bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainty stress, and its impact on disease fear and prevention behaviors during the COVID-19 epidemic in China: A panel study
Authors: Yang Xiaozhao Yousef , Peng Sihui , Yang Tingzhong , Zhang Weifang , Wang Huihui , Cottrell Randall R 
Published: June 2020

AbstractObjectiveTo examine changing trends of uncertainty stress, and its impact on disease fear and prevention behaviors during the Chinese COVID-19 epidemic using a prospective observational study.MethodsThe study employed a longitudinal design. Participants were recruited for an online panel survey from chat groups on social media platforms. There were 5 waves of interviews. Information on uncertainty stress and related variables were collected via the online survey. Descriptive statistics and the GIM program were used for data analysis.ResultsParticipants numbered 150 for the linkable baseline survey and 102 (68%) for the final survey. Uncertainty stress(β: -0.047, S.E: 0.118, p>0.05) did not show a statistically significant temporal change trend over the observation period. Disease fear manifested a statistically significant downwards trend (β: -0.342, S.E: 0.157, p<0.05), and prevention behaviors indicated an upwards trend (β: 0.048, S.E: 0.021, p<0.05) during the observation period. Uncertainty stress was positively associated with disease fear (β: 0.45046, S.E: 0.05964, p<0.0001), and negatively associated with self-efficacy (β: -0.6698, S.E: 0.01035, p<0.0001), and prevention behaviors (β:-0.02029, S.E: 0.00876, p: 0.0209).ConclusionThis study yielded new information about uncertainty stress among Chinese people during the COVID-19 epidemic. Policy changes and public education are essential for minimizing the negative effects of uncertainty stress in disease prevention.
Human papillomavirus type 16 sub-lineages and integration in cancer
Authors: Jackson Robert , Ortigas-Vásquez Alejandro , Zehbe Ingeborg 
Published: June 2020

ABSTRACTOur lab has been intrigued by the fact that viral genomes often take on the role of mobile elements to perpetuate their existence in a complex organism’s genome. Multiple DNA viruses such as Epstein-Barr virus, hepatitis B virus, and human papillomavirus (HPV) can invade their host genome, as “genomic parasites”. We have been investigating HPV type 16 (HPV16), which is a prominent human tumour virus. In our recentin vitrowork using 3D organoids, a common variant of HPV16’s coding region elicited early integration into the host genome compared to the HPV16 prototype sequence. Next-generation sequencing (NGS) data confirmed a transcriptomic profile of increased proliferation and chromosomal instability—both hallmarks of cancer. Epidemiologically, this variant is associated with a high cervical cancer incidence. To take inquiries a step further, we investigated variant-specific integration across HPV16-related cancers using NGS data from population-derived clinical samples in The Cancer Genome Atlas (TCGA)-curated database. Data were analyzed for HPV16 positivity, sub-lineage, and viral-host integration using a bioinformatic pipeline of open-source tools, including HPVDetector. Here, we report the analysis of 120 cervical cancer cases comprising HPV16 positive and negative samples as well as their different sub-lineage and integration status. The integration signature between variant and prototype did not differ quantitatively but qualitatively: that of the variant being related to hypoxia/energetics (Warburg effect) and that of the prototype being much more varied to include host immune abrogation and cancer pathways activation. We conclude by discussing challenges and future directions for expanding these analyses.
S-IRFindeR: stable and accurate measurement of intron retention
Authors: Broseus Lucile , Ritchie William 
Published: June 2020

AbstractAccurate quantification of intron retention levels is currently the crux for detecting and interpreting the function of retained introns. Using both simulated and real RNA-seq datasets, we show that current methods suffer from several biases and artefacts, which impair the analysis of intron retention. We designed a new approach to measure intron retention levels called the Stable Intron Retention ratio that we have implemented in a novel algorithm to detect and measure intron retention called S-IRFindeR. We demonstrate that it provides a significant improvement in accuracy, higher consistency between replicates and agreement with IR-levels computed from long-read sequencing data.S-IRFindeR is freely available at:https://github.com/lbroseus/SIRFindeR/.
Novel PE and APC Tandems: Additional Near-Infrared Fluorochromes for Use in Spectral Flow Cytometry
Authors: Seong Yekyung , Wu Yian , Nguyen Denny , Thakur Archana , Nguyen Tuan Andrew , Harding Fiona 
Published: June 2020

