bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 neutralising antibody activity in a highly vaccinated population: Longitudinal serology studies in Singapore
Authors: Clapham Hannah E , Chia Wanni , Zhang Jinyan , Wang Lin-Fa , Tam Clarence C 
Published: May 2022

AbstractBackgroundThere is continuing uncertainty regarding the longevity of immunological responses to both SARS-CoV-2 natural infection and COVID-19 vaccines.MethodsWe analysed data from two serological cohorts in Singapore among residents of a COVID-19 affected migrant worker dormitory between May-July 2020, and among mRNA COVID-19 vaccine recipients between May 2021 and January 2022. We compared SARS-CoV-2 neutralising antibody levels by age group, sex, presence of pre-existing medical conditions, type of mRNA vaccine received and number of doses received. We investigated the effect of time since infection or vaccination on antibody levels in naturally infected individuals and two- and three-dose vaccinees.ResultsAfter two vaccine doses, neutralising antibody responses were higher in Spikevax (Moderna) recipients, females, younger individuals and those with no underlying medical conditions. However, antibody levels waned to similar levels in all groups over time. A third dose boosted these to similarly high levels in all groups. Waning was apparent among two-dose but not three-dose recipients over a period of six months. Both two and three-dose vaccine recipients showed consistently higher neutralising antibody levels compared with naturally infected individuals over the 12-week period following infection or vaccination.ConclusionsOur findings support the broad use of booster doses to improve population protection from COVID-19. However, recent increases in transmission of new SARS-CoV-2 variants, even in the presence of high levels of neutralising antibody in a highly vaccinated population, point to vaccine breakthrough as an important mechanism for maintaining SARS-CoV-2 circulation and indicate the need for variant-specific or universal COVID-19 vaccines.SummaryYounger individuals, females and those with no pre-existing conditions have higher neutralising antibody levels after two doses of COVID-19 mRNA vaccine. Subsequently these wane to levels seen in other groups. A booster dose promotes similarly high levels in all groups.
Single cell RNA-seq by mostly-natural sequencing by synthesis
Authors: Simmons Sean K. , Lithwick-Yanai Gila , Adiconis Xian , Oberstrass Florian , Iremadze Nika , Geiger-Schuller Kathryn , Thakore Pratiksha I. , Frangieh Chris J. , Barad Omer , Almogy Gilad , Rozenblatt-Rosen Orit , Regev Aviv , Lipson Doron , Levin Joshua Z. 
Published: May 2022

AbstractMassively parallel single cell RNA-seq (scRNA-seq) for diverse applications, from cell atlases to functional screens, is increasingly limited by sequencing costs, and large-scale low-cost sequencing can open many additional applications, including patient diagnostics and drug screens. Here, we adapted and systematically benchmarked a newly developed, mostly-natural sequencing by synthesis method for scRNA-seq. We demonstrate successful application in four scRNA-seq case studies of different technical and biological types, including 5’ and 3’ scRNA-seq, human peripheral blood mononuclear cells from a single individual and in multiplex, as well as Perturb-Seq. Our data show comparable results to existing technology, including compatibility with state-of-the-art scRNA-seq libraries independent of the sequencing technology used – thus providing an enhanced cost-effective path for large scale scRNA-seq.
Lack of ITS sequence homogenization in congeneric plant species with different ploidy levels
Authors: Osuna-Mascaró Carolina , de Casas Rafael Rubio , Berbel Modesto , Gómez José M. , Perfectti Francisco 
Published: May 2022

AbstractThe internal transcribed spacers (ITS) exhibit concerted evolution by the fast homogenization of these sequences at the intragenomic level. However, the rate and extension of this process are unclear and might be conditioned by the number and divergence of the different ITS copies. In some cases, such as hybrid species and polyploids, ITS sequence homogenization appears incomplete, resulting in multiple haplotypes within the same organism. Here, we studied the dynamics of concerted evolution in 85 individuals of seven plant species of the genus Erysimum (Brassicaceae) with multiple ploidy levels. We estimated the rate of concerted evolution and the degree of sequence homogenization separately for ITS1 and ITS2 and whether these varied with ploidy. Our results showed incomplete sequence homogenization, especially for polyploid samples, indicating a lack of concerted evolution in these taxa. Homogenization was usually higher in ITS2 than in ITS1, suggesting that concerted evolution operates more efficiently on the former. Furthermore, the hybrid origin of several species appears to contribute to the maintenance of high haplotype diversity, regardless of the level of ploidy. These findings indicate that sequence homogenization of ITS is a dynamic and complex process that might result in varying intra- and inter-genomic diversity levels.
Genomics for reproduction in Anas platyrynchos-a novel report
Authors: Debnath Manti , Pal Aruna , Chakraborty Argha , Pal Subhomoy , Pal Abantika 
Published: May 2022

