bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracing the Indian Population Ancestry bycis-linked Mutations inHBBGene
Authors: Panja Amrita , Chowdhury Prosanto , basu Anupam 
Published: April 2021

AbstractBackgroundHuman left their genetic footprints during the time of migration throughout the different countries all over the world. Human evolution was studied through various markers. India is a country of rich heritage and cultural diversity. The modern Indian population is derived from two ancestral groups, viz.-Ancestral North Indians (ANI) and Ancestral South Indians (ASI).AimFinding out the migratory route of the modern Indian population by studying ‘cis’ acting mutations of human beta-globin (HBB) genes.Subjects and methodsA total of 120 thalassemia subjects were enrolled. DNA sequencing was done for mutation detection in theHBBgene. Some previous literature reviews were gone through for tracing mutations, all over the world and in the Indian subcontinent.ResultsNine thalassemia patients were found whereHBB:c.92G>C andHBB:c.-92C>G mutations co-exist together in ‘cis’ condition. Only one patient hadHBB:c.51delC andHBB:c.33C>A. The pedigree analysis confirmed the presence of these mutations in ‘cis’ condition and vertical transmission from one generation to the next. Literature reviews also reassure the co-existence of these mutations from different countries.ConclusionThe co-existence of these ‘cis’ acting mutations helps to point out the possible migratory route of ANI population after venturing out of Africa.
B and T cell immune responses elicited by the BNT162b2 (Pfizer–BioNTech) COVID-19 vaccine in nursing home residents
Authors: Torres Ignacio , Albert Eliseo , Giménez Estela , Alcaraz María Jesús , Botija Pilar , Amat Paula , Remigia María José , Beltrán María José , Rodado Celia , Huntley Dixie , Olea Beatriz , Navarro David 
Published: April 2021

ABSTRACTObjectivesThe immunogenicity of the BNT162b2 COVID-19 vaccine is understudied in elderly people with comorbidities. We assessed SARS-CoV-2-S-targeted antibody and T cell responses following full vaccination in nursing home residents (NHR).MethodsWe recruited 60 NHR (44 female; median age, 87.5 years), of whom 10 had previously had COVID-19, and 18 healthy controls (15 female; median age, 48.5 years). Pre- and post-vaccination blood specimens were available for quantitation of total antibodies binding RBD and enumeration of SARS-CoV-2-S-reactive IFN-γ CD4+ and CD8+ T cells by flow cytometry.ResultsThe seroconversion rate in presumably SARS-CoV-2 naïve NHR (95.3%), either with or without comorbidities, was similar to controls (94.4%). A robust booster effect was documented in NHR with prior COVID-19. Plasma antibody levels were higher in convalescent NHR than in individuals across the other two groups. A large percentage of NHR had SARS-CoV-2 S-reactive IFN-γ CD8+ and/or CD4+ T cells at baseline, in contrast to healthy controls. Either CD8+ and/or CD4+ T-cell responses were documented in all control subjects after vaccination. Contrariwise, the percentage of NHR exhibiting detectable SARS-CoV-2 IFN-γ CD8+ or CD4+ T-cell responses (or both), irrespective of their baseline SARS-CoV-2 infection status, dropped consistently after vaccination. Overall, SARS-CoV-2 IFN-γ CD8+ and CD4+ T-cell responses in NHR decreased in post-vaccination specimens.ConclusionThe BNT162b2 COVID-19 vaccine elicits robust SARS-CoV-2-S antibody responses in NHR. Nevertheless, the frequency and magnitude of detectable SARS-CoV-2 IFN-γ T-cell responses after vaccination was lower in NHR compared to controls.
SCALP HIGH FREQUENCY OSCILLATION RATE DEPENDS ON SLEEP STAGE AND DECREASES WITH TIME SPENT IN SLEEP
Authors: Cserpan Dorottya , Rosch Richard , Lo Biundo Santo Pietro , Sarnthein Johannes , Ramantani Georgia 
Published: April 2021

