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Item Metadata only Acceptability and tolerability of liquid versus gel and standard versus virucidal alcohol-based hand rub formulations among dental students(American Journal of Infection Control, 2013-11-01) Stauffer, Fritz; Griess, Marion; Pleininger, Gabriele; Zhumadilova, Anara; Assadian, Ojan; Fritz, StaufferBackgroundHand hygiene is effective to prevent the transmission of microorganisms in health care settings, but compliance remains low, even when easy access to hand cleaning agents is provided. ObjectiveFormulation of alcohol-based hand rub (ABHRs) may influence staff compliance to hand hygiene. The aim of this prospective longitudinal study (1 week) was to investigate possible differences of 4 different gel or liquid ABHR formulations, with or without virucidal claim among dental students. MethodsParticipants were randomly assigned to dental treatment cubicles, equipped with either a gel or a liquid based ABHRs, with our without a virucidal claim. Participants assessed the subjective acceptability and the tolerability of test formulations on their hands over a period of 1 week using the 14 item, 7-point Lickert scale World Health Organization questionnaire. ResultsAll tested ABHRs passed the subjective acceptability criteria of ≥50% above 4 for the items “color and fragrance” and for all other items of >75% above 4 and may be regarded as “good.” Significant differences were observed between the 2 gels but not between the 2 liquid ABHRs. For subjective skin tolerability, no significant difference was observed between the liquid formulations after 1 consecutive week of application. However, the difference between the 2 gels was highly significant. ConclusionVirucidal ABHR formulations may be better accepted and tolerated over prolonged periods by dental students than anticipated. The user acceptability of ABHRs depend more on the specific product's formula than its general category.Item Open Access Advances in Computational Immunology(Journal of Immunology Research, 2015) Pappalardo, Francesco; Brusic, Vladimir; Pennisi, Marzio; Zhang, GuanglanItem Open Access Association between 28 single nucleotide polymorphisms and type 2 diabetes mellitus in the Kazakh population: a case-control study(BMC Medical Genetics, 2017-07-24) Sikhayeva, Nurgul; Iskakova, Aisha; Saigi-Morgui, Nuria; Zholdybaeva, Elena; Eap, Chin-Bin; Ramanculov, ErlanBackground: We evaluated the associations between single nucleotide polymorphisms and different clinical parameters related to type 2 diabetes mellitus (T2DM), obesity risk, and metabolic syndrome (MS) in a Kazakh cohort. Methods: A total of 1336 subjects, including 408 T2DM patients and 928 control subjects, were recruited from an outpatient clinic and genotyped for 32 polymorphisms previously associated with T2DM and obesity-related phenotypes in other ethnic groups. For association studies, the chi-squared test or Fisher’s exact test for binomial variables were used. Logistic regression was conducted to explore associations between the studied SNPs and the risk of developing T2DM, obesity, and MS, after adjustments for age and sex. Results: After excluding four SNPs due to Hardy-Weinberg disequilibrium, significant associations in age-matched cohorts were found betweenT2DM and the following SNPs: rs9939609 (FTO), rs13266634 (SLC30A8), rs7961581 (TSPAN8/LGR5), and rs1799883 (FABP2). In addition, examination of general unmatched T2DM and control cohorts revealed significant associations between T2DM and SNPsrs1799883 (FABP2) and rs9939609 (FTO). Furthermore, polymorphisms in the FTO gene were associated with increased obesity risk, whereas polymorphisms in the FTO and FABP2 genes were also associated with the risk of developing MS in general unmatched cohorts. Conclusion: We confirmed associations between polymorphisms within the SLC30A8, TSPAN8/LGR5, FABP2, and FTO genes and susceptibility to T2DM in a Kazakh cohort, and revealed significant associations with anthropometric and metabolic traits. In particular, FTO and FABP2 gene polymorphisms were significantly associated with susceptibility to MS and obesity in this cohort.Item Open Access Autoantibodies to tissue transglutaminase target epitopes dependent on residues in the N-terminal domain(Coeliac