AbstractAnas platyrynchos (ducks) are reared mostly for egg, which are very nutritious, that fetch better prices, however duck meat possess rich nutrient content. They possess the unique characteristics of disease resistance to the common avian diseases, even asymptomatic to avian influenza, with a scopeto evolve as one of the best poultry species The major limitation encountered is the lowered average egg production as well as higher age at first egg (an indicator for sexual maturity) for the indigenous ducks compared to that of exotic ones. In this current study, we attempt to explore the genes responsible for duck reproduction in terms of sexual maturity,egg production and fertility of the ducks. We had compared the genomic constitution for the Bengal duck with highest egg production with that of non-layer (infertile or sexually immature) ducks. We characterized the genes in indigenous ducks from ovarian tissues, identified important domains for characterized genes for the first time, and studied differential mRNA expression profiling for these genes with respect to layer and non-layer groups. Upregulation was observed for ESR2, DIAPH2, KMT2E, ASCF2 genes for Bengal duck in highest egg producing duck in comparison to non-layer duck, whereas downregulation was observed for KSR1, A2M, BMPR1B, ACVR1. In the next step, we explored the association with the genes which were actually responsible for egg production. Thus, duck may be utilized as a model for studying the molecular aspect of reproduction. Genes upregulated may be utilized forknock inof gene, whereas down regulated genes may beknocked outorknocked downthrough gene editing technologies for the improvement of reproductive performance of the duck in future. Molecular biomarkers may be developed with these genes for early selection of better reproducing ducks at day of hatch or even earlier.
Respiratory mucosal vaccination of peptide-poloxamine-DNA nanoparticles provides complete protection against lethal SARS-CoV-2 challenge
Authors: Sun Si , Li Entao , Zhao Gan , Tang Jie , Zuo Qianfei , Cai Larry , Xu Chuanfei , Sui Cheng , Ou Yangxue , Liu Chang , Li Haibo , Ding Yuan , Li Chao , Lu Dongshui , Zhang Weijun , Luo Ping , Cheng Ping , Gao Yuwei , Tu Changchun , Pitard Bruno , Rosenecker Joseph , Wang Bin , Liu Yan , Zou Quanming , Guan Shan 
Published: May 2022

AbstractThe ongoing SARS-CoV-2 pandemic represents a brutal reminder of the continual threat of mucosal infectious diseases. Mucosal immunity may provide robust protection at the predominant sites of SARS-CoV-2 infection. However, it remains unclear whether respiratory mucosal administration of DNA vaccines could confer protective immune responses against SARS-CoV-2 challenge due to the insurmountable barriers posed by the airway. Here, we applied self-assembled peptide-poloxamine nanoparticles with mucus-penetrating properties for pulmonary inoculation of a COVID-19 DNA vaccine (pSpike/PP-sNp). Not only displays the pSpike/PP-sNp superior gene-transfection and favorable biocompatibility in the mouse airway, but pSpike/PP-sNp promotes a tripartite immunity consisting of systemic, cellular and mucosal immune responses that are characterized by mucosal IgA secretion, high levels of neutralizing antibodies, and resident memory phenotype T-cell responses in the lungs of mice. Most importantly, pSpike/PP-sNp completely eliminates SARS-CoV-2 infection in both upper and lower respiratory tracts and enables 100% survival rate of mice following lethal SARS-CoV-2 challenge. Our findings indicate PP-sNp might be a promising platform in mediating DNA vaccines to elicit all-around mucosal immunity against SARS-CoV-2.
Arabidopsis thaliana induces multigenerational stress tolerance against biotic and abiotic stressors and memorization of host colonization in Bacillus subtilis
Authors: Gilhar Omri , Olender Tsviya , Aharoni Asaph , Friedman Jonathan , Kolodkin-Gal Ilana 
Published: May 2022