ABSTRACTHigh frequency oscillations (HFO) in scalp EEG are a new and promising epilepsy biomarker. HFO analysis is typically restricted to random and relatively brief sleep segments. However, considerable fluctuations of HFO rates have been observed over the recording nights, particularly in relation to sleep stages and cycles. Here, we identify the timing within the sleep period and the minimal data interval length that allow for sensitive and reproducible detection of scalp HFO. We selected 16 seizure-free whole-night scalp EEG recordings of children and adolescents with focal lesional epilepsy (median age 7.6 y, range 2.2-17.4 y). We used an automated and clinically validated HFO detector to determine HFO rates (80-250 Hz) in bipolar channels. To identify significant variability over different NREM sleep stages and over time spent in sleep, we modelled HFO rate as a Poisson process. We analysed the test-retest reliability to evaluate the reproducibility of HFO detection across recording intervals. Scalp HFO rates were higher in N3 than in N2 sleep and highest in the first sleep cycle, decreasing with time spent in sleep. In N3 sleep, the median reliability of HFO detection increased from 67% to 79% to 100% for 5-, 10-, and 15-min data intervals, improving significantly (p=0.004) from 5 to 10 min but not from 10 to 15 min. In this analysis of whole-night scalp EEG, we identified the first N3 sleep stage as the most sensitive time window for HFO rate detection. N3 data intervals of 10 min duration are required and sufficient for reliable measurements of HFO rates. Our study provides a robust and reliable framework for implementing scalp HFO as an EEG biomarker in pediatric epilepsy.
ReCOVer study: A Cross-sectional Observational Study to Identify the Rehabilitation Need in Post-discharge COVID-19 Survivors
Authors: Swarnakar Raktim , Yadav S. L. , Srikumar V , Soni Kapil Dev , Aggrawal Richa , Trikha Anjan 
Published: April 2021

AbstractIntroductionWith the increasing number of Coronavirus disease-2019 (COVID-19) cases there is simultaneous increase in recovered cases too. There are many post-covid complications where need for rehabilitation intervention is very conspicuous especially pulmonary, neurological complications. Hence data are of utmost importance to find out those rehabilitation needs among post-covid survivors.Methods and analysisReCOVer (Rehabilitation Need in Post-discharge COVID-19 Survivors), a cross-sectional observational study protocol has been planned to find out rehab-need by assessing International Classification of Functioning, Disability and Health (ICF) core data set, COVID-19 Yorkshire Rehab Screen (C19-YRS) tool, The Post-COVID-19 Functional Status (PCFS) scale, barriers to functional independence and rehab services (affordability & availability). Post-discharge (minimum 1 weeks) Covid patients (required hospitalisation) will be included in the study. Study will be conducted through Telerehabilitation facility. Study will conform to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.Ethics and disseminationStudy received ethical approval from Institute Ethics Committee, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Findings will be disseminated at scientific conferences/meetings, peer-reviewed journals, and to relevant stakeholders including the ministry of health (if required).
Accounting for age-of-onset and family history improves power in genome-wide association studies
Authors: Pedersen Emil M , Agerbo Esben , Plana-Ripoll Oleguer , Grove Jakob , Dreier Julie W. , Musliner Katherine L. , Bækvad-Hansen Marie , Athanasiadis Georgios , Schork Andrew , Bybjerg-Grauholm Jonas , Hougaard David M. , Werge Thomas , Nordentoft Merete , Mors Ole , Dalsgaard Søren , Christensen Jakob , Børglum Anders D. , Mortensen Preben B. , McGrath John J. , Privé Florian , Vilhjálmsson Bjarni J. 
Published: April 2021

AbstractGenome-wide association studies (GWAS) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified by examining the age-of-onset distribution and the age of the controls or the age-of-onset for cases. The age-of-onset distribution may also depend on information such as sex and birth year. In addition, family history is not routinely included in the assessment of control status. Here we present LT-FH++, an extension of the liability threshold model conditioned on family history (LT-FH), that jointly accounts for age-of-onset and sex, as well as family history. Using simulations, we show that, when family history and the age-of-onset distribution are available, the proposed approach yields large power gains over both LT-FH and genome-wide association study by proxy (GWAX). We applied our method to four psychiatric disorders available in the iPSYCH data, and to mortality in the UK Biobank, finding 20 genome-wide significant associations with LT-FH++, compared to 10 for LT-FH and 8 for a standard case-control GWAS. As more genetic data with linked electronic health records become available to researchers, we expect methods that account for additional health information, such as LT-FH++, to become even more beneficial.
Strengthened mutualistic adaptation between teosinte and its rhizosphere biota in cold climates
Authors: O’Brien Anna M. , Sawers Ruairidh J.H. , Gasca-Pineda Jaime , Baxter Ivan , Eguiarte Luis E. , Ross-Ibarra Jeffrey , Strauss Sharon Y. 
Published: April 2021