UK's Research Conference, 2017-03-24) Kozhakhmetova, A; Wyatt, R; Elvers, K; Emery, D; Williams, C; Annis, P; Lampasona, V; Gillespie, K; Williams, AINTRODUCTION: Tissue transglutaminase (tTG), is the main autoantigen of coeliac disease (CD). Specific tTG epitopes, including N-and C-terminal sites as well as the catalytic triad, have been reported to be targeted by autoantibodies in CD, but the findings are controversial. We aimed to confirm which of the tTG sites, catalytic core, C- or N-terminus, are critical for antibody binding as this could aid the design of more specific assays and inform studies of disease pathogenesis. METHODS: Plasmid DNA encoding human tTG was mutated at sites in the catalytic core (Cys277, His335, Asp358 to alanine), N- (Arg19, Glu153 to serine) and C-terminal domains (Met659 to serine) using PAGE-purified mutagenic primers. Antibody binding to a panel of 35S-labelled tTG mutant antigens synthesized in vitro was assessed by radioimmunoassay in sera from 111 TGA-positive individuals (mean age 40 years, range 1.1-80 years) out of 445 patients sent for measurement of CD-associated autoantibodies to the Cork University Hospital, Eire. Wilcoxon signed-ranks test (SPSS) was used for statistical analysis. RESULTS: Showed that single mutation of catalytic core amino acids C277A, D358A, H335A had little effect on the relative binding (RB) of antibodies to antigen compared with native tTG (median RB; p-values: 100%; 0.723, 93%; 6.1E-5, 106%; 0.019, respectively for each mutant, while the triple Cys277/His335/Asp358 mutation slightly decreased RB (85%; 3.7E-16). Single mutation of the N-terminal amino acids, Arg19 or Glu153, elicited significantly decreased RB in ≥90% of sera (66%; 4.2E-17, 76%; 1.0E-11, respectively), as well as for the double Arg19/Glu153 (48%; 3.1E-17) and triple Arg19/Glu153/Met659 (48%; 1.1E—15) mutants. Mutation of Met659 alone had a variable effect, decreasing binding in others (102%; 0.004). The combined Cys277/His335/Asp358 and Arg19/Glu153/Met659 tTG mutations reduced binding in 96% of sera (60%; 2.2E-19). DISCUSSION: The N-terminal domain of tTG involving amino acids Arg19 and Glu153 is important to the integrity of tTG autoantibody epitopes in CD. Simultaneous mutation of these two amino acids has the highest impact on antibody-binding to tTG, while modifying catalytic core previously reported as being important, had little effect on binding. Effect of C-terminal mutation is more variable. These findings suggest that a major epitope is located in the N-terminal, but additional regions of the antigen are likely to contribute to antibody-binding. Characterization of mechanisms and epitopes involved in anti-tTG autoimmunity is important for development of targeted therapeutic manipulations in CD patients or at-risk individuals.Item Open Access CFD Modeling of Chamber Filling in a Micro- Biosensor for Protein Detection(Biosensors, 2017-10) Islamov, Meiirbek; Sypabekova, Marzhan; Kanayeva, Damira; Rojas-Solórzano, LuisTuberculosis (TB) remains one of the main causes of human death around the globe. The mortality rate for patients infected with active TB goes beyond 50% when not diagnosed. Rapid and accurate diagnostics coupled with further prompt treatment of the disease is the cornerstone for controlling TB outbreaks. To reduce this burden, the existing gap between detection and treatment must be addressed, and dedicated diagnostic tools such as biosensors should be developed. A biosensor is a sensing micro-device that consists of a biological sensing element and a transducer part to produce signals in proportion to quantitative information about the binding event. The micro-biosensor cell considered in this investigation is designed to operate based on aptamers as recognition elements against Mycobacterium tuberculosis secreted protein MPT64, combined in a microfluidic-chamber with inlet and outlet connections. The microfluidic cell is a miniaturized platform with valuable advantages such as low cost of analysis with low reagent consumption, reduced sample volume, and shortened processing time with enhanced analytical capability. The main purpose of this study is to assess the flooding characteristics of the encapsulated microfluidic cell of an existing micro-biosensor using Computational Fluid Dynamics (CFD) techniques. The main challenge in the design of the microfluidic cell lies in the extraction of entrained air bubbles, which may remain after the filling process is completed, dramatically affecting the performance of the sensing element. In this work, a CFD model was developed on the platform ANSYS-CFX using the finite volume method to discretize the domain and solving the Navier–Stokes equations for both air and water in a Eulerian framework. Second-order space discretization scheme and second-order Euler Backward time discretization were used in the numerical treatment of the equations. For a given inlet–outlet diameter and dimensions of an in-house built cell chamber, different inlet liquid flow rates were explored to determine an appropriate flow condition to guarantee an effective venting of the air while filling the chamber. The numerical model depicted free surface waves as promoters of air entrainment that ultimately may explain the significant amount of air content in the chamber observed in preliminary tests after the filling process is completed. Results demonstrated that for the present design, against the intuition, the chamber must be filled with liquid at a modest flow rate to minimize free surface waviness during the flooding stage of the chamber.Item Open Access Characterization of biochemical properties of an apurinic/apyrimidinic endonuclease from Helicobacter pylori(PLoS ONE, 2018-08-15) Turgimbayeva, Aigerim; Abeldenov, Sailau; Zharkov, Dmitry O.; Ishchenko, Alexander A.; Ramankulov, Yerlan; Saparbaev, Murat; Khassenov, BekbolatApurinic/apyrimidinic (AP) endonucleases play critical roles in the repair of abasic sites and strand breaks in DNA. Complete genome sequences of Helicobacter pylori reveal that this bacterial specie has a single AP endonuclease. An H. pylori homolog of Xth (HpXth) is a member of exonuclease III family, which is represented by Escherichia coli Xth. Currently, it remains unknown whether this single AP endonuclease has DNA repair activities similar to those of its counterpart in E. coli and other bacteria. We report that HpXth possesses efficient AP site cleavage, 3’-repair phosphodiesterase, and 3’-phosphatase activities but not the nucleotide incision repair function...Item Open Access Characterization of Legumain(Biological Chemistry, 2002-11) Schwarz, Gerold; Brandenburg, Jens; Reich, Michael; Burster, Timo; Driessen, Christoph; Kalbacher, HubertThe mammalian legumain, also called asparaginyl endopeptidase (AEP), is critically involved in the processing of bacterial antigens for MHC class II presentation. In order to investigate the substrate specificity of AEP in the P1’ position, we created a peptide library and digested it with purified pig kidney AEP. Digestion was less efficient only when proline was in the P1’ position. Maximum AEP activity was found in lysosomal fractions of different types of antigen presenting cells (APC). When the multiple sclerosis-associated autoantigen myelin basic protein (MBP) was digested with AEP, the immunodominant epitope 83 – 99 was destroyed. Myoglobin as an alternative substrate was AEP resistant. These results suggest an important, but not necessarily critical role for AEP in lysosomal antigen degradationItem Open Access CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application(Frontiers in Cell and Developmental Biology, 2015-02-20) Winkler, B.Sophia; Oltmer, Franziska; Richter, Julia; Bischof, Joachim; Xu, Pengfei; Burster, Timo; Leithäuser, Frank; Knippschild, UweThe prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as in non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasmsItem Open Access Computational and Bioinformatics Techniques for Immunology(BioMed Research International, 2014-12-31) Pappalardo, Francesco; Brusic, Vladimir; Castiglione, Filippo; Schönbach, ChristianItem Open Access Discovery and Characterization of an Endogenous CXCR4 Antagonist(Cell Reports, 2015-05-05) O., Zirafi; K-A., Kim; L., Ständker; K. B., Mohr; D., Sauter; A., Heigele; S. F., Kluge; E., Wiercinska; D., Chudziak; R., Richter; B., Moepps; P., Gierschik; V., Vas; H., Geiger; M., Lamla; T., Weil; T., Burster; A., Zgraja; F., Daubeuf; N., Frossard; Timo, Burster; Timo, BursterCXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPIX4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.Item