AbstractBacillus subtilis is a beneficial bacterium that supports plant growth and protects it from bacterial, fungal, and viral infections. Here using a simplified system of B. subtilis, and Arabidopsis thaliana interactions, we found that history-dependent behavior is a potentially important manifestation of host colonization, worth classifying and quantifying. To study history-dependent adaptation to plant hosts, we develop a simple framework for measuring the physiological memory of B. subtilis following its interaction with Arabidopsis thaliana. We found that A. thaliana secretions reduce the lag time in pre-exposed bacteria compared with naïve B. subtilis cells, even after their complete removal. Pre-exposed B. subtilis cells colonized plant roots more efficiently than naïve bacteria, and were more resistant to biotic and abiotic stressors such as salicylic acid, and high salinity. Descendants of bacteria treated with plant secretions had an advantage in the competition against unexposed bacteria for root colonization. The effect of plant secretions was independent of their roles as nitrogen and carbon sources. Transcriptome analysis of both ancestors and descendants revealed that a specific set of plant-induced processes, among them c-di-AMP homeostasis, and the general stress response, maintain the signature of association with the plant in descendants of pre-exposed bacteria. Consistently, plant secretions compensated for the loss of c-di-AMP cyclases but required the general stress response and the master regulator Spo0A to exert their short and long-term effects.Overall, our work demonstrates that bacterial memory manifested by multigenerational reversible adaptation to plant hosts confirms an advantage to symbiotic bacteria during competition.
Age and cognitive load affect muscle activation profiles in response to physical perturbations while walking
Authors: Rosenblum Uri , Melzer Itshak , Friger Michael , Zeilig Gabi , Plotnik Meir 
Published: May 2022

AbstractTo maintain balance during walking, the central nervous system must adjust the base of support (i.e., modulation of step length and step width) to the center of mass displacement in every step. We aimed to explore age and concurrent cognitive attention-demanding task effects on lower limb muscle fiber type recruitment in response to unexpected loss of balance during walking i.e., perturbation. Twenty young (YA) and 18 older adults (OA), (27.00±2.79 and 70.13±3.95 years old, respectively) were exposed to unexpected perturbations, while walking on a treadmill, in virtual reality environment. Surface electromyography (sEMG) total spectral power for frequency bands associated with muscle fibers type I (40-60Hz), type IIa (60-150Hz) and type IIb (150-250Hz), from tibialis-anterior and vastus-lateralis muscles were analyzed. Four Generalized Estimating Equations models assessed age and cognitive attention-demanding task’s load association with lower-limb muscle activation patterns resulting from perturbation in single- and double-support phases of the gait cycle. Results show that OA employ a muscle fiber type IIa dominant increase strategy while YA show muscle fiber type IIb dominant increase in muscle fiber type recruitment in response to unexpected perturbations during walking. This suggests that the ability to recruit fast-twitch muscle fibers is deteriorated with age and thus may be related to insufficient balance recovery response.
A dual role for CRTH2 in acute lung injury
Authors: Bhattacharya Shreya , Ristic Nick , Cohen Avi J. , Tsang Derek , Gwin Meredith S. , Howell Rebecca , Young Grant M. , Jung Eric , Dela Cruz Charles S. , Gautam Samir 
Published: May 2022