SummaryWhile abiotic environments consistently shape local adaptation, the strength of local adaptation to biotic interactions may vary more. One theory, COCO (CO-evolutionary Outcomes across Conditionality), predicts it may be strongest where species experience greater stress, because stress increases fitness impacts of species interactions. For example, in plant interactions with rhizosphere biota, positive outcomes increase with stress from low soil fertility, drought and cold.To investigate the influence of abiotic stress gradients on adaptation between plants and rhizosphere biota, we used a greenhouse common garden experiment recombining teosinte,Zea maysssp.mexicana(wild relative of maize), and rhizosphere biota, collected across a stress gradient (elevational variation in temperature, precipitation, and nutrients).We found stronger local adaptation between teosinte and rhizosphere biota from colder, more stressful sites, as expected by COCO. However, biota from less stressful, warmer sites provided greater average benefits across teosinte populations. Links between plant traits and 20-element profiles of plant leaves explained fitness variation, persisted in the field, were influenced by both plants and biota, and largely reflected patterns of local adaptation.In sum, we uncovered greater local adaptation to biotic interactions in colder sites, and that both plants and rhizosphere biota affect the expression of plant phenotypes.
TheMagnaporthe oryzaeMAP kinase Pmk1 regulates polycomb repressive complex 2 to reprogram genes expression for biotrophic growth
Authors: Cai Xuan , Tang Bozeng , Hendy Ahmed , Ren Zhiyong , Liu Caiyun , Kamran Muhammad , Xing Junjie , Zheng Lu , Liu Hao , Huang Junbing , Chen Xiao-Lin 
Published: April 2021

SUMMARYBiotrophic and hemibiotrophic fungi have evolved the ability to colonize living plant cells, but how they establish biotrophic growth by remodeling gene expression is poorly understood. By usingin plantainvasive hyphae (IH) ofMagnaporthe oryzaeto perform an integrated Chromatin immunoprecipitation sequencing (ChIPseq) and RNA-seq analysis, combining with biological and cellular analyses, we found Polycomb repressive complex 2 (PRC2)-mediated epigenetic repression plays a key role in regulating biotrophic growth. ChIPseq for biotrophic IH samples identified 1701 PRC2 target genes. RNA-seq analysis showed that expression of 462 PRC2 target genes were up-regulated in the Δsuz12mutant, while 82 were down-regulated, indicating a major role of PRC2 in gene repression of IH. During biotrophic growth, PRC2 repressed fungal cell wall synthesis genes and extracellular enzyme genes required for penetration, and secondary metabolites biosynthesis genes required for necrotrophic growth. A great number of effector-encoding genes were repressed by PRC2, which were highly expressed during penetration stage, suggesting PRC2 coordinates biotrophic growth by regulating effector suppression for immune evasion. This regulation was finely coordinated by Pmk1, through regulating phosphorylation, nuclear localization and protein abundance of Suz12. Our results indicate that the Pmk1-PRC2 regulatory module is required for gene remodeling to facilitate biotrophic growth inM. oryzae.IMPORTANCEBiotrophic and hemibiotrophic fungi establish a biotrophic stage for infection in host cells. For example,M. oryzaeforms appressoria to penetrate host cell and establish a biotrophic growth stage for infection. How gene expression patterns are elaborately controlled for fungal biotrophic growth is largely unknown. In this study, we found that, the PRC2-mediated H3K27me3 repressed fungal penetration-required cell wall synthesis genes and extracellular enzyme genes, and necrotrophic growth-required secondary metabolites biosynthesis genes for biotrophic growth. Interestingly, a great number of effector-encoding genes were also repressed by PRC2 at biotrophic stage, which were highly expressed at penetration stage, suggesting PRC2 coordinates biotrophic growth by regulating effector suppression for immune evasion. The PRC2-mediated epigenetic repression is therefore required for the gene expression remodeling during fungal infection. This regulation was finely coordinated by Pmk1, through regulating nuclear localization and protein abundance of the PRC2 component Suz12.
HIV-1 provirus transcription and translation in macrophages differs from pre-integrated cDNA complexes and requires E2F transcriptional programs
Authors: Lim Albebson L. , Moos Philip , Pond Christopher D. , Larson Erica C. , Martins Laura J. , Szaniawski Matthew A , Planelles Vicente , Barrows Louis R. 
Published: April 2021