ABSTRACTRecent advances in flow cytometry instrumentation and fluorochrome chemistries have greatly increased fluorescent conjugated antibody combinations that can be used reliably and easily in routine experiments. The Cytek Aurora flow cytometer has three excitation lasers (405nm, 488nm, and 640nm) and incorporates the latest Avalanche Photodiode (APD) technology, demonstrating significant improvement in sensitivity for fluorescent emission signals longer than 800nm. However, there are limited commercially available fluorochromes capable of excitation with peak emission signals beyond 800nm. To address this gap, we engineered 6 new fluorochromes: PE-750, PE-800, PE-830 for the 488nm laser and APC-750, APC-800, APC-830 for the 640nm laser. Utilizing the principal of fluorescence resonance energy transfer (FRET), these novel structures were created by covalently linking a protein donor dye with an organic small molecule acceptor dye. Additionally, each of these fluorochrome conjugates were shown to be compatible with Fixation/Permeabilization buffer reagents, and demonstrated acceptable brightness and stability when conjugated to antigen-specific monoclonal antibodies. These six novel fluorochrome reagents can increase the numbers of fluorochromes that can be used on a 3-laser spectral flow cytometer.
NRF-1 and HIF-1α modulate activity of human VDAC1 gene promoter during starvation and hypoxia in HeLa cells
Authors: Guarino Francesca , Zinghirino Federica , Mela Lia , Pappalardo Xena , Messina Angela , De Pinto Vito 
Published: June 2020

AbstractVDAC (Voltage Dependent Anion Channel) is a family of pore forming protein located in the outer mitochondrial membrane. Its channel property ensures metabolites exchange between mitochondria and the rest of the cell resulting in metabolism and bioenergetics regulation, and in cell death and life switch. VDAC1 is the best characterized and most abundant isoform, and is involved in many pathologies, as cancer or neurodegenerative diseases. However, little information is available about its gene expression regulation in normal and/or pathological conditions. In this work, we explored VDAC1 gene expression regulation in normal conditions and in the contest of metabolic and energetic mitochondrial dysfunction and cell stress. The most active area of the putative promoter region was characterized in terms of transcription factors responsive elements both by bioinformatic studies and promoter activity experiments. In particular, we found a predominant presence of NRF-1 together with other transcription factors binding sites, involved in cell growth, proliferation, development and we studied their prevalence in gene activity. Furthermore, upon depletion of nutrients or controlled hypoxia, as reported in various pathologies, we found that VDAC1 transcripts levels were significantly increased in a time related manner. VDAC1 promoter activity was also validated by gene reporter assays. According to PCR real-time data, it was confirmed that VDAC1 promoter activity is further stimulated when are exposed to stress. A bioinformatic survey suggested NRF-1 e HIF-1α as the most active TFBS. Their validation was obtained by mutagenesis and overexpression experiments. In conclusion, we demonstrated experimentally the involvement of both NRF-1 and HIF-1α in the regulation of VDAC1 promoter activation at basal level and in cell stress conditions.
Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease
Authors: Audain E , Wilsdon A , Breckpot J , Izarzugaza JMG , Fitzgerald TW , Kahlert AK , Sifrim A , Wünnemann F , Perez-Riverol Y , Abdul-Khaliq H , Bak M , Bassett AS , Belmont JW , Benson DW , Berger F , Daehnert I , Devriendt K , Dittrich S , Daubeney P , Garg V , Hackmann K , Hoff K , Hofmann P , Dombrowsky G , Pickardt T , Bauer U , Keavney BD , Klaassen S , Kramer HH , Marshall CR , Milewicz DM , Lemaire SA , Coselli J , Mitchell ME , Tomita-Mitchell A , Prakash SK , Stamm K , Stewart AFR , Silversides CK , Siebert R , Stiller B , Rosenfeld JA , Vater I , Postma AV , Caliebe A , Brook JD , Andelfinger G , Hurles ME , Thienpont B , Larsen LA , Hitz MP 
Published: June 2020

