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Sample records for associados pelotas rs

  1. Biochronostratigraphy and paleoenvironment analysis of Neogene deposits from the Pelotas Basin (well 2-TG-96-RS), Southernmost Brazil.

    PubMed

    Silva, Wagner G; Zerfass, Geise S A; Souza, Paulo A; Helenes, Javier

    2015-09-01

    This paper presents the integration of micropaleontological (palynology and foraminifera) and isotopic (87Sr/86Sr) analysis of a selected interval from the well 2-TG-96-RS, drilled on the onshore portion of the Pelotas Basin, Rio Grande do Sul, Brazil. A total of eight samples of the section between 140.20 and 73.50 m in depth was selected for palynological analysis, revealing diversified and abundant palynomorph associations. Species of spores, pollen grains and dinoflagellate cysts are the most common palynomorphs found. Planktic and benthic calcareous foraminifera were recovered from the lowest two levels of the section (140.20 and 134.30 m). Based on the stratigraphic range of the species of dinoflagellate cysts and sporomorphs, a span age from Late Miocene to Early Pliocene is assigned. The relative age obtained from the 87Sr/86Sr ratio in shells of calcareous foraminifers indicates a Late Miocene (Messinian) correspondence, corroborating the biostratigraphic positioning performed with palynomorphs. Paleoenvironmental interpretations based on the quantitative distribution of organic components (palynomorphs, phytoclasts and amorphous organic matter) throughout the section and on foraminiferal associations indicate a shallow marine depositional environment for the section. Two palynologicals intervals were recognized based on palynofacies analysis, related to middle to outer shelf (140.20 to 128.90 m) and inner shelf (115.75 to 73.50 m) conditions.

  2. Social Mobility and Mental Disorders at 30 Years of Age in Participants of the 1982 Cohort, Pelotas, Rio Grande Do Sul – RS

    PubMed Central

    de Quadros, Lenice de Castro Muniz; Quevedo, Luciana de Avila; Motta, Janaína Vieira dos Santos; Carraro, André; Ribeiro, Felipe Garcia; Horta, Bernardo Lessa; Gigante, Denise Petrucci

    2015-01-01

    This study aimed to evaluate the relationship between mental disorders at 30 years of age and social mobility by formally testing three hypotheses: Risk Accumulation; Critical Period; and Social Mobility. The study was performed using data from the 30-year follow-up of the Pelotas Birth Cohort Study, conducted in 1982, and data from previous follow-ups. The tool used to evaluate mental health was the Self Report Questionnaire (SRQ-20). For the statistical analysis, the chi-square test with the Yates correction was used to estimate the prevalence of mental disorder, and the Poisson regression with robust variance was used to formally test the hypotheses according to the Risk Accumulation, Critical Period and Social Mobility Models. The analyses were stratified by gender. The prevalence of Common Mental Disorders (CMDs) was 24.3% (95% CI 22.9–25.7) when the whole sample was considered. The highest prevalence, 27.1% (95% CI 25.1–29.2), was found in women, and the difference between genders was significant (p < 0.001). CMDs were more frequent in participants who remained “poor” in the three follow-ups. In both men and women, the best fit was obtained with the Risk Accumulation Model, with p = 0.6348 and p = 0.2105, respectively. The results indicate the need to rethink public income maintenance policies. Finally, we suggest further studies to investigate the role of different public policies in decreasing the prevalence of mental disorders and thus contribute proposals of new policies that may contribute to the prevention of these disorders. PMID:26448480

  3. Cohort Profile Update: The 1982 Pelotas (Brazil) Birth Cohort Study

    PubMed Central

    Horta, Bernardo Lessa; Gigante, Denise P; Gonçalves, Helen; dos Santos Motta, JanainaVieira; Loret de Mola, Christian; Oliveira, Isabel O; Barros, Fernando C; Victora, Cesar G

    2015-01-01

    In this manuscript, we update the profile of the 1982 Pelotas Birth Cohort Study.In 1982, 5914 live births whose families lived in the urban are of Pelotas were enrolled in the cohort. In 2012–13, we tried to locate the whole original cohort; 3701 participants were interviewed who, added to the 325 known deaths, represented a follow-up rate of 68.1%. In contrast to the previous home interviews, in this wave all participants were invited to visit the research clinic to be interviewed and examined. The visit was carried out at a mean age of 30.2 years and mainly focused on four categories of outcomes: (i) mental health; (ii) body composition; (iii) precursors of complex chronic diseases; and (iv) human capital. Requests for collaboration by outside researchers are welcome. PMID:25733577

  4. Cohort Profile Update: The 1982 Pelotas (Brazil) Birth Cohort Study.

    PubMed

    Horta, Bernardo Lessa; Gigante, Denise P; Gonçalves, Helen; dos Santos Motta, JanainaVieira; Loret de Mola, Christian; Oliveira, Isabel O; Barros, Fernando C; Victora, Cesar G

    2015-04-01

    In this manuscript, we update the profile of the 1982 Pelotas Birth Cohort Study.In 1982, 5914 live births whose families lived in the urban are of Pelotas were enrolled in the cohort. In 2012-13, we tried to locate the whole original cohort; 3701 participants were interviewed who, added to the 325 known deaths, represented a follow-up rate of 68.1%. In contrast to the previous home interviews, in this wave all participants were invited to visit the research clinic to be interviewed and examined. The visit was carried out at a mean age of 30.2 years and mainly focused on four categories of outcomes: (i) mental health; (ii) body composition; (iii) precursors of complex chronic diseases; and (iv) human capital. Requests for collaboration by outside researchers are welcome.

  5. FUNGI ISOLATED FROM THE EXCRETA OF WILD BIRDS IN SCREENING CENTERS IN PELOTAS, RS, BRAZIL

    PubMed Central

    Mendes, Josiara Furtado; Albano, Ana Paula Neuschrank; Coimbra, Marco Antônio A.; de Ferreira, Gracialda Ferreira; Gonçalves, Carolina Lambrecht; Nascente, Patrícia da Silva; de Mello, João Roberto Braga

    2014-01-01

    The identification of the fungal species belonging to the healthy microflora in animals is a precondition for the recognition of pathological processes causing them. The aim of this study was to investigate the presence of potentially pathogenic fungi in the feces of wild birds collected in Screening Centers. Samples were collected from the feces of 50 cages with different species of birds. The samples were processed according to the modified method STAIB and the plates incubated at 32 °C for up to ten days with daily observation for detection of fungal growth. The isolation of the following species was observed: Malassezia pachydermatis, Candida albicans, C. famata, C. guilliermondii, C. sphaerica, C. globosa, C. catenulata, C. ciferri, C. intermedia, Cryptococcus laurentii, Trichosporon asahii, Geotrichum klebahnii, Aspergillus spp., A. niger and Penicillium spp. Knowing the character of some opportunistic fungi is important in identifying them, facilitating the adoption of preventive measures, such as proper cleaning of cages, since the accumulation of excreta may indicate a risk for both health professionals and centers for screening public health. PMID:25351548

  6. Methodological aspects of the 1993 Pelotas (Brazil) Birth Cohort Study

    PubMed Central

    Victora, Cesar Gomes; Araújo, Cora Luiza Pavin; Menezes, Ana Maria Batista; Hallal, Pedro Curi; Vieira, Maria de Fátima; Neutzling, Marilda Borges; Gonçalves, Helen; Valle, Neiva Cristina; Lima, Rosangela Costa; Anselmi, Luciana; Behague, Dominique; Gigante, Denise Petrucci; Barros, Fernando Celso

    2010-01-01

    This paper describes the main methodological aspects of a cohort study, with emphasis on its recent phases, which may be relevant to investigators planning to carry out similar studies. In 1993, a population based study was launched in Pelotas, Southern Brazil. All 5,249 newborns delivered in the city’s hospitals were enrolled, and sub-samples were visited at the ages of one, three and six months and of one and four years. In 2004-5 it was possible to trace 87.5% of the cohort at the age of 10-12 years. Sub-studies are addressing issues related to oral health, psychological development and mental health, body composition, and ethnography. Birth cohort studies are essential for investigating the early determinants of adult disease and nutritional status, yet few such studies are available from low and middle-income countries where these determinants may differ from those documented in more developed settings. PMID:16410981

  7. Fighting for Excellence: The Case of the Federal University of Pelotas

    ERIC Educational Resources Information Center

    Santana, Silvina; Moreira, Cristiane; Roberto, Teresa; Azambuja, Flavia

    2010-01-01

    This paper investigates the implementation and evaluation of quality management systems within the higher education sector in Brazil. It is based on Institutional and Neo Institutional theories and presents the case of the Federal University of Pelotas, to discuss higher education institutions' options in a context of wide and complex…

  8. Characterization of Listeria monocytogenes isolated from a fresh mixed sausage processing line in Pelotas-RS by PFGE

    PubMed Central

    von Laer, Ana Eucares; de Lima, Andréia Saldanha; Trindade, Paula dos Santos; Andriguetto, Cristiano; Destro, Maria Teresa; da Silva, Wladimir Padilha

    2009-01-01

    Listeria monocytogenes is a bacterium capable to adhere to the surfaces of equipment and utensils and subsequently form biofilms. It can to persist in the food processing environmental for extended periods of time being able to contaminate the final product. The aim of this study was to trace the contamination route of L. monocytogenes on a fresh mixed sausage processing line, from raw material to the final product. The isolates obtained were characterized by serotyping and molecular typing by pulsed-field gel electrophoresis (PFGE) using the restriction enzymes ApaI and AscI. L. monocytogenes was detected in 25% of the samples. The samples of raw material were not contaminated, however, the microorganism was detected in 21% of the environmental samples (food contact and non-food contact), 20.8% of the equipments, 20% of the food worker’s hands, 40% of the mass ready to packaging and in all the final products samples, demonstrating that the contamination of final product occurred during the processing and the importance of cross contamination. PFGE yielded 22 pulsotypes wich formed 7 clusters, and serotyping yielded 3 serotypes and 1 serogroup, however, the presence of serotypes 4b and 1/2b in the final product is of great concern for public health. The tracing of contamination showed that some strains are adapted and persisted in the processing environment in this industry. PMID:24031402

  9. [Laboratory performance of primary care units in tuberculosis diagnosis in Pelotas, Brazil].

    PubMed

    Vieira Beduhn, Dagoberta Alves; Harter, Jenifer; Pieren Dos Reis, Simone; Barbosa Antunes, Luize; Cardozo-Gonzales, Roxana Isabel

    2013-01-01

    In order to assess laboratory performance of Primary Care Units (UAP, Spanish acronym) in TB diagnosis though the sputum smear test in Pelotas, Brazil, a descriptive study was completed which included all sputum smear tests requested at eleven primary care units from 2007 to 2010. To assess laboratory performance, the number of sputum smear tests requested was quantified as well as the time between the request and the reading of the glass slides at the lab. 477 requests were registered at UAP. Of this total, only 51,8% were found in the laboratory’s record book, the lowest performance was 24,2% and the highest 71,4%. Regarding the reading of glass slides, it was determined that 27,7% readings took 8 days or more. It is concluded that the primary care units in Pelotas have a low laboratory performance in TB diagnosis by sputum smear tests.

  10. [MaRS Project

    NASA Technical Reports Server (NTRS)

    Aruljothi, Arunvenkatesh

    2016-01-01

    The Space Exploration Division of the Safety and Mission Assurances Directorate is responsible for reducing the risk to Human Space Flight Programs by providing system safety, reliability, and risk analysis. The Risk & Reliability Analysis branch plays a part in this by utilizing Probabilistic Risk Assessment (PRA) and Reliability and Maintainability (R&M) tools to identify possible types of failure and effective solutions. A continuous effort of this branch is MaRS, or Mass and Reliability System, a tool that was the focus of this internship. Future long duration space missions will have to find a balance between the mass and reliability of their spare parts. They will be unable take spares of everything and will have to determine what is most likely to require maintenance and spares. Currently there is no database that combines mass and reliability data of low level space-grade components. MaRS aims to be the first database to do this. The data in MaRS will be based on the hardware flown on the International Space Stations (ISS). The components on the ISS have a long history and are well documented, making them the perfect source. Currently, MaRS is a functioning excel workbook database; the backend is complete and only requires optimization. MaRS has been populated with all the assemblies and their components that are used on the ISS; the failures of these components are updated regularly. This project was a continuation on the efforts of previous intern groups. Once complete, R&M engineers working on future space flight missions will be able to quickly access failure and mass data on assemblies and components, allowing them to make important decisions and tradeoffs.

  11. Disruption of the Pelota Gene Causes Early Embryonic Lethality and Defects in Cell Cycle Progression

    PubMed Central

    Adham, Ibrahim M.; Sallam, Mahmoud A.; Steding, Gerd; Korabiowska, Monika; Brinck, Ulrich; Hoyer-Fender, Sigrid; Oh, Changkyu; Engel, Wolfgang

    2003-01-01

    Mutations in either the Drosophila melanogaster pelota or pelo gene or the Saccharomyces cerevisiae homologous gene, DOM34, cause defects of spermatogenesis and oogenesis in Drosophila, and delay of growth and failure of sporulation in yeast. These phenotypes suggest that pelota is required for normal progression of the mitotic and meiotic cell cycle. To determine the role of the pelota in mouse development and progression of cell cycle, we have established a targeted disruption of the mouse Pelo. Heterozygous animals are variable and fertile. Genotyping of the progeny of heterozygous intercrosses shows the absence of Pelo−/− pups and suggests an embryo-lethal phenotype. Histological analyses reveal that the homozygous Pelo deficient embryos fail to develop past day 7.5 of embryogenesis (E7.5). The failure of mitotic active inner cell mass of the Pelo−/− blastocysts to expand in growth after 4 days in culture and the survival of mitotic inactive trophoplast indicate that the lethality of Pelo-null embryos is due to defects in cell proliferation. Analysis of the cellular DNA content reveals the significant increase of aneuploid cells in Pelo−/− embryos at E7.5. Therefore, the percent increase of aneuploid cells at E7.5 may be directly responsible for the arrested development and suggests that Pelo is required for the maintenance of genomic stability. PMID:12556505

  12. Geologic evolution and sequence stratigraphy of the offshore Pelotas Basin, southeast Brazil

    SciTech Connect

    Abreu, V.S.

    1996-12-31

    The Brazilian marginal basins have been studied since the beginning of the 70s. At least nine large basins are distributed along the entire Eastern continental margin. The sedimentary infill of these basins consists of lower Cretaceous (continental/lacustrine) rift section underlying marine upper Cretaceous (carbonate platforms) and marine upper Cretaceous/Tertiary sections, corresponding to the drift phase. The sedimentary deposits are a direct result of the Jurassic to lower Cretaceous break-up of the Pangea. This study will focus on the geologic evolution and sequence stratigraphic analysis of the Pelotas basin (offshore), located in the Southeast portion of the Brazilian continental margin between 28{degrees} and 34{degrees} S, covering approximately 50,000 Km{sup 2}. During the early Cretaceous, when the break-up of the continent began in the south, thick basaltic layers were deposited in the Pelotas basin. These basalts form a thick and broad wedge of dipping seaward reflections interpreted as a transitional crust. During Albian to Turonian times, due to thermal subsidence, an extensive clastic/carbonate platform was developed, in an early drift stage. The sedimentation from the upper Cretaceous to Tertiary was characterized by a predominance of siliciclastics in the southeast margin, marking an accentuate deepening of the basin, showing several cycles related to eustatic fluctuations. Studies have addressed the problems of hydrocarbon exploration in deep water setting within a sequence stratigraphic framework. Thus Pelotas basin can provide a useful analogue for exploration efforts worldwide in offshore passive margins.

  13. Geologic evolution and sequence stratigraphy of the offshore Pelotas Basin, southeast Brazil

    SciTech Connect

    Abreu, V.S. )

    1996-01-01

    The Brazilian marginal basins have been studied since the beginning of the 70s. At least nine large basins are distributed along the entire Eastern continental margin. The sedimentary infill of these basins consists of lower Cretaceous (continental/lacustrine) rift section underlying marine upper Cretaceous (carbonate platforms) and marine upper Cretaceous/Tertiary sections, corresponding to the drift phase. The sedimentary deposits are a direct result of the Jurassic to lower Cretaceous break-up of the Pangea. This study will focus on the geologic evolution and sequence stratigraphic analysis of the Pelotas basin (offshore), located in the Southeast portion of the Brazilian continental margin between 28[degrees] and 34[degrees] S, covering approximately 50,000 Km[sup 2]. During the early Cretaceous, when the break-up of the continent began in the south, thick basaltic layers were deposited in the Pelotas basin. These basalts form a thick and broad wedge of dipping seaward reflections interpreted as a transitional crust. During Albian to Turonian times, due to thermal subsidence, an extensive clastic/carbonate platform was developed, in an early drift stage. The sedimentation from the upper Cretaceous to Tertiary was characterized by a predominance of siliciclastics in the southeast margin, marking an accentuate deepening of the basin, showing several cycles related to eustatic fluctuations. Studies have addressed the problems of hydrocarbon exploration in deep water setting within a sequence stratigraphic framework. Thus Pelotas basin can provide a useful analogue for exploration efforts worldwide in offshore passive margins.

  14. RS-84 Engine

    NASA Technical Reports Server (NTRS)

    Stegman, E.

    2003-01-01

    The RS-84 is the first reusable hydrocarbon staged combustion liquid rocket engine. This engine is being developed to meet NASA s crew safety goals with a highly reliable and low cost main engine as a part of the NASA Space Launch Initiative program for the next generation reusable launch system. The NASA-MSFC and Rocketdyne team brings over 50 years of successful rocket engine development experience to meet the challenges of this new program. This team s extensive design database has been anchored with almost five decades of hydrocarbon rocket engine development and flight operations experience including Delta, Atlas, and Saturn vehicles and nearly three decades of successfully operating the world s only reusable pump-fed rocket engine, the Space Shuttle Main Engine. The team also fully benefits from the proven and experienced engineering staffs that recently completed the successful MC-1 FASTRAC , XRS-2200, and RS-68 engine development programs and the ongoing IPD and RS-76 technology development. Advances in integrated parametric design and analysis tools, advanced materials knowledge base, and state-of-the-art fabrication processes anchored and refined during the recent engine development programs are already being used by the team to design this engine.

