Epidemics of enterovirus infection in Chungnam Korea, 2008 and 2009

Previously, we explored the epidemic pattern and molecular characterization of enteroviruses isolated in Chungnam, Korea from 2005 to 2006. The present study extended these observations to 2008 and 2009. In this study, enteroviruses showed similar seasonal prevalent pattern from summer to fall and age distribution to previous investigation. The most prevalent month was July: 42.9% in 2008 and 31.9% in 2009. The highest rate of enterovirus-positive samples occurred in children < 1-year-old-age. Enterovirus-positive samples were subjected to sequence determination of the VP1 region, which resolved the isolated enteroviruses into 10 types in 2008 (coxsackievirus A4, A16, B1, B3, echovirus 6, 7, 9, 11, 16, and 30) and 8 types in 2009 (coxsackievirus A2, A4, A5, A16, B1, B5, echovirus 11, and enterovirus 71). The most prevalent enterovirus serotype in 2008 and 2009 was echovirus 30 and coxsackievirus B1, respectively, whereas echovirus 18 and echovirus 5 were the most prevalent types in 2005 and 2006, respectively. Comparison of coxsackievirus B1 and B5 of prevalent enterovirus type in Korea in 2009 with reference strains of each same serotype were conducted to genetic analysis by a phylogenetic tree. The sequences of coxsackievirus B1 strains segregated into four distinct clusters (A, B, C, and D) with some temporal and regional sub-clustering. Most of Korean coxsackievirus B1 strains in 2008 and 2009 were in cluster D, while only "Kor08-CVB1-001CN" was cluster C. The coxsackievirus B5 strains segregated in five distinct genetic groups (clusters A-E) were supported by high bootstrap values. The Korean strains isolated in 2001 belonged to cluster D, whereas Korean strains isolated in 2005 and 2009 belonged to cluster E. Comparison of the VP1 amino acid sequences of the Korean coxsackievirus B5 isolates with reference strains revealed amino acid sequence substitutions at nine amino acid sequences (532, 562, 570, 571, 576-578, 582, 583, and 585)

Differentially Expressed Potassium Channels Are Associated with Function of Human Effector Memory CD8+T cells

The voltage-gated potassium channel, Kv1.3, and the Ca2+-activated potassium channel, KCa3.1, regulate membrane potentials in T cells, thereby controlling T cell activation and cytokine production. However, little is known about the expression and function of potassium channels in human effector memory ( EM) CD8+ T cells that can be further divided into functionally distinct subsets based on the expression of the interleukin ( IL)-7 receptor alpha ( IL-7R alpha) chain. Herein, we investigated the functional expression and roles of Kv1.3 and KCa3.1 in EM CD8+ T cells that express high or low levels of the IL-7 receptor alpha chain ( IL-7R alpha(high) and IL-7R alpha(low), respectively). In contrast to the significant activity of Kv1.3 and KCa3.1 in IL-7Rahigh EM CD8+ T cells, IL-7Ralow EM CD8+ T cells showed lower expression of Kv1.3 and insignificant expression of KCa3.1. Kv1.3 was involved in the modulation of cell proliferation and IL-2 production, whereas KCa3.1 affected the motility of EM CD8+ T cells. The lower motility of IL-7Ralow EM CD8+ T cells was demonstrated using transendothelial migration and motility assays with intercellular adhesion molecule 1-and/or chemokine stromal cell-derived factor-1 alpha-coated surfaces. Consistent with the lower migration property, IL-7Ralow EM CD8+ T cells were found less frequently in human skin. Stimulating IL-7Ralow EM CD8+ T cells with IL-2 or IL-15 increased their motility and recovery of KCa3.1 activity. Our findings demonstrate that Kv1.3 and KCa3.1 are differentially involved in the functions of EM CD8+ T cells. The weak expression of potassium channels in IL-7Ralow EM CD8+ T cells can be revived by stimulation with IL-2 or IL-15, which restores the associated functions. This study suggests that IL-7Rahigh EM CD8+ T cells with functional potassium channels may serve as a reservoir for effector CD8+ T cells during peripheral inflammation.112Ysciescopu

Simultaneous detection of microsatellite repeats and SNPs in the macrophage migration inhibitory factor (MIF) gene by thin-film biosensor chips and application to rural field studies