AbstractCongenital Heart Disease (CHD) affects approximately 7-9 children per 1000 live births. Numerous genetic studies have established a role for rare genomic variants at the copy number variation (CNV) and single nucleotide variant level. In particular, the role ofde novomutations (DNM) has been highlighted in syndromic and non-syndromic CHD. To identify novel haploinsufficient CHD disease genes we performed an integrative analysis of CNVs and DNMs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm (TAA). We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed mutation rate testing for DNMs identified in 2,489 parent-offspring trios. Our combined analysis revealed 21 genes which were significantly affected by rare genomic deletions and/or constrained non-synonymousde novomutations in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5BandWHSC1) have only been associated in singletons and small cases series, or show new associations with CHD. In addition, a systems level analysis revealed shared contribution of CNV deletions and DNMs in CHD probands, affecting protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes.
Sex-linked gene expression and the reversion to hermaphroditism inCarica papayaL. (Caricaceae)
Authors: Chae T , Harkess A , Moore RC 
Published: June 2020

ABSTRACTOne evolutionary path from hermaphroditism to dioecy is via a gynodioecious intermediate. The evolution of dioecy may also coincide with the formation of sex chromosomes that possess sex-determining loci that are physically linked in a region of suppressed recombination. Dioecious papaya (Carica papaya) has an XY chromosome system, where the presence of a Y chromosome determines males. However, in cultivation, papaya is gynodioecious, due to the conversion of the male Y chromosome to a hermaphroditic Yhchromosome during its domestication. We investigated gene expression linked to the X, Y, and Yhchromosomes at different floral developmental stages in order to identify differentially expressed genes (DEGs) that may be involved in the sexual reversion of males to hermaphrodites. We identified 309 sex-biased genes found on the sex chromosomes, most of which are found in the pseudoautosomal regions (PARs). Female (XX) expression in the sex determining region (SDR) was almost double that of X-linked expression in males (XY) and hermaphrodites (XYh), which rules out dosage compensation for most sex-linked gene; although, an analysis of hemizygous X-linked loci found evidence of partial dosage compensation. Furthermore, we identified a potential candidate gene associated with both sex determination and the transition to hermaphroditism, a homolog of the MADS-box proteinSHORT VEGETATIVE PHASE(SVG).
A new method for counting reproductive structures in digitized herbarium specimens using Mask R-CNN
Authors: Davis Charles , Champ Julien , Park Daniel S. , Breckheimer Ian , Lyra Goia M. , Xie Junxi , Joly Alexis , Tarapore Dharmesh , Ellison Aaron M. , Bonnet Pierre 
Published: June 2020

AbstractPhenology–the timing of life-history events–is a key trait for understanding responses of organisms to climate. The digitization and online mobilization of herbarium specimens is rapidly advancing our understanding of plant phenological response to climate and climatic change. The current practice of manually harvesting data from individual specimens, however, greatly restricts our ability to scale-up data collection. Recent investigations have demonstrated that machine-learning approaches can facilitate this effort. However, present attempts have focused largely on simplistic binary coding of reproductive phenology (e.g., presence/absence of flowers). Here, we use crowd-sourced phenological data of buds, flowers, and fruits from>3000 specimens of six common wildflower species of the eastern United States (Anemone canadensisL.,A. hepaticaL.,A. quinquefoliaL.,Trillium erectumL.,T. grandiflorum(Michx.) Salisb., andT. undulatumWild.) to train models using Mask R-CNN to segment and count phenological features. A single global model was able to automate the binary coding of each of the three reproductive stages with>87% accuracy. We also successfully estimated the relative abundance of each reproductive structure on a specimen with ≥ 90% accuracy. Precise counting of features was also successful, but accuracy varied with phenological stage and taxon. Specifically, counting flowers was significantly less accurate than buds or fruits likely due to their morphological variability on pressed specimens. Moreover, our Mask R-CNN model provided more reliable data than non-expert crowd-sourcers but not botanical experts, highlighting the importance of high-quality human training data. Finally, we also demonstrated the transferability of our model to automated phenophase detection and counting of the threeTrilliumspecies, which have large and conspicuously-shaped reproductive organs. These results highlight the promise of our two-phase crowd-sourcing and machine-learning pipeline to segment and count reproductive features of herbarium specimens, thus providing high-quality data with which to investigate plant response to ongoing climatic change.
The causal role of three frontal cortical areas in grasping
Authors: Caprara I , Janssen P 
Published: June 2020

