3,151 research outputs found
Data of methylome and transcriptome derived from human dilated cardiomyopathy
No full textAbstractAlterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1]
Overlooked KCNQ4 variants augment the risk of hearing loss
No full textAbstract Pathogenic variants of KCNQ4 cause symmetrical, late-onset, progressive, high-frequency-affected hearing loss, which eventually involves all frequencies with age. To understand the contribution of KCNQ4 variants to hearing loss, we analyzed whole-exome and genome sequencing data from patients with hearing loss and individuals whose hearing phenotypes were unknown. In KCNQ4, we identified seven missense variants and one deletion variant in 9 hearing loss patients and 14 missense variants in the Korean population with an unknown hearing loss phenotype. The p.R420W and p.R447W variants were found in both cohorts. To investigate the effects of these variants on KCNQ4 function, we performed whole-cell patch clamping and examined their expression levels. Except for p.G435Afs*61, all KCNQ4 variants exhibited normal expression patterns similar to those of wild-type KCNQ4. The p.R331Q, p.R331W, p.G435Afs*61, and p.S691G variants, which were identified in patients with hearing loss, showed a potassium (K+) current density lower than or similar to that of p.L47P, a previously reported pathogenic variant. The p.S185W and p.R216H variants shifted the activation voltage to hyperpolarized voltages. The channel activity of the p.S185W, p.R216H, p.V672M, and p.S691G KCNQ4 proteins was rescued by the KCNQ activators retigabine or zinc pyrithione, whereas p.G435Afs*61 KCNQ4 proteins were partially rescued by sodium butyrate, a chemical chaperone. Additionally, the structure of the variants predicted using AlphaFold2 showed impaired pore configurations, as did the patch-clamp data. Our findings suggest that KCNQ4 variants may be overlooked in hearing loss that starts in adulthood. Some of these variants are medically treatable; hence, genetic screening for KCNQ4 is important
Franny Choi, 41st Annual ODU Literary Festival
No full textFranny Choi is a queer, Korean-American poet, playwright, teacher, organizer, pottymouth, GryffinClaw, and general overachiever. She is the author of Floating, Brilliant, Gone (2014), and a chapbook, Death by Sex Machine (2017). She has received awards from the Poetry Foundation and the Helen Zell Writers Program, as well as fellowships from the Vermont Studio Center and the Rhode Island State Council on the Arts. Her poems have appeared in journals including Poetry magazine, American Poetry Review, New England Review, and her work has been featured by the Huffington Post, PBS NewsHour, and Angry Asian Man
Findings of a 1303 Korean whole-exome sequencing study
No full textEthnically specific data on genetic variation are crucial for understanding human biology and for clinical interpretation of variant pathogenicity. We analyzed data obtained by deep sequencing 1303 Korean whole exomes; the data were generated by three independent whole exome sequencing projects (named the KOEX study). The primary focus of this study was to comprehensively analyze the variant statistics, investigate secondary findings that may have clinical actionability, and identify loci that should be cautiously interpreted for pathogenicity. A total of 495 729 unique variants were identified at exonic regions, including 169 380 nonsynonymous variants and 4356 frameshift insertion/deletions. Among these, 76 607 were novel coding variants. On average, each individual had 7136 nonsynonymous single-nucleotide variants and 74 frameshift insertion/deletions. We classified 13 pathogenic and 13 likely pathogenic variants in 56 genes that may have clinical actionability according to the guidelines of the American College of Medical Genetics and Genomics, and the Association for Molecular Pathology. The carrier frequency of these 26 variants was 2.46% (95% confidence interval 1.73-3.46). To identify loci that require cautious interpretation in clinical sequencing, we identified 18 genes that are prone to sequencing errors, and 671 genes that are highly polymorphic and carry excess nonsynonymous variants. The catalog of identified variants, its annotation and frequency information are publicly available (http://koex.snu.ac.kr). These findings should be useful resources for investigating ethnically specific characteristics in human health and disease.Y
Interaction effect between NAFLD severity and high carbohydrate diet on gut microbiome alteration and hepatic de novo lipogenesis