AbstractHIV-1 cDNA pre-integration complexes have been shown to persist for weeks in macrophages and to be transcriptionally active. Early and late gene transcripts are produced, along with some viral proteins, yet whole virus is not. While previous work has focused on the transcription and translation of HIV-1 genes; our understanding of cellular milieu that accompanies viral production is incomplete. We have used anin vitrosystem to model HIV-1 infection of macrophages, and single cell RNA sequencing (scRNA-seq) to compare the transcriptomes of uninfected cells, cells harboring pre-integration HIV-1 complexes (PIC) and those containing integrated provirus and actively making late HIV proteins. These are also compared to control cells, not exposed to virus.Several observations provide new perspective on the effects of HIV-1 transcription from pre-integrated cDNA versus from integrated provirus. First, HIV-1 transcript levels do not necessarily correlate with virus production, cells harboring PIC cDNA have transcript loads comparable to cells transcribing from provirus and making p24, mCherry, and vpu proteins. Second, all HIV-1 transcripts are easily detectable in abundance from PIC cDNA transcription, as is the case with cells transcribing from provirus, although the frequency of PIC cells with detectable gag-pol, tat, env, and nef transcripts is higher than the corresponding frequencies observed for “Provirus cells”. Third, the background transcriptomes of cells harboring pre- integrated HIV-1 cDNA are not otherwise detectably altered from cells not containing any HIV- 1 transcript. Fourth, integration and production of p24, mCherry, and Vpu proteins is accompanied by a switch from transcriptomes characterized by NFkB and AP-1 promoted transcription to a transcriptome characterized by E2F family transcription products. While some of these observations may seem heretical, single cell analysis provides a more nuanced understanding of PIC cDNA transcription and the transcriptomic changes that support HIV-1 protein production from integrated provirus.Author SummarySingle cell analysis is able to distinguish between HIV-1 infected macrophage cells that are transcribing pre-integrated HIV-1 cDNA and those transcribing HIV-1 provirus. Only cells transcribing HIV-1 provirus are making p24, marker mCherry and Vpu proteins, which corresponds with a change in the host cell’s background transcriptome from one expressing viral restriction and immunological response genes to one that is expressing genes associated with cell replication and oxidative phosphorylation.
Viromes in Marine Ecosystems Reveal Remarkable Invertebrate RNA Virus Diversity
Authors: Zhang Yu-Yi , Chen Yicong , Wei Xiaoman , Cui Jie 
Published: April 2021

AbstractOcean viromes remain poorly understood and little is known about the ecological factors driving aquatic RNA virus evolution. In this study, we used a meta-transcriptomic approach to characterize the viromes of 58 marine invertebrate species across three seas. This revealed the presence of 315 newly identified RNA viruses in nine viral families or orders (Durnavirales, Totiviridae, Bunyavirales, Hantaviridae, Picornavirales, Flaviviridae, Hepelivirales, SolemoviridaeandTombusviridae), with most of them are sufficiently divergent to the documented viruses. With special notice that we first time revealed an ocean virus rooting to mammalian hantaviruses. We also found evidence for possible host sharing and switch events during virus evolution. In sum, we demonstrated the hidden diversity of marine invertebrate RNA viruses.
Three bacterium-plasmid golden combinations facilitate the spread of ST11/CG258 carbapenemase-producingKlebsiella pneumoniaein China
Authors: Li Cuidan , Jiang Xiaoyuan , Yang Tingting , Ju Yingjiao , Yin Zhe , Yue Liya , Ma Guanan , Wang Xuebing , Jing Ying , Luo Xinhua , Li Shuangshuang , Yang Xue , Chen Fei , Zhou Dongsheng 
Published: April 2021