AbstractEfficient object grasping requires the continuous control of arm and hand movements based on visual information. Previous studies have identified a network of parietal and frontal areas that is crucial for the visual control of prehension movements. Electrical microstimulation of 3D shape-selective clusters in AIP during fMRI activates areas F5a and 45B, suggesting that these frontal areas may represent important downstream areas for object processing during grasping, but the role of area F5a and 45B in grasping is unknown. To assess their causal role in the frontal grasping network, we reversibly inactivated 45B, F5a and F5p during visually-guided grasping in macaque monkeys. First, we recorded single neuron activity in 45B, F5a and F5p to identify sites with object responses during grasping. Then, we injected muscimol or saline to measure the grasping deficit induced by the temporary disruption of each of these three nodes in the grasping network. The inactivation of all three areas resulted in a significant increase in the grasping time in both animals, with the strongest effect observed in area F5p. These results not only confirm a clear involvement of F5p, but also indicate causal contributions of area F5a and 45B in visually-guided object grasping.
Whole genomes reveal severe bottleneck among Asian hunter-gatherers following the invention of agriculture
Authors: Chakraborty Saikat , Basu Analabha ,   the GenomeAsia 100K Consortium
Published: June 2020

AbstractThe invention of agriculture (IOA) by anatomically modern humans (AMH) around 10,000 years before present (ybp) is known to have led to an increase in AMH’s carrying capacity and hence its population size. Reconstruction of historical demography using high coverage (~30X) whole genome sequences (WGS) from >700 individuals from different South Asian (SAS) and Southeast Asian (SEA) populations reveals that although several present day populous groups did indeed experience a positive Neolithic Demographic Transition (NDT), most hunter-gatherers (HGs) experienced a demographic decrease. Differential fertility between HGs and non-HGs, exposure of HGs to novel pathogens from non-HGs could have resulted in such contrasting patterns. However, we think the most parsimonious explanation of the drastic decrease in population size of HGs is their displacement/enslavement by non-HGs.Significance StatementThe invention of agriculture, around 10000 years ago, facilitated more food production which could feed larger populations. This had far-reaching socio-political and demographic impacts, including a ~10,000 fold increase in global population-size in the last 10,000 years. However, this increase in population size is not a universal truth and present day hunter-gatherer populations, in contrast, have dwindled in size, often drastically. The signatures of this rise in population size are discernible from the genomes of present-day individuals. Using genomic data, we show that for the majority of Asian hunter-gatherers, population-sizes drastically decreased following the invention of agriculture. We argue that a combination of displacement, enslavement and disease resulted in the decimation of hunter-gatherer societies.
Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumour immunity
Authors: Manczinger Máté , Balogh Gergő , Tamás Papp Benjamin , Koncz Balázs , Asztalos Leó , Kemény Lajos , Papp Balázs , Pál Csaba 
Published: June 2020