  15. The Pelotas Birth Cohort Study, Rio Grande do Sul, Brazil, 1982-2001

    PubMed Central

    2010-01-01

    Given the growing recognition of the importance of the life course approach for the determination of chronic diseases, birth cohort studies are becoming increasingly important. This paper describes the methods used in the 1982 Pelotas (Brazil) birth cohort study, one of the largest and longest studies of this type in developing countries. All 5,914 hospital births occurring in Pelotas in 1982 (over 99% of all deliveries) were studied prospectively. The main stages of the study took place in 1983, 1984, 1986, 1995, 1997, 2000, and 2001. More than two thousand variables are available for each subject who participated in all stages of the study. Recent phases of the study included the examination of 2,250 males when presenting for the army recruitment exam in 2000, the study of a 27% sample of men and women in 2001 through household visits, and the study of over 400 children born to the cohort women. Follow-up rates in the recent stages of the cohort were 78.9% for the army examination and 69.0% for the household visits. Ethnographic and oral health studies were conducted in sub-samples. Some recent results on blood pressure, adolescent pregnancy, and asthma are presented as examples of utilization of the data. Suggestions on lessons learned for other cohort studies are proposed. PMID:14666206

  16. Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis

    PubMed Central

    Hartwig, Fernando Pires; Horta, Bernardo Lessa; Smith, George Davey; de Mola, Christian Loret; Victora, Cesar Gomes

    2016-01-01

    Background: Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population. Methods: We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis. Results: In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with −0.26 (95% CI: −0.33; −0.19) kg/m2 in BMI and −0.31 (95% CI: −0.46; −0.16) and -0.35 (95% CI: −0.46; −0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m2] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP. Conclusions: Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP. PMID:27170764

  17. Cohort profile update: The 1993 Pelotas (Brazil) birth cohort follow-up visits in adolescence.

    PubMed

    Gonçalves, Helen; Assunção, Maria Cf; Wehrmeister, Fernando C; Oliveira, Isabel O; Barros, Fernando C; Victora, Cesar G; Hallal, Pedro C; Menezes, Ana Mb

    2014-08-01

    In this paper we update the profile of the 1993 Pelotas (Brazil) Birth Cohort Study, with emphasis on a shift of priority from maternal and child health research topics to four main categories of outcome variables, collected throughout adolescence: (i) mental health; (ii) body composition; (iii) risk factors for non-communicable diseases (NCDs); (iv) human capital. We were able to trace 81.3% (n = 4106) of the original cohort at 18 years of age. For the first time, the 18-years visit took place entirely on the university premises, in a clinic equipped with state-of-the-art equipment for the assessment of body composition. We welcome requests for data analyses from outside scientists. For more information, refer to our website (http://www.epidemio-ufpel.org.projetos_de_pesquisas/estudos/coorte_1993) or e-mail the corresponding author.

  18. [Adult obesity in Pelotas, Rio Grande do Sul, Brazil, and the association with socioeconomic status].

    PubMed

    Gigante, Denise Petrucci; Dias-da-Costa, Juvenal Soares; Olinto, Maria Teresa Anselmo; Menezes, Ana Maria Baptista; Silvia, Macedo

    2006-09-01

    The objectives of this study were to: (1) describe obesity prevalence in a Brazilian city; (2) test the association between obesity and socio-demographic variables; and (3) compare results with a survey in the same city in 1994. A cross-sectional population-based study was carried out in a random sample of 1,968 20-69-year-olds residing in the urban area of Pelotas, Rio Grande do Sul State. Obesity was defined as Body Mass Index (BMI) > 30 kg/m(2). Age and sex-adjusted obesity prevalence was 19.4%. Schooling was not associated with obesity in men. Obesity prevalence was higher in middle-income men. Women with more schooling had lower obesity rates. There was a non-statistically significant reduction in obesity rates compared to a similar study from 1994.

  19. Post-collisional subvolcanic rhyolites associated with the Neoproterozoic Pelotas Batholith, southern Brazil

    NASA Astrophysics Data System (ADS)

    Oliveira, Diego Skieresz de; Sommer, Carlos Augusto; Philipp, Ruy Paulo; Lima, Evandro Fernandes de; Basei, Miguel Ângelo Stipp

    2015-11-01

    Neoproterozoic volcanic and subvolcanic rhyolitic systems in southernmost Brazil are correlated with acid magmatism linked to different petrotectonic associations of the Sul-Rio-Grandense Shield. A portion of this volcanism in the Dom Feliciano Belt is associated with the Pelotas Batholith, which resulted from magmatic episodes associated with the Ediacaran post-collisional evolution of southern Brazil. Ana Dias Rhyolite is the main subvolcanic occurrence of this volcanism that took place in the Quitéria region, in the central part of Rio Grande do Sul State. The acid magmatism has been commonly associated with the most differentiated granite suite phases during the final stages of emplacement of the Pelotas Batholith. The Ana Dias Rhyolite is characterized as an intrusive body with rocks that present a porphyritic to seriated texture and a gradational variation to fine-grained equigranular rocks. New zircon U-Pb dating indicates crystallization age of 581.9 ± 1.9 Ma for the Ana Dias Rhyolite. Geochemistry data characterize the rhyolites as belonging to the alkaline series; they present a metaluminous to peraluminous character; elevated SiO2 and alkali concentrations, high FeOt/FeOt + MgO ratios and agpaitic index; and low Al2O3, CaO, and MgO contents. The Zr, Rb, Y, Nb, and Ga concentrations are moderate when compared with the relatively low Ba and Sr contents. These geochemistry characteristics are common in acid magmas with alkaline affinity. The behavior of certain trace elements and REE demonstrate enrichment in more incompatible elements, in addition to the negative anomaly of Ba, the slight enrichment in Ce relative to adjacent elements, as well as the enrichment in K2O and Rb relative to Nb, suggesting magmas derived from mantle sources enriched in incompatible elements with some crustal contamination. The chemical characteristics are similar to those of A-type granites associated with Neoproterozoic post-collision magmatism in the Sul

  20. PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity in Latvians, Lithuanians and Taiwanese

    PubMed Central

    Sjakste, Tatjana; Paramonova, Natalia; Wu, Lawrence Shi-Shin; Zemeckiene, Zivile; Sitkauskiene, Brigita; Sakalauskas, Raimundas; Wang, Jiu-Yao; Sjakste, Nikolajs

    2014-01-01

    PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity was investigated in 1438 unrelated subjects from Latvia, Lithuania and Taiwan. In general, polymorphism of each individual locus showed tendencies similar to determined previously in HapMap populations. Main differences concern Taiwanese and include presence of rs2277460 rare allele A not found before in Asians and absence of rs2295827 rare alleles homozygotes TT observed in all other human populations. Observed patterns of SNPs and haplotype diversity were compatible with expectation of neutral model of evolution. Linkage disequilibrium between the rs2295826 and rs2295827 was detected to be complete in Latvians and Lithuanians (D´ = 1; r2 = 1) and slightly disrupted in Taiwanese (D´ = 0.978; r2 = 0.901). Population differentiation (FST statistics) was estimated from pairwise population comparisons of loci variability, five locus haplotypes and PSMA6 and PSMC6 two locus haplotypes. Latvians were significantly different from all Asians at each of 5 SNPs and from Lithuanians at the rs1048990 and PSMC6 loci. Lithuanian and Asian populations exhibited similarities at the PSMC6 loci and were different at the PSMA6 and PSMA3 SNPs. Considering five locus haplotypes all European populations were significantly different from Asian; Lithuanian population was different from both Latvian and CEU. Allele specific patterns of transcription factor binding sites and splicing signals were predicted in silico and addressed to eventual functionality of nucleotide substitutions and their potential to be involved in human genome evolution and geographical adaptation. Current study represents a novel step toward a systematic analysis of the proteasomal gene genetic diversity in human populations. PMID:25606411

  1. Tracking of physical activity during adolescence: the 1993 Pelotas Birth Cohort, Brazil

    PubMed Central

    Azevedo, Mario Renato; Menezes, Ana Maria; Assunção, Maria Cecília; Gonçalves, Helen; Arumi, Ignasi; Horta, Bernardo Lessa; Hallal, Pedro Curi

    2014-01-01

    OBJECTIVE To analyze physical activity during adolescence in participants of the 1993 Pelotas Birth Cohort Study, Brazil. METHODS Data on leisure time physical activity at 11, 15, and 18 years of age were analyzed. At each visit, a cut-off point of 300 min/week was used to classify adolescents as active or inactive. A total of 3,736 participants provided data on physical activity at each of the three age points. RESULTS A significant decline in the proportion of active adolescents was observed from 11 to 18 years of age, particularly among girls (from 32.9% to 21.7%). The proportions of girls and boys who were active at all three age points were 28.0% and 55.1%, respectively. After adjustment for sex, economic status, and skin color, participants who were active at 11 and 15 years of age were 58.0% more likely to be active at 18 years of age compared with those who were inactive at 11 and 15 years of age. CONCLUSIONS Physical activity declined during adolescence and inactivity tended to track over time. Our findings reinforce the need to promote physical activity at early stages of life, because active behavior established early tends to be maintained over time. PMID:26039395

  2. Criminal victimization in childhood and adolescence according to official records: the Pelotas (Brazil) birth cohort study

    PubMed Central

    Giraldo Gallo, Erika Alejandra; Menezes, Ana Maria B.; Murray, Joseph; Duarte da Silva, Luciana Anselmi; Wehrmeister, Fernando César; Gonçalves, Helen; Barros, Fernando

    2016-01-01

    This article describes different types of officially recorded victimization among 5,249 children in the 1993 birth cohort in the city of Pelotas, Rio Grande do Sul State, Brazil. Official data were obtained from the Secretariat for Public Security and the Special Court for Children and Youth. Victimization was registered for in 1,150 cohort members, with 1,396 incidents recorded as of December 31, 2012. The total incidence of victimization was 15.7 ocorrences per 1,000 person-years, with the majority involving violent victimization (12.7 per 1,000 person-years). Victimization increased gradually in childhood and rapidly throughout adolescence. The highest incidence rates were among females (p < 0.05), the poor (p < 0.05), children of adolescent mothers (p < 0.001), and children of single mothers (p < 0.05). The most common violent victimization types were physical injuries, robbery, and crimes against personal freedom; non-violent victimization mainly involved theft. Studies like this help identify lifetime risk and protective factors for victimization, highlighting the importance of surveillance and control measures against violence. PMID:27580232

  3. Taming troubled teens: The social production of mental morbidity amongst young mothers in Pelotas, Brazil

    PubMed Central

    Béhague, D.P.; Gonçalves, H.D.; Gigante, D.; Kirkwood, B.R.

    2012-01-01

    Explanations for the association between teen-childbearing and subsequent mental morbidity vary considerably, from those based on neurological theories of development to those investigating underlying social and economic determinants. Based on longitudinal epidemiological and ethnographic sub-studies of the 1982 Pelotas birth cohort study, this paper explores the hypothesis that teen childbearing and subsequent mental morbidity have become associated through the interplay of culture, society, and biology in situations where teen pregnancy has become a stigmatised object of scientific and public health attention. Results show that the effect of teen childbearing on subsequent mental morbidity remained significant in the multivariate analysis. Ethnographic analysis, together with epidemiological effect modification analyses, suggest that this association is partially accounted for by the fact that it is more pronounced amongst a specific subgroup of women of low socio-economic status who, being more politicised about societal injustice, were also more critically engaged with – and thus troubled by – the inequitable institutionalisation of life-cycle transitions. With time, these women became highly critical of the institutionalised identification of early childbearing as a key violation of life-cycle norms and the differential class-based application of scientific knowledge on its causes and consequences. Public health campaigns should consider how the age-based institutionalisation of developmental norms has enabled the stigmatisation of those identified as transgressors. PMID:22196249

  4. Education and work in the Pelotas birth cohort from 1982 to 2004-5, Southern Brazil

    PubMed Central

    Barros, Fernando C; Gigante, Denise P; Horta, Bernardo L; Victora, Cesar G

    2009-01-01

    OBJECTIVE: To analyze the influence of biological and socioeconomic factors throughout life on entry into the university and insertion in the work force of young adults from the 1982 birth cohort. METHODS: Longitudinal study of 5,914 births that took place in the city of Pelotas, Southern Brazil, in 1982. Data was collected by means of questionnaires applied on young adults when accompanying the 1982 cohort in 2004-5. Information was gathered concerning educational level and insertion in the labor market. Poisson Regression was utilized to study the effect of demographic and socioeconomic variables, as well as birth weight and maternal breastfeeding, on the outcomes. RESULTS: On the average, these young adults had 9.4 (± 3.1) years of schooling and 42% of them were attending school in 2004-5. One in five young adults had entered a university and approximately two thirds were working during the month prior to the interview. Entry in the university was determined by economic conditions. Furthermore, women's birth weight and breastfeeding among men influenced this outcome. Insertion in the labor market was more frequent among the poorer men, but this did not affect women's outcomes in this respect. CONCLUSIONS: The low inclusion in the university and the need to enter the labor market among the poor families maintains a vicious circle that reproduces the dominant social hierarchy. PMID:19142341

  5. Trajectories of maternal depression and offspring psychopathology at 6 years: 2004 Pelotas cohort study

    PubMed Central

    Matijasevich, Alicia; Murray, Joseph; Cooper, Peter J.; Anselmi, Luciana; Barros, Aluísio J.D.; Barros, Fernando C.; Santos, Iná S.

    2015-01-01

    Background Few studies have addressed the course and severity of maternal depression and its effects on child psychiatric disorders from a longitudinal perspective. This study aimed to identify longitudinal patterns of maternal depression and to evaluate whether distinct depression trajectories predict particular psychiatric disorders in offspring. Methods Cohort of 4231 births followed-up in the city of Pelotas, Brazil. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 3, 12, 24 and 48 months and 6 years after delivery. Psychiatric disorders in 6-year-old children were evaluated through the development and well-being assessment (DAWBA) instrument. Trajectories of maternal depression were calculated using a group-based modelling approach. Results We identified five trajectories of maternal depressive symptoms: a “low” trajectory (34.8%), a “moderate low” (40.9%), a “increasing” (9.0%), a “decreasing” (9.9%), and a “high-chronic” trajectory (5.4%). The probability of children having any psychiatric disorder, as well as both internalizing and externalizing problems, increased as we moved from the “low” to the “high-chronic” trajectory. These differences were not explained by maternal and child characteristics examined in multivariate analyses. Limitations Data on maternal depression at 3-months was available on only a sub-sample. In addition, we had to rely on maternal report of child’s behavior alone. Conclusions The study revealed an additive effect on child outcome of maternal depression over time. We identified a group of mothers with chronic and severe symptoms of depression throughout the first six years of the child life and for this group child psychiatric outcome was particularly compromised. PMID:25553403

  6. Maternity and paternity in the Pelotas birth cohort from 1982 to 2004-5, Southern Brazil

    PubMed Central

    Gigante, Denise P; Barros, Fernando C; Veleda, Rosângela; Gonçalves, Helen; Horta, Bernardo L; Victora, Cesar G

    2009-01-01

    OBJECTIVE To describe the prevalence of maternity and paternity among subjects and its association with perinatal, socioeconomic and demographic variables. METHODS The participants were youth, aged 23, on the average, accompanied in a cohort study since they were born, in 1982, in Pelotas (Southern Brazil) and interviewed in 2004-5. Those who were considered eligible referred having had one or more children, whether these were liveborns or stillborns. Data was collected on reproductive health as well as socioeconomic and demographic information, by means of two different instruments. The independent variables were sex and skin color, family income in 1982 and in 2004-5, changes in income, birth weight and educational level when aged 23 years old. Crude and adjusted analysis were conducted by means of Poisson regression so as to investigate the effects of the independent variables on maternity/paternity during adolescence. RESULTS Among the 4,297 youth interviewed, 1,373 (32%) were parents and 842 (19.6%) of these had experienced maternity/paternity during their adolescence. Planned pregnancy of the first child was directly related to the youth’s age. Socioeconomic variables were inversely related to the occurrence of maternity/paternity during adolescence. The probability of being an adolescent mother was higher among black and mixed skin colored women, but skin color was not associated to adolescent paternity. CONCLUSIONS There was a strong relation between adolescent maternity/paternity and socioeconomic conditions, which should be taken into consideration when delineating preventive actions in the field of public health. PMID:19142344

  7. Early age at menarche and wheezing in adolescence. The 1993 Pelotas (Brazil) birth cohort study

    PubMed Central

    Joseph, Gary; Baptista Menezes, Ana Maria; Wehrmeister, Fernando C.

    2015-01-01

    Objective To evaluate the effect of menarche before 11 years of age on the incidence of wheezing/asthma in girls 11 to 18 years of age. Methods The study sample comprised 1,350 girls from a birth cohort that started in 1993 in the urban area of the city of Pelotas, southern Brazil; this cohort was followed until 18 years of age. We assessed wheezing by the question, “Have you ever had wheezing in the chest at any time in the past?,” from the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Early menarche was defined as occurring before 11 years of age. We estimated the cumulative incidence of wheezing excluding from the analysis all those participants who reported wheezing before age of 11 years. We performed the chi-square test to assess the association between ever wheezing and independent variables. Poisson regression models with robust variance were used to estimate cumulative incidence ratios. Results The average age at menarche in the cohort girls was 12 years (95% CI: 11.1–12.1). The prevalence of early menarche before 11 years of age was 11% (95% CI: 9.7–12.3). The cumulative incidence of wheezing from 11 to 18 years of age was 33.5% (95% CI: 30.9– 36.0). The crude association between ever wheezing in adolescence and early menarche before age 11 was 1.19 (95% CI: 0.96–1.48). After adjusting for early childhood and contemporaneous variables, no significant association for early menarche before 11 years of age and wheezing during adolescence was found (CIR: 1.18; CI95%: 0.93-1.49). Conclusion Early menarche before 11 years of age is not associated with an increased risk of wheezing during adolescence. PMID:26870751

  8. Prevalence of wheezing in the chest among adults from the 1982 Pelotas birth cohort, Southern Brazil

    PubMed Central

    Menezes, Ana M B; Lima, Rosângela C; Minten, Gicele C; Hallal, Pedro C; Victora, Cesar G; Horta, Bernardo L; Gigante, Denise P; Barros, Fernando C

    2009-01-01

    OBJECTIVE: To estimate the prevalence of wheezing in the chest among adults, and to explore the effect of some variables on the prevalence of this condition. METHODS: This was a prospective cohort study on individuals born in the city of Pelotas (Southern Brazil) in 1982. A total of 4,297 subjects was traced in 2004-5, representing 77.4% of the original cohort. Data were collected by means of interviews using the ISAAC (International Study of Asthma and Allergies in Childhood Steering Committee) questionnaire. Associations between the outcome “occurrence of wheezing in the chest within the 12 months prior to the interview” and the variables of socioeconomic, demographic and birth characteristics were tested by means of multivariable analyses, using Poisson regression. RESULTS: The prevalence of wheezing over the preceding year was 24.9%. Among the individuals reporting wheezing, 54.6% reported difficulty in sleeping, and 12.9% reported difficulty in speaking due to wheezing. The prevalence of wheezing in the chest was significantly higher among women. This association was maintained in analyses adjusted for non-white skin color, family history of asthma and low socioeconomic level. Among men, there was no significant association in the analyses adjusted for skin color and family income at birth. Family histories of asthma and poverty throughout life presented significant associations with wheezing in the chest. For both sexes, there were no associations with the variables of birth weight and breastfeeding duration. CONCLUSIONS: The prevalence of wheezing in the chest was high, and subjects with low family income at birth were more likely to have had wheezing in the chest over the preceding year. PMID:19142351

  9. RS CVn stars - Chromospheric phenomena

    NASA Technical Reports Server (NTRS)

    Bopp, B. W.

    1983-01-01

    The observational information regarding chromospheric emission features in surface-active RS CVn stars is reviewed. Three optical features are considered in detail: Ca II H and K, Balmer H-alpha and He I 10830 A. While the qualitative behavior of these lines is in accord with solar-analogy/rotation-activity ideas, the quantitative variation and scaling are very poorly understood. In many cases, the spectroscopic observations with sufficient SNR and resolution to decide these questions have simply not yet been made. The FK Com stars, in particular, present extreme examples of rotation that may well tax present understanding of surface activity to its limits.

  10. Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children.