Open Access Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation(Cell Reports, 2016-06-07) Sun, Xiaoming; Shi, Yi; Akahoshi, Tomohiro; Fujiwara, Mamoru; Gatanaga, Hiroyuki; Schönbach, Christian; Kuse, Nozomi; Appay, Victor; Gao, George F.; Oka, Shinichi; Takiguchi, Masafumi; Xiaoming, SunSummary The mechanistic basis for the progressive accumulation of Y135F Nef mutant viruses in the HIV-1-infected population remains poorly understood. Y135F viruses carry the 2F mutation within RW8 and RF10, which are two HLA-A∗24:02-restricted superimposed Nef epitopes recognized by distinct and adaptable CD8+ T cell responses. We combined comprehensive analysis of the T cell receptor repertoire and cross-reactive potential of wild-type or 2F RW8- and RF10-specific CD8+ T cells with peptide-MHC complex stability and crystal structure studies. We find that, by affecting direct and water-mediated hydrogen bond networks within the peptide-MHC complex, the 2F mutation reduces both TCR and HLA binding. This suggests an advantage underlying the evolution of the 2F variant with decreased CD8+ T cell efficacy. Our study provides a refined understanding of HIV-1 and CD8+ T cell co-adaptation at the population level.Item Open Access Epidemiology of Brucellosis and Genetic Diversity of Brucella abortus in Kazakhstan(Plos One, 2016-12-01) Shevtsova, Elena; Shevtsov, Alexandr; Mukanov, Kasim; Filipenko, Maxim; Kamalova, Dinara; Sytnik, Igor; Syzdykov, Marat; Kuznetsov, Andrey; Akhmetova, Assel; Zharova, Mira; Karibaev, Talgat; Tarlykov, Pavel; Ramanculov, ErlanBrucellosis is a major zoonotic infection in Kazakhstan. However, there is limited data on its incidence in humans and animals, and the genetic diversity of prevalent strains is virtually unstudied. Additionally, there is no detailed overview of Kazakhstan brucellosis control and eradication programs. Here, we analyzed brucellosis epidemiological data, and assessed the effectiveness of eradication strategies employed over the past 70 years to counteract this infection. We also conducted multiple loci variable-number tandem repeat analysis (MLVA) of Brucella abortus strains found in Kazakhstan. We analyzed official data on the incidence of animal brucellosis in Kazakhstan. The records span more than 70 years of antibrucellosis campaigns, and contain a brief description of the applied control strategies, their effectiveness, and their impact on the incidence in humans. The MLVA-16 method was used to type 94 strains of B. abortus and serial passages of B. abortus 82, a strain used in vaccines. MLVA-8 and MLVA-11 analyses clustered strains into a total of four and sevengenotypes, respectively; it is the first time that four of these genotypes have been described. MLVA-16 analysis divided strains into 28 distinct genotypes having genetic similarity coefficient that varies from 60 to100% and a Hunter & Gaston diversity index of 0.871. MST analysis reconstruction revealed clustering into "Kazakhstani-Chinese (Central Asian)", "European" and "American" lines. Detection of multiple genotypes in a single outbreak confirms that poorly controlled trade of livestock plays a crucial role in the spread of infection. Notably, the MLVA-16 profile of the B. abortus 82 strain was unique and did not change during 33 serial passages. MLVA genotyping may thus be useful for epidemiological monitoring of brucellosis, and for tracking the source(s) of infection. We suggest that countrywide application of MLVA genotyping would improve the control of brucellosis in Kazakhstan.Item Open Access Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells(Oncotarget, 2016-10-28) Giese, Madleen; Turiello, Nadine; Molenda, Nicole; Palesch, David; Meid, Annika; Schroeder, Roman; Basilico, Paola; Benarafa, Charaf; Halatsch, Marc-Eric; Zimecki, Michal; Westhoff, Mike-Andrew; Rainer Wirtz, Christian; Burster, TimoMajor histocompatibility complex (MHC) class I molecules present antigenic peptides to cytotoxic T cells. During an adaptive immune response, MHC molecules are regulated by several mechanisms including lipopolysaccharide (LPS) and interferon gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G (CatG), which is generally secreted by neutrophils at the site of inflammation, might regulate MHC