AbstractThe human leukocyte antigen class I (HLA-I) genes shape our immune response against pathogens and cancer. Certain HLA-I variants can bind a much wider range of peptides than others, a feature that could be favorable against a range of viral diseases. However, the implications of this phenomenon on cancer immune response is unknown. In this paper, we quantified peptide repertoire breadth (or promiscuity) of a representative set of HLA-I alleles, and found that cancer patients that carry HLA-I alleles with high peptide binding promiscuity are characterized by significantly worse prognosis after immune checkpoint inhibitor treatment. This trend can be explained by a reduced capacity of promiscuous HLA-I molecules to discriminate between human self and tumour peptides, yielding a shift in regulation of T-cells in the tumour microenvironment from activation to tolerance. In summary, HLA-I peptide binding specificity shapes neopeptide immunogenicity and the self-immunopeptidome repertoire in an antagonistic manner. It could also underlie a negative trade-off between antitumour immunity and the genetic susceptibility to viral infections.
Development of a Finite Element Model to Predict the Cellular Micromechanical Environment in Tissue Engineering Scaffolds
Authors: Page Mitchell I , Linde Peter E , Puttlitz Christian M 
Published: June 2020

AbstractCell fate in tissue engineering (TE) strategies is paramount to regenerate healthy, functional organs. The mechanical loads experienced by cells play an important role in cell fate. However, in TE scaffolds with a cell-laden hydrogel matrix, it is prohibitively complex to prescribe and measure this cellular micromechanical environment (CME). Accordingly, this study aimed to develop a finite element (FE) model of a TE scaffold unit cell that can be subsequently implemented to predict the CME and cell fates under prescribed loading. The compressible hyperelastic mechanics of a fibrin hydrogel were characterized by fitting unconfined compression and confined compression experimental data. This material model was implemented in a unit cell FE model of a TE scaffold. The FE mesh and boundary conditions were evaluated with respect to the mechanical response of a region of interest (ROI). A compressible second-order reduced polynomial hyperelastic model gave the best fit to the experimental data (C10= 1.72×10-4, C20= 3.83×10-4, D1= 3.41, D2= 8.06×10-2). A mesh with seed sizes of 40 μm and 60 μm in the ROI and non-ROI regions, respectively, yielded a converged model in 54 minutes. The in-plane boundary conditions demonstrated minimal influence on ROI mechanics for a 2-by-2 unit cell. However, the out-of-plane boundary conditions did exhibit an appreciable influence on ROI mechanics for a two bilayer unit cell. Overall, the developed unit cell model facilitates the modeling of the mechanical state of a cell-laden hydrogel within a TE scaffold under prescribed loading. This model will be utilized to characterize the CME in future studies, and 3D micromechanical criteria may be applied to predict cell fate in these scaffolds.
Genotyping by sequencing for identification and mapping of QTLs for bioenergy-related traits in sweet sorghum
Authors: Teingtham Kanokwan , Braun David M. , Dweikat Ismail 
Published: June 2020

AbstractSweet sorghum (Sorghum bicolorL. Moench) is a promising bioenergy crop. To increase the productivity of this crop, marker-assisted breeding will be important to advance genetic improvement of sweet sorghum. The objective of the present study was to identify quantitative trait loci (QTLs) associated with bioenergy-related traits in sweet sorghum. We used 188 F7recombinant inbred lines (RILs) derived from a cross between sweet sorghum (Wray) and grain sorghum (Macia). The RILs and their parental lines were grown at two locations in 2012 and 2013. Genotyping-by-sequencing analysis of the RILs allowed the construction of a map with 979 single nucleotide polymorphisms. Using the inclusive composite interval mapping of additive QTLs, major QTLs for flowering time and head moisture content were detected on chromosome 6, and explained 29.45% and 20.65% of the phenotypic variances (PVE), respectively. Major QTLs for plant height (29.51% PVE) and total biomass yield (16.46% PVE) were detected on chromosome 7, and QTLs for stem diameter (9.43% PVE) and 100 seed weight (22.97% PVE) were detected on chromosome 1. A major QTL for brix (39.92% PVE) and grain yield (49.14%) PVE co-localized on chromosome 3, was detected consistently across four environments, and is closely associated with a SWEET sugar transporter gene. Additionally, several other QTLs for brix identified in this study or reported previously were found to be associated with sugar transporter genes. The identified QTLs in this study will help to further understand the underlying genes associated with bioenergy-related traits and could be used for development of molecular markers for marker-assisted selection.