Microsatellite repeat and single nucleotide polymorphisms (SNPs) are abundant sources of genetic variation, but existing methodologies cannot simultaneously detect these variants in a facile or inexpensive way. We describe herein a thin-film biosensor chip based on an allele-discriminating oligonucleotide array that enables genotyping for both microsatellite repeats and SNPs in a single analysis. We validated this methodology for the functionally polymorphic −794 CATT(5–8) repeat and −173 G/C SNP present in the promoter of the human gene for macrophage migration inhibitory factor (MIF). In a comparison of 30 samples collected at a rural hospital in Zambia, we observed a 100% concordance for both the CATT repeat and G/C SNP between the biosensor methodology and the conventional capillary electrophoresis. The biosensor chips are low in cost and once printed, they are robust and require no instrumentation for analysis. When combined with multiple displacement amplification, this methodology can be utilized in primitive settings for the genotyping of nanogram quantities of DNA present in blood, dried and stored on filter paper samples. We applied this methodology to a field study of MIF genotype in children with malaria, and provide first evidence for a potential association between MIF alleles and malaria infection. We also present data supporting significant population stratification of the low- versus high-expression forms of MIF that may bear on the role of this gene in infectious diseases

A protein domain interaction interface database: InterPare.

BACKGROUND: Most proteins function by interacting with other molecules. Their interaction interfaces are highly conserved throughout evolution to avoid undesirable interactions that lead to fatal disorders in cells. Rational drug discovery includes computational methods to identify the interaction sites of lead compounds to the target molecules. Identifying and classifying protein interaction interfaces on a large scale can help researchers discover drug targets more efficiently. DESCRIPTION: We introduce a large-scale protein domain interaction interface database called InterPare http://interpare.net. It contains both inter-chain (between chains) interfaces and intra-chain (within chain) interfaces. InterPare uses three methods to detect interfaces: 1) the geometric distance method for checking the distance between atoms that belong to different domains, 2) Accessible Surface Area (ASA), a method for detecting the buried region of a protein that is detached from a solvent when forming multimers or complexes, and 3) the Voronoi diagram, a computational geometry method that uses a mathematical definition of interface regions. InterPare includes visualization tools to display protein interior, surface, and interaction interfaces. It also provides statistics such as the amino acid propensities of queried protein according to its interior, surface, and interface region. The atom coordinates that belong to interface, surface, and interior regions can be downloaded from the website. CONCLUSION: InterPare is an open and public database server for protein interaction interface information. It contains the large-scale interface data for proteins whose 3D-structures are known. As of November 2004, there were 10,583 (Geometric distance), 10,431 (ASA), and 11,010 (Voronoi diagram) entries in the Protein Data Bank (PDB) containing interfaces, according to the above three methods. In the case of the geometric distance method, there are 31,620 inter-chain domain-domain interaction interfaces and 12,758 intra-chain domain-domain interfaces

Cyclin-Dependent Kinase Inhibitor p27Kip1 Controls Growth and Cell Cycle Progression in Human Uterine Leiomyoma

The molecular mechanism of the cell-cycle machinery in uterine leiomyoma has not yet been fully elucidated. Among the various types of cell-cycle regulators, p27Kip1 (p27) is considered to be a potent tumor suppressor. To provide further molecular basis for understanding the progression of uterine leiomyoma, our objective was to evaluate the expression level of p27 in normal myometrium and uterine leiomyoma tissue and its effect on cytogenic growth. Western blot analysis, real-time polymerase chain reaction (PCR) and immunohistochemical staining revealed that p27 protein and messenger RNA were down-regulated in uterine leiomyoma tissue and cultured cells compared to normal myometerium. Full-length human p27 cDNA was transferred using a replication-deficient recombinant adenoviral vector (Ad.p27) into uterine leiomyoma cells and evaluated the effect on cell proliferation. Transfection of Ad.p27 into uterine leiomyoma cells resulted in the induction of apoptosis, reduction in viability and proliferation of uterine leiomyoma cells. Our results suggest a new paradigm that down-regulated p27 protein expression is the possible underlying mechanism for the growth of uterine leiomyoma and over-expression of p27 induces cell death. This study provides better understanding of the control exerted by p27 in regulating growth and disease progression of uterine leiomyoma

Ethical Considerations and Adverse Events in Cyanoacrylate Embolization for Non-Saphenous Veins: A Case Report

The cyanoacrylate embolization (CAE) technique for chronic venous disease treatment is less painful and leads to a faster recovery than conventional endovenous thermal treatment. According to the instructions for use (IFU) of the VenaSeal closure system (Medtronic), a representative CAE product, it has only been approved for treating saphenous veins, not non-saphenous veins. Here, we report a case of ignoring the VenaSeal IFU for treating testicular pain using CAE for non-saphenous veins within the abdominal wall, which is a baseless and non-scientific approach nearing malpractice. Hence, it is imperative for physicians to rigorously adhere to the IFU and abstain from experimenting with new treatment methods solely based on personal experience