Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates.

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing

Fifteen new nucleotide substitutions in variants of human papillomavirus 18 in Korea

High-risk human papillomavirus (HPV) infection is an essential factor for the development of cervical cancer. HPV18 is the second most common carcinogenic HPV type following HPV16, but the lineages of HPV18 have been less well studied than those of HPV 16. The purpose of this study was to analyze the nucleotide variants in the E6, E7, and L1 genes of HPV18, to assess the prevalence of HPV18 variants in Korea and to explore the relationship between HPV18 genetic variants and the risk for cervical cancer. A total of 170 DNA samples from HPV18-positive cervical specimens were collected from women admitted to a secondary referral hospital located in Seoul. Among them, the lineages of the 97 samples could be successfully determined by historical nomenclature. All the studied HPV 18 variants were lineage A. Sublineages A1 and A4 comprised 91.7% (89/97) and 1.0% (1/97), respectively. Sublineages other than A1 or A4 comprised 7.2% (7/97). We identified 15 new nucleotide substitutions among 44 nucleotide substitutions: C158T, T317G, T443G, A560G, A5467G, A5560C, A5678C, A6155G, G6462A, T6650G, G6701A, T6809C, A6823G, T6941C and T6953C. Among them, 6 substitutions at positions 317, 443, 5467, 5560, 6462, and 6823 resulted in amino acid changes (E6: F71L and N113K; L1: H13R, H44P, A345T, and N465S, respectively). The pathologic results were classified as normal in 25.8% (25/97) of the women, atypical squamous cells of undermined significance (ASCUS) in 7.2% (7/97), cervical intraepithelial neoplasia (CIN) 1 in 36.1% (35/97), CIN2/3 in 19.6% (18/97), and carcinoma in 12.4% (12/97). There was no significant association between the HPV18 sublineages and the severity of pathologic lesion or the disease progression. This study is the first to analyze the distribution of HPV18 variants in Korean and to associate the results with pathologic findings. Although the HPV18 variants had no significant effect on the degree and progression of the disease, the newly discovered nonsynonymous mutation in L1 might serve as a database to determine vaccine efficacy in Korean women

Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling

Abstract Background Human mesenchymal stem cells (hMSCs) therapy has recently been considered a promising treatment for atopic dermatitis (AD) due to their immunomodulation and tissue regeneration ability. In our previous studies, we demonstrated that hMSCs alleviate allergic inflammation in murine AD model by inhibiting the activation of mast cells and B cells. Also our phase I/IIa clinical trial showed clinical efficacy and safety of hMSCs in moderate-to-severe adult AD patients. However, hMSCs therapy against atopic dermatitis have had poor results in clinical field. Therefore, we investigated the reason behind this result. We hypothesized that drug–cell interaction could interfere with the therapeutic efficacy of stem cells, and investigated whether coadministration with pimecrolimus, one of the topical calcineurin inhibitors, could influence the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in AD. Methods hUCB-MSCs were subcutaneously injected to AD-induced mice with or without pimecrolimus topical application. To examine whether pimecrolimus influenced the immunomodulatory activity of hUCB-MSCs, hUCB-MSCs were treated with pimecrolimus. Results Pimecrolimus disturbed the therapeutic effect of hUCB-MSCs when they were co-administered in murine AD model. Moreover, the inhibitory functions of hUCB-MSCs against type 2 helper T (Th2) cell differentiation and mast cell activation were also deteriorated by pimecrolimus treatment. Interestingly, we found that pimecrolimus decreased the production of PGE2, one of the most critical immunomodulatory factors in hUCB-MSCs. And we demonstrated that pimecrolimus downregulated COX2-PGE2 axis by inhibiting nuclear translocation of NFAT3. Conclusions Coadministration of pimecrolimus with hMSCs could interfere with the therapeutic efficacy of hMSCs in atopic dermatitis, and this is the first study that figured out the interaction of hMSCs with other drugs in cell therapy of atopic dermatitis. Therefore, this study might give rise to improvement of the clinical application of hMSCs therapy and facilitate the widespread application of hMSCs in clinical field

Candida haemulonii and Closely Related Species at 5 University Hospitals in Korea: Identification, Antifungal Susceptibility, and Clinical Features

