bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalytic Promiscuity of Rice 2-Oxoglutarate/Fe(II)-Dependent Dioxygenases Supports Xenobiotic Metabolism
Authors: Takamura Natsuki , Yamazaki Akihiko , Sakuma Nozomi , Hirose Sakiko , Takani Yukie , Sakai Motonari , Oshima Masahiro , Kuroki Makoto , Tozawa Yuzuru 
Published: December 2020

ABSTRACTThe rice 2-oxoglutarate/Fe(II)–dependent dioxygenase HIS1 mediates the catalytic inactivation of five distinct β-triketone herbicides (bTHs). During a search for potential inhibitors of HIS1, we found that it mediates the hydroxylation of trinexapac-ethyl (TE) in the presence of Fe2+and 2-oxoglutarate. TE is a plant growth regulator that blocks gibberellin biosynthesis, and we observed that its addition to culture medium induced growth retardation of rice seedlings in a concentration-dependent manner. Similar treatment with hydroxylated TE revealed that hydroxylation greatly attenuated the inhibitory effect of TE on plant growth. Forced expression ofHIS1in a ricehis1mutant also reduced its sensitivity to TE compared with that of the nontransformant. These results indicated that HIS1 metabolizes TE and thereby markedly reduces its ability to slow plant growth. Furthermore, testing of five HIS1-related proteins (HSLs) of rice revealed that OsHSL2 and OsHSL4 also metabolize TE in vitro. HSLs from wheat and barley also showed such activity. In contrast, OsHSL1, which shares the highest amino acid sequence identity with HIS1 and metabolizes the bTH tefuryltrione, did not manifest TE-metabolizing activity. Site-directed mutagenesis of OsHSL1 informed by structural models showed that substitution of three amino acids with the corresponding residues of HIS1 conferred TE-metabolizing activity similar to that of HIS1. Our results thus reveal a catalytic promiscuity of HIS1 and its related enzymes that supports xenobiotic metabolism in plants.One-sentence summaryThe rice 2-oxoglutarate/Fe(II)-dependent dioxygenase HIS1 and related enzymes show broad substrate specificity and mediate metabolism of the growth regulator trinexapac-ethyl as well as of herbicides.
Real time, field-deployable whole genome sequencing of malaria parasites using nanopore technology
Authors: Razook Zahra , Mehra Somya , Gilchrist Brittany , Utama Digjaya , Lautu-Gumal Dulcie , Fola Abebe , Menard Didier , Kazura James , Laman Moses , Mueller Ivo , Robinson Leanne J. , Bahlo Melanie , Barry Alyssa E. 
Published: December 2020

ABSTRACTMalaria parasite genomes have been generated predominantly using short read sequencing technology which can be slow, requires advanced laboratory training and does not adequately interrogate complex genomic regions that harbour important malaria virulence determinants. The portable Oxford Nanopore Technologies MinION platform generates long reads in real time and may overcome these limitations. We present compelling evidence that Nanopore sequencing delivers valuable additional information for malaria parasites with comparable data fidelity for single nucleotide variant (SNV) calls, compared to standard Illumina whole genome sequencing. We demonstrate this through sequencing of purePlasmodium falciparumDNA, mock infections and natural isolates. Nanopore has low error rates for haploid SNV genotyping and identifies structural variants (SVs) not detected with short reads. Nanopore genomes are directly comparable to publically available genomes and produce high quality end to end chromosome assemblies. Nanopore sequencing will expedite genomic surveillance of malaria and provide new insights into parasite genome biology.
The dynamic landscape of parasitaemia dependent intestinal microbiota shifting at species level and the correlated gut transcriptome during Plasmodiumyoeliiinfection
Authors: Yawen Zong , Lei Cheng , Xiangyun Cheng , Binyou Liao , Xingchen Ye , Taiping Liu , Jiyao Li , Xuedong Zhou , Wenyue Xu , Biao Ren 
Published: December 2020