    PubMed

    Muñoz-Yáñez, C; Pérez-Morales, R; Moreno-Macías, H; Calleros-Rincón, E; Ballesteros, G; González, R A; Espinosa, J

    2016-01-01

    Concerning the genetic factors of obesity, no consistent association between populations has been reported, which may be due to the frequency of polymorphisms, the lifestyle of studied populations and its interaction with other factors. We studied a possible association of polymorphisms FTO rs9939609, PPARG rs1801282, and ADIPOQ rs4632532 and rs182052 with obesity phenotypes in 215 Mexican children. Glucose, triglycerides, cholesterol, HDL and LDL were measured. In addition, weight, height, waist circumference and triceps skin thickness were recorded. High-energy diets and sedentary behavior were evaluated with a validated questionnaire. In contrast with other reports, only FTO rs9939609 was associated with obesity related-traits, including BMI (p = 0.03), waist circumference (p = 0.02), triceps skinfold (p = 0.03) and waist/height ratio (p = 0.01), and also with cholesterol levels (p = 0.02) and LDL (p = 0.009). Lower levels of triglycerides (p=0.04) were related with presence of PPARG rs1801282, while ADIPOQ rs4632532 showed an effect on HDL (p = 0.03) levels. On the other hand, diet, physical activity and screen time were not related with obesity. In summary, only FTO rs9939609 was associated with obesity related-traits, while PPARG2 rs1801282 and ADIPOQ rs4632532 were involved in lipid metabolism.

  11. Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children

    PubMed Central

    Muñoz-Yáñez, C; Pérez-Morales, R; Moreno-Macías, H; Calleros-Rincón, E; Ballesteros, G; González, R. A; Espinosa, J

    2016-01-01

    Abstract Concerning the genetic factors of obesity, no consistent association between populations has been reported, which may be due to the frequency of polymorphisms, the lifestyle of studied populations and its interaction with other factors. We studied a possible association of polymorphisms FTO rs9939609, PPARG rs1801282, and ADIPOQ rs4632532 and rs182052 with obesity phenotypes in 215 Mexican children. Glucose, triglycerides, cholesterol, HDL and LDL were measured. In addition, weight, height, waist circumference and triceps skin thickness were recorded. High-energy diets and sedentary behavior were evaluated with a validated questionnaire. In contrast with other reports, only FTO rs9939609 was associated with obesity related-traits, including BMI (p = 0.03), waist circumference (p = 0.02), triceps skinfold (p = 0.03) and waist/height ratio (p = 0.01), and also with cholesterol levels (p = 0.02) and LDL (p = 0.009). Lower levels of triglycerides (p=0.04) were related with presence of PPARG rs1801282, while ADIPOQ rs4632532 showed an effect on HDL (p = 0.03) levels. On the other hand, diet, physical activity and screen time were not related with obesity. In summary, only FTO rs9939609 was associated with obesity related-traits, while PPARG2 rs1801282 and ADIPOQ rs4632532 were involved in lipid metabolism. PMID:27560839

  12. BODY COMPOSITION AND SOMATOTYPE OF PROFESSIONAL AND U23 HAND BASQUE PELOTA PLAYERS.

    PubMed

    Urdampilleta, Aritz; Mielgo-Ayuso, Juan; Valtueña, Jara; Holway, Francis; Cordova, Alfredo

    2015-11-01

    Introducción: casi no hay ninguna referencia sobre las características antropométricas, la composición corporal y el somatotipo de la mano de los jugadores de pelota vasca (pelotaris) en la literatura científica. Objetivos: el objetivo de esta investigación fue comparar la composición corporal de pelotaris profesionales y sub-23 para crear el perfil antropométrico de este deporte. Métodos: participaron diez pelotaris sub-23 y ocho pelotaris profesionales. Las medidas antropométricas fueron recogidas siguiendo el protocolo de la Sociedad Internacional de Promoción de Protocolo Cineantropometría (ISAK). La masa grasa (FM) se calculó utilizando la ecuación Yushasz modificada por Carter, y la masa muscular (MM) mediante la ecuación de Lee. Los componentes del somatotipo fueron estimados mediante la ecuación Carter y Heath. El nivel de hidratación de los pelotaris se midió con un analizador tetrapolar de impedancia bioeléctrica (BIA). Resultados: los pelotaris profesionales tienen significativamente menor FM (en % (p = 0,001); en kg (p = 0,025) y en los sumatorios de 4, 6 y 8 pliegues cutáneos (p = 0,001); mayor MM (p = 0,015) y un menor componente endomórfico (p < 0,001) que los pelotaris sub-23. Asimismo, los profesionales tienen una mayor cantidad de agua corporal (p = 0,001) y un diámetro mayor biestiloideo de muñeca (p = 0,014). Los pelotaris profesionales son un morfotipo caracterizado por una baja FM (8,9 ± 1,1%) y una intermedia MM (47 ± 1,7%), además de tener una altura de 183,0 ± 7,1 cm y un peso de 85,9 ± 7,6 kg. Conclusión: los principales resultados de este estudio mostraron que las características antropométricas no modificables por el entrenamiento (por ejemplo, altura, envergadura y diámetro de la muñeca) son componentes importantes para convertirse en un pelotari profesional. Por otra parte, las características relacionadas con el entrenamiento y la dieta han mostrado ser mejores en los pelotaris profesionales (menor FM

  13. Maternal education inequalities in height growth rates in early childhood: 2004 Pelotas birth cohort study.

    PubMed

    Matijasevich, Alicia; Howe, Laura D; Tilling, Kate; Santos, Iná S; Barros, Aluísio J D; Lawlor, Debbie A

    2012-05-01

    Socio-economic inequalities in attained height have been reported in many countries. The aim of this study was to explore the age at which maternal education inequalities in child height emerge among children from a middle-income country. Using data from the 2004 Pelotas cohort study from Brazil we modelled individual height growth trajectories in 2106 boys and 1947 girls from birth to 4 years using a linear spline mixed-effects model. We examined the associations of maternal education with birth length and trajectories of growth in length/height, and explored the effect of adjusting for a number of potential confounder or mediator factors. We showed linear and positive associations of maternal education with birth length and length/height growth rates at 0-3 months and 12-29/32 months with very little association at 3-12 months, particularly in boys. By age 4 years the mean height of boys was 101.06 cm (SE = 0.28) in the lowest and 104.20 cm (SE = 0.15) in the highest education category (mean difference 3.14 cm, SE = 0.32, P < 0.001). Among girls the mean height was 100.02 cm (SE = 0.27) and 103.03 cm (SE = 0.15) in the lowest and highest education categories, respectively (mean difference 3.01 cm, SE = 0.31, P < 0.001). For both boys and girls there was on average a 3-cm difference between the extreme education categories. Adjusting for maternal height reduced the observed birth length differences across maternal education categories, but differences in postnatal growth rates persisted. Our data demonstrate an increase in the absolute and relative inequality in height after birth; inequality increases from approximately 0.2 standard deviations of birth length to approximately 0.7 standard deviations of height at age 4, indicating that height inequality, which was already present at birth, widened through differential growth rates to age 2 years.

  14. Increase in child behavior problems among urban Brazilian 4-year olds: 1993 and 2004 Pelotas birth cohorts

    PubMed Central

    Matijasevich, Alicia; Murray, Elizabeth; Stein, Alan; Anselmi, Luciana; Menezes, Ana M; Santos, Iná S; Barros, Aluísio JD; Gigante, Denise P; Barros, Fernando C; Victora, Cesar G

    2014-01-01

    Background There are an increasing number of reports on time trends in child and adolescent psychological problems but none from low- and middle-income countries, and very few covering the preschool period. The aim was to investigate changes in preschool behavioral/emotional problems in two birth cohorts from a middle-income country born 11 years apart. Methods We analyzed data from the 1993 and 2004 Pelotas birth cohort studies from Brazil. A subsample of 4-year olds from the 1993 cohort (634) and all 4-year olds from the 2004 cohort (3750) were assessed for behavioral/emotional problems through maternal report using the Child Behavior Checklist (CBCL). Response rates in these two population-based cohorts were above 90%. Results We found a significant increase in CBCL total problems, internalizing and externalizing mean scores over the 11-year period. For 1993 and 2004 Pelotas cohorts, respectively, CBCL mean values (SE) total problems scores were 27.9 (0.8) and 34.7 (0.3); for internalizing scores, 5.7 (0.2) and 6.3 (0.1) and for externalizing scores, 12.4 (0.4) and 15.5 (0.1). After adjusting for confounding variables, the largest increase from 1993 to 2004 was identified in the aggressive behavior syndrome score (Cohen's d = .50), followed by the externalizing problem score (Cohen's d = .40) and CBCL total problem score (Cohen's d = .36), respectively. The rise in child psychological problems was more marked in children from families with fewer assets and with less educated mothers. Conclusions Our findings provide evidence for a substantial increase in preschool behavioral problems among children in Brazil over an 11-year period. PMID:24735354

  15. Systematic Pressure and Temperature Differences between Vaisala RS80 and RS92 Radiosonde-Systems

    NASA Astrophysics Data System (ADS)

    Steinbrecht, W.; Claude, H.; Schönenborn, F.

    2008-12-01

    National meteorological centers are replacing the widely used Vaisala RS80 radiosonde with the newer RS90 or RS92. Such change-overs often introduce erroneous steps into long-term atmospheric temperature records. We show that twin-flight campaigns with RS80 and RS92 sondes on the same balloon, and the transition from RS80 to RS92 in operational radio-soundings over Germany, consistently indicate higher temperature readings from RS92 sondes in the stratosphere. In our presentation we summarize these main differences between RS80 and RS92. Significant differences are found in the stratosphere, above the 100~hPa level. The accuracy of our temperature results is of the order of 0.1 to 0.5~K, and at this level we were not able to find significant differences in the troposphere, although there are indications for slightly higher daytime temperatures from RS92 sondes. During day-time and near 50~hPa, RS92s report +0.3 ± 0.2~K higher temperature than RS80s, increasing to +0.7 ± 0.4~K near 10~hPa (2σ uncertainties). At night, the difference is smaller, +0.1 ± 0.1~K near 50~hPa to +0.35 ± 0.2~K near 10~hPa. The mean day-to-night difference (12-00~UT) is also larger for RS92s, by 0.1± 0.06~K near 70~hPa, and by 0.76± 0.16~K near 10~hPa. The main contribution to this stratospheric day-time difference comes from an over-correction of the radiation error in the Vaisala RS80 data processing. The night-time difference at stratospheric levels (and part of the day-time difference) is due to a low bias of the RS80 pressure measurement, typically by -0.4~hPa near 10~hPa. This shifts temperature readings to lower pressure/ higher altitude. For stratospheric levels, it results in lower temperatures from RS80 sondes (due to the vertical temperature increase). Generally, RS92s give better temperature repeatabiliy, ±0.25~K (2σ) near 50~hPa, and much more precise pressure, ±0.2~hPa near 50~hPa, compared to RS80 systems, ±0.5~K, or ±1.5~hPa. Geopotential heights from RS92s are

  16. Search for RS-gravitons at CDF

    SciTech Connect

    Strologas, John; /New Mexico U.

    2011-09-01

    We present a search for Randall-Sundrum (RS) gravitons decaying to diphotons or dielectrons or dimuons, performed with the CDF II detector and using up to 5.7 fb{sup -1} of integrated luminosity. The respective mass spectra are consistent with the ones expected by the standard model. For the RS-model parameter k/{bar M}{sub Pl} = 0.1, RS-gravitons with mass less than 1111 GeV/c{sup 2} are excluded at 95% CL.

  17. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains site

    SciTech Connect

    Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri; Lehtinen, Raisa; Baxter, Shannon; Toto, Tami; Johnson, Karen L.

    2016-06-20

    In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 and RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. These results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.

  18. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains Site

    SciTech Connect

    Jensen, M. P.; Holdridge, D.; Survo, P.; Lehtinen, R.; Baxter, S.; Toto, T.; Johnson, K. L.

    2015-11-02

    In the fall of 2013, the Vaisala RS41-SG (4th generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity and pressure. Thus, in order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Facility site in north Central Oklahoma USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results suggest that the RS92 and RS41 measurements generally agree within manufacturer specified tolerances with notable exceptions when exiting liquid cloud layers where the "wet bulbing" effect is mitigated in the RS41 observations. The RS41 measurements also appear to show a smaller impact from solar heating. These results suggest that the RS41 does provide important improvements, particularly in cloudy conditions, but under most observational conditions the RS41 and RS92 measurements agree within the manufacturer specified limits and so a switch to RS41 radiosondes will have little impact on long-term observational records.

  19. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains Site

    DOE PAGES

    Jensen, M. P.; Holdridge, D.; Survo, P.; ...

    2015-11-02

    In the fall of 2013, the Vaisala RS41-SG (4th generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity and pressure. Thus, in order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Facility site in north Central Oklahoma USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results suggest that the RS92 and RS41 measurements generally agree within manufacturermore » specified tolerances with notable exceptions when exiting liquid cloud layers where the "wet bulbing" effect is mitigated in the RS41 observations. The RS41 measurements also appear to show a smaller impact from solar heating. These results suggest that the RS41 does provide important improvements, particularly in cloudy conditions, but under most observational conditions the RS41 and RS92 measurements agree within the manufacturer specified limits and so a switch to RS41 radiosondes will have little impact on long-term observational records.« less

  20. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains site

    SciTech Connect

    Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri; Lehtinen, Raisa; Baxter, Shannon; Toto, Tami; Johnson, Karen L.

    2016-07-20

    In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 and RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. In addition, these results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.

  1. Role of redoximiRs in fibrogenesis.

    PubMed

    Fierro-Fernández, Marta; Miguel, Verónica; Lamas, Santiago

    2016-04-01

    Fibrosis can be defined as an excessive accumulation of extracellular matrix (ECM) components, ultimately leading to stiffness, scarring and devitalized tissue. MicroRNAs (miRNAs) are short, 19-25 nucleotides (nt), non-coding RNAs involved in the post-transcriptional regulation of gene expression. Recently, miRNAs have also emerged as powerful regulators of fibrotic processes and have been termed "fibromiRs". Oxidative stress represents a self-perpetuating mechanism in fibrogenesis. MiRNAs can also influence the expression of genes responsible for the generation of reactive oxygen species (ROS) and antioxidant defence and are termed "redoximiRs". Here, we review the current knowledge of mechanisms by which "redoximiRs" regulate fibrogenesis. This new set of miRNAs may be called "redoxifibromiRs".

  2. Exploring multiple trajectories of causality: collaboration between Anthropology and Epidemiology in the 1982 birth cohort, Pelotas, Southern Brazil

    PubMed Central

    Béhague, Dominique P; Gonçalves, Helen

    2009-01-01

    OBJECTIVE: Although the relationship between epidemiology and anthropology has a long history, it has generally been comprised of the integration of quantitative and qualitative methods. Only recently have the two fields begun to converge along theoretical lines, leading to a growing mutual interest in explaining rather than simply describing phenomena. This paper aimed to illustrate how ethnographic analyses can be used to assist with the in-depth and theoretically-imbued interpretation of epidemiological results. METHODS: The anthropological analysis presented in this paper used ethnographic data collected as part of the ongoing 1982 birth cohort study, between 1997 and 2007 in Pelotas, Southern Brazil. Analyses were framed according to the results presented in two of the epidemiological articles published in this series on the determinants of mental morbidity and age of sexual initiation. RESULTS AND CONCLUSIONS: The ethnographic results show that statistical associations consist of multiple pathways of influence and causality that generally correspond to the unique experiences of specific subgroups. In exploring these pathways, the paper highlights the importance of an additional set of mediating factors that account for epidemiological results; these include the awareness and experience of inequities, the role of violence in everyday life, traumatic life events, increasing social isolation and emotional introversion as a response to life's difficulties, and differing approaches towards socio-psychological maturation. Theoretical and methodological collaboration between anthropology and epidemiology is important for public health, as it has positively modified both fields. PMID:19142353

  3. Maternal anthropometric characteristics in pregnancy and blood pressure among adolescents: 1993 live birth cohort, Pelotas, southern Brazil

    PubMed Central

    2010-01-01

    Background We investigated the association between maternal anthropometric measurements in prepregnancy and at the end of pregnancy and their children's systolic (SBP) and diastolic (DBP) blood pressure at 11 years of age, in a prospective cohort study. Methods All hospital births which took place in 1993 in the city of Pelotas - Brazil, were identified (5,249 live births). In 2004, the overall proportion of follow-up was 85% and we obtained arterial blood pressure measurements of 4,452 adolescents. Results Independent variables analyzed included maternal prepregnancy weight and body mass index (BMI) and maternal weight, and height at the end of pregnancy. Multiple linear regression analysis controlling for the following confounders were carried out: adolescent's skin color, family income at birth, smoking, alcohol intake during pregnancy, and gestational arterial hypertension. Mean SBP and DBP were 101.9 mmHg (SD 12.3) and 63.4 mmHg (SD 9.9), respectively. Maternal prepregnancy weight and BMI, and weight at the end of pregnancy were positively associated with both SBP and DBP in adolescent subjects of both sexes; maternal height was positively associated with SBP only among males. Conclusions Adequate evaluation of maternal anthropometric characteristics during pregnancy may prevent high levels of blood pressure among adolescent children. PMID:20653949

  4. Factors associated to leisure-time sedentary lifestyle in adults of 1982 birth cohort, Pelotas, Southern Brazil

    PubMed Central

    Azevedo, Mario R; Horta, Bernardo L; Gigante, Denise P; Victora, Cesar G; Barros, Fernando C

    2009-01-01

    OBJECTIVE To assess factors associated to leisure-time physical activity and sedentary lifestyle. METHODS Prospective cohort study of people born in 1982 in the city of Pelotas, southern Brazil. Data were collected at birth and during in a visit in 2004-5 when 77.4% of the cohort were evaluated, making a total of 4,297 people studied. Information about leisure-time physical activity was collected using the International Physical Activity Questionnaire. Sedentary people were defined as those with weekly physical activity below 150 minutes. The following independent variables were studied: gender, skin color, birth weight, family income at birth and income change between birth and 23 years of age. Poisson’s regression with robust adjustment of variance was used for the assessment of risk factors of sedentary lifestyle. RESULTS Men reported 334 min of weekly leisure-time physical activity compared to 112 min among women. The prevalence of sedentary lifestyle was 80.6% in women and 49.2% in men. Scores of physical activity increased as income at birth increased. Those who were currently poor or who became poor during adult life were more sedentary. CONCLUSIONS Leisure-time sedentary lifestyle in young adults was high especially among women. Physical activity during leisure time is determined by current socioeconomic conditions. PMID:19142347

  5. [Methodological description of accelerometry for measuring physical activity in the 1993 and 2004 Pelotas (Brazil) birth cohorts].

    PubMed

    Knuth, Alan Goularte; Assunção, Maria Cecília F; Gonçalves, Helen; Menezes, Ana Maria B; Santos, Iná S; Barros, Aluísio J D; Matijasevich, Alicia; Ramires, Virgílio Viana; Silva, Inácio Crochemore Mohnsamb da; Hallal, Pedro Curi

    2013-03-01

    The aim of this study was to characterize the methodology of data collection on physical activity using accelerometry in two birth cohorts (2004 and 1993) in Pelotas, Rio Grande do Sul State, Brazil, at the 6-7 and 18-year follow-up visits, respectively. During visits to the study headquarters for a health evaluation, cohort subjects received the accelerometer to be worn on the wrist for 5 to 8 days, after which the device was retrieved at their homes. Genea and GENEActiv triaxial estimators of gravity (g) acceleration were employed. Accelerometry data were collected from 3,331 children (93.7% of those included in follow-up) and 3,816 adolescents (99% of those in follow-up). The study characterizes the data collection methodology in more than 7,000 individuals and discusses issues in its implementation. It thus provides a methodological framework aimed at helping to plan future population-based studies with the use of such technology and to improve understanding of physical activity in the context of epidemiological studies.