No full textNonalcoholic fatty liver disease (NAFLD) is associated with high carbohydrate (HC) intake. We investigated whether the relationship between carbohydrate intake and NAFLD is mediated by interactions between gut microbial modulation, impaired insulin response, and hepatic de novo lipogenesis (DNL). Stool samples were collected from 204 Korean subjects with biopsy-proven NAFLD (n = 129) and without NAFLD (n = 75). The gut microbiome profiles were analyzed using 16S rRNA amplicon sequencing. Study subjects were grouped by the NAFLD activity score (NAS) and percentage energy intake from dietary carbohydrate. Hepatic DNL-related transcripts were also analyzed (n = 90). Data from the Korean healthy twin cohort (n = 682), a large sample of individuals without NAFLD, were used for comparison and validation. A HC diet rather than a low carbohydrate diet was associated with the altered gut microbiome diversity according to the NAS. Unlike individuals from the twin cohort without NAFLD, the abundances of Enterobacteriaceae and Ruminococcaceae were significantly different among the NAS subgroups in NAFLD subjects who consumed an HC diet. The addition of these two microbial families, along with Veillonellaceae, significantly improved the diagnostic performance of the predictive model, which was based on the body mass index, age, and sex to predict nonalcoholic steatohepatitis in the HC group. In the HC group, two crucial regulators of DNL (SIRT1 and SREBF2) were differentially expressed among the NAS subgroups. In particular, kernel causality analysis revealed a causal effect of the abundance of Enterobacteriaceae on SREBF2 upregulation and of the surrogate markers of insulin resistance on NAFLD activity in the HC group. Consuming an HC diet is associated with alteration in the gut microbiome, impaired glucose homeostasis, and upregulation of hepatic DNL genes, altogether contributing to NAFLD pathogenesis
RNA‐seq profiling of tubulointerstitial tissue reveals a potential therapeutic role of dual anti‐phosphatase 1 in glomerulonephritis
No full textTranscriptome profiling of tubulointerstitial tissue in glomerulonephritis may reveal a potential tubulointerstitial injury‐related biomarker. We profiled manually microdissected tubulointerstitial tissue from biopsy cores of 65 glomerulonephritis cases, including 43 patients with IgA nephropathy, 3 with diabetes mellitus nephropathy, 3 with focal segmental glomerulosclerosis, 3 with lupus nephritis, 4 with membranous nephropathy and 9 with minimal change disease, and additional 22 nephrectomy controls by RNA sequencing. A potential biomarker was selected based on the false discovery rate, and experiments were performed in TNF‐α‐stimulated primary cultured human tubular epithelial cells (hTECs). We identified 3037 genes with low expression and 2852 genes with high expression in the disease samples compared to the controls. Dual‐specificity phosphatase 1 (DUSP1) exhibited universal low expression in various diseases (log2 fold change, −3.87), with the lowest false discovery rate (7.03E‐132). In further experimental validation study, DUSP1 overexpression ameliorated inflammatory markers related to MAP kinase pathways in hTECs, while pharmacologic inhibition of DUSP1 increased these markers. The combination of DUSP1 overexpression with low‐concentration corticosteroid treatment resulted in more potent suppression of inflammation than high‐concentration corticosteroid treatment alone. The profiled transcriptomes provide insights into the pathophysiology of tubulointerstitial injury in kidney diseases and may reveal a potential therapeutic biomarker
QJE-STD-18-253.R2-Supplementary_Material – Supplemental material for Development and assessment of the Korean Author Recognition Test
No full textSupplemental material, QJE-STD-18-253.R2-Supplementary_Material for Development and assessment of the Korean Author Recognition Test by Hyosun Lee, Eunjin Seong, Wonil Choi and Matthew W Lowder in Quarterly Journal of Experimental Psychology</p
From the Margins to the Forefront: Tillie Olsen's Mediation as Figure and Author
No full text45 pg.Tillie Olsen's life experiences and self-identification as a working class woman provide a strong basis for analyzing her fiction as partly autobiographical. As she wrote, she developed her position as a recognized and award winning author into that of a literary mediator for socially marginalized subjects, actively working to represent certain conditions of exclusion due to social, racial, economic, and sexual factors during the 1970's and 1980's. Through analysis of her fiction and non-fiction texts, her use of modernist writing techniques, her purpose as a writer, and her impact on the literary canon, it becomes possible to see how she has altered the literary landscape and has made those who suffer exclusion visible and legible.Advisor(s): Choi, Helen . Committee Member(s): Marshik, Celia.Stony Brook University Libraries. SBU Graduate School in Department of English. Charles Taber (Dean of Graduate School)
Replicating “Predicting the present with Google trends” by Hyunyoung Choi and Hal Varian (The Economic Record, 2012)
No full textIn this note, the author describes different ways one could try to replicate Choi and Varian (Predicting the present with Google trends, The Economic Record, 2012)
Replicating "Predicting the present with Google trends" by Hyunyoung Choi and Hal Varian (The Economic Record, 2012)
No full textIn this note, the author describes different ways one could try to replicate Choi and Varian (Predicting the present with Google trends, The Economic Record, 2012)
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