AbstractBackgroundMalaria, caused byPlasmodium, is a global life-threatening infection disease especially during the COVID-19 pandemic. However, it is still unclear about the dynamic change and the interactions between intestinal microbiota and host immunity. Here, we investigated the change of intestinal microbiome and transcriptome during the wholePlasmodiuminfection process in mice to analyze the dynamic landscape of parasitaemia dependent intestinal microbiota shifting and related to host immunity.ResultsThere were significant parasitaemia dependent changes of intestinal microbiota and transcriptome, and the microbiota was significantly correlated to the intestinal immunity. We found that (i) the diversity and composition of the intestinal microbiota represented a significant correlation along with thePlasmodiuminfection in family, genus and species level; (ii) the up-regulated genes from the intestinal transcriptome were mainly enriched in immune cell differentiation pathways along with the malaria development, particularly, naive CD4+ T cells differentiation; (iii) the abundance of the parasitaemia phase-specific microbiota represented a high correlation with the phase-specific immune cells development, particularly, Th1 cell with familyBacteroidalesBS11 gut group, generaPrevotella9,RuminococcaceaeUCG 008,Moryellaand specieSutterella*, Th2 cell with specieSutterella*, Th17 cell with familyPeptococcaceae, genusLachnospiraceaeFCS020 group and spicesRuminococcus1*,RuminococcusUGG 014* andEubacterium plexicaudatumASF492, Tfh and B cell with generaMoryellaand speciesErysipelotrichaceae bacterium canine oral taxon255.ConclusionThere was a remarkable dynamic landscape of the parasitaemia dependent shifting of intestinal microbiota and immunity, and a notable correlation between the abundance of intestinal microbiota.
Temporal kinetics of RNAemia and associated systemic cytokines in hospitalized COVID-19 patients
Authors: van Riel Debby , Embregts Carmen W.E. , Sips Gregorius J. , van den Akker Johannes P.C. , Endeman Henrik , van Nood Els , van Kampen Jeroen , Molenkamp Richard , Koopmans Marion , van de Vijver David , GeurtsvanKessel Corine H. 
Published: December 2020

SummaryCOVID-19 is associated to a wide range of extra-respiratory complications, of which the pathogenesis is currently not fully understood. In this study we report the temporal kinetics of viral RNA and inflammatory cytokines and chemokines in serum during the course of COVID-19. We show that a RNAemia occurs more frequently and lasts longer in patients that develop critical disease compared to patients that develop moderate or severe disease. Furthermore we show that concentrations of IL-10 and MCP-1—but not IL-6—are associated with viral load in serum. However, higher levels of IL-6 were associated with the development of critical disease. The direct association of inflammatory cytokines with viral load or disease severity highlights the complexity of systemic inflammatory response and the role of systemic viral spread.
Epidemiology of developmental dyslexia: A comparison of DSM-5 and ICD-11 criteria
Authors: Di Folco Cécile , Guez Ava , Peyre Hugo , Ramus Franck 
Published: December 2020

AbstractThe two major medical classifications (ICD-11 and DSM-5), define diagnostic criteria for developmental dyslexia that partly differ and that are open to multiple interpretations, inducing different prevalence estimates and discordant cases. The present study evaluates the prevalence of developmental dyslexia for the first time in France in an extensive population representative of French sixth-graders (N=25,000), investigating the consequences of using one classification or the other, and of the different ways of implementing each criterion. Moreover, students diagnosed with dyslexia were compared with the reference population in the other available characteristics. Overall, prevalence estimates ranged from 1.3% to 17.2% depending on the criteria and thresholds used. A reasonable set of criteria and thresholds (−1.5 SD below mean for reading score, -0.5 SD for achievement) yielded a prevalence of dyslexia in France of 6.6% according to DSM-5 and 3.5% according to ICD-11. Factors that had the greatest influence on prevalence estimates were the criteria relative to 1) IQ, and 2) impact on academic achievement. DSM-5, being more liberal than ICD-11 on the IQ criterion, included more cases with relatively low IQ and thus yielded higher prevalence estimates. Compared with the reference population, children with dyslexia were more likely to be boys, to be schooled in a disadvantaged area, and to have lower SES, IQ, and math results. Our results emphasize that the choice of classification and the operationalization of specific criteria have a large impact on who is diagnosed with dyslexia.
EBV deletions as biomarkers of response to treatment of Chronic Active Epstein Barr Virus
Authors: Venturini Cristina , Houldcroft Charlotte J , Lazareva Arina , Wegner Fanny , Morfopoulou Sofia , Amrolia Persis J. , Golwala Zainab , Rao Anupama , Marks Stephen D. , Simmonds Jacob , Yoshikawa Tetsushi , Farrell Paul J. , Cohen Jeffrey I. , Worth Austen J. , Breuer Judith 
Published: December 2020