  6. COMT and prenatal maternal smoking in associations with conduct problems and crime: the Pelotas 1993 birth cohort study.

    PubMed

    Salatino-Oliveira, Angélica; Murray, Joseph; Kieling, Christian; Genro, Júlia Pasqualini; Polanczyk, Guilherme; Anselmi, Luciana; Wehrmeister, Fernando; de Barros, Fernando C; Menezes, Ana Maria Baptista; Rohde, Luis Augusto; Hutz, Mara Helena

    2016-07-18

    Conduct problems in childhood and adolescence are significant precursors of crime and violence in young adulthood. The purpose of the current study is to test the interaction between prenatal maternal smoking and COMT Val(158)Met in conduct problems and crime in the 1993 Pelotas Birth Cohort Study. Conduct problems were assessed through the parent version of the Strengths and Difficulties Questionnaire at ages 11 and 15 years. A translated version of a confidential self-report questionnaire was used to collect criminal data at 18 years of age. Negative binomial regression analyses showed an association between prenatal maternal smoking and SDQ conduct problem scores (IRR = 1.24; 95% CI: 1.14-1.34; p < 0.001) at 11 years of age. However, no evidence was found for an association between COMT genotypes and conduct scores or for an interaction between maternal smoking and this gene in predicting conduct problems. Very similar results were obtained using the 15 years conduct scores and crime measure at age 18. Prenatal maternal smoking was associated with crime (IRR = 1.28; 95% CI: 1.09-1.48; p = 0.002) but neither COMT genotypes nor the possible interaction between gene and maternal smoking were significantly associated with crime. Replications of GxE findings across different social contexts are critical for testing the robustness of findings.

  7. Is the number of siblings associated with dietary patterns in adolescents? The 1993 birth cohort of Pelotas (Brazil)

    PubMed Central

    Meller, F. O.; Assunção, M. C. F.; Schäfer, A. A.; Loret de Mola, C.; Dahly, D. L.; Vaz, J. S.; Barros, F. C.

    2017-01-01

    Our study aimed to estimate the association between number of siblings and dietary patterns in adolescents. Prospective longitudinal study was developed using data from the birth cohort of the city of Pelotas, Brazil, which included 5249 participants. At the 18-year-old follow-up, from 4563 individuals located, 4106 were interviewed (follow-up rate 81.3%). Of these, 3751 were included in our principal component analysis of dietary patterns. Regular dietary intake of 45 food groups over the previous year was measured with a food frequency questionnaire. We identified four patterns, which accounted for 40% of the total variance in food group consumption. These were labeled “Protein and fast food”, “Fruit and vegetables”, “Common Brazilian”, and “Sweets, soft drinks, and dairy products”. Crude and adjusted analyses of the association between number of siblings and dietary patterns were performed using linear regression. The number of siblings was positively associated with a higher adherence to each dietary pattern, with the exception of the “Common Brazilian” patterns, for which there was no apparent relationship with number of siblings. The findings showed that a greater number of siblings is related to a more diverse diet in the later adolescence, which may predict better nutrient adequacy and health outcomes. PMID:28333975

  8. Children's eating behavior: comparison between normal and overweight children from a school in Pelotas, Rio Grande do Sul, Brazil

    PubMed Central

    dos Passos, Darlise Rodrigues; Gigante, Denise Petrucci; Maciel, Francine Villela; Matijasevich, Alicia

    2015-01-01

    OBJECTIVE: To evaluate differences in children's eating behavior in relation to their nutritional status, gender and age. METHODS: Male and female children aged six to ten years were included. They were recruited from a private school in the city of Pelotas, Rio Grande do Sul, southern Brazil, in 2012. Children´s Eating Behaviour Questionnaire (CEBQ) subscales were used to assess eating behaviors: Food Responsiveness (FR), Enjoyment of Food (EF), Desire to Drink (DD), Emotional Overeating (EOE), Emotional Undereating (EUE), Satiety Responsiveness (SR), Food Fussiness (FF) and Slowness in Eating (SE). Age-adjusted body mass index (BMI) z-scores were calculated according to the WHO recommendations to assess nutritional status. RESULTS: The study sample comprised 335 children aged 87.9±10.4 months and 49.3% had normal weight (n=163), 26% were overweight (n=86), 15% were obese (n=50) and 9.7% were severely obese (n=32). Children with excess weight showed higher scores at the CEBQ subscales associated with "food approach" (FR, EF, DD, EOE, p<0.001) and lower scores on two "food avoidance" subscales (SR and SE, p<0.001 and p=0.003, respectively) compared to normal weight children. Differences in the eating behavior related to gender and age were not found. CONCLUSIONS: "Food approach" subscales were positively associated to excess weight in children, but no associations with gender and age were found. PMID:25662562

  9. Oral health follow-up studies in the 1993 Pelotas (Brazil) birth cohort study: methodology and principal results

    PubMed Central

    Peres, Marco A.; Barros, Aluísio Jardim; Peres, Karen Glazer; Araújo, Cora Luiza; Menezes, Ana M. B.; Hallal, Pedro C.; Victora, Cesar G.

    2013-01-01

    The aim of this study was to describe oral health follow-up studies nested in a birth cohort. A population-based birth cohort was launched in 1993 in Pelotas, Rio Grande do Sul State, Brazil. Two oral health follow-up studies were conducted at six (n = 359) and 12 (n = 339) years of age. A high response rate was observed at 12 years of age; 94.4% of the children examined at six years of age were restudied in 2005. The mean DMF-T index at age 12 was 1.2 (SD = 1.6) for the entire sample, ranging from 0.6 (SD = 1.1) for children that were caries-free at age six, 1.3 (SD = 1.5) for those with 1-3 carious teeth at six years, and 1.8 (SD = 1.8) for those with 4-19 carious teeth at six years (p < 0.01). The number of individuals with severe malocclusions at 12 years was proportional to the number of malocclusions at six years. Oral health problems in early adolescence were more prevalent in individuals with dental problems at six years of age. PMID:20963297

  10. Diet quality of preschool children aged 2 to 5 years living in the urban area of Pelotas, Brazil

    PubMed Central

    Leal, Katharine Konrad; Schneider, Bruna Celestino; França, Giovanny Vinicius Araújo; Gigante, Denise Petrucci; dos Santos, Iná; Assunção, Maria Cecília Formoso

    2015-01-01

    Abstract Objective: To assess the dietary quality of preschool children in the urban area of Pelotas, Rio Grande do Sul, southern Brazil. Methods: Dietary quality was measured according to the Healthy Eating Index (HEI), adapted to Brazil. Food consumption was obtained using the Food Frequency Questionnaire (FFQ). The index score was obtained by a score, ranging from 0 to 100, distributed in 13 food groups that characterize different components of a healthy diet. The better the quality of the diet, the closer the score is to 100. Results: Dietary quality was evaluated in 556 preschoolers. The mean HEI score value was 74.4 points, indicating that diets need improvement. The mean scores were significantly higher among girls and in children from families with income between one and less than three minimum wages. Conclusions: The children showed vegetable consumption below the recommended level, while foods of the food group of oils and fats, as well as the group of sugars, candies, chocolates and snacks, were consumed in excess. It is important to reinforce guidelines to promote healthier eating habits, which may persist later in life. PMID:26122208

  11. Sedentary behavior in adolescents: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study.

    PubMed

    Dumith, Samuel C; Hallal, Pedro C; Menezes, Ana M B; Araújo, Cora Luiza

    2010-10-01

    The aim of this study was to estimate the prevalence of sedentary behavior and investigate associated factors in adolescents 11 years of age from the 1993 birth cohort in Pelotas, Rio Grande do Sul State, Brazil. Sedentary behavior was investigated with a questionnaire, and was defined as spending more than two hours per day watching television, playing videogames, or using the computer. Of the 4,452 adolescents interviewed, 98% reported watching television, 44% playing videogames, and 22% using the computer. The average time spent on each of these electronic media was 197, 36, and 17 minutes per day, respectively. Prevalence of sedentary behavior was 79.7% (95%CI: 78.6; 80.9) and showed a positive association with socioeconomic level and nutritional status and a negative association with well-being. These 11-year-olds spent extensive time at TV viewing, videogames, and the computer. Special attention should be given to the most exposed groups of adolescents, including the more affluent, overweight, and those with limited schooling.

  12. COMT and prenatal maternal smoking in associations with conduct problems and crime: the Pelotas 1993 birth cohort study

    PubMed Central

    Salatino-Oliveira, Angélica; Murray, Joseph; Kieling, Christian; Genro, Júlia Pasqualini; Polanczyk, Guilherme; Anselmi, Luciana; Wehrmeister, Fernando; de Barros, Fernando C.; Menezes, Ana Maria Baptista; Rohde, Luis Augusto; Hutz, Mara Helena

    2016-01-01

    Conduct problems in childhood and adolescence are significant precursors of crime and violence in young adulthood. The purpose of the current study is to test the interaction between prenatal maternal smoking and COMT Val158Met in conduct problems and crime in the 1993 Pelotas Birth Cohort Study. Conduct problems were assessed through the parent version of the Strengths and Difficulties Questionnaire at ages 11 and 15 years. A translated version of a confidential self-report questionnaire was used to collect criminal data at 18 years of age. Negative binomial regression analyses showed an association between prenatal maternal smoking and SDQ conduct problem scores (IRR = 1.24; 95% CI: 1.14–1.34; p < 0.001) at 11 years of age. However, no evidence was found for an association between COMT genotypes and conduct scores or for an interaction between maternal smoking and this gene in predicting conduct problems. Very similar results were obtained using the 15 years conduct scores and crime measure at age 18. Prenatal maternal smoking was associated with crime (IRR = 1.28; 95% CI: 1.09–1.48; p = 0.002) but neither COMT genotypes nor the possible interaction between gene and maternal smoking were significantly associated with crime. Replications of GxE findings across different social contexts are critical for testing the robustness of findings. PMID:27426045

  13. Determinants of early sexual initiation in the Pelotas birth cohort from 1982 to 2004-5, Southern Brazil

    PubMed Central

    Gonçalves, Helen; Béhague, Dominique P; Gigante, Denise P; Minten, Gicele C; Horta, Bernardo L; Victora, Cesar G; Barros, Fernando C

    2009-01-01

    OBJECTIVE To analyze social determinants of early sexual initiation among young adults from a birth cohort. METHODS Individuals from the 1982 birth cohort (N=4,297) were interviewed in 2004-5, city of Pelotas, Southern Brazil. Early sexual initiation (≤13 years of age) was the outcome. Descriptive and stratified analyses were performed according to sex. Variables analyzed were family income in 1982, ethnicity, young adult’s level of education and change in income (between 1982 and 2004-5). Ethnographic data were used to complement result analysis. RESULTS Prevalence of early sexual initiation was higher among black and mixed men, and those with low level of education and low family income in 1982 and 2004-5. More traditional male sexual role requirements, such as virility and sexual initiative, showed more repercussion and adherence from an early age among men. Young family women with higher income and level of education tended to delay their sexual initiation. Imposition of traditional values was found to influence early sexual initiation among men and women with lower level of education and income. CONCLUSIONS Results found re-established the economic factor as a determinant of behavior or uses of sexuality for both sexes. To focus on political efforts that help the economically disadvantaged to have opportunities and egalitarian future perspectives is an important strategy for health outcomes. PMID:19142343

  14. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains site

    DOE PAGES

    Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri; ...

    2016-07-20

    In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 andmore » RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. In addition, these results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.« less

  15. Associations between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian cancer

    PubMed Central

    Zhang, Wei; Zhang, Zhifen

    2016-01-01

    Recent studies explored XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian cancer (OC) risk. However, the association between these two single nucleotide polymorphisms and OC risk remains conflicting. Thus, we conducted a comprehensive systematic review and meta-analysis to investigate the association. We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. 15 case-control studies published in 11 papers including 4,757 cases and 8,431 controls were included in this meta-analysis. No associations were obtained between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and OC risk. Stratification analyses of Hardy–Weinberg equilibrium status indicated that rs3218536 polymorphism was associated with the decreased risk of OC when in analysis of combined HWE positive studies. In conclusion, this meta-analysis indicates that XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms may not be associated with the risk of OC. PMID:27863412

  16. Pattern of health services utilization by adults of the Pelotas birth cohort from 1982 to 2004-5, Southern Brazil

    PubMed Central

    Dias-da-Costa, Juvenal S; Gigante, Denise P; Horta, Bernardo L; Barros, Fernando C; Victora, Cesar G

    2009-01-01

    OBJECTIVE To describe the pattern of health services utilization by young adults. METHODS Longitudinal study in Pelotas (Southern Brazil), in which the individuals were identified at birth in 1982 and followed up until 23 years of age. The outcome was defined by information collected about visits to health professionals that were attended in the year before the interview, between 2004 and 2005. The places where the visits occurred were categorized as public, private or belonging to health plan systems. Descriptive analyses were carried out for utilization and type of health service. Poisson Regression was employed in the adjusted analysis. RESULTS Of the interviewees, 72.0% visited health professionals in the year before the interview; 86.2% (95% CI 84.7;87.7) of the women and 59.3% (95% CI 57.3;61.3) of the men. Even when gynecological visits were excluded, the women still attended more visits than the men, 68.4% (95% CI 66.4;70.4). Health services utilization was more frequent among interviewees of better socioeconomic level. A difference of lower use in relation to non-white skin color was observed only among male youths. There were differences regarding the type of professional visited by men and women and also according to family income. Men and women used more frequently the public system, the health plan system and, in a smaller proportion, the private system. CONCLUSIONS The socioeconomic situation influenced the utilization and the type of health service, with men and women classified as “poor at the moment”, which indicates lower utilization of services. Such socioeconomic differences may indicate difficulties in the access to the health system. PMID:19142345

  17. Antenatal and postnatal maternal mood symptoms and psychiatric disorders in pre-school children from the 2004 Pelotas Birth Cohort

    PubMed Central

    Santos, Iná S.; Matijasevich, Alicia; Barros, Aluísio J.D.; Barros, Fernando C.

    2014-01-01

    Background Maternal mood symptoms have been associated with psychiatric disorders in children. This study aimed to assess critical periods when maternal symptoms would be more deleterious. Methods Cohort of 4231 births followed-up in the city of Pelotas, Brazil. Mood symptoms during pregnancy were self-reported by mothers at perinatal interview; and at 3-months postpartum, mothers answered the Self-Reporting Questionnaire. Psychiatric disorders in 6-year-old children were evaluated through the Development and Well-Being Assessment instrument. Odds ratios with 95% confidence intervals (95% CI) were calculated by logistic regression. Results Prevalence of mood symptoms in pregnancy was 24.6% (23.2–26.0%) and at three months postpartum 22.5% (21.1–23.9%). Prevalence of mental disorders in children was 13.3% (12.2–14.4%). After adjustment for confounders children of mothers with mood symptoms during pregnancy were 82% more likely of presenting psychiatric disorders than children of mothers that did not (1.82; 1.48–2.25); and the chance of having mental disorders among children whose mothers had positive SRQ-20 at three months postpartum was 87% greater than the observed among children whose mothers had it negative (1.87; 1.50–2.33). Limitations Because maternal anxiety/depression may interfere with interpretation of the child behavior, child׳s mental health being obtained by interviewing the mother is a limitation of this study. Lack of information on other risk factors may have lead to residual confounding on the effect of maternal mood symptoms at three months postpartum. Conclusions Children of mothers presenting mood symptoms during pregnancy and in the first months postpartum are more likely to present psychiatric disorders at 6 years of age. PMID:24856563

  18. PTK2 rs7460 and rs7843014 Polymorphisms and Exceptional Longevity: A Functional Replication Study

    PubMed Central

    Fuku, Noriyuki; He, Zi-hong; Tian, Ye; Arai, Yasumichi; Abe, Yukiko; Murakami, Haruka; Miyachi, Motohiko; Yvert, Thomas; Venturini, Letizia; Santiago, Catalina; Santos-Lozano, Alejandro; Rodríguez, Gabriel; Ricevuti, Giovanni; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Emanuele, Enzo; Hirose, Nobuyoshi; Lucia, Alejandro

    2014-01-01

    Abstract Focal adhesion is critical for cell survival. The focal adhesion kinase (FAK, or PTK2) is an important component of the human interactome and thus is a potential longevity-related protein. Here we studied the association between two PTK2 gene single-nucleotide polymorphisms (SNPs) (rs7843014, rs7460) and exceptional longevity (EL). In addition to gaining insight into their functionality by determining luciferase gene reporter activity, we studied the genotype/allele frequency of these two SNPs among three different cohorts: (1) Spanish centenarians (n=175, 100–111 years, 144 women) and healthy controls (n=355, 20–50 years, 284 women); (2) Italian centenarians (n=79, 100–104 years, 40 women) and controls (n=316, 29–50 years, 156 women); and (3) Japanese centenarians (n=742, 100–116 years, 623 women) and healthy controls (n=499, 23–59 years, 356 women). Both SNPs had functional significance, with the A allele up-regulating luciferase activity compared to the other allele (rs7460 T allele and rs7843014 C allele, respectively). The A allele of both SNPs was negatively associated with EL in the Spanish cohort (rs7460, odds ratio [OR] adjusted by sex=0.40, 95% confidence intervals [CI] 0.3, 0.6, p<0.001); rs7843014, OR=0.37, 95% CI 0.3, 0.5, p<0.001). The OR of being a centenarian if having the rs7460-TT genotype was 6.68 (95% CI 4.1, 10.8, p<0.001). The rs7843014 CC genotype was also positively associated with EL (OR=7.58, 95% CI 4.6, 12.3, p<0.001]. No association was, however, found for the Italian or Japanese cohorts. Thus, two genotypes of the FAK gene, rs7460 TT and rs7843014 CC, are possibly associated with lower gene expression and might favor the likelihood of reaching EL in the Spanish population. Further research is needed to unveil the mechanisms by which FAK expression could perhaps influence the rate of aging. PMID:24930376

  19. SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression

    PubMed Central

    Christophersen, Mikael K.; Jöud, Magnus; Ajore, Ram; Vege, Sunitha; Ljungdahl, Klara W.; Westhoff, Connie M.; Olsson, Martin L.; Storry, Jill R.; Nilsson, Björn

    2017-01-01

    The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing. PMID:28084402

  20. Complex Bedforms and Complex Water Masses: A Case Study from the Tertiary to Present-day, Pelotas Basin, Offshore Uruguay

    NASA Astrophysics Data System (ADS)

    Thompson, P.; Badalini, G.; Wrigley, S.; Walker, R.; Argent, J.; Hernandez-Molina, J.; de Santa Ana, H.; Soto, M.; Tomasini, J.

