bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMRT1, aPlasmodiumspecific parasite plasma membrane transporter is essential for asexual and sexual blood stage development
Authors: Wichers Jan Stephan , Mesén-Ramírez Paolo , Fuchs Gwendolin , Yu-Strzelczyk Jing , Stäcker Jan , von Thien Heidrun , Alder Arne , Henshall Isabelle , Liffner Benjamin , Nagel Georg , Löw Christian , Wilson Danny , Spielmann Tobias , Gao Shiqiang , Gilberger Tim-Wolf , Bachmann Anna , Strauss Jan 
Published: December 2021

AbstractMembrane transport proteins perform crucial roles in cell physiology. The obligate intracellular parasitePlasmodium falciparum, an agent of human malaria, relies on membrane transport proteins for the uptake of nutrients from the host, disposal of metabolic waste, exchange of metabolites between organelles and generation and maintenance of transmembrane electrochemical gradients for its growth and replication within human erythrocytes. Despite their importance forPlasmodiumcellular physiology, the functional roles of a number of membrane transport proteins remain unclear, which is particularly true for orphan membrane transporters that have no or limited sequence homology to transporter proteins in other evolutionary lineages. Therefore, in the current study, we applied endogenous tagging, targeted gene disruption, conditional knockdown and knockout approaches to investigate the subcellular localization and essentiality of six membrane transporters during intraerythrocytic development ofP. falciparumparasites. They are localized at different subcellular structures – the food vacuole, the apicoplast, and the parasite plasma membrane – and four out of the six membrane transporters are essential during asexual development. Additionally, the plasma membrane resident transporter 1 (PMRT1, PF3D7_1135300), a uniquePlasmodium-specific plasma membrane transporter, was shown to be essential for gametocytogenesis and functionally conserved within the genusPlasmodium. Overall, we reveal the importance of four orphan transporters to blood stageP. falciparumdevelopment, which have diverse intracellular localizations and putative functions.ImportancePlasmodium falciparum-infected erythrocytes possess multiple compartments with designated membranes. Transporter proteins embedded in these membranes do not only facilitate movement of nutrients, metabolites and other molecules between these compartments, but are common therapeutic targets and can also confer antimalarial drug resistance. Orphan membrane transporter inP. falciparumwithout sequence homology to transporters in other evolutionary lineages and divergent to host transporters may constitute attractive targets for novel intervention approaches. Here, we localized six of these putative transporters at different subcellular compartments and probed into their importance during asexual parasite growth using reverse genetic approaches. In total, only two candidates turned out to be dispensable for the parasite, highlighting four candidates as putative targets for therapeutic interventions. This study reveals the importance of several orphan transporters to blood stageP. falciparumdevelopment.
Omicron outbreak at a private gathering in the Faroe Islands, infecting 21 of 33 triple-vaccinated healthcare workers
Authors: Helmsdal Gunnhild , Hansen Olga K , Møller Lars F , Christiansen Debes H , Petersen Maria Skaalum , Kristiansen Marnar F 
Published: December 2021

AbstractThere are concerns that the SARS-CoV-2 Omicron variant evades immune responses due to unusually high numbers of mutations on the spike protein. Here we report a super-spreading event of Omicron infections amongst triple-vaccinated healthcare workers, infecting 21 of 33 attending a private gathering in the Faroe Islands.
Neutralization of SARS-CoV-2 Omicron pseudovirus by BNT162b2 vaccine-elicited human sera
Authors: Muik Alexander , Lui Bonny Gaby , Wallisch Ann-Kathrin , Bacher Maren , Mühl Julia , Reinholz Jonas , Ozhelvaci Orkun , Beckmann Nina , Caridad Güimil Garcia Ramón de la , Poran Asaf , Shpyro Svetlana , Cai Hui , Yang Qi , Swanson Kena A. , Türeci Özlem , Sahin Ugur 
Published: December 2021