AbstractCarbapenemase-producingKlebsiella pneumoniae(cpKP) poses serious threats to public health. Previous studies showed that only ST11/CG258-cpKP successfully disseminated in China, however, the underlying genetic bases are still unknown. We conducted a comprehensive genomic-epidemiology analysis on 420 cpKP isolates from 70 hospitals in 24 Chinese provinces during 2009-2017 based on short-/long-reads sequencing. Three ‘golden’ combinations of host––blaKPC-carrying plasmids (Clade 3.1+3.2—IncFIIpHN7A8, Clade 3.1+3.2—IncFIIpHN7A8:IncR, Clade 3.3—IncFIIpHN7A8:IncpA1763-KPC) endowed cpKP with advantages both in genotypes (strong-correlation/co-evolution) and phenotypes (resistance/growth/competition), thereby facilitating nationwide spread of ST11/CG258-cpKP. Intriguingly, Bayesian skyline illustrated that the three ‘golden’ combinations might directly lead to the strong population expansion during 2007-2008 and subsequent maintenance of the dissemination of ST11/CG258-cpKP after 2008. We tested drug-resistance profiles and proposed combination treatment regimens for CG258/non-CG258 cpKP. Our findings systematically revealed the molecular-epidemiology and genetic-basis for dissemination of Chinese ST11/CG258 cpKP and reminded us to monitor the ‘golden’ combinations of cpKP- plasmid closely.
Mapping the biogenesis of forward programmed megakaryocytes from induced pluripotent stem cells
Authors: Lawrence Moyra , Shahsavari Arash , Bornelöv Susanne , Moreau Thomas , Kania Katarzyna , Paramor Maike , McDonald Rebecca , Baye James , Perrin Marion , Steindel Maike , Jimenez-Gomez Paula , Penfold Christopher , Mohorianu Irina , Ghevaert Cedric 
Published: April 2021

SummaryPlatelet deficiency, known as thrombocytopenia, can cause haemorrhage and is treated with platelet transfusions. We developed a system for the production of platelet precursor cells, megakaryocytes, from pluripotent stem cells. These cultures can be maintained for >100 days, implying culture renewal by megakaryocyte progenitors (MKPs). However, it is unclear whether the MKP statein vitromirrors the statein vivo, and MKPs cannot be purified using conventional surface markers. We performed single cell RNA sequencing throughoutin vitrodifferentiation and mapped each state to its equivalentin vivo. This enabled the identification of 5 surface markers which reproducibly purify MKPs, allowing us an insight into their transcriptional and epigenetic profiles. Finally, we performed culture optimisation, increasing MKP production. Altogether, this study has mapped parallels between the MKP statesin vivoandin vitroand allowed the purification of MKPs, accelerating the progress ofin vitro-derived transfusion products towards the clinic.
Evolutionary rates of testes-expressed genes differ in monogamous and promiscuousPeromyscusspecies
Authors: Gozashti Landen , Corbett-Detig Russell , Roy Scott W. 
Published: April 2021

AbstractReproductive proteins, including those expressed in the testes, are among the fastest evolving proteins across the tree of life. Sexual selection on traits involved in sperm competition is thought to be a primary driver of testes gene evolution and is expected to differ between promiscuous and monogamous species due to intense competition between males to fertilize females in promiscuous lineages and lack thereof in monogamous ones. Here, we employ the rodent genusPeromyscusas a model to explore differences in evolutionary rates between testes-expressed genes in monogamous and promiscuous species. We find candidate genes that may be associated with increased sperm production in promiscuous species and gene ontology categories that show patterns of molecular convergence associated with phenotypic convergence in independently evolved monogamous species. Overall, our results highlight the possible molecular consequences of differences in mating system, likely due to differences in selective pressures.
No evidence that HLA genotype influences the driver mutations that occur in cancer patients
Authors: Kherreh Noor , Cleary Siobhán , Seoighe Cathal 
Published: April 2021

AbstractThe major histocompatibility (MHC) molecules are capable of presenting neoantigens resulting from somatic mutations on cell surfaces, potentially directing immune responses against cancer. This led to the hypothesis that cancer driver mutations may occur in gaps in the capacity to present neoantigens that are dependent on MHC genotype. If this is correct, it has important implications for understanding oncogenesis and may help to predict driver mutations based on genotype data. In support of this hypothesis, it has been reported that driver mutations that occur frequently tend to be poorly presented by common MHC alleles and that the capacity of a patient’s MHC alleles to present the resulting neoantigens is predictive of the driver mutations that are observed in their tumour. Here we show that these reports of a strong relationship between driver mutation occurrence and patient MHC alleles are a consequence of unjustified statistical assumptions. Our reanalysis of the data provides no evidence of an effect of MHC genotype on the oncogenic mutation landscape.