I molecules. We identified CatG, and to a higher extend CatG and lactoferrin (LF), as an exogenous regulator of cell surface MHC I expression of immune cells and glioblastoma stem cells. In addition, levels of MHC I molecules are reduced on dendritic cells from CatG deficient mice compared to their wild type counterparts. Furthermore, cell surface CatG on immune cells, including T cells, B cells, and NK cells triggers MHC I on THP-1 monocytes suggesting a novel mechanism for CatG to facilitate intercellular communication between infiltrating cells and the respective target cell. Subsequently, our findings highlight the pivotal role of CatG as a checkpoint protease which might force target cells to display their intracellular MHC I:antigen repertoireItem Metadata only Extracellular vesicles in gastrointestinal cancer in conjunction with microbiota: On the border of Kingdoms(Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2017-12-01) Barteneva, Natasha S.; Baiken, Yeldar; Fasler-Kan, Elizaveta; Alibek, Kenneth; Wang, Sheng; Maltsev, Natalia; Ponomarev, Eugene D.; Sautbayeva, Zarina; Kauanova, Sholpan; Moore, Anna; Beglinger, Christoph; Vorobjev, Ivan A.; Natasha S., BartenevaAbstract Extracellular vesicle (EV) production is a universal feature of metazoan cells as well as prokaryotes (bMVs - bacterial microvesicles). They are small vesicles with phospholipid membrane carrying proteins, DNA and different classes of RNAs and are heavily involved in intercellular communication acting as vectors of information to target cells. For the last decade, the interest in EV research has exponentially increased though thorough studies of their roles in various pathologies that was not previously possible due to technical limitations. This review focuses on research evaluating the role of EV production in gastrointestinal (GI) cancer development in conjunction with GI microbiota and inflammatory diseases. We also discuss recent studies on the promising role of EVs and their content as biomarkers for early diagnosis of GI cancers.The bMVs have also been implicated in the pathogenesis of GI chronic inflammatory diseases, however, possible role of bMVs in tumorigenesis remains underestimated. We propose that EVs from eukaryotic cells as well as from different microbial, fungi, parasitic species and edible plants in GI tract act as mediators of intracellular and inter-species communication, particularly facilitating tumor cell survival and multi-drug resistance.In conclusion, we suggest that matching sequences from EV proteomes (available from public databases) with known protein sequences of microbiome gut bacteria will be useful in identification of antigen mimicry between evolutionary conservative protein sequences. Using this approach we identified Bacteroides spp. pseudokinase with activation loop and homology to PDGFRα, providing a proof-of-concept strategy. We speculate that existence of microbial pseudokinase that ‘mimics’ PDGFRα may be related to PDGFRα and Bacteroides spp. roles in colorectal carcinogenesis that require further investigation.Item Metadata only Genetic diversity of Brucella abortus and Brucella melitensis in Kazakhstan using MLVA-16(Infection, Genetics and Evolution, 2015-08-01) Shevtsov, Alexandr; Ramanculov, Erlan; Shevtsova, Elena; Kairzhanova, Alma; Tarlykov, Pavel; Filipenko, Maxim; Dymova, Maya; Abisheva, Gulzada; Jailbekova, Aygul; Kamalova, Dinara; Chsherbakov, Andrei; Tulegenov, Samat; Akhmetova, Assel; Sytnik, Igor; Karibaev, Talgat; Mukanov, Kasim; Alexandr, ShevtsovAbstract Brucellosis is an endemic disease in Central Asia characterized by high infection rates in humans and animals. Currently, little is known about the genetic diversity of Brucella spp. circulating in the region, despite the high prevalence of brucellosis. This study aimed to analyze the genetic diversity of Brucella melitensis and Brucella abortus strains circulating in the Republic of Kazakhstan. We genotyped 128 B. melitensis and 124 B. abortus strains collected in regions with the highest prevalence of brucellosis. Genotyping was performed using multi-locus variable-number tandem-repeat analysis (MLVA). Analysis of a subset of 8 loci (MLVA-8) of 128 B. melitensis strains identified genotypes 42 (n=108), 43 (n=2), and 63 (n=19) related to the ‘East