AbstractChronic active Epstein Barr Virus (CAEBV) is a rare condition occurring in previously healthy individuals associated with persistent EBV viraemia, fever, lymphadenopathy and hepatosplenomegaly. Viral deletions have been found in CAEBV and other lymphomas. However, it is unclear how stable these deletions are, whether they are present in different sites and how they evolve overtime. We sequenced fourteen longitudinal blood samples from three European CAEBV patients and compared with CAEBV saliva samples and other sequences from EBV-related conditions. We observed large EBV deletions in blood, but not saliva from CAEBV patients. Deletions were stable over time but were lost following successful treatment. Our results are consistent with the likelihood that certain deletions in the virus from CAEBV patients are associated with the evolution and persistence of haematological clones. We propose that the loss of deletions following successful treatment should be investigated as a potential biomarker to aid CAEBV management.
Coinfection with Respiratory Pathogens in COVID-19 in Korea
Authors: Roh Kyoung Ho , Kim Yu Kyung , Kim Shin-Woo , Kang Eun-Rim , Yang Yong-Jin , Jung Sun-Kyung , Lee Sun-Hwa , Sung Nackmoon 
Published: December 2020

AbstractDetection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in upper and lower respiratory specimens and coinfection with other respiratory pathogens in patients with coronavirus disease 2019 (COVID-19) were investigated. From the study subjects (N = 258) retrospectively enrolled when confirmed as SARS-CoV-2 positive, nasopharyngeal (NPS), oropharyngeal swabs (OPS), and sputum specimens were restored for retesting SARS-CoV-2 and detecting respiratory pathogens. Majority of the study subjects (95.7%, N = 247) were confirmed as SARS-CoV-2 positive using NPS/OPS specimens, suggesting that the upper respiratory specimen is most valuable in detecting SARS-CoV-2. Coinfection rates in COVID-19 patients (N = 258) with respiratory pathogens were 9.7% (N = 25); 8.5% (N = 22) respiratory viruses and 1.2% (N = 3) Mycoplasma pneumoniae, an atypical bacterium. Of the respiratory virus coinfection cases (N = 22), 20 (90.9%) were co-infected with a single respiratory virus and 2 (0.8%) (metapneumovirus/adenovirus and rhinovirus/bocavirus 1/2/3/4) with two viruses. Respiratory viruses in single viral coinfection cases with SARS-CoV-2 were as follows: non-SARS-CoV-2 coronaviruses (229E, NL63, and OC43, N = 5, 1.9%), rhinovirus (N = 4, 1.6%), metapneumovirus (N = 3, 1.2%), influenza A (N = 3, 1.2%), respiratory syncytial virus A and B (N = 3, 1.2%), and adenovirus (N = 2, 0.8%). No mixed coinfections with respiratory viruses and M. pneumoniae were found. In conclusion, the diagnostic value of utilizing NPS/OPS specimen is excellent, and, as the first report in Korea, coinfection with respiratory pathogens were detected at a rate of 9.7% in patients with COVID-19.
Are college campuses superspreaders? A data-driven modeling study
Authors: Lu Hannah , Weintz Cortney , Pace Joseph , Indana Dhiraj , Linka Kevin , Kuhl Ellen 
Published: December 2020