    2015-12-01

    Contour currents are commonly associated with bedform development on modern seabeds yet there is a general paucity of published examples from the ancient record. Recently acquired 3D seismic data, covering over 13000km2 of the Pelotas Basin, offshore Uruguay, provides a unique opportunity to study the architecture and development of a variety of bedform. The data shows that, throughout the Tertiary, contour currents were the dominant control on sedimentation along the Uruguayan margin. The first evidence of contour current activity is during the Early Tertiary in the form of a major regional unconformity that, even though it was fully subaqueous, does not show any major features associated with downslope sedimentation. In the mid-slope region, the unconformity coincides with an extensive (1500km2) intra-slope scour-field orientated parallel to the slope. Individual scours are up to 40m deep, 500m wide and 3km long. Coeval with these scours are a group of coalesced basin floor scours, which run parallel to the base of slope and extend over 400km2. Individual scours exhibit an asymmetric shape - similar to giant flute marks - that are up to 150m deep, 20km wide and extend for at least 40km along slope. The development of these scoured areas shows clear evidence of two major north-flowing water masses. Directly above this regional unconformity are a series of ribbon-like bedforms that developed oblique to the slope. Individual bedforms are up to 40km in length with wavelengths of 5km and heights up to 100m. These bedforms are overlain by a set of barchan-like dunes, up to 30km in length with wavelengths of 10km. Individual dunes are in the order of 100m thick and stack to form an overall package up to 500m thick. These features show a clear change from erosion/bypass to deposition/reworking that is linked to a decrease in ocean current velocity and/ or sediment supply. The features observed suggest a complex oceanic regime was present throughout the Tertiary that

  1. 40 CFR 180.1114 - Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas syringae 742RS...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas syringae 742RS; exemptions from the requirement of a tolerance... Tolerances § 180.1114 Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas...

  2. AB111. Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population

    PubMed Central

    Zhang, Yu; Hu, Hailong; Tian, Dawei; Wu, Changli

    2016-01-01

    Objective Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Methods we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. Results We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer [adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09–0.81; P=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10–2.91; P=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (P>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. Conclusions The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population.

  3. Mass and Reliability System (MaRS)

    NASA Technical Reports Server (NTRS)

    Barnes, Sarah

    2016-01-01

    The Safety and Mission Assurance (S&MA) Directorate is responsible for mitigating risk, providing system safety, and lowering risk for space programs from ground to space. The S&MA is divided into 4 divisions: The Space Exploration Division (NC), the International Space Station Division (NE), the Safety & Test Operations Division (NS), and the Quality and Flight Equipment Division (NT). The interns, myself and Arun Aruljothi, will be working with the Risk & Reliability Analysis Branch under the NC Division's. The mission of this division is to identify, characterize, diminish, and communicate risk by implementing an efficient and effective assurance model. The team utilizes Reliability and Maintainability (R&M) and Probabilistic Risk Assessment (PRA) to ensure decisions concerning risks are informed, vehicles are safe and reliable, and program/project requirements are realistic and realized. This project pertains to the Orion mission, so it is geared toward a long duration Human Space Flight Program(s). For space missions, payload is a critical concept; balancing what hardware can be replaced by components verse by Orbital Replacement Units (ORU) or subassemblies is key. For this effort a database was created that combines mass and reliability data, called Mass and Reliability System or MaRS. The U.S. International Space Station (ISS) components are used as reference parts in the MaRS database. Using ISS components as a platform is beneficial because of the historical context and the environment similarities to a space flight mission. MaRS uses a combination of systems: International Space Station PART for failure data, Vehicle Master Database (VMDB) for ORU & components, Maintenance & Analysis Data Set (MADS) for operation hours and other pertinent data, & Hardware History Retrieval System (HHRS) for unit weights. MaRS is populated using a Visual Basic Application. Once populated, the excel spreadsheet is comprised of information on ISS components including

  4. Nucleotide sequence analysis of pRS2 and pRS3, two small cryptic plasmids from Oenococcus oeni.

    PubMed

    Mesas, J M; Rodríguez, M C; Alegre, M T

    2001-09-01

    Nucleotide sequence analysis of two cryptic plasmids, pRS2 (2544 bp) and pRS3 (3948 bp), from Oenococcus oeni revealed the presence in both of three major open reading frames with significant similarity to other small cryptic plasmids from O. oeni. The results suggest that those plasmids could be separated into two subfamilies, one represented by pLo13 and pRS3, the other represented by pOg32, pRS1, and pRS2.

  5. Intake of fat and fiber-rich foods according to socioeconomic status: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study

    PubMed Central

    Neutzling, Marilda B.; Araújo, Cora Luiza; Vieira, Maria de Fátima A.; Hallal, Pedro C.; Menezes, Ana M. B.; Victora, Cesar G.

    2013-01-01

    This study describes the food intake of adolescents participating in the 1993 birth cohort from Pelotas, Southern Brazil, according to socioeconomic position. We carried out a cross-sectional analysis of data collected in the 2004-2005 follow-up visit. Food intake in the previous year was evaluated using the Block questionnaire. Socioeconomic status was evaluated based on an assets index, divided into quintiles. Foods with the highest frequency of daily intake were white bread (83%), butter or margarine (74.6%), beans (66.4%) and milk (48.5%). Intake of butter or margarine, bread, and beans was more frequent among poorer adolescents, and the inverse was true for milk. Intake of fruits and vegetables was low in all socioeconomic strata, but particularly low among the poor. In early adolescence, all socioeconomic groups showed high consumption of foods rich in fat and low consumption of foods rich in fiber. PMID:20963287

  6. Birth weight, intrauterine growth restriction and nutritional status in childhood in relation to grip strength in adults: from the 1982 Pelotas (Brazil) birth cohort

    PubMed Central

    Bielemann, Renata Moraes; Gigante, Denise Petrucci; Horta, Bernardo Lessa

    2016-01-01

    Objective The aim of this study was to evaluate the association among birth weight, intrauterine growth, and nutritional status in childhood with grip strength in young adults from the 1982 Pelotas (Brazil) birth cohort. Methods In 1982, the hospital live births of Pelotas were followed. In 2012, grip strength was evaluated using a hand dynamometer and the best of the six measurements was used. Birth weight was analyzed as z-score for gestational age according to Williams (1982) curve. Weight-for-age, weight-for-length/height, and length/height-for-age at 2 and 4 y were analyzed in z-scores according to 2006 World Health Organization Child Growth Standards. Lean mass at 30 y was included as possible mediator using the g-computation formula. Results In 2012, 3701 (68.1%) individuals were interviewed and 3470 were included in the present analyses. An increase of 1 z-score in birth weight was associated with an increase of 1.5 kg in grip strength in males (95% confidence interval, 1.1–1.9). Positive effect of birth weight on grip strength was found in females. Grip strength was greater in individuals who were born with appropriate size for gestational age and positively associated with weight- and length/height-for-age z-score at 2 and 4 y of age. A positive association between birth weight and grip strength was only partially mediated by adult lean mass (50% and 33% of total effect in males and females), whereas direct effect of weight at 2 y was found only in males. Conclusions It is suggested that good nutrition in prenatal and early postnatal life has a positive influence on adult muscle strength. The results from birth weight were suggestive of fetal programming on grip strength measurement. PMID:26678603

  7. Characterization of RsMYB28 and RsMYB29 transcription factor genes in radish (Raphanus sativus L.).

    PubMed

    Luo, X B; Liu, Z; Xu, L; Wang, Y; Zhu, X W; Zhang, W; Chen, W; Zhu, Y L; Su, X J; Everlyne, M; Liu, L W

    2016-09-23

    Glucosinolates (GSLs) are important secondary metabolites in Brassicaceae plants. Previous studies have mainly focused on GSL contents, types, and biosynthesis-related genes, but the molecular characterization patterns of GSL biosynthesis-related transcription factors remain largely unexplored in radish (Raphanus sativus L.). To isolate transcription factor genes regulating the GSL biosynthesis, genomic DNA and cDNA sequences of RsMYB28 and RsMYB29 genes were isolated in radish. Two R2R3-MYB domains were identified in the deduced amino acid sequences. Subcellular localization and yeast-one hybrid assays indicated that both the RsMYB28 and RsMYB29 genes were located in the nucleus and possessed transactivation activity. Reverse transcription quantitative analysis showed that the RsMYB28 and RsMYB29 genes were expressed in seeds, leaves, stems, and roots at the seedling, taproot thickening, and mature stages. Both genes were highly expressed during the seedling and taproot thickening stages. The expression level of RsMYB28 was found to be up-regulated following wounding, glucose, and abscisic acid treatments, whereas RsMYB29 was up-regulated following wounding and methyl jasmonate treatments. These results provide insights into the biological function and characterization of the RsMYB28 and RsMYB29 genes, and facilitate further dissection of the molecular regulatory mechanism underlying the GSL biosynthesis in radish.

  8. The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms.

    PubMed

    Vriens, Kim; Cools, Tanne L; Harvey, Peta J; Craik, David J; Braem, Annabel; Vleugels, Jozef; De Coninck, Barbara; Cammue, Bruno P A; Thevissen, Karin

    2016-01-01

    The radish defensin RsAFP2 was previously characterized as a peptide with potent antifungal activity against several plant pathogenic fungi and human pathogens, including Candida albicans. RsAFP2 induces apoptosis and impairs the yeast-to-hypha transition in C. albicans. As the yeast-to-hypha transition is considered important for progression to mature biofilms, we analyzed the potential antibiofilm activity of recombinant (r)RsAFP2, heterologously expressed in Pichia pastoris, against C. albicans biofilms. We found that rRsAFP2 prevents C. albicans biofilm formation with a BIC-2 (i.e., the minimal rRsAFP2 concentration that inhibits biofilm formation by 50% as compared to control treatment) of 1.65 ± 0.40 mg/mL. Moreover, biofilm-specific synergistic effects were observed between rRsAFP2 doses as low as 2.5 μg/mL to 10 μg/mL and the antimycotics caspofungin and amphotericin B, pointing to the potential of RsAFP2 as a novel antibiofilm compound. In addition, we characterized the solution structure of rRsAFP2 and compared it to that of RsAFP1, another defensin present in radish seeds. These peptides have similar amino acid sequences, except for two amino acids, but rRsAFP2 is more potent than RsAFP1 against planktonic and biofilm cultures. Interestingly, as in case of rRsAFP2, also RsAFP1 acts synergistically with caspofungin against C. albicans biofilms in a comparable low dose range as rRsAFP2. A structural comparison of both defensins via NMR analysis revealed that also rRsAFP2 adopts the typical cysteine-stabilized αβ-motif of plant defensins, however, no structural differences were found between these peptides that might result in their differential antifungal/antibiofilm potency. This further suggests that the conserved structure of RsAFP1 and rRsAFP2 bears the potential to synergize with antimycotics against C. albicans biofilms.

  9. Association Study of Single Nucleotide Polymorphisms Rs4552569/Rs17095830 with Ankylosing Spondylitis in A Chinese Population

    PubMed Central

    Wang, Qingwen; Yang, Yuanyuan; Lv, Jiyang; Lin, Qi; Wang, Luo; Fanga, Zhengyu

    2016-01-01

    Genetics play a key role in ankylosing spondylitis (AS). A previous genome-wide association study (GWAS) showed that rs4552569 (on 5q14.3) and rs17095830 (on 12q12) were associated with the risk of AS in Han Chinese, which was not replicated in other two studies. In the current study, rs4552569 and rs17095830 were genotyped in 735 Han Chinese AS patients and 1204 healthy controls using high resolution melting analysis (HRMA). We compared the distributions of genotypes and alleles between AS cases and healthy controls. Rs30187 and rs10865331, which were reported to be associated with AS susceptibility in various populations, were also genotyped and analyzed as positive controls. The results showed that no association between rs4552569/rs17095830 polymorphisms and AS susceptibility was found. On the other hand, an association between rs17095830 and one of AS complication (inflammatory bowel disease) was observed (allelic P value=0.0180; odds ratio[OR]=1.739; 95% confidence interval [CI]=1.146-2.639). PMID:27047576

  10. Polymorphisms in Four Genes (KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963) and Their Correlation with Type 2 Diabetes Mellitus in Han Chinese in Henan Province, China.

    PubMed

    Gao, Kaiping; Wang, Jinjin; Li, Linlin; Zhai, Yujia; Ren, Yongcheng; You, Haifei; Wang, Bingyuan; Wu, Xuli; Li, Jianna; Liu, Zichen; Li, Xiong; Huang, Yaxin; Luo, Xin-Ping; Hu, Dongsheng; Ohno, Kinji; Wang, Chongjian

    2016-02-26

    Genetic variants at KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963 have been associated with type 2 diabetes mellitus (T2DM), but the results are contradictory in Chinese populations. The aim of the present study was to investigate the association of these four SNPs with T2DM in a large population of Han Chinese at Henan province, China. Seven-hundred-thirty-six patients with T2DM (cases) and Seven-hundred-sixty-eight healthy glucose-tolerant controls were genotyped for KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963. The association of genetic variants in these four genes with T2DM was analyzed using multivariate logistic regression. Genotypes and allele distributions of KCNQ1 rs151290 were significantly different between the cases and controls (p < 0.05). The AC and CC genotypes and the combined AC + CC genotype of rs151290 in KCNQ1 were associated with increases risk of T2DM before (OR = 1.482, 95% CI = 1.062-2.069; p = 0.021; OR = 1.544, 95% CI = 1.097-2.172, p = 0.013; and OR = 1.509, 95% CI = 1.097-2.077, p = 0.011, respectively) and after (OR = 1.539, 95% CI = 1.015-2.332, p = 0.042; OR = 1.641, 95% CI = 1.070-2.516, p = 0.023; and OR = 1.582, 95% CI = 1.061-2.358, p = 0.024; respectively) adjustment for sex, age, anthropometric measurements, biochemical indexes, smoking and alcohol consumption. Consistent with results of genotype analysis, the C allele of rs151290 in KCNQ1 was also associated with increased risk of T2DM (OR = 1.166, 95% CI = 1.004-1.355, p = 0.045). No associations between genetic variants of KLF14 rs972283, GCKR rs780094 or MTNR1B rs10830963 and T2DM were detected. The AC and CC genotypes and the C allele of rs151290 in KCNQ1 may be risk factors for T2DM in Han Chinese in Henan province.

  11. Configuration control plan for the ports NCS IBM RS/6000

    SciTech Connect

    Brown, A.S.

    1996-07-01

    This document describes the actions and responsibilities for maintaining the quality and integrity of the NS software resident on the IBM RS/6000 workstation managed by the Nuclear Criticality Safety group at the Portsmouth Gaseous Diffusion Plant. This document does not address the validation of NS software packages for the RS/6000.

  12. Responding to the 5Rs: An Alternate Perspective of Slowmation

    ERIC Educational Resources Information Center

    Kidman, Gillian; Keast, Stephen; Cooper, Rebecca

    2012-01-01

    This paper is a response to Hoban and Neilsen's (2010) Five Rs model for understanding how learners engage with slowmation. An alternative model (the Learning MMAEPER Model) that builds on the 5Rs model is explained in terms of its use in secondary science preservice teacher education. To probe into the surface and deep learning that can occur…

  13. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  14. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  15. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS). 103.1...

  16. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  17. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  18. Radio emission from RS CVn binary systems

    SciTech Connect

    Doiron, D.J.

    1984-01-01

    The RS CVn binary stellar systems UX Ari, HR 1099, AR Lac, HR 5110, II Peg, lambda And, and SZ Psc were investigated by use of radio interferometry during the period from July 1982 through August 1983. Interferometry took two forms: Very Large Array (VLA) observations and Very Long Baseline Interferometry (VLBI). The VLA observations determined the characteristic polarization and flux behavior of the centimeter wavelength radio emission. The observed spectral index was near zero during quiescent periods, rising to between 0.5 and 1.0 during active periods. No net linear polarization is observed to a limit of 1.7%. This is expected since the Faraday depth of thermal electrons deduced from x-ray observations is approx. 10/sup 5/. Circular polarization is observed to be less than 20% at all frequencies often with a helicity reversal between 1.6 GHz and 5 GHz. The VLBI observations have shown that the brightness temperatures are often T/sub B/ approx.> 10/sup 10/ /sup 0/K and size sources smaller than or comparable to the overall size of the binary system. These data are consistent with incoherent gyrosynchrotron emission from mildly relativistic electrons which are optically thick to their own radiation at 1.6 GHz and optically thin at 5 GHz and above. The spectral behavior suggests that the radio emission is due to a power-law distribution of electrons.

  19. High pressure intensification of cassava resistant starch (RS3) yields.

    PubMed

    Lertwanawatana, Proyphon; Frazier, Richard A; Niranjan, Keshavan

    2015-08-15

    Cassava starch, typically, has resistant starch type 3 (RS3) content of 2.4%. This paper shows that the RS3 yields can be substantially enhanced by debranching cassava starch using pullulanase followed by high pressure or cyclic high-pressure annealing. RS3 yield of 41.3% was obtained when annealing was carried out at 400MPa/60°C for 15 min, whereas it took nearly 8h to obtain the same yield under conventional atmospheric annealing at 60°C. The yield of RS3 could be further significantly increased by annealing under 400 MPa/60°C pressure for 15 min followed by resting at atmospheric pressure for 3h 45 min, and repeating this cycle for up to six times. Microstructural surface analysis of the product under a scanning electron microscope showed an increasingly rigid density of the crystalline structure formed, confirming higher RS3 content.

  20. Leukocyte Telomere Length-Related rs621559 and rs398652 Genetic Variants Influence Risk of HBV-Related Hepatocellular Carcinoma

    PubMed Central

    Shi, Juan; Lu, Chao; Wei, Jinyu; Li, Lichao; Zhou, Changchun; Yuan, Qipeng; Zhou, Liqing; Yang, Ming

    2014-01-01

    Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10−6). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10−6). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population. PMID:25365256

  1. Association between RAD 51 rs1801320 and susceptibility to glioblastoma.

    PubMed

    Franceschi, S; Tomei, S; Mazzanti, C M; Lessi, F; Aretini, P; La Ferla, M; De Gregorio, V; Pasqualetti, F; Zavaglia, K; Bevilacqua, G; Naccarato, A G

    2016-01-01

    Glioblastoma is the most common and aggressive malignant primary brain tumor. Despite decades of research and the advent of new therapies, patients with glioblastoma continue to have a very poor prognosis. Radiation therapy has a major role as adjuvant treatment for glioblastoma following surgical resection. Many studies have shown that polymorphisms of genes involved in pathways of DNA repair may affect the sensitivity of the cells to treatment. Although the role of these polymorphisms has been investigated in relation to response to radiotherapy, their role as predisposing factors to glioblastoma has not been clarified yet. In the present study, we evaluated the association between polymorphisms in DNA repair genes, namely: XRCC1 rs25487, XRCC3 rs861539 and RAD51 rs1801320, with the susceptibility to develop glioblastoma. Eighty-five glioblastoma patients and 70 matched controls were recruited for this study. Data from the 1000 Genomes Project (98 Tuscans) were also downloaded and used for the association analysis. Subjects carrying RAD51 rs1801320 GC genotype showed an increased risk of glioblastoma (GC vs GG, χ(2) = 10.75; OR 3.0087; p = 0.0010). The C allele was also significantly associated to glioblastoma (χ(2) = 8.66; OR 2.5674; p = 0.0032). Moreover, RAD51 rs1801320 C allele increased the risk to develop glioblastoma also when combined to XRCC1 rs25487 G allele and XRCC3 rs861539 C allele (χ(2) = 6.558; p = 0.0053).