ABSTRACTAcute respiratory distress syndrome (ARDS) is a life-threatening clinical condition defined by rapid-onset respiratory failure following acute lung injury (ALI). The high mortality rate and rising incidence of ARDS due to COVID-19 make it an important research priority. Here we sought to investigate the role of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) in ARDS. CRTH2 is a G protein-coupled receptor best studied in the context of type 2 immunity, but it also exerts effects on neutrophilic inflammation. To evaluate its role in mouse models of ARDS, we first examined its expression pattern on murine neutrophils. We found it is expressed on neutrophils, but only after extravasation into the lung. Next, we showed that CRTH2 expression on extravasated lung neutrophils promotes cell survival, as genetic deletion of CRTH2 and pharmacologic inhibition of CRTH2 using fevipiprant both led to increased apoptosis in vitro. We then evaluated the role of CRTH2 in vivo using a murine model of LPS-induced ALI. In line with the pro-inflammatory effects of CRTH2 in vitro, we observed improvement of lung injury in CRTH2-deficient mice in terms of vascular leak, weight loss and survival after LPS administration. However, neutrophilic inflammation was elevated, not suppressed in the CRTH2 KO. This finding indicated a second mechanism offsetting the pro-survival effect of CRTH2 on neutrophils. Bulk RNAseq of lung tissue indicated impairments in type 2 immune signaling in the CRTH2 KO, and qPCR and ELISA confirmed downregulation of IL-4, which is known to suppress neutrophilic inflammation. Thus, CRTH2 may play a dual role in ALI, directly promoting neutrophil cell survival, but indirectly suppressing neutrophil effector function via IL-4.
Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform
Authors: Almogy Gilad , Pratt Mark , Oberstrass Florian , Lee Linda , Mazur Dan , Beckett Nate , Barad Omer , Soifer Ilya , Perelman Eddie , Etzioni Yoav , Sosa Martin , Jung April , Clark Tyson , Trepagnier Eliane , Lithwick-Yanai Gila , Pollock Sarah , Hornung Gil , Levy Maya , Coole Matthew , Howd Tom , Shand Megan , Farjoun Yossi , Emery James , Hall Giles , Lee Samuel , Sato Takuto , Magner Ricky , Low Sophie , Bernier Andrew , Gandi Bharathi , Stohlman Jack , Nolet Corey , Donovan Siobhan , Blumenstiel Brendan , Cipicchio Michelle , Dodge Sheila , Banks Eric , Lennon Niall , Gabriel Stacey , Lipson Doron 
Published: May 2022

AbstractWe introduce a massively parallel novel sequencing platform that combines an open flow cell design on a circular wafer with a large surface area and mostly natural nucleotides that allow optical end-point detection without reversible terminators. This platform enables sequencing billions of reads with longer read length (∼300bp) and fast runs times (<20hrs) with high base accuracy (Q30 > 85%), at a low cost of $1/Gb. We establish system performance by whole-genome sequencing of the Genome-In-A-Bottle reference samples HG001-7, demonstrating high accuracy for SNPs (99.6%) and Indels in homopolymers up to length 10 (96.4%) across the vast majority (>98%) of the defined high-confidence regions of these samples. We demonstrate scalability of the whole-genome sequencing workflow by sequencing an additional 224 selected samples from the 1000 Genomes project achieving high concordance with reference data.
Uncovering Hidden Enhancers Through Unbiased In Vivo Testing
Authors: Mannion Brandon J. , Osterwalder Marco , Tran Stella , Plajzer-Frick Ingrid , Novak Catherine S. , Afzal Veena , Akiyama Jennifer A. , Barton Sarah , Beckman Erik , Garvin Tyler H. , Godfrey Patrick , Godoy Janeth , Hunter Riana D. , Kato Momoe , Kosicki Michal , Kronshage Anne N. , Lee Elizabeth A. , Meky Eman M. , Pham Quan T. , Maydell Kianna von , Zhu Yiwen , Lopez-Rios Javier , Dickel Diane E. , Visel Axel , Pennacchio Len A. 
Published: May 2022