Background. Candida haemulonii, a yeast species that often exhibits antifungal resistance, rarely causes human infection. During 2004-2006, unusual yeast isolates with phenotypic similarity to C. haemulonii were recovered from 23 patients (8 patients with fungemia and 15 patients with chronic otitis media) in 5 hospitals in Korea. Methods. Isolates were characterized using D1/D2 domain and ITS gene sequencing, and the susceptibility of the isolates to 6 antifungal agents was tested in vitro. Results. Gene sequencing of the blood isolates confirmed C. haemulonii group I (in 1 patient) and Candida pseudohaemulonii (in 7 patients), whereas all isolates recovered from the ear were a novel species of which C. haemulonii is its closest relative. The minimum inhibitory concentration (MIC) ranges of amphotericin B, fluconazole, itraconazole, and voriconazole for all isolates were 0.5-32 mu g/mL (MIC(50), 1 mu g/mL), 2-128 mu g/mL (MIC(50), 4 mu g/mL), 0.125-4 mu g/mL (MIC(50), 0.25 mu g/mL), and 0.03-2 mu g/mL (MIC(50), 0.06 mu g/mL), respectively. All isolates were susceptible to caspofungin (MIC, 0.125-0.25 mu g/mL) and micafungin (MIC, 0.03-0.06 mu g/mL). All cases of fungemia occurred in patients with severe underlying diseases who had central venous catheters. Three patients developed breakthrough fungemia while receiving antifungal therapy, and amphotericin B therapeutic failure, which was associated with a high MIC of amphotericin B (32 mu g/mL), was observed in 2 patients. Conclusions. Candida species that are closely related to C. haemulonii are emerging sources of infection in Korea. These species show variable patterns of susceptibility to amphotericin B and azole antifungal agents.Shin JH, 2007, J CLIN MICROBIOL, V45, P2385, DOI 10.1128/JCM.00381-07Khan ZU, 2007, J CLIN MICROBIOL, V45, P2025, DOI 10.1128/JCM.00222-07Lee JS, 2007, J CLIN MICROBIOL, V45, P1005, DOI 10.1128/JCM.02264-06Pfaller MA, 2006, J CLIN MICROBIOL, V44, P819, DOI 10.1128/JCM.44.3.819-826.2006Sugita T, 2006, MICROBIOL IMMUNOL, V50, P469Clancy CJ, 2005, ANTIMICROB AGENTS CH, V49, P3171, DOI 10.1128/AAC.49.8.3171-3177.2005Odds FC, 2004, J CLIN MICROBIOL, V42, P3475, DOI 10.1128/JCM.42.8.3475-3482.2004Rodero L, 2002, J CLIN MICROBIOL, V40, P2266, DOI 10.1128/JCM.40.6.2266-2269.2002*CLSI, 2002, M27A2 CLSISugita T, 1999, J CLIN MICROBIOL, V37, P1985Pfaller MA, 1998, DIAGN MICR INFEC DIS, V32, P223Nguyen MH, 1998, J INFECT DIS, V177, P425Kurtzman CP, 1997, J CLIN MICROBIOL, V35, P1216LEHMANN PF, 1993, J CLIN MICROBIOL, V31, P1683GARGEYA IB, 1991, J MED VET MYCOL, V29, P335

Bioinformatics services for analyzing massive genomic datasets

The explosive growth of next-generation sequencing data has resulted in ultra-large-scale datasets and ensuing computational problems. In Korea, the amount of genomic data has been increasing rapidly in the recent years. Leveraging these big data requires researchers to use large-scale computational resources and analysis pipelines. A promising solution for addressing this computational challenge is cloud computing, where CPUs, memory, storage, and programs are accessible in the form of virtual machines. Here, we present a cloud computing-based system, Bio-Express, that provides user-friendly, cost-effective analysis of massive genomic datasets. Bio-Express is loaded with predefined multi-omics data analysis pipelines, which are divided into genome, transcriptome, epigenome, and metagenome pipelines. Users can employ predefined pipelines or create a new pipeline for analyzing their own omics data. We also developed several web-based services for facilitating down-stream analysis of genome data. Bio-Express web service is freely available at https://www. bioexpress.re.kr/. ?? 2020, Korea Genome Organization

Using Cabri3D Program for Developing Student’s Problem Solving Ability

technologies The goal of Japanese mathematical education is the calculus. In this learning we do not use IT machine which is the graphic calculator or the computer. In this paper, we use the graphic calculator for seeing the graph of the function y^(n) = y? We want to find out the functions that satisfy y^(n) = y? Abstract for 1299

Proteomics data for "Mercury alters endogenous phosphorylation profiles of SYK in murine B cells.

Supplementary proteomics data. Search results for LC/MS/MS experiments are in the form of Scaffold files (a free viewer can be downloaded from http://www.proteomesoftware.com/products/scaffold/download/). These data identified phosphorylation sites of murine SYK protein in WEHI cells treated with either inorganic mercury (Hg), pervanadate (PV), or BCR activating antibody (Ab). Raw data for quantitation of SYK phosphorylation status of selected sites were obtained using multiple reaction monitoring (MRM) on a TSQ triple quadrupole mass spectrometer. Detailed parameters including peptide and fragment mass lists can be found in the Methods section

Validation of the Child Post-Traumatic Cognitions Inventory in Korean survivors of sexual violence

Abstract Background Dysfunctional cognitions related to trauma is an important factor in the development and maintenance of post-traumatic stress disorder symptoms in children and adolescents. The Child Post-traumatic Cognitions Inventory (CPTCI) assesses such cognitions about trauma. We investigated the psychometric properties of the Korean version of CPTCI and its short form by surveying child and adolescent survivors of sexual violence. Methods Children and adolescents aged 7–16 years (N = 237, M age = 12.6, SD = 2.3, 222 [93.7%] were female) who were exposed to sexual violence were included in this survey. We assessed the factor structure, internal consistency, and validity of the CPTCI and its short form through data analysis. Results Confirmatory factor analysis results supported the two-factor model presented in the original study. The total scale, its subscales, and the short form had good internal consistency (Cronbach’s α = .96 for total scale and .91–.95 for the other scales). The CPTCI showed high correlations with scales measuring post-traumatic stress symptoms (r = .77–.80), anxiety (r = .69–.71), and depression (r = .74–.77); the correlation with post-traumatic stress symptoms was the highest. The differences in CPTCI scores per post-traumatic stress symptom levels were significant (all p  .05 for all comparisons); however, the scores exhibited differences per age group (all p < .001). Conclusions The results indicate that the Korean version of the CPTCI is a valid and reliable scale; therefore, it may be a valuable tool for assessing maladaptive cognitions related to trauma in research and clinical settings