EmA in Africa.
Top-down specific preparatory activations for Selective Attention and Perceptual Expectations
Authors: Peñalver José M. G. , López-García David , González-García Carlos , Aguado-López Blanca , Górriz Juan M. , Ruz María 
Published: September 2022

SummaryProactive cognition brain models are mainstream nowadays. Within these, preparation is understood as an endogenous, top-down function that takes place prior to the actual perception of a stimulus and improves subsequent behavior. Neuroimaging has shown the existence of such preparatory activity separately in different cognitive domains, however no research to date has sought to uncover their potential similarities and differences. Two of these, often confounded in the literature, are Selective Attention (information relevance) and Perceptual Expectation (information probability). We used EEG to characterize the mechanisms that pre-activate specific contents in Attention and Expectation. In different blocks, participants were cued to therelevanceor to theprobabilityof target categories, faces vs. names, in a gender discrimination task. Multivariate Pattern (MVPA) and Representational Similarity Analyses (RSA) during the preparation window showed that both manipulations led to a significant, ramping-up prediction of the relevant or expected target category. However, classifiers trained on data from one condition did not generalize to the other, indicating the existence of unique anticipatory neural patterns. In addition, a Canonical Template Tracking procedure showed that there was stronger anticipatory perceptual reinstatement for relevance than for expectation blocks. Overall, results indicate that preparation during attention and expectation acts through distinguishable neural mechanisms. These findings have important implications for current models of brain functioning, as they are a first step towards characterizing and dissociating the neural mechanisms involved in top-down anticipatory processing.
Spatially resolved transcriptomic profiling of degraded and challenging fresh frozen samples
Authors: Mirzazadeh Reza , Andrusivova Zaneta , Larsson Ludvig , Newton Phillip T. , Galicia Leire Alonso , Abalo Xesús M. , Avijgan Mahtab , Kvastad Linda , Denadai-Souza Alexandre , Stakenborg Nathalie , Firsova Alexandra B. , Shamikh Alia , Jurek Aleksandra , Schultz Niklas , Nistér Monica , Samakovlis Christos , Boeckxstaens Guy , Lundeberg Joakim 
Published: September 2022

AbstractSpatially resolved transcriptomics (SRT) has enabled precise genome-wide mRNA expression profiling within tissue sections. The performance of unbiased SRT methods targeting the polyA tail of mRNA, relies on the availability of specimens with high RNA quality. Moreover, the high cost of currently available SRT assays requires a careful sample screening process to increase the chance of obtaining high-quality data. Indeed, the upfront analysis of RNA quality can show considerable variability due to sample handling, storage, and/or intrinsic factors. We present RNA-Rescue Spatial Transcriptomics (RRST), an SRT workflow designed to improve mRNA recovery from fresh frozen (FF) specimens with moderate to low RNA quality. First, we provide a benchmark of RRST against the standard Visium spatial gene expression protocol on high RNA quality samples represented by mouse brain and prostate cancer samples. Then, we demonstrate the RRST protocol on tissue sections collected from 5 challenging tissue types, including: human lung, colon, small intestine, pediatric brain tumor, and mouse bone/cartilage. In total, we analyzed 52 tissue sections and our results demonstrate that RRST is a versatile, powerful, and reproducible protocol for FF specimens of different qualities and origins.
Elucidating polymorphs of crystal structures with intensity-based hierarchical clustering analysis on multiple diffraction datasets
Authors: Matsuura Hiroaki , Sakai Naoki , Toma-Fukai Sachiko , Muraki Norifumi , Hayama Koki , Kamikubo Hironari , Aono Shigetoshi , Kawano Yoshiaki , Yamamoto Masaki , Hirata Kunio 
Published: September 2022

AbstractIn macromolecular structure determination using X-ray diffraction from multiple crystals, the presence of different structures (structural polymorphs) necessitates the classification of diffraction data for appropriate structural analysis. Hierarchical clustering analysis (HCA) is a promising technique that has so far been used to extract isomorphous data, mainly for single structure determination. Although in principle the use of HCA can be extended to detect polymorphs, the absence of a reference for defining a threshold used for grouping the isomorphous datasets (‘isomorphic threshold’) poses a challenge. Here, we have applied unit cell-based and intensity-based HCAs to the datasets of apo-trypsin and inhibitor-bound trypsin that were mixed post-data acquisition to investigate how effective HCA is in classifying polymorphous datasets. Single-step intensity-based HCA successfully classified polymorphs with a certain ‘isomorphic threshold’. In datasets of several samples containing an unknown degree of structural heterogeneity, polymorphs could be identified by intensity-based HCA using the suggested ‘isomorphic threshold’. Polymorphs were also detected in single crystals using the data collected by the continuous helical scheme. These findings are expected to facilitate the determination of multiple structural snapshots by exploiting automated data collection and analysis.SynopsisSingle-step intensity-based hierarchical clustering is demonstrated to allow the detection of structural polymorphs in the diffraction datasets obtained from multiple crystals. By splitting the datasets collected by continuous helical scheme into several chunks, both inter and intra-crystal polymorphs can be successfully analyzed.
Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation
Authors: Ridwan Sharif M. , Twillie Autumn , Poursaeid Samaneh , Beard Emma Kristine , Bener Muhammed Burak , Antel Matthew , Cowan Ann E. , Matsuda Shinya , Inaba Mayu 
Published: September 2022