AbstractTranscriptional enhancers are a predominant class of noncoding regulatory elements that activate cell type-specific gene expression. Tissue-specific enhancer-associated chromatin signatures have proven useful to identify candidate enhancer elements at a genome-wide scale, but their sensitivity for the comprehensive detection of all enhancers active in a given tissue in vivo remains unclear. Here we show that a substantial proportion of in vivo enhancers are hidden from discovery by conventional chromatin profiling methods. In an initial comparison of over 1,200 in vivo validated tissue-specific enhancers with tissue-matched mouse developmental epigenome data, 14% (n=286) of active enhancers did not show canonical enhancer-associated chromatin signatures in the tissue in which they are active. To assess the prevalence of enhancers not detectable by conventional chromatin profiling approaches in more detail, we used a high throughput transgenic enhancer reporter assay to systematically screen over 1.3 Mb of mouse genomic sequence at two critical developmental loci, assessing a total of 281 consecutive 5kb regions for in vivo enhancer activity in mouse embryos. We observed reproducible enhancer-reporter activity in 88 tissue-specific elements, 26% of which did not show canonical enhancer-associated chromatin signatures in the corresponding tissues. Overall, we find these hidden enhancers are indistinguishable from marked enhancers based on levels of evolutionary conservation, enrichment of transcription factor families, and genomic positioning relative to putative target genes. In combination, our retrospective and prospective studies assessed only 0.1% of the mouse genome and identified 309 tissue-specific enhancers that are hidden from current chromatin-based enhancer identification approaches. Our findings suggest the existence of tens of thousands of active enhancers throughout the genome that remain undetected by current chromatin profiling approaches and are an unappreciated source of additional genome function of import in interpreting growing whole human genome sequencing data.
Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection
Authors: VanDyke Derek , Iglesias Marcos , Tomala Jakub , Young Arabella , Smith Jennifer , Perry Joseph A. , Gebara Edward , Cross Amy R. , Cheung Laurene S. , Dykema Arbor G. , Orcutt-Jahns Brian T. , Henclová Tereza , Golias Jaroslav , Balolong Jared , Tomasovic Luke M. , Funda David , Meyer Aaron S. , Pardoll Drew M. , Hester Joanna , Issa Fadi , Hunter Christopher A. , Anderson Mark S. , Bluestone Jeffrey A. , Raimondi Giorgio , Spangler Jamie B 
Published: May 2022

SummaryLow dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due to the cytokine’s preferential expansion of immunosuppressive regulatory T cells (TRegs). However, high toxicity, short serum half-life, and off-target immune cell activation limit the clinical potential of IL-2 treatment. Recent work showed that complexes comprising hIL-2 and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating TRegs over immune effector cells. Although promising, therapeutic translation of this approach is complicated by the need to optimize dosing ratios and by the instability of the cytokine/antibody complex. We leveraged structural insights to engineer a single-chain hIL-2/F5111 antibody fusion protein, termed F5111 immunocytokine (IC), that potently and selectively activates and expands TRegs. F5111 IC conferred protection in mouse models of colitis and checkpoint inhibitor-induced diabetes mellitus. These results provide a roadmap for IC design and establish a TReg-biased immunotherapy that could be clinically translated for autoimmune disease treatment.
Topography of mutational signatures in human cancer
Authors: Otlu Burcak , Díaz-Gay Marcos , Vermes Ian , Bergstrom Erik N , Zhivagui Maria , Barnes Mark , Alexandrov Ludmil B. 
Published: May 2022

SUMMARYThe somatic mutations found in a cancer genome are imprinted by different mutational processes. Each process exhibits a characteristic mutational signature, which can be affected by the genome architecture. However, the interplay between mutational signatures and topographical genomic features has not been extensively explored. Here, we integrate mutations from 5,120 whole-genome sequenced tumours from 40 cancer types with 516 topographical features from ENCODE to evaluate the effect of nucleosome occupancy, histone modifications, CTCF binding, replication timing, and transcription/replication strand asymmetries on the cancer-specific accumulation of mutations from distinct mutagenic processes. Most mutational signatures are affected by topographical features with signatures of related aetiologies being similarly affected. Certain signatures exhibit periodic behaviours or cancer-type specific enrichments/depletions near topographical features, revealing further information about the processes that imprinted them. Our findings, disseminated via COSMIC, provide a comprehensive online resource for exploring the interactions between mutational signatures and topographical features across human cancer.GRAPHICAL ABSTRACTHIGHLIGHTSComprehensive topography analysis of mutational signatures encompassing 82,890,857 somatic mutations in 5,120 whole-genome sequenced tumours integrated with 516 tissue-matched topographical features from the ENCODE project.The accumulation of somatic mutations from most mutational signatures is affected by nucleosome occupancy, histone modifications, CTCF binding sites, transcribed regions, or replication strand/timing.Mutational signatures with related aetiologies are consistently characterized by similar genome topographies across tissue types.Topography analysis allows both separating signatures from different aetiologies and understanding the genomic specificity of clustered somatic mutations.A comprehensive online resource, disseminate through the COSMIC signatures database, that allows researchers to explore the interactions between somatic mutational processes and genome architecture within and across cancer types.