  2. Enantioselective degradation of (2RS,3RS)-paclobutrazol in peach and mandarin under field conditions.

    PubMed

    Wang, Xiangyun; Qi, Peipei; Yang, Guiling; Wang, Xinquan; Zhang, Hu; Xu, Hao; Wang, Zhiwei; Wang, Qiang

    2014-08-01

    In this study we investigated the enantioselective degradation of (2RS,3RS)-paclobutrazol in peach and mandarin fruits under field conditions after foliar treatment at 500 mg active ingredient/L using a Lux Cellulose-1 chiral column on a reverse-phase liquid chromatography-tandem mass spectrometry system. Degradations of paclobutrazol in both fruits followed first-order kinetics, with half-lives of about 9 days. Initial deposits were 1.63 mg/kg on peach and 1.99 mg/kg on mandarin; terminal concentrations were lower than 0.05 mg/kg, which was acceptable in most cases. As anticipated, paclobutrazol levels in peels of mature mandarin were about 6.3 times higher than in pulp, indicating the potential risk of peel consumption. We also observed that paclobutrazol degradation in mature mandarin was relatively slow, indicating it might not be efficient enough to hold mandarin fruits on trees for lowering paclobutrazol concentrations. Significant enantioselectivity was observed: the (2R,3R)-enantiomer was preferentially degraded in mandarin (whole fruit, peels, and pulp) but enriched in peach. Because of its more rapid degradation in mandarin and the lower levels observed in pulp compared with peels, potential endocrine-related side effects due to the (2R,3R)-enantiomer pose less of a risk in mandarin than in peach.

  3. Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock

    PubMed Central

    Cardoso, Cristina Padre; de Oliveira, Argenil José de Assis; Botoni, Fernando Antônio; Rezende, Isabela Cristina Porto; Alves-Filho, Jose Carlos; Cunha, Fernando de Queiroz; Estanislau, Juliana de Assis Silva Gomes; Magno, Luiz Alexandre Viana; Rios-Santos, Fabricio

    2015-01-01

    Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock. PMID:26038959

  4. RS-34 Phoenix (Peacekeeper Post Boost Propulsion System) Utilization Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Kos, Larry; Burnside, Christopher G.; Bruno, Cy

    2013-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) in conjunction with Pratt & Whitney Rocketdyne conducted a study to evaluate potential in-space applications for the Rocketdyne produced RS-34 propulsion system. The existing RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper ICBM program, specifically the pressure-fed storable bipropellant Stage IV Post Boost Propulsion System, renamed Phoenix. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in October 2009. RS-34 propulsion system components were harvested from stages supplied by the USAF and used on the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. MSFC is working closely with the USAF to obtain RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. As originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Phoenix Utilization Study sought to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions: 1) small satellite delivery (SSD), 2) orbital debris removal (ODR), 3) ISS re-supply, 4) SLS kick stage, 5) manned GEO servicing precursor mission, and an Earth-Moon L-2 Waypoint mission. The small satellite delivery and orbital debris removal missions were found to closely mimic the heritage RS-34 mission. It is believed that this technology will enable a small, low-cost multiple satellite delivery to multiple orbital locations with a single boost. For both the small

  5. RS-34 Phoenix (Peacekeeper Post Boost Propulsion System) Utilization Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Kos, Larry; Bruno, Cy

    2012-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) in conjunction with Pratt & Whitney Rocketdyne conducted a study to evaluate potential in-space applications for the Rocketdyne produced RS-34 propulsion system. The existing RS-34 propulsion system is a remaining asset from the decommissioned United States Air Force Peacekeeper ICBM program; specifically the pressure-fed storable bipropellant Stage IV Post Boost Propulsion System, renamed Phoenix. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in October 2009. RS-34 propulsion system components were harvested from stages supplied by the USAF and used on the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC is working closely with the USAF to obtain all the remaining RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Phoenix Utilization Study sought to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions: 1) small satellite delivery (SSD), 2) orbital debris removal (ODR), 3) ISS re-supply, 4) SLS kick stage, 5) manned GEO servicing precursor mission, and an Earth-Moon L-2 Waypoint mission. The small satellite delivery and orbital debris removal missions were found to closely mimic the heritage RS-34 mission. It is believed that this technology will enable a small, low-cost multiple satellite delivery to multiple orbital locations with a single

  6. Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population

    PubMed Central

    Wang, Xi-Jing; Kang, Hua-Feng; Jin, Tian-Bo; Zhang, Shu-Qun; Guan, Hai-Tao; Yang, Peng-Tao; Liu, Kang; Liu, Xing-Han; Xu, Peng; Zheng, Yi; Dai, Zhi-Jun

    2017-01-01

    Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.   PMID:28228606

  7. Association of Renalase SNPs rs2296545 and rs2576178 with the Risk of Hypertension: A Meta-Analysis

    PubMed Central

    Ma, Wang-Ge; Yan, Ding-Yi; Zheng, Wen-Ling; Chu, Chao; Guo, Tong-Shuai; Yuan, Zu-Yi; Mu, Jian-Jun

    2016-01-01

    Background/Aims Two renalase single nucleotide polymorphisms (SNPs) rs2296545 and rs2576178 have been reported to be associated with the susceptibility to hypertension (HT). Given the inconsistent results, we conducted a meta-analysis to assess the association between these two SNPs and the risk of HT. Methods Electronic databases were systematically searched to find relevant studies. Subgroup analysis was conducted according to the different concomitant diseases and ethnicities in the study population. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed-effect or random-effect models. Results A total of six case–control studies on rs2296545 and six studies on rs2576178 were included. In the combined analysis, results showed a significant association between SNP rs2296545 and risk of HT in all genetic models (dominant model CG+CC/GG: OR = 1.43, 95% CI = 1.24–1.65; recessive model CC/CG+GG: OR = 1.36, 95% CI = 1.09–1.69; codominant model CC/GG: OR = 1.63, 95% CI = 1.20–2.20, CG/GG: OR = 1.30, 95% CI = 1.12–1.52; allelic model C/G: OR = 1.29, 95% CI = 1.10–1.51). In subgroup analysis, we observed a significant association between rs2296545 and risk of essential HT. Although we did not observe an association between rs2576178 polymorphism and HT in the combined analysis, an increased risk was observed in the essential HT patients versus healthy controls (subgroup 1) analysis under the dominant, recessive, and codominant genetic models. Conclusions Renalase gene rs2296545 polymorphism is significantly associated with increased risk of HT, whereas rs2576178 polymorphism may not be associated with the susceptibility to HT. PMID:27434211

  8. Association between miR-199a rs74723057 and MET rs1621 polymorphisms and the risk of hepatocellular carcinoma

    PubMed Central

    Li, Qiang; Qin, Linyuan; Tan, Shengkui; Zeng, Xiaoyun; Qiu, Xiaoqiang; Tang, Bo; Jin, Junfei; Liao, Weijia; Qiu, Moqin; Tan, Lijun; He, Gaofeng; Li, Xiaomei; He, Songqing; Yu, Hongping

    2016-01-01

    MicroRNAs (miRNAs) can regulate gene expression at post-transcriptional levels, thereby influence cancer risk. The aim of the current study is to investigate association between miR-199a rs74723057 and MET rs1621 and HCC risk in 1032 HCC patients and 1060 cancer-free controls. These two SNPs were genotyped by using the Agena MassARRAY genotyping system. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to assess the strength of the associations. We found that compared with the wild-type AA genotype of MET rs1621, the variant GG genotype was associated with a decreased risk for HCC (OR = 0.24, 95% CI = 0.06–0.96, P = 0.043). No association between miR-199a rs74723057 and HCC risk was observed. In addition, an interaction effect on HCC risk between the selected two SNPs was found. Among those who carried the CG/GG genotypes of miR-199a rs74723057, those who carried the GG genotype of MET rs1621 had a reduced risk of HCC, when compared with those who carried the AG/AA genotypes of MET rs1621 (OR = 0.15, 95% CI = 0.03~0.73, P for interaction = 0.018). Our results suggest that MET rs1621 polymorphism, alone and combined with miR-199a rs74723057, may influence susceptibility to HCC. Further large-scale association studies and functional studies are needed to validate our findings. PMID:27813498

  9. Factors associated with weight loss dieting among adolescents: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study.

    PubMed

    Madruga, Samanta W; Azevedo, Mario Renato de; Araújo, Cora Luiza; Menezes, Ana M B; Hallal, Pedro C

    2010-10-01

    Evidence has shown the negative effects of unsupervised diets and those with excessive calorie restriction. The aim of this study was to determine the proportion of adolescents engaging in weight loss dieting and associated factors. This was a cross-sectional study of 4,452 adolescents born in Pelotas, Rio Grande do Sul State, Brazil, in 1993. The outcome was defined as adolescents that reported having practiced some type of weight loss dieting in the previous 12 months. Prevalence of such dieting was 8.6% (95%CI: 7.7;9.4), and was higher in girls. Elevated maternal body mass index (BMI) was associated with dieting among girls. The adolescent's and parents' view of the adolescent's weight, excess weight, and consumption of diet or light soft drinks were associated with adolescent dieting. There was a positive association between dieting and socioeconomic status. The findings provide important backing for policies aimed at improving adolescents' diet, since they express a major concern over weight and thus a significant percentage of individuals with erroneous and unhealthy behaviors.

  10. A SURVEY OF ORAL AND MAXILLOFACIAL BIOPSIES IN CHILDREN. A SINGLE-CENTER RETROSPECTIVE STUDY OF 20 YEARS IN PELOTAS-BRAZIL

    PubMed Central

    Lima, Giana da Silveira; Fontes, Silvia Terra; de Araújo, Lenita Maria Aver; Etges, Adriana; Tarquinio, Sandra Beatriz Chaves; Gomes, Ana Paula Neutzling

    2008-01-01

    Despite the large number of published cases about oral and maxillofacial pediatric lesions, the literature is scarce on epidemiological studies regarding the prevalence of these entities. This study retrieved oral and maxillofacial pediatric lesions from the Center of Diagnosis of Oral Diseases (CDDB) at the Dental School of the Federal University of Pelotas (UFPEL), comprising a 20-year period (1983-2002). From the total of 9,465 biopsies received in this period, 625 (6.6%) were from children aged 0 to 14 years. Regardless of the histopathological diagnosis, patient data referring to lesion location, sex and age were collected. Diagnoses were grouped in 13 categories. As much as 89% of the cases occurred in patients aged 7 to 14 years (53% in females and 47% in males). Mucocele (17.2%) was the most common type of lesion, followed by dentigerous cyst (8.6%). In the category of odontogenic tumors, odontoma was the most frequent lesion (64.2%). Malignant lesions were observed in a small section of the sample (1.2%). Generally, the results of the present study are in line with those reported in the literature concerning the most prevalent lesions in the pediatric population. Most lesions were benign, and malignant lesions were diagnosed in a very small part of the sample. PMID:19082398

  11. Cohort Profile Update: 2004 Pelotas (Brazil) Birth Cohort Study. Body composition, mental health and genetic assessment at the 6 years follow-up

    PubMed Central

    Santos, Iná S; Barros, Aluísio JD; Matijasevich, Alicia; Zanini, Roberta; Chrestani Cesar, Maria Aurora; Camargo-Figuera, Fabio Alberto; Oliveira, Isabel O; Barros, Fernando C; Victora, Cesar G

    2014-01-01

    This is an update of the 2004 Pelotas Birth Cohort profile, originally published in 2011. In view of the high prevalence of overweight and mental health problems among Brazilian children, together with the availability of state-of-the-art equipment to assess body composition and diagnostic tests for mental health in childhood, the main outcomes measured in the fifth follow-up (mean age 6.8 years) included child body composition, mental health and cognitive ability. A total of 3722 (90.2%) of the original mothers/carers were interviewed and their children examined in a clinic where they underwent whole-body dual X-ray absorptiometry (DXA), air displacement plethysmography and a 3D photonic scan. Saliva samples for DNA were obtained. Clinical psychologists applied the Development and Well-Being Assessment questionnaire and the Wechsler Intelligence Scale for Children to all children. Results are being compared with those of the two earlier cohorts to assess the health effects of economic growth and full implementation of public policies aimed at reducing social inequalities in the past 30 years. For further information visit the programme website at [http://www.epidemio-ufpel.org.br/site/content/coorte_2004/questionarios.php]. Applications to use the data should be made by contacting 2004 cohort researchers and filling in the application form available at [http://www.epidemio-ufpel.org.br/site/content/estudos/formularios.php]. PMID:25063002

  12. Cohort profile update: 2004 Pelotas (Brazil) Birth Cohort Study. Body composition, mental health and genetic assessment at the 6 years follow-up.

    PubMed

    Santos, Iná S; Barros, Aluísio J D; Matijasevich, Alicia; Zanini, Roberta; Chrestani Cesar, Maria Aurora; Camargo-Figuera, Fabio Alberto; Oliveira, Isabel O; Barros, Fernando C; Victora, Cesar G

    2014-10-01

    This is an update of the 2004 Pelotas Birth Cohort profile, originally published in 2011. In view of the high prevalence of overweight and mental health problems among Brazilian children, together with the availability of state-of-the-art equipment to assess body composition and diagnostic tests for mental health in childhood, the main outcomes measured in the fifth follow-up (mean age 6.8 years) included child body composition, mental health and cognitive ability. A total of 3722 (90.2%) of the original mothers/carers were interviewed and their children examined in a clinic where they underwent whole-body dual X-ray absorptiometry (DXA), air displacement plethysmography and a 3D photonic scan. Saliva samples for DNA were obtained. Clinical psychologists applied the Development and Well-Being Assessment questionnaire and the Wechsler Intelligence Scale for Children to all children. Results are being compared with those of the two earlier cohorts to assess the health effects of economic growth and full implementation of public policies aimed at reducing social inequalities in the past 30 years. For further information visit the programme website at [http://www.epidemio-ufpel.org.br/site/content/coorte_2004/questionarios.php]. Applications to use the data should be made by contacting 2004 cohort researchers and filling in the application form available at [http://www.epidemio-ufpel.org.br/site/content/estudos/formularios.php].

  13. Relationship Between Chronic Tinnitus and Glial Cell Line-Derived Neurotrophic Factor Gene rs3812047, rs1110149, and rs884344 Polymorphisms in a Turkish Population.

    PubMed

    Orenay-Boyacioglu, Seda; Coskunoglu, Aysun; Caki, Zerrin; Cam, Fethi Sirri

    2016-08-01

    Glial cell line-derived neurotrophic factor (GDNF) plays a key role in early development of central auditory pathway and the inner ear. However, the auditory pathway studies of GDNF gene polymorphisms are scarce in the literature, and the studies especially associated with tinnitus are limited. Our study aimed to identify whether GDNF gene polymorphisms play any roles in the pathophysiology of tinnitus by investigating the relationship between tinnitus and GDNF polymorphisms. A total of 52 patients with chronic tinnitus and ages ranging from 18 to 55 were admitted to the Ear-Nose-Throat outpatient clinic of Celal Bayar University Medical Faculty Hospital of Manisa, Turkey and constituted the study group. Another 42 patients of the same age range, without tinnitus symptoms and lacking any systemic disease, were also admitted to the clinic and formed the control group. The tympanometric, audiological, and psychoacoustic assessments of the subjects were performed. Deoxyribonucleic acid samples obtained using venous blood taken for routine inspections were used to investigate GDNF gene polymorphisms (rs884344, rs3812047, and rs1110149) by polymerase chain reaction-based restriction fragment length polymorphism method. No correlation could be detected between GDNF rs884344 and rs3812047 polymorphisms and subjects with tinnitus (p > 0.05). Heterozygosity was significantly lower for GDNF rs1110149 polymorphism in tinnitus subjects compared to the controls (p < 0.05). However, the allele frequencies for all 3 polymorphisms were not significantly different between tinnitus and control groups (p > 0.05). Failure to detect correlations between tinnitus and GDNF gene polymorphisms suggests this may be due to the fact that the GDNF gene has a variable expression pattern in different tissues and pathologies. Therefore, the study should be improved and its scope should be expanded by including a larger group of patients and different tissues to investigate the expression

  14. AirMSPI SEAC4RS Ellipsoid Data

    Atmospheric Science Data Center

    2017-03-16

    ... AirMSPI SEAC4RS Ellipsoid-projected Georegistered Radiance Data AirMSPI Ellipsoid-Projected Georegistered Radiance Product ... Polarized Radiance DOLP AOLP Order Data:  Earthdata Search:  Earthdata Search SCAR-B ...

  15. AirMSPI SEAC4RS Terrain Data

    Atmospheric Science Data Center

    2017-03-16

    ... AirMSPI SEAC4RS Terrain-projected Georegistered Radiance Data AirMSPI Terrain-Projected Georegistered Radiance Product ... Polarized Radiance DOLP AOLP Order Data:  Earthdata Search:  Earthdata Search Read ...

  16. Regional Science and Technology (RS&T) Organizations

    EPA Pesticide Factsheets

    EPA’s RS&T Organizations perform analytical and other work that: practices sound science, implements the principles of environmental protection, and promotes partnerships with states, Indian Nations, and local governments.