Mediterranean’ group. An MLVA-16 assay sorted 128 B. melitensis strains into 25 different genotypes. Excluding one variable locus, MLVA-15 of B. melitensis was distinct from strains originating in the Mediterranean region; however, 77% of them were identical to strains isolated in China. A minimum spanning tree for B. melitensis using MLVA-15 analysis clustered the local strains together with strains previously collected in China. MLVA-8 analysis of 124 B. abortus strains identified them as genotype 36, suggesting Eurasian distribution of this lineage. Complete MLVA-16 assay analysis clustered the strains into five genotypes, revealing little diversity of B. abortus when compared on the global scale. A minimum spanning tree for B. abortus obtained using MLVA-15 analysis clustered the 2 most prevalent genotypes (n=117) together with strains previously collected in China. Thus, MLVA analysis was used to characterize 252 strains of Brucella collected in Kazakhstan. The analysis revealed genetic homogeneity among the strains. Interestingly, identical MLVA-15 profiles were found in seemingly unrelated outbreaks in China, Turkey, and Kazakhstan. Further analysis is needed for better understanding of the epidemiology of brucellosis in Asia.Item Open Access Genetic Diversity of Brucella melitensis in Kazakhstan in Relation to World-Wide Diversity(FRONTIERS MEDIA SA, 2019-08-13) Shevtsova, Elena; Vergnaud, Gilles; Shevtsov, Alexandr; Shustov, Alexandr; Berdimuratova, Kalysh; Mukanov, Kasim; Syzdykov, Marat; Kuznetsov, Andrey; Lukhnova, Larissa; Izbanova, Uinkul; Filipenko, Maxim; Ramankulov, YerlanWe describe the genetic diversity of 1327 Brucella strains from human patients in Kazakhstan using multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA). All strains were assigned to the Brucella melitensis East Mediterranean group and clustered into 16 MLVA11 genotypes, nine of which are reported for the first time. MLVA11 genotype 116 predominates (86.8%) and is present all over Kazakhstan indicating existence and temporary preservation of a "founder effect" among B. melitensis strains circulating in Central Eurasia. The diversity pattern observed in humans is highly similar to the pattern previously reported in animals. The diversity observed by MLVA suggested that the epidemiological status of brucellosis in Kazakhstan is the result of the introduction of a few lineages, which have subsequently diversified at the most unstable tandem repeat loci. This investigation will allow to select the most relevant strains for testing these hypotheses via whole genome sequencing and to subsequently adjust the genotyping scheme to the Kazakhstan epidemiological situation.Item Open Access Genetic risk factors for restenosis after percutaneous coronary intervention in Kazakh population(Human Genomics, 2016) Zholdybayeva, Elena V.; Talzhanov, Yerkebulan A.; Aitkulova, Akbota M.; Tarlykov, Pavel V.; Kulmambetova, Gulmira N.; Iskakova, Aisha N.; Dzholdasbekova, Aliya U.; Visternichan, Olga A.; Taizhanova, Dana Zh.; Ramanculov, Yerlan M.Background: After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population. Methods: Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2. Results: A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR = 2.924, P = 2.3E−06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR = 0.08033, P = 2.11E−09) and dominant models (OR = 0.05359, P = 4.15E−11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR = 20.05, P = 2.74 E−12) and recessive models (OR = 22.24, P = 6.811E−10). Conclusions: Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results.Item Open Access GIW and InCoB are advancing bioinformatics in the Asia-Pacific(BMC Bioinformatics, 2015-12-18) Schönbach, Christian; Horton, Paul; Yiu, Siu Ming; Tan, Tin Wee; Ranganathan, ShobaGIW/InCoB2015 the joint 26th International Conference on Genome Informatics (GIW) and 14th International Conference on Bioinformatics (InCoB) held in Tokyo, September 9-11, 2015 was attended by over 200 delegates. Fifty-one out of 89 oral presentations were based on research articles accepted for publication in four BMC journal supplements and three other journals. Sixteen articles in this supplement and six articles in the BMC Systems Biology GIW/InCoB2015 Supplement are covered by this