AbstractA new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage, B.1.1.529, was recently detected in Botswana and South Africa and is now circulating globally. Just two days after it was first reported to the World Health Organization (WHO), this strain was classified as a variant of concern (VOC) and named Omicron. Omicron has an unusually large number of mutations, including up to 39 amino acid modifications in the spike (S) protein, raising concerns that its recognition by neutralizing antibodies from convalescent and vaccinated individuals may be severely compromised. In this study, we tested pseudoviruses carrying the SARS-CoV-2 spike glycoproteins of either the Wuhan reference strain, the Beta, the Delta or the Omicron variants of concern with sera of 51 participants that received two doses or a third dose (≥6 months after dose 2) of the mRNA-based COVID-19 vaccine BNT162b2. Immune sera from individuals who received two doses of BNT162b2 had more than 22-fold reduced neutralizing titers against the Omicron as compared to the Wuhan pseudovirus. One month after a third dose of BNT162b2, the neutralization titer against Omicron was increased 23-fold compared to two doses and antibody titers were similar to those observed against the Wuhan pseudovirus after two doses of BNT162b2. These data suggest that a third dose of BNT162b2 may protect against Omicron-mediated COVID-19, but further analyses of longer-term antibody persistence and real-world effectiveness data are needed.
Cleaning and disinfecting surfaces in hospitals and long-term care facilities for reducing hospital and facility-acquired bacterial and viral infections: A systematic review
Authors: Thomas Roger E. , Thomas Bennett C. , Conly John , Lorenzetti Diane 
Published: December 2021

SUMMARYBackgroundMultiply drug-resistant organisms (MDROs) in hospitals and long-term care facilities (LTCFs) of particular concern include meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus, multidrug-resistant Acinetobacter species and extended spectrum beta-lactamase producing organisms. Respiratory viruses include influenza and SARS-CoV-2.AimTo assess effectiveness of cleaning and disinfecting surfaces in hospitals and LTCFs.MethodsCINAHL, Cochrane CENTRAL Register of Controlled Trials, EMBASE, Medline, and Scopus searched inception to 28 June 2021, no language restrictions, for randomized controlled trials, cleaning, disinfection, hospitals, LTCFs. Abstracts and titles were assessed and data abstracted independently by two authors.FindingsOf fourteen c-RCTs in hospitals and LTCFs, interventions in ten were focused on reducing patient infections of four MDROs and/or healthcare-associated infections (HAIs). In four c-RCTs patient MDRO and/or HAI rates were significantly reduced with cleaning and disinfection strategies including bleach, quaternary ammonium detergents, ultraviolet irradiation, hydrogen peroxide vapour and copper-treated surfaces or fabrics. Of three c-RCTs focused on reducing MRSA rates, one had significant results and one on Clostridioides difficile had no significant results. Heterogeneity of populations, methods, outcomes and data reporting precluded meta-analysis. Overall risk of bias assessment was low but high for allocation concealment, and GRADE assessment was low risk. No study assessed biofilms.ConclusionsTen c-RCTs focused on reducing multiple MDROs and/or HAIs and four had significant reductions. Three c-RCTs reported only patient MRSA colonization rates (one significant reductions), and one focused on Clostridioides difficile (no significant differences). Standardised primary and secondary outcomes are required for future c-RCTs including detailed biofilm cleaning/disinfection interventions.
Parental preferences for a mandatory vaccination scheme in England; a discrete choice experiment
Authors: Smith Louise E , Carter Ben 
Published: December 2021

AbstractBackgroundMandatory vaccination has been mooted to combat falling childhood vaccine uptake rates in England. This study investigated parental preferences for a mandatory vaccination scheme.MethodsDiscrete choice experiment. Six attributes were investigated: vaccine (MMR, 6-in-1), child age group (2 years and older, 5 years and older), incentive (£130 cash incentive for parent, £130 voucher incentive for child, no incentive), penalty (£450 fine, parent not able to claim Child Benefits for an unvaccinated child, unvaccinated child not able to attend school or day care), ability to opt out (medical exemption only, medical and religious belief exemption), and compensation scheme (not offered, offered). Mixed effects conditional logit regression models were used to investigate parental preferences and relative importance of attributes.FindingsParticipants were 1,001 parents of children aged 5 years and under (53% female, mean age=33·6 years, SD=7·1, 84% white British). Parental preferences were mostly based on incentives (slight preference for cash pay-out for the parent versus a voucher for the child) and penalties (preference for schemes that did not allow unvaccinated children to attend school or day care and those that withheld financial benefits for parents of unvaccinated children). Parents also preferred schemes that: offered a compensation scheme, mandated the 6-in-1 vaccine, mandated vaccination in children aged 2 years and older, and that offered only medical exemptions.InterpretationResults can inform policymakers’ decisions about how best to implement a mandatory childhood vaccination scheme in England.FundingData collection was funded by a British Academy/Leverhulme Small Research Grants (SRG1920\101118).Research in contextEvidence before this studyUptake of childhood vaccines in high-income countries has decreased in recent years. Making vaccination mandatory has the potential to increase uptake. There is no standard approach to mandatory vaccination schemes. Research suggests that the cultural context will affect perceived acceptability of vaccine laws. Mandatory vaccination has been mooted in England as a way to increase vaccine uptake. However, there is no recent research investigating parental preferences for how a mandatory vaccine scheme could be implemented.Added value of this studyWe used a discrete choice experiment to investigate English parents’ preferences for a mandatory vaccination scheme. Variables included were parameters that are likely to be considered by policymakers if a mandatory vaccination scheme were to be proposed.Implications of all the available evidenceStudy results indicate that parents prefer mandatory vaccination schemes that offer financial incentives for vaccination. The penalty imposed for missing a vaccine dose, and the inclusion of a compensation scheme for severe adverse effects also influenced preferences. These results can be used to inform policy should a mandatory vaccination scheme be proposed in England.
SARS-CoV-2 Antigen Tests Predict Infectivity Based on Viral Culture: Comparison of Antigen, PCR Viral Load, and Viral Culture Testing on a Large Sample Cohort
Authors: Kirby James E. , Riedel Stefan , Dutta Sanjucta , Arnaout Ramy , Cheng Annie , Ditelberg Sarah , Hamel Donald J. , Chang Charlotte A. , Kanki Phyllis J. 
Published: December 2021