  17. Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population

    PubMed Central

    Chandra, Vishal; Kim, Jong Joo; Gupta, Usha; Mittal, Balraj; Rai, Rajani

    2016-01-01

    Multiple studies have investigated the association of gene variant of Deleted in colorectal carcinoma (DCC) and Prostate Stem cell antigen (PSCA) with various cancer susceptibility; however, the results are discrepant. Since SNPs are emerging as promising biomarker of cancer susceptibility, here, we aimed to execute a meta-analysis of DCC (rs714 A > G) and PSCA (rs2294008 C > T, rs2976392 G > A) polymorphism to demonstrate the more accurate strength of these associations. We followed a rigorous inclusion/exclusion criteria and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Overall, the pooled analysis showed that the DCC rs714 conferred increased risk of cancer only in Asians (AA vs. GG: OR = 1.86, p ≤ 0.0001; AG vs. GG: OR = 1.43, p = 0.005; GA + AA vs. GG: OR = 1.66, p ≤ 0.0001; AA vs. GG + GA; OR = 1.52, p ≤ 0.004, A vs. G allele: OR = 1.41, p ≤ 0.0001). PSCA rs2294008 was associated with increased overall cancer risk (TT vs. CC: OR = 1.28, p = 0.002; CT vs. CC: OR = 1.21, p ≤ 0.0001; CT + TT vs. CC: OR = 1.24, p ≤ 0.0001; TT vs. CC + CT; OR = 1.17, p ≤ 0.005, T vs. C allele: OR = 1.16, p ≤ 0.0001); however, in stratified analysis this association was limited only to gastric and bladder cancer and the strength was more prominent in Asians. In contrast, the PSCA rs2976392 SNP did not modulate the cancer risk. Therefore, we concluded that rs714 and rs2294008 polymorphism may represent a potential genetic biomarker for cancer risk in Asians and gastric as well as bladder cancer, respectively. However, since our study is limited to Asians and cancer types, further larger studies involving other cancers and/or population, gene-environment interactions and the mechanism of DCC and PSCA gene deregulation are desired to define the role of genotype with overall cancer risk. PMID:26891331

  18. Exosomal miRs in Lung Cancer: A Mathematical Model

    PubMed Central

    Lai, Xiulan; Friedman, Avner

    2016-01-01

    Lung cancer, primarily non-small-cell lung cancer (NSCLC), is the leading cause of cancer deaths in the United States and worldwide. While early detection significantly improves five-year survival, there are no reliable diagnostic tools for early detection. Several exosomal microRNAs (miRs) are overexpressed in NSCLC, and have been suggested as potential biomarkers for early detection. The present paper develops a mathematical model for early stage of NSCLC with emphasis on the role of the three highest overexpressed miRs, namely miR-21, miR-205 and miR-155. Simulations of the model provide quantitative relationships between the tumor volume and the total mass of each of the above miRs in the tumor. Because of the positive correlation between these miRs in the tumor tissue and in the blood, the results of the paper may be viewed as a first step toward establishing a combination of miRs 21, 205, 155 and possibly other miRs as serum biomarkers for early detection of NSCLC. PMID:28002496

  19. Determination of RS,E/Z-tocotrienols by HPLC.

    PubMed

    Drotleff, A M; Ternes, W

    2001-02-16

    Synthetic alpha-tocotrienol was separated into four geometrical E/Z side chain isomers by preparative HPLC (permethylated beta-cyclodextrin phase). The isolated isomers were resolved in ethylene glycol dimethyl ether, converted into the corresponding methyl ether using dimethyl sulfate, and the tocotrienol methyl ethers were extracted with n-hexane. A subsequent HPLC separation on a chiral phase (adsorbent cellulose derivated with 3,5-dimethyl phenyl carbamate) discriminates between the enantiomers of each E/Z side chain isomer, achieving the complete resolution of the eight occurring synthetic RS,E/Z-alpha-tocotrienols. The method can be shortened by omitting the preparative separation of the E/Z tocotrienol isomers prior to the chromatography on the chiral dimethyl phenyl carbamate phase. The simplified method achieved the following separation: RS,E/Z-alpha-tocotrienol separated into five peaks, RS,E/Z-beta-tocotrienol into eight, RS,E/Z-gamma-tocotrienol into six and RS,E/Z-delta-tocotrienol into eight peaks. The naturally occurring R,E-E-tocotrienol isomer could be identified within the synthetic RS,E/Z-isomers by co-chromatography with tocotrienol methyl ethers derived from natural sources, respectively.

  20. Correction: Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock.

    PubMed

    2015-11-01

    Vol. 110 (4): 453-460, 2015. p. 453. "Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock" should read: "Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock". == Vol. 110 (6): 797-800, 2015 .p. 797. "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E-26/110.497/2011), CNPq (458858/2014-5)" should read: "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E-26/110.497/2011), CNPq (458858/2014-5),FAPEAM/CNPq/PPP-FAPEAM (010/2011), MCT/CNPq (014/2011)"

  1. Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor)

    PubMed Central

    Lagmay, Joanne P.; London, Wendy B.; Gross, Thomas G.; Termuhlen, Amanda; Sullivan, Nicholas; Axel, Amy; Mundy, Bethany; Ranalli, Mark; Canner, Jason; McGrady, Patrick; Hall, Brett

    2009-01-01

    Purpose Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression. Experimental design DNA samples from 96 high risk neuroblastoma patients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor (IL-6R), rs1800795 and rs8192284 respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was performed to determine SNP-related event free survival (EFS) and overall survival (OS) rates. Results The rs1800795 IL-6 promoter SNP is an independent prognostic factor for EFS and OS in -high risk neuroblastoma patients. In contrast, the rs8192284 IL-6 receptor SNP revealed no prognostic value. Conclusions The rs1800795 SNP (-174 IL-6 (G>C) represents a novel and independent prognostic marker for both EFS and OS in high risk neuroblastoma. Since the rs1800795 SNP (-174 IL-6 (G>C) has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma. PMID:19671870

  2. NEURL rs6584555 and CAND2 rs4642101 contribute to postoperative atrial fibrillation: a prospective study among Chinese population

    PubMed Central

    Liu, Chong; Shen, Jiayi; Huang, Ying

    2016-01-01

    Postoperative atrial fibrillation (POAF) is a serious, common complication after coronary artery bypass grafting (CABG) surgery. Recently, 5 novel loci were identified to be associated with atrial fibrillation susceptibility using a combination of genotyping, eQTL mapping, and functional validation. In current study, we aim to evaluated the positive findings for POAF susceptibility after CABG among Chinese population, using a population-based, two-stage, nested case-control study with 1,400 patients. NEURL rs12415501 and CAND2 rs4642101 were significantly associated with POAF susceptibility after CABG among Chinese population in both stages. When pooled together, the ORs for each additional copy of minor allele was 1.29 (95% CI: 1.13-1.48, P = 1.7×10−4) for NEURL rs12415501, and 1.21 (95% CI: 1.08-1.36, P = 9.8×10−4) for CAND2 rs4642101. Functional validation experiments found the AF risk allele of NEURL rs6584555 and CAND2 rs4642101 correlated with an increased expression of its corresponding genes (P<0.001). In this independently collected cardiac surgery cohort, we replicated the previous findings, and 2 novel loci are independently associated with POAF risk in patients who undergo CABG surgery in Chinese population. PMID:27203392

  3. Association between IL-1α rs17561 and IL-1β rs1143634 polymorphisms and periodontitis: a meta-analysis.

    PubMed

    Yin, W T; Pan, Y P; Lin, L

    2016-02-05

    Genetic variations in human interleukin-1 (IL-1) genes are known to be involved in inflammatory disorders. The rs17561 and rs1143634 polymorphisms of IL-1α and IL-1β, respectively, have been increasingly recognized as important regulators in the development of periodontitis. However, the existence of a specific association remains controversial. Therefore, we performed a meta-analysis to explore the relationship between IL-1 polymorphism and periodontitis risk. Based on our inclusion criteria, six case-control studies were used, involving a total of 336 periodontitis cases and 366 healthy controls. Our meta-analysis results showed that the T allele of IL-1α rs17561 is positively associated with periodontitis susceptibility. In addition, carriers of this allele (TC + TT genotypes) demonstrated increased risk of this disease. The IL-1β rs1143634 T allele was also positively connected to periodontitis, with TC + TT genotype carriers being significantly more at risk. These results demonstrate that the IL-1α rs17561 and IL-1β rs1143634 polymorphisms are associated with periodontitis.

  4. CREM variants rs4934540 and rs2295415 conferred susceptibility to nonobstructive azoospermia risk in the Chinese population.

    PubMed

    He, Xiao-Jin; Song, Bing; Du, Wei-Dong; Cao, Yun-Xia; Zhang, Yan; Ruan, Jian; Tian, Hui; Zhou, Fu-Sheng; Zuo, Xian-Bo; Wu, Huan; Zha, Xing; Xie, Xu-Shi; Wei, Zhao-Lian; Zhou, Ping

    2014-08-01

    To evaluate the association of variants related to spermatogenesis with susceptibility to Chinese idiopathic nonobstructive azoospermia (NOA), seventeen tag single-nucleotide polymorphisms (SNPs) in CREM, ACT, KIF17b, and SPAG8 were analyzed in 361 NOA patients and 368 controls by Sequenom iplex technology. The results showed that two CREM SNPs, rs4934540 and rs22954152, were significantly associated with NOA and played protective roles against the disease (P value with Bonferroni correction = 0.00017, odds ratio [OR] = 0.624 and P = 0.012, OR = 0.686, respectively). Haplotype analysis of CREM gene variants suggested that haplotype CGTG of the SNPs, rs4934540, rs2295415, rs11592356, and rs1148247, exhibited significant protective effect against the occurrence of NOA (P = 0.001, OR = 0.659). The haplotype TATG conferred a significantly increased risk of NOA (P = 0.011, OR = 1.317). Furthermore, making use of quantitative RT-PCR, we demonstrated that relative mRNA expression of CREM in NOA patients with maturation arrest was only one-third of that in the controls with normal spermatogenesis (P < 0.0001). Our findings indicated that the polymorphisms of CREM gene were associated with NOA in the Chinese population and low CREM expression might be involved in the pathogenesis of spermatogenesis maturation arrest.

  5. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    NASA Astrophysics Data System (ADS)

    Hoobakht, Fatemeh; Ganji, Fariba; Vasheghani-Farahani, Ebrahim; Mousavi, Seyyed Mohammad

    2013-09-01

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 °C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1-4 and 20 % of loaded PB released from the nanocarriers within 100 h.

  6. Assessment of IL-28: rs12979860 and rs8099917 Polymorphisms in a Cohort of Cuban Chronic HCV Genotype 1b Patients

    PubMed Central

    Palenzuela Gardón, Daniel; Guillen, Isabel Alicia; Fernández, Julio R.; Camacho, Hamlet; Estevez, Zurina Cinza; Dueñas, Santiago; Alvares-Lajonchere, Liz; Amador, Yalena; Martinez-Donato, Gillian; Han, Junsong; Zhang, Zhiming; Zhang, Xiaona; Gao, Yang; Campaña, Juan Roca; Novoa, Lidia I.

    2016-01-01

    Hepatitis C virus (HCV) is a significant global public health problem with >185 million infections worldwide. A series of genome-wide association studies (GWAS) has identified IL-28B polymorphisms as a predictor of sustained virologic response (SVR), as well as spontaneous clearance in chronic HCV genotype 1 patients. The objective of this work was to evaluate the prevalence of IL-28B rs12979860 and rs8099917 polymorphisms in Cuban chronic HCV patients. The study cohort included 73 chronic HCV patients treated with concomitant administration of CIGB-230 and nonpegylated IFN-α plus ribavirin (non-pegIFN-α/R) antiviral therapy. The genotype distribution of IL-28B rs12979860CC, -CT, and -TT was 29, 41, and 30%, respectively, and the distribution for rs8099917TT, -TG, and -GG was 63, 31, and 5%, respectively. The allele frequencies for rs12979860C and -T alleles were 51 and 49%, respectively, and for rs8099917G and -T alleles, the values were 21 and 79%, respectively. SVR rates were 55, 42, and 35% for rs12979860CC, -CT, and -TT, respectively, and 52, 30, and 25% for rs8099917TT, -GT, and -GG, respectively. The combined assessment of both single nucleotide polymorphisms (SNPs) resulted in 3 major genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TT, and rs12979860CT/rs8099917GG) with a frequency of 30.1, 21.9, and 20.5%, respectively. In patients with heterozygous variant rs12979860CT, the additional genotyping of rs8099917 contributed to increase the SVR rate. It is concluded that in Cuban HCV-infected patients, the responder homogeneous variant rs8099917TT is the most frequent genotype. The simultaneous genotyping of 2 IL-28B SNPs could improve the prediction of SVR contributing to better therapeutic decisions and treatment management. PMID:28058039

  7. Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis.

    PubMed

    Liu, Yong; Chen, Qicong; Liu, Xu; Dou, Mengmeng; Li, Silu; Zhou, Jiahui; Liu, Hong; Wu, Yongfu; Huang, Zunnan

    2016-01-01

    Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62-0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01-1.37, homozygous: OR = 1.63, 95% CI: 1.09-2.42, and recessive: OR = 1.65, 95% CI: 1.20-2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05-2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01-1.48; homozygous: OR = 2.24, 95% CI: 1.48-3.39; dominant: OR = 1.21, 95% CI: 1.06-1.40; and recessive: OR = 2.18, 95% CI: 1.45-3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD.

  8. Distribution of Glycated Haemoglobin According to Early-Life and Contemporary Characteristics in Adolescents and Adults without Diabetes: The 1982 and 1993 Pelotas Birth Cohorts

    PubMed Central

    Restrepo-Méndez, María Clara; Silveira, Vera M.; Miranda, Jaime J.; Gonçalves, Helen D.; Oliveira, Isabel O.; Horta, Bernardo L.; Gigante, Denise P.; Menezes, Ana Maria; Assunção, Maria Cecília F.

    2016-01-01

    Aim Glycated haemoglobin (HbA1c), a marker of glucose control in individuals with diabetes mellitus, is also related with the incidence of cardiometabolic risk in populations free of disease. The aim of this study was to describe the distribution of HbA1c levels according to early-life and contemporary factors in adolescents and adults without diabetes mellitus. Methods HbA1c was measured in adults aged 30 years and adolescents aged 18 years who are participants in the 1982 and 1993 Pelotas Birth Cohorts, respectively. Bivariate and multivariate analyses were performed to describe the HbA1c mean values according to early-life and contemporary characteristics collected prospectively since birth. Results The distribution of the HbA1c was approximately normal in both cohorts, with a mean (SD) 5.10% (0.43) in the 1982 cohort, and 4.89% (0.50) in the 1993 cohort. HbA1c mean levels were significantly higher in individuals self-reported as black/brown skin color compared to those self-reported as white in both cohorts. Parental history of diabetes was associated with higher HbA1c mean in adults, while stunting at one year old presented an inverse relation with the outcome in adolescents. No other early and contemporary factors were associated with HbA1c levels in adults or adolescents. Conclusions We found a consistent relationship between HbA1c and skin color in both cohorts. Further research is needed to understand the role of genomic ancestry on levels of HbA1c concentrations which may inform policies and preventive actions for diabetes mellitus and cardiometabolic risk. PMID:27626274

  9. COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect

    PubMed Central

    Akutagava-Martins, Glaucia C.; Salatino-Oliveira, Angelica; Kieling, Christian; Genro, Julia P.; Polanczyk, Guilherme V.; Anselmi, Luciana; Menezes, Ana M.B.; Gonçalves, Helen; Wehrmeister, Fernando C.; Barros, Fernando C.; Callegari-Jacques, Sidia M.; Rohde, Luis A.; Hutz, Mara H.

    2016-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population. Methods We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes. Results Linear regression analyses demonstrated that the increasing number of COMT158Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049, t = 2.189, p = 0.029, R2 = 0.012, and β coefficient = 0.064, t = 2.832, p = 0.005, R2 = 0.008, respectively). The presence of both COMT158Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ2 = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048–5.838) from this cohort. We did not observe these associations in girls. Limitations Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated. Conclusion This study demonstrates a role for COMT and DAT1 genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism on COMT and DAT1 gene expression. PMID:27327562

  10. Theoretical studies of the RS Canum Venaticorum stars

    NASA Technical Reports Server (NTRS)

    Mullan, D. J.

    1982-01-01

    The activity in RS Canum Venaticorum (CVn) is investigated. Models for chromospheric structure are developed and the role of magnetic fields both in the photosphere as well as in the chromosphere and upper atmosphere are examined. T Tau stars are also studied from the same points of view. The properties of magnetic field loops are used to help understand the atmospheric structure in RS CVn stars. The concepts developed in the case of these stars appear to be applicable over a much broader region of the HR diagram. The absence of stable magnetic loops in the atmospheres of late type giant stars suggests that the atmospheres of RS CVn active components are qualitatively distinct from the solar atmosphere.

  11. NeurimmiRs: microRNAs in the neuroimmune interface.

    PubMed

    Soreq, Hermona; Wolf, Yochai

    2011-10-01

    Recent reports of microRNA (miR) modulators of both neuronal and immune processes (here termed NeurimmiRs) predict therapeutic potential for manipulating NeurimmiR levels in diseases affecting both the immune system and higher brain functions, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and anxiety-related disorders. In our opinion, NeurimmiRs that function within both the nervous and the immune systems, such as miR-132 and miR-124, may act as 'negotiators' between these two interacting compartments. We suggest that NeurimmiRs primarily target transcriptional or other regulatory genes, which enables modulation of both immune and cognitive processes through direct or indirect alterations of neuron-glia and/or brain-to-body signaling. Thus, manipulating NeurimmiR control over the immune contributions to cognitive pathways may offer new therapeutic targets.

  12. Polymorphisms rs12998 and rs5780218 in KiSS1 Suppressor Metastasis Gene in Mexican Patients with Breast Cancer

    PubMed Central

    Cruz Quevedo, Edhit Guadalupe; Mimendi Aguilar, Gabriela Monserrat; Juárez Aguilar, Luis Anselmo; Gutierrez Rubio, Susan Andrea; Flores Martínez, Silvia Esperanza; Dávalos Rodríguez, Ingrid Patricia; Sánchez Corona, José; Torres Morán, Martha Isabel; Rosales Gómez, Roberto Carlos; Morán Moguel, María Cristina

    2015-01-01

    Aims. KiSS1 is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along the KiSS-1 gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT) and the rs12998 (E20K) KiSS1 polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP) and patients with benign breast disease (BBD) or breast cancer (BC). Results. The rs5780218 polymorphism was individually associated with breast cancer (P = 0.0332) and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD) groups were compared (P < 0.0001). The H1 Haplotype (G/-) occurred more frequently in BC group (0.4256) whereas H2 haplotype (G/T) was the most prevalent in BBD group (0.4674). Conclusions. Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant) in KiSS1 gene must be analyzed in other populations. PMID:25810563

  13. Restoring New Agegraphic Dark Energy in RS II Braneworld

    NASA Astrophysics Data System (ADS)

    Jamil, Mubasher; Karami, K.; Sheykhi, A.

    2011-10-01

    Motivated by recent works (Saridakis in Phys. Lett. B 660:138, 2008; Sheykhi in Int. J. Mod. Phys. D 19(3):305, 2010), we investigate the new agegraphic model of dark energy in the framework of RS II braneworld. We also include the case of variable gravitational constant G in our model. Moreover, we reconstruct the potential and the dynamics of the quintessence, tachyon, K-essence and dilaton scalar field models according to the evolutionary behavior of the new agegraphic dark energy model in RS II braneworld cosmology including varying G.

  14. MMP-9 gene polymorphisms (rs3918242, rs3918254 and rs4810482) and the risk of psoriasis vulgaris: No evidence for associations in a Chinese Han population.

    PubMed

    Liang, Jingyao; Zhao, Tian; Yang, Juan; Li, Wei; Zhang, Fang; Zhang, Sanquan; Huang, Zhenming; Lin, Rihua; Zhang, Xibao

    2015-12-01

    Several previous studies including one of them co-authored by our group have revealed that serum and psoriatic plaque expression of matrix metalloproteinase-9 (MMP-9) was significantly upregulated in psoriasis. The aim of this study was to investigate the association of three single nucleotide polymorphisms (SNPs) and haplotypes of MMP-9 (rs3918242, rs3918254 and rs4810482) with psoriasis vulgaris in a Chinese Han population. The serum levels of MMP-9 in 245 psoriasis vulgaris cases and 256 healthy controls were assessed using ELSA kits, and the three SNPs were genotyped using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Four haplotypes based on the three SNPs were also analyzed. Our study showed that the serum MMP-9 levels in patients with psoriasis vulgaris were significantly higher than that in controls (P<0.05). However, the three SNPs were not significantly associated with psoriasis vulgaris susceptibility (all P>0.05). Similar results were found in further subgroup analysis based on gender, age of onset, family history, and serum MMP-9 levels, except that a protective effect of psoriasis vulgaris was detected among female subjects with the CT genotype of rs3918254 (OR=0.47, 95% CI=0.23-0.96, P=0.038), but this association did not survive after Bonferroni correction (P(adj)=0.076). The haplotype analysis also failed to show any association with psoriasis vulgaris. We found no evidence for the association between the MMP-9 polymorphisms and psoriasis vulgaris susceptibility in a Chinese Han population.