introduction. The topics range from genome informatics, protein structure informatics, image analysis to biological networks and biomarker discovery.Item Open Access GIW and InCoB, two premier bioinformatics conferences in Asia with a combined 40 years of history(BMC, 2015) Schönbach, Christian; Horton, Paul; Yiu, Siu Ming; Tan, Tin Wee; Ranganathan, ShobaKnowledge discovery in bioinformatics thrives on joint and inclusive efforts of stakeholders. Similarly, knowledge dissemination is expected to be more effective and scalable through joint efforts. Therefore, the International Conference on Bioinformatics (InCoB) and the International Conference on Genome Informatics (GIW) were organized as a joint conference for the first time in 13 years of coexistence. The Asia-Pacific Bioinformatics Network (APBioNet) and the Japanese Society for Bioinformatics (JSBi) collaborated to host GIW/InCoB2015 in Tokyo, September 9-11, 2015. The joint endeavour yielded 51 research articles published in seven journals, 78 poster and 89 oral presentations, showcasing bioinformatics research in the Asia-Pacific region. Encouraged by the results and reduced organizational overheads, APBioNet will collaborate with other bioinformatics societies in organizing co-located bKnowledge discovery in bioinformatics thrives on joint and inclusive efforts of stakeholders. Similarly, knowledge dissemination is expected to be more effective and scalable through joint efforts. Therefore, the International Conference on Bioinformatics (InCoB) and the International Conference on Genome Informatics (GIW) were organized as a joint conference for the first time in 13 years of coexistence. The Asia-Pacific Bioinformatics Network (APBioNet) and the Japanese Society for Bioinformatics (JSBi) collaborated to host GIW/InCoB2015 in Tokyo, September 9-11, 2015. The joint endeavour yielded 51 research articles published in seven journals, 78 poster and 89 oral presentations, showcasing bioinformatics research in the Asia-Pacific region. Encouraged by the results and reduced organizational overheads, APBioNet will collaborate with other bioinformatics societies in organizing co-located bioinformatics research and training meetings in the future. InCoB2016 will be hosted in Singapore, September 21-23, 2016.ioinformatics research and training meetings in the future. InCoB2016 will be hosted in Singapore, September 21-23, 2016.Item Metadata only Histological and biochemical analysis of DNA damage after BNCT in rat model(Applied Radiation and Isotopes, 2014-06-01) Masutani, Mitsuko; Baiseitov, Diaz; Itoh, Tasuku; Hirai, Takahisa; Berikkhanova, Kulzhan; Murakami, Yasufumi; Zhumadilov, Zhaxybay; Imahori, Yoshio; Hoshi, Masaharu; Itami, Jun; Mitsuko, MasutaniAbstract To understand the mechanism of tumor cell death induced by boron neutron capture therapy (BNCT) and to optimize BNCT condition, we used rat tumor graft models and histological and biochemical analyses were carried out focusing on DNA damage response. Rat lymphosarcoma cells were grafted subcutaneously into male Wister rats. The rats with developed tumors were then treated with neutron beam irradiation 45min after injection of 330mg/kg bodyweight boronophenylalanine (10BPA) (+BPA) or saline control (–BPA). BNCT was carried out in the National Nuclear Center of the Republic of Kazakhstan (neutron flux: 1×109nvt/s, fluence: 6×1011nvt) with the presence of background γ-irradiation of 33Gy. 6 and 20h after BNCT treatment, tumors were resected, fixed and subjected to immunohistochemistry and biochemical analyses. Immunostaining of nuclei showed that double strand break (DSB) marker gamma H2AX staining was high in 20h/+BPA sample but not in 20h/–BPA samples. Poly(ADP-ribose), DSB and single strand break markers of DNA, also demonstrated this tendency. These two markers were observed at low levels in unirradiated tissues or 6h after BNCT either under −BPA and +BPA conditions. HMGB1 level increased in 6h/+BPA but not in 6h/−BPA or 20h/+BPA samples. The persistent staining of γH2AX and poly(ADP-ribose) in +BPA group suggests accumulated DSB damage after BNCT. The early HMGB1 upregulation and γH2AX and poly(ADP-ribose) observed later might be the markers for monitoring the DNA damage induced by BNCT.
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