AbstractThe relationship of SARS-CoV-2 antigen testing results, viral load, and viral culture detection remains to be fully defined. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals, and thereby inform how and where to most appropriately deploy available diagnostic testing modalities. We therefore determined the relationship of antigen testing results from three lateral flow and one microfluidics assay to viral culture performed in parallel in 181 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. We found that antigen tests were predictive of viral culture positivity, with the LumiraDx method showing enhanced sensitivity (90%; 95% confidence interval (95% CI) 83-94%) compared with the BD Veritor (74%, 95%CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver-operator characteristic curves (ROCs) of 0.94-0.97 and 0.92, respectively. In particular, a viral load threshold of 100,000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Taken together, the detection of SARS-CoV-2 antigen identified highly infectious individuals, some of whom may harbor 10,000-fold more virus in their samples than those with any detectable infectious virus. As such, our data support use of antigen testing in defining infectivity status at the time of sampling.
Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome
Authors: Horlacher Marc , Oleshko Svitlana , Hu Yue , Ghanbari Mahsa , Cantini Giulia , Schinke Patrick , Vergara Ernesto Elorduy , Bittner Florian , Mueller Nikola S. , Ohler Uwe , Moyon Lambert , Marsico Annalisa 
Published: December 2021

ABSTRACTStrong evidence suggests that human human RNA-binding proteins (RBPs) are critical factors for viral infection, yet there is no feasible experimental approach to map exact binding sites of RBPs across the SARS-CoV-2 genome systematically at a large scale. We investigated the role of RBPs in the context of SARS-CoV-2 by constructing the first in silico map of human RBP / viral RNA interactions at nucleotide-resolution using two deep learning methods (pysster and DeepRiPe) trained on data from CLIP-seq experiments. We evaluated conservation of RBP binding between 6 other human pathogenic coronaviruses and identified sites of conserved and differential binding in the UTRs of SARS-CoV-1, SARS-CoV-2 and MERS. We scored the impact of variants from 11 viral strains on protein-RNA interaction, identifying a set of gain-and loss of binding events. Lastly, we linked RBPs to functional data and OMICs from other studies, and identified MBNL1, FTO and FXR2 as potential clinical biomarkers. Our results contribute towards a deeper understanding of how viruses hijack host cellular pathways and are available through a comprehensive online resource (https://sc2rbpmap.helmholtz-muenchen.de).
Copy number variation of the putative speciation genes in the European house mouse hybrid zone
Authors: Yanchukov Alexey , Hiadlovská Zuzana , Pezer Zeljka , Macholán Miloš , Piálek Jaroslav , Baird Stuart J.E. 
Published: December 2021

AbstractHybrid zones have long been described as “windows on the evolutionary process”, and studying them has become even more important since the advance in the genome analysis tools. The hybrid zone between two subspecies of the house mouse (Mus musculus musculusandMus m. domesticus) is a unique model speciation system to study fine scale interactions of recently diverged genomes. Here, we explore the role of gene Copy Number Variation in shaping the barrier to introgression in the hybrid zone within a previously established transect in Central Europe. The CNV of seven pre-selected candidate genes was determined via droplet-digital PCR and analyzed in the context of ~500k SNPs, with the ancestral population (i.e.musculusordomesticus) of every SNP allele previously inferred in the admixed individuals (Baird et al.,in prep.). The copy numbers of five genes were clearly associated with the prevalence of eithermusculusordomesticusgenomes across the hybrid zone. In three cases, the highest and/or outlying levels of association were observed at or very close to the annotated positions of the respective gene amplicons, demonstrating the power of our approach in confirming the reference locations of copy number variants. Notably, several other reference locations were recognized as positive outliers in the association with particular CNV genes, possibly representing the extra gene copies and/or their epistatic interaction sites.
Epistatic selection on a selfish Segregation Distorter supergene: drive, recombination, and genetic load
Authors: Navarro-Domínguez Beatriz , Chang Ching-Ho , Brand Cara L. , Muirhead Christina A. , Presgraves Daven C. , Larracuente Amanda M. 
Published: December 2021

AbstractMeiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation to gain preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing alternative alleles. While at least two loci are important for male drive— the driver and the target— linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversion on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over and with wildtype chromosomes only via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly.
High-throughput UHPLC-MS to screen metabolites in feces for gut metabolic health
Authors: de Zawadzki Andressa , Thiele Maja , Suvitaival Tommi , Wretlind Asger , Kim Min , Ali Mina , Bjerre Annette F. , Stahr Karin , Matilla Ismo , Hansen Torben , Krag Aleksander , Legido-Quigley Cristina 
Published: December 2021

Abstract(1)BackgroundFeces are the product of our diets and have been linked to diseases of the gut, including Chron’s disease and metabolic diseases such as diabetes. For screening metabolites in heterogeneous samples such as feces, it is necessary to use fast and reproducible analytical methods that maximize metabolite detection.(2)MethodsAs sample preparation is crucial to obtain high quality data in MS-based clinical metabolomics, we developed a novel, efficient and robust method for preparing fecal samples for analysis with a focus in reducing aliquoting and detecting both polar and non-polar metabolites. Fecal samples (n= 475) from patients with alcohol-related liver disease and healthy controls were prepared according to the proposed method and analyzed in an UHPLC-QQQ targeted platform in order to obtain a quantitative profile of compounds that impact liver-gut axis metabolism.(3)ResultsMS analyses of the prepared fecal samples have shown reproducibility and coverage of n=28 metabolites, mostly comprising bile acids and amino acids. We report metabolite-wise relative standard deviation (RSD) in quality control samples, inter-day repeatability, LOD, LOQ and range of linearity. The average concen-trations for 135 healthy participants are reported here for clinical applications.(4)Conclusionsour high-throughput method provides an efficient tool for investigating gut-liver axis metabolism in liver-related diseases using a noninvasive collected sample.
HSFA1 proteins mediate heat-induced accumulation of CPT7-derived polyprenols affecting thylakoid organization
Authors: Buszewicz Daniel , Kowalewska Łucja , Mazur Radosław , Zajbt-Łuczniewska Marta , Surmacz Liliana , Sosnowska Katarzyna , Welc Renata , Jemioła-Rzemińska Małgorzata , Link-Lenczowski Paweł , Onysk Agnieszka , Skorupinska-Tudek Karolina , Liu Hsiang-Chin , Charng Yee-Yung , Archacki Rafał , Gruszecki Wieslaw I. , Swiezewska Ewa 
Published: December 2021

AbstractPolyprenols are ubiquitous isoprenoid compounds that accumulate in large quantities in plant photosynthetic tissues. While our knowledge of polyprenol biochemistry is constantly expanding, the regulation of their biosynthesis as well as the molecular basis of their cellular action are still poorly understood. In Arabidopsis, the polyprenols Pren-9, −10 and −11, synthesized by cis-prenyltransferase 7 (CPT7), are localized in plastidial membranes and affect the photosynthetic performance of chloroplasts.In this report we present evidence that plastidial polyprenols are among the major constituents of thylakoid membranes. Disturbances in polyprenol level, caused by alterations in CPT7 expression, change chloroplast ultrastructure, affect aggregation of LHCII complexes and modulate non-photochemical quenching (NPQ). Moreover, we show that Arabidopsis responds to high temperature by upregulating expression of CPT7 and increasing the accumulation of CPT7-derived polyprenols. These heat-induced changes in polyprenol biosynthesis are mediated by Heat Shock Transcription Factors of the HSFA1 family, the master regulators of heat stress response. Collectively, results presented in this report bring us closer to understanding the mechanisms by which polyprenols affect plant physiology and provide an additional link between chloroplast biology and plant responses to changing environmental conditions.One sentence summaryHeat Shock Transcription Factors induce biosynthesis of polyprenols - isoprenoid compounds that affect the organization and function of chloroplasts.