  15. The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis

    PubMed Central

    Iannaconne, Marco; McEwen, Gayle; Ciontea, Marius Sorin; Olaru, Marian; Capparelli, Rosanna; Ioana, Mihai; Kaufmann, Stefan H. E.; Dorhoi, Anca

    2016-01-01

    Genetic variants in the CARD9 gene predispose to inflammatory disorders and chronic infectious diseases. Tuberculosis (TB), a chronic infectious disease affecting the lung, is lethal in Card9-deficient mice. We hypothesized that polymorphisms in the CARD9 gene influence TB progression and disease-associated lung damage in humans. We tested genotype distributions of the CARD9 polymorphisms rs4077515, rs10781499 and rs10870077 in TB patients and healthy subjects in a Caucasian cohort. SNPs were in linkage disequilibrium and none of the haplotypes was significantly enriched in the TB group. We determined total and differential leukocyte count, erythrocyte sedimentation rate and plasma abundance of cytokines and chemokines as markers for systemic inflammation and scored chest X-rays to assess lung involvement in TB subjects. Most disease parameters segregated independently of the CARD9 haplotypes. In contrast to multifactorial chronic inflammation, selected genetic variants in the CARD9 gene leave host responses apparently unaffected in TB, at least in the population analyzed here. PMID:27684065

  16. Association of Versican (VCAN) gene polymorphisms rs251124 and rs2287926 (G428D), with intracranial aneurysm

    PubMed Central

    Sathyan, Sanish; Koshy, Linda V.; Balan, Shabeesh; Easwer, H.V.; Premkumar, S.; Nair, Suresh; Bhattacharya, R.N.; Alapatt, Jacob P.; Banerjee, Moinak

    2014-01-01

    Intracranial aneurysm (IA) accounts for 85% of Subarachnoid Hemorrhage (SAH) and is mainly caused due to the weakening of arterial wall. The structural integrity of the intracranial arteries is mainly influenced by the extracellular matrix (ECM) remodeling. The Proteoglycan Versican plays an important role in extracellular matrix assembly and plays a major role in the pathogenesis of IA. The linkage studies also indicated VCAN as a putative candidate gene for IA in the 5q22–31 region. Using a case–control study design, we tested the hypothesis whether the variants in VCAN gene, nonsynonymous variants in the coding region of Glycosaminoglycan α (GAG-α) and GAG-β and two reported SNPs involved in splicing rs251124 and rs173686 can increase the risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We selected 200 radiologically confirmed aneurysmal cases and 250 ethnically, age and sex matched controls from the Dravidian Malayalam speaking population of South India. The present study reiterated the earlier association of rs251124 with intracranial aneurysm (P = 0.0002) and also found a novel association with rs2287926 (G428D) in exon 7 coding for GAG-α with intracranial aneurysm (P = 0.0015). Interestingly, both these SNPs contributed to higher risk for aneurysm in males. In-silico analysis predicted this SNP to have the highest functional relevance in the gene which might have a potentially altered regulatory role in transcription and splicing. Using meta-analysis with available literature rs251124 was found to be the strongest intracranial aneurysm marker for global ethnicities. This study with a novel functional SNP rs2287926 (G428D) further substantiates the potential role of VCAN in the pathogenesis of IA. PMID:25606449

  17. The influence of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms on prostate cancer risk.

    PubMed

    Fu, Chenying; Dong, Wen-Qi; Wang, Ani; Qiu, Guozhen

    2014-08-01

    Estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) may play a role in the development of prostate cancer. Many studies focused on ESR1 rs9340799 and ESR2 rs1256049 polymorphisms to explore associations with prostate cancer risk. These studies showed inconsistent and conflicting results. The aim of this meta-analysis was to investigate the pooled association of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms with prostate cancer risk. A systematic literature search was conducted to identify related studies (up to February 2014) in several online databases including PubMed, Google Scholar, CNKI and Wanfang online libraries. A total of 16 eligible articles were enrolled in this updated meta-analysis. The result suggested that ESR1 rs9340799 polymorphism was significantly associated with prostate cancer in overall populations (GG+GA vs. AA: P = 0.002; G vs. A: P = 0.004), Caucasians (GG+GA vs. AA: P = 0.008; G vs. A: P = 0.016) and Africans (GG+GA vs. AA: P = 0.005; G vs. A: P = 0.006), but not in Asians (GG+GA vs. AA: P = 0.462; G vs. A: P = 0.665). The result also showed that there was a significant association between ESR2 rs1256049 polymorphism and prostate cancer in Caucasians (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG: P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P = 0.707). The cumulative meta-analysis and sensitivity analysis showed the results were robust. In conclusion, this meta-analysis indicated that ESR1 rs9340799 polymorphism was associated with prostate cancer risk in overall populations, Caucasians and Africans, while ESR2 rs1256049 polymorphism was associated with prostate cancer risk in Caucasians. However, the biological mechanisms need to be further investigated.

  18. Sirtuin 1 rs1467568 and rs7895833 in South African Indians with early-onset coronary artery disease

    PubMed Central

    Ramkaran, Prithiksha; Moodley, Devapregasan; Chuturgoon, Anil A; Phulukdaree, Alisa; Khan, Sajidah

    2016-01-01

    Summary Background Sirtuin 1 (SIRT1), a class III histone deacetylase, has been identified as a candidate molecule affecting the epigenetic mechanisms of cardiovascular disease (CVD). Previous studies have shown that some SIRT1 single-nucleotide polymorphisms (SNPs) are associated with body mass index, diabetes, blood pressure, cholesterol metabolism and coronary artery calcification. We investigated two A>G SIRT1 SNPs, rs1467568 and rs7895833, in young South African (SA) Indians with coronary artery disease (CAD) and compared them to Indian and black controls. Methods For rs1467568, a total of 287 subjects were recruited into this study (104 CAD patients, 99 age-, gender- and race-matched controls, and 84 age- and gender-matched black controls). For rs7895833, a total of 281 subjects were recruited into this study (100 CAD patients, 99 age-, gender- and race-matched controls, and 82 age- and gender-matched black controls). All patients were male, of Indian ethnicity, stable CAD confirmed on angiography, mean age 37.5 years; range 24–45. All subjects were genotyped using TaqMan SNP genotyping assays. Results The variant allele for both SNPs was found at a higher frequency in the total Indian group compared to the total black population (rs1467568: 41 vs 18.5%, respectively, p < 0.0001, OR = 3.190, 95% CI: 2.058–40943; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.466, 95% CI: 1.620– 3.755). Indian controls presented with a higher frequency for both SNPs compared to black controls (rs1467568: 40 vs 18.5%, respectively, p < 0.0001, OR = 2.996, 95% CI: 1.850– 4.853; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.513, 95% CI: 1.578–4.004). No difference was seen in the distribution of both SNPs between CAD patients and either control group. We did not observe any association between the SNPs and clinical parameters in CAD patients and controls. Conclusion: Both SNP variant alleles occurred more frequently in SA Indians than in SA

  19. INFeRS: Interactive Numeric Files Retrieval System. Final Report.

    ERIC Educational Resources Information Center

    Chiang, Katherine; And Others

    In 1988 Mann Library at Cornell University proposed to develop a computer system that would support interactive access to significant electronic files in agriculture and the life sciences. This system was titled the Interactive Numeric Files Retrieval System (INFeRS). This report describes how project goals were met and it presents the project's…

  20. Work in Progress: The Seven Rs of Team Building

    ERIC Educational Resources Information Center

    Brunelli, Jean; Schneider, Elaine Fogel

    2004-01-01

    This article argues that supportive teams--including professionals, paraprofessionals, and parents--can teach staff members how to identify and implement best practices in early intervention settings. The authors describe "the seven Rs of team building" distilled from their many years of team building and maintenance: 1) Reading cues; 2) Regular…

  1. Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.

    PubMed

    Flores, Yvonne N; Velázquez-Cruz, Rafael; Ramírez, Paula; Bañuelos, Manuel; Zhang, Zuo-Feng; Yee, Hal F; Chang, Shen-Chih; Canizales-Quinteros, Samuel; Quiterio, Manuel; Cabrera-Alvarez, Guillermo; Patiño, Nelly; Salmerón, Jorge

    2016-12-01

    There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a 6 month period, during 2004-2006 and 2011-2013. TaqMan assays were used to genotype the SNPs. The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR 2.28, 95 % CI 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of adults in Mexico.

  2. Peraluminous leucogranites of the Cordilheira Suite: A record of Neoproterozoic collision and the generation of the Pelotas Batholith, Dom Feliciano Belt, Southern Brazil

    NASA Astrophysics Data System (ADS)

    Philipp, Ruy Paulo; Massonne, Hans-Joachim; de Campos, Roberto Sacks

    2013-04-01

    The Cordilheira Suite is comprised of peraluminous granites that constitute, together with the Quitéria granite, the beginning of the formation of the Pelotas Batholith in the central portion of the Dom Feliciano Belt. The batholith is composed of seven granitic suites with minor occurrences of gabbro, diorite and subvolcanic rocks. Its evolution between 650 and 550 million years ago is characterised by a ranging from metaluminous to peraluminous rocks and from calc-alkaline to alkaline and peralkaline series. The Cordilheira Suite is composed of the Cordilheira, Arroio Francisquinho, Butiá and Três Figueiras granites, which contain muscovite and/or biotite, with the following accessory minerals: tourmaline, garnet, sillimanite, apatite, zircon, monazite and ilmenite. The granitic bodies are elongate; their ascent and emplacement were controlled by high-angle shear zones oriented at N45-70°E. They have mylonitic structures with magmatic foliation accompanied by a low-angle stretching lineation, indicating that these bodies were emplaced under syn-kinematic conditions during a transcurrent event. The granites have high-K calc-alkaline affinity and are peraluminous. The LILE and REE contents are low. The K2O/Na2O and CaO/Na2O ratios are approximately 1 and less than 0.3, respectively. Pseudosections calculated using the Perple X program suggests that the granites were formed at partial melting temperatures between 740 and 820 °C and pressure between 8.5 and 9 kbar. Petrographic and chemical data suggest that the magmas were generated by the partial melting of the migmatitic pelitic gneisses of the Várzea do Capivarita Complex and, to a lesser degree, orthogneisses of the Arroio dos Ratos Complex, which left a granulitic residue. UHT conditions of granulite facies metamorphism were recorded in the Várzea do Capivarita paragneisses by mineral paragenesis and indicate that temperatures between 900 and 1000 °C and pressures between 4 and 8 kbar were required for

  3. XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk.

    PubMed

    Pérez, Luis Orlando; Crivaro, Andrea; Barbisan, Gisela; Poleri, Lucia; Golijow, Carlos Daniel

    2013-07-01

    Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.

  4. Association of rs10757274 and rs2383206 Polymorphisms on 9p21 locus with Coronary Artery Disease in Turkish Population

    PubMed Central

    Okyay, Kaan; Yılmaz, Akın; Şahinarslan, Asife; Yar Sağlam, Atiye Seda; Eyiol, Azmi; Bolayır, Hasan Ata; Sezenöz, Burak; Menevşe, Sevda; Çengel, Atiye

    2016-01-01

    Background and Objectives Genetic predisposition is an important risk factor for coronary artery disease (CAD). In this study, we aimed to evaluate the impact of rs10757274 and rs2383206 polymorphisms in chromosome 9p21 on presence and severity of CAD in a Turkish population. Subjects and Methods A total of 646 patients who underwent coronary angiography were included in this study. Coronary vessel score and Gensini score were calculated to assess the angiographic severity of CAD. Alleles of AA, AG, and GG were determined for rs10757274 (polymorphism-1) and rs2383206 (polymorphism-2) polymorphisms located in chromosome 9p21 from the blood samples. Results There was a significant difference between the alleles in polymorphism-1 in the presence of coronary artery disease (38.9% in AA, 48.0% in GG and 56.4% in AG, p=0.017). However, there was no difference between the alleles in polymorphism-2. According to vessel scores, there was a significant difference between the alleles in polymorphism-1 (AA 0.71±1.04, GG 0.88±1.07, AG 1.06±1.12, p=0.018). In polymorphism-2, vessel scores did not show a difference between the alleles. In polymorphism-1, there was a significant difference in Gensini score (p=0.041). Gensini scores did not differ between the alleles in polymorphism-2 (p>0.05 for all). In multivariate analyses, none of the alleles was an independent factor for presence of CAD. Conclusion The presence of rs10757274 polymorphism including AG allele in chromosome 9p21 was related to CAD. However, this relationship was not independent of other cardiovascular risk factors. PMID:27721851

  5. Association of the IGF-1 rs35767 and rs972936 polymorphisms with the risk of osteoporosis in a Chinese postmenopausal female population.

    PubMed

    Wei, Y K; Ma, H L; Guo, Y Z; Yang, B H; Pang, W X

    2015-11-13

    The aim of our study was to conduct a case-control study in a Chinese postmenopausal population to evaluate the roles of the IGF-1 rs35767 and rs972936 polymorphisms on bone mineral density (BMD) levels and osteoporosis risk. A total of 272 consecutive postmenopausal women with a primary diagnosis of osteoporosis and 272 controls were enrolled in the study between 2012 and 2014. The polymerase chain reaction-restriction fragment length polymorphism method was used to genotype the rs35767 and rs972936 IGF-1 polymorphisms. By comparing the demographic characteristics between patients and controls, patients with osteoporosis were found to be more likely to have a habit of alcohol drinking (P = 0.023). Furthermore, the BMD levels of the L1-L4 vertebrae, femoral necks, total hips, and trochanters in patients with osteoporosis were significantly lower than those in controls. By conditional regression analysis, we found that the IGF-1 rs2288377 and rs972936 gene polymorphisms were not associated with the risk of osteoporosis (P < 0.05). However, the CT+TT genotype of rs35767 and the AG+GG genotype of rs972936 were significantly associated with lower BMD levels in the femoral neck. Overall, our study suggests that IGF-1 rs2288377 and rs972936 gene polymorphisms do not influence the risk osteoporosis.

  6. Evolved Expandable Launch Vehicle System: RS-68 Main Engine Development

    NASA Astrophysics Data System (ADS)

    Portanova, P. L.; Conley, D. S., , Capt; Lee, N. Y.; Wood, B. K.

    2002-01-01

    Delta IV is one of two competing Evolved Expendable Launch Vehicle (EELV) systems being developed in an industry/United States Government partnership to meet the need for the new era of space transportation for the early decades of the 21st Century. The Boeing Company, Rocketdyne, and United States Air Force have developed a 650 Klbf (2.9 NM) class liquid hydrogen/liquid oxygen main engine for the Delta IV family of EELV. The purpose of this paper is to present the innovative approach to the design, development, testing, and certification of the RS-68 engine over the last several years. With the initial production process underway, RS-68 is implementing additional innovative concepts to produce an affordable main engine, and provide assured access to space. 1) The Aerospace Corporation3) The Aerospace Corporation 2) Captain, United States Air Force4) The Boeing Company/Rocketdyne

  7. Journal editorial policies, animal welfare, and the 3Rs.

    PubMed

    Osborne, Nicola J; Payne, Daisy; Newman, Michael L

    2009-12-01

    This study evaluates the editorial policies of a randomized sample of English language peer-reviewed journals that publish original research involving the use of animals. The aim is to identify whether journals have editorial policies relating to the use of animals in the research that they are prepared to publish and whether any policies are likely to promote animal welfare and dissemination of information on the 3Rs (reduction, refinement, replacement) within the scientific community. The results demonstrate that a significant proportion of journals publishing original research involving animals do not have any editorial policy relating to the use of animals. Of those journals that do have policies the majority simply request that the research be carried out in accordance with standard regulatory requirements. This paper aims to provide editors and publishers with the information they need to review their own editorial policies to ensure they are fulfilling their potential to promote animal welfare and dissemination of the 3Rs.

  8. Radiation Dry Bias of the Vaisala RS92 Humidity Sensor

    NASA Technical Reports Server (NTRS)

    Vomel, H.; Selkirk, H.; Miloshevich, L.; Valverde-Canossa, J.; Valdes, J.; Kyro, E.; Kivi, R.; Stolz, W.; Peng, G.; Diaz, J. A.

    2007-01-01

    The comparison of simultaneous humidity measurements by the Vaisala RS92 radiosonde and by the Cryogenic Frostpoint Hygrometer (CFH) launched at Alajuela, Cosla Rica, during July 2005 reveals a large solar radiation dry bias of the Vaisala RS92 humidity sensor and a minor temperature-dependent calibration error. For soundings launched at solar zenith angles between 10" and 30 , the average dry bias is on the order of 9% at the surface and increases to 50% at 15 km. A simple pressure- and temperature-dependent correction based on the comparison with the CFH can reduce this error to less than 7% at all altitudes up to 15.2 km, which is 700 m below the tropical tropopause. The correction does not depend on relative humidity, but is able to reproduce the relative humidity distribution observed by the CFH.

  9. Higher Curvature Effects in the ADD and RS Models

    SciTech Connect

    Rizzo, Thomas G.; /SLAC

    2006-07-05

    Over the last few years several extra-dimensional models have been introduced in attempt to deal with the hierarchy problem. These models can lead to rather unique and spectacular signatures at Terascale colliders such as the LHC and ILC. The ADD and RS models, though quite distinct, have many common feature including a constant curvature bulk, localized Standard Model(SM) fields and the assumption of the validity of the EH action as a description of gravitational interactions.

  10. Association of vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the nephrolithiasis susceptibility.

    PubMed

    Zhou, Tian-Biao; Jiang, Zong-Pei; Li, Ai-Hua; Ju, Lang

    2015-04-01

    Association of vitamin D receptor (VDR) gene polymorphism with the risk of nephrolithiasis from the published reports is still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk of nephrolithiasis using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with nephrolithiasis susceptibility. In this meta-analysis, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis susceptibility for overall populations and in Caucasians. However, the Fok1 f allele and ff genotype were associated with the risk of nephrolithiasis in Asians, but the FF genotype not. Furthermore, TaqI TT genotype was associated with the risk of nephrolithiasis in Asians, but the t allele and tt genotype not. However, ApaI gene polymorphism was not associated with nephrolithiasis susceptibility in Asians. In conclusion, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis risk in overall populations and in Caucasians. But, the Fok1 f allele and ff genotype, TaqI TT genotype, ApaI gene polymorphism were associated with the risk of nephrolithiasis in Asians. However, more studies should be conducted to confirm it.

  11. Alkaline protease from Thermoactinomyces sp. RS1 mitigates industrial pollution.

    PubMed

    Verma, Amit; Ansari, Mohammad W; Anwar, Mohmmad S; Agrawal, Ruchi; Agrawal, Sanjeev

    2014-05-01

    Proteases have found a wide application in the several industrial processes, such as laundry detergents, protein recovery or solubilization, prion degradation, meat tenderizations, and in bating of hides and skins in leather industries. But the main hurdle in industrial application of proteases is their economical production on a large scale. The present investigation aimed to exploit the locally available inexpensive agricultural and household wastes for alkaline protease production using Thermoactinomyces sp. RS1 via solid-state fermentation (SSF) technique. The alkaline enzyme is potentially useful as an additive in commercial detergents to mitigate pollution load due to extensive use of caustic soda-based detergents. Thermoactinomyces sp. RS1 showed good protease production under SSF conditions of 55 °C, pH 9, and 50 % moisture content with potato peels as solid substrate. The presented findings revealed that crude alkaline protease produced by Thermoactinomyces sp