ABSTRACTThe COVID-19 pandemic continues to present enormous challenges for colleges and universities and strategies for save reopening remain a topic of ongoing debate. Many institutions that reopened cautiously in the fall experienced a massive wave of infections and colleges were soon declared as the new hotspots of the pandemic. However, the precise effects of college outbreaks on their immediate neighborhood remain largely unknown. Here we show that the first two weeks of instruction present a high-risk period for campus outbreaks and that these outbreaks tend to spread into the neighboring communities. By integrating a classical mathematical epidemiology model and Bayesian learning, we learned the dynamic reproduction number for 30 colleges from their daily case reports. Of these 30 institutions, 14 displayed a spike of infections within the first two weeks of class, with peak seven-day incidences well above 1,000 per 100,000, an order of magnitude larger than the nation-wide peaks of 70 and 150 during the first and second waves of the pandemic. While most colleges were able to rapidly reduce the number of new infections, many failed to control the spread of the virus beyond their own campus: Within only two weeks, 17 campus outbreaks translated directly into peaks of infection within their home counties. These findings suggests that college campuses are at risk to develop an extreme incidence of COVID-19 and become superspreaders for neighboring communities. We anticipate that tight test-trace-quarantine strategies, flexible transition to online instruction, and–most importantly–compliance with local regulations will be critical to ensure a safe campus reopening after the winter break.
Assessment of effective mitigation and prediction of the spread of SARS-CoV-2 in Germany using demographic information and spatial resolution
Authors: Kühn Martin J. , Abele Daniel , Mitra Tanmay , Koslow Wadim , Abedi Majid , Rack Kathrin , Siggel Martin , Khailaie Sahamoddin , Klitz Margrit , Binder Sebastian , Spataro Luca , Gilg Jonas , Kleinert Jan , Häberle Matthias , Plötzke Lena , Spinner Christoph D. , Stecher Melanie , Zhu Xiao Xiang , Basermann Achim , Meyer-Hermann Michael 
Published: December 2020

AbstractNon-pharmaceutical interventions (NPIs) are important to mitigate the spread of infectious diseases as long as no vaccination or outstanding medical treatments are available. We assess the effectiveness of the sets of non-pharmaceutical interventions that were in place during the course of the Coron-avirus disease 2019 (Covid-19) pandemic in Germany. Our results are based on hybrid models, combining SIR-type models on local scales with spatial resolution. In order to account for the age-dependence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we include realistic pre-pandemic and recently recorded contact patterns between age groups. The implementation of non-pharmaceutical interventions will occur on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. In order to account for spatial heterogeneity, we use a graph approach and we include high-quality information on commuting activities combined with traveling information from social networks. The remaining uncertainty will be accounted for by a large number of randomized simulation runs. Based on the derived factors for the effectiveness of different non-pharmaceutical interventions over the past months, we provide different forecast scenarios for the upcoming time.Mathematics Subject Classification (2010) 00A72 · 65L05 · 68U20
Real Bodies Not Required? Placebo Analgesia and Pain Perception in Immersive Virtual and Augmented Reality
Authors: Ho Jasmine T. , Krummenacher Peter , Lesur Marte Roel , Lenggenhager Bigna 
Published: December 2020

AbstractPain represents an embodied process, wherein inferences are not only drawn from sensory inputs, but also from bodily states. Previous research has demonstrated that a placebo administered to an embodied rubber hand can effectively induce analgesia, providing first evidence that placebos can work even when applied to temporarily embodied, artificial body parts. Using a heat pain paradigm, the present study investigates placebo analgesia and pain perception during virtual embodiment. We examined whether a virtual placebo (a sham heat protective glove) can successfully induce analgesia, even when administered to a virtual body. The analgesic efficacy of the virtual placebo to the real hand (augmented reality setting) or virtual hand (virtual reality setting) was compared to a physical placebo administered to the own, physical body (physical reality setting). Furthermore, pain perception and subjective embodiment were compared between settings. Healthy participants (n=48) were assigned to either an analgesia-expectation or control-expectation group, where subjective and objective pain was measured at pre- and post-intervention time points. Results evinced that pre-intervention pain intensity was lower in the virtual reality setting, and that participants in the analgesia-expectation condition, after the intervention, exhibited significantly higher pain thresholds, and lower pain intensity and unpleasantness ratings than control-expectation participants, independent of the setting. Our findings evince that a virtual placebo can elicit placebo analgesia comparable to that of a physical placebo, and that administration of a placebo does not necessitate physical bodily interaction to produce analgesic responses, which might pave the way for effective new non-pharmacological approach for pain management.
Evolution and insights into the structure and function of the DedA superfamily containing TMEM41B and VMP1
Authors: Okawa Fumiya , Hama Yutaro , Zhang Sidi , Morishita Hideaki , Yamamoto Hayashi , Levine Tim P. , Mizushima Noboru 
Published: December 2020