AbstractDrosophilamale germline stem cells (GSCs) reside at the tip of the testis and surround a cluster of niche cells. It has been believed that the niche-derived Decapentaplegic (Dpp) has a role in maintaining stem cells in close proximity but has no role in the differentiating cells spaced one-cell layer away. However, the range of Dpp diffusion has never been tested. Here, using genetically encoded nanobodies called Morphotrap, we physically block Dpp diffusion without interfering with niche-stem cell signaling and find that diffusible fraction of Dpp is required to ensure differentiation of GSC daughter cells, opposite of its role in maintenance of GSC in the niche. Our work provides an example in which a soluble niche ligand induces opposed cellular responses in stem cells and in differentiating descendants so that the niche can tightly restrict its space. This may be a common mechanism to regulate tissue homeostasis.One sentence summaryBMP ligand diffuses from the niche and has dual, and opposite roles on stem cells and differentiating daughter cells.
Detecting changes in population trends in infection surveillance using community SARS-CoV-2 prevalence as an exemplar
Authors: Pritchard Emma , Vihta Karina-Doris , Eyre David W. , Hopkins Susan , Peto Tim EA , Matthews Philippa C. , Stoesser Nicole , Studley Ruth , Rourke Emma , Diamond Ian , Pouwels Koen B. , Walker Ann Sarah ,   the COVID-19 Infection Survey Team
Published: September 2022

AbstractBackgroundMonitoring infection trends is vital to informing public health strategy. Detecting and quantifying changes in growth rates can inform policymakers’ rationale for implementing or continuing interventions aimed at reducing impact. Substantial changes in SARS-CoV-2 prevalence with emergence of variants provides opportunity to investigate different methods to do this.MethodsWe included PCR results from all participants in the UK’s COVID-19 Infection Survey between 1 August 2020-30 June 2022. Change-points for growth rates were identified using iterative sequential regression (ISR) and second derivatives of generalised additive models (GAMs).Consistency between methods and timeliness of detection were compared.FindingsOf 8,799,079 visits, 147,278 (1·7%) were PCR-positive. Over the time period, change-points associated with emergence of major variants were estimated to occur a median 4 days earlier (IQR 0-8) in GAMs versus ISR, with only 2/48 change-points identified by only one method. Estimating recent change-points using successive data periods, four change-points (4/96) identified by GAMs were not found when adding later data or by ISR; 77% (74/96) of change-points identified by successive GAMs were identified by ISR. Change-points were detected 3-5 weeks after they occurred in both methods but could be detected earlier within specific subgroups.InterpretationChange-points in growth rates of SARS-CoV-2 can be detected in near real-time using ISR and second derivatives of GAMs. To increase certainty about changes in epidemic trajectories both methods could be run in parallel. Running either method in near real-time on different infection surveillance data streams could provide timely warnings of changing underlying epidemiology.FundingUK Health Security Agency, Department of Health and Social Care (UK), Welsh Government, Department of Health (on behalf of the Northern Ireland Government), Scottish Government, National Institute for Health Research.
Structure-Function analysis of Lactiplantibacillus plantarum DltE reveals D-alanylated lipoteichoic acids as direct symbiotic cues supporting Drosophila juvenile growth
Authors: Nikolopoulos Nikos , Matos Renata C. , Ravaud Stéphanie , Courtin Pascal , Akherraz Houssam , Palussière Simon , Gueguen-Chaignon Virginie , Salomon-Mallet Marie , Guillot Alain , Guerardel Yann , Chapot-Chartier Marie-Pierre , Grangeasse Christophe , Leulier François 
Published: September 2022

AbstractMetazoans establish mutually beneficial interactions with their resident microorganisms. However, our understanding of the microbial cues contributing to host physiology remains elusive. Previously, we identified a bacterial machinery encoded by the dlt operon involved in Drosophila melanogaster’s juvenile growth promotion by Lactiplantibacillus plantarum. Here, using crystallography combined with biochemical and cellular approaches, we investigate the physiological role of an uncharacterized protein (DltE) encoded by this operon. We show that LTAs but not WTAs are D-alanylated in Lactiplantibacillus plantarumNC8 cell envelope and demonstrate that DltE is a D-Ala carboxyesterase removing D-Ala from LTA. Using the mutualistic association of L. plantarumNC8 and Drosophila melanogaster as a symbiosis model, we establish that D-Ala-LTAs are direct symbiotic cues supporting intestinal peptidase expression and juvenile growth in Drosophila. Our results pave the way to probing the contribution of D-Ala-LTA to host physiology in other symbiotic models.