ABSTRACTTMEM41B and VMP1 are endoplasmic reticulum (ER)-localizing multi-spanning membrane proteins required for ER-related cellular processes such as autophagosome formation, lipid droplet homeostasis, and lipoprotein secretion in eukaryotes. Both proteins have a VTT domain, which is similar to the DedA domain found in bacterial DedA family proteins. However, the molecular function and structure of the DedA and VTT domains (collectively referred to as DedA domains) and the evolutionary relationships among the DedA domain-containing proteins are largely unknown. Here, we conduct remote homology search and identify a new clade consisting mainly of bacterial PF06695 proteins of unknown function. Phylogenetic analysis reveals that the TMEM41, VMP1, DedA, and PF06695 families form a superfamily with a common origin, which we term the DedA superfamily. Coevolution-based structural prediction suggests that the DedA domain contains two reentrant loops that face each other in the membrane. This topology is biochemically verified by the substituted cysteine accessibility method. The predicted structure is topologically similar to that of the substrate-binding region of Na+-coupled glutamate transporter solute carrier 1. A potential ion-coupled transport function of the DedA superfamily proteins is discussed.
HPF1 and nucleosomes mediate a dramatic switch in activity of PARP1 from polymerase to hydrolase
Authors: Rudolph Johannes , Roberts Genevieve , Muthurajan Uma M. , Luger Karolin 
Published: December 2020

AbstractPoly(ADP-ribose) polymerase 1 (PARP1) is an important player in the response to DNA damage. Recently, histone PARylation factor (HPF1) was shown to be a critical modulator of the activity of PARP1 by facilitating PARylation of histones and redirecting the target amino acid specificity from acidic to serine residues. Here we investigate the mechanism and specific consequences of HPF1-mediated PARylation using nucleosomes as both activators and substrates for PARP1. HPF1 provides that catalytic base Glu284 to substantially redirect PARylation by PARP1 such that the histones in nucleosomes become the primary recipients of PAR chains. Surprisingly, HPF1 partitions most of the reaction product to free ADPR, resulting in much shorter PAR chains compared to reactions in the absence of HPF1. This HPF1-mediated switch from polymerase to hydrolase has important implications for the PARP1-mediated response to DNA damage and raises interesting new questions about the role of intracellular ADPR and depletion of NAD+.
Cannabidiol effects on cocaine-seeking behaviour and incubation of craving in mice
Authors: Alegre-Zurano Laia , Luján Miguel Á. , Cantacorps Lídia , Martín-Sánchez Ana , García-Baos Alba , Valverde Olga 
Published: December 2020

ABSTRACTBackground and PurposeTo remain abstinent represents one of the major challenges for the treatment of cocaine use disorder. Cocaine seeking elicited by drug-associated cues progressively intensifies during abstinence in a process termed incubation of craving, representing an aggravating factor for relapse. Cannabidiol is a phytocannabinoid that exerts protecting effects upon cocaine-seeking behaviour, although its effects on cocaine-craving incubation have never been elucidated.Experimental ApproachWe developed a mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving. Changes in the protein expression of AMPAR subunits and ERK1/2phosphorylation were analysed. We also assessed the effects of cannabidiol (20 mg·kg-1) administered either during acquisition of cocaine self-administration or abstinence.Key ResultsMice efficiently performed the demand task and incubation of cocaine craving. Besides, changes in GluA1 and GluA2 protein levels were found along the abstinence in prelimbic cortex, ventral striatum and amygdala, as well as a decrease in ERK1/2phosphorylation in ventral striatum. Cannabidiol reduced ongoing cocaine intake when administered during the acquisition phase of the self-administration, but failed to alter the subsequent demand task performance and incubation of cocaine craving. No effects were found when cannabidiol was administered during the abstinence period.Conclusion and ImplicationsWe provide here a novel model of behavioural economic analysis of demand curves and cue-induced incubation of cocaine-seeking behaviour for mice. Moreover, we show that cannabidiol exerts differential effects on the current model depending on the self-administration phase in which it was administered.What is already knownBehavioural economics and incubation of cocaine craving are well-stablished paradigms to evaluate cocaine seeking in rats.CBD reduces cocaine-seeking and cocaine-taking behaviours.What this study addsA mouse model of behavioural economic analysis of demand curves and incubation of cue-induced cocaine craving.CBD reduces cocaine self-administration and has no effect over demand task and cocaine-craving incubation.Clinical significanceA new behavioural model for studying cocaine addiction in mice.CBD exerts differential effects depending on when it was administered in the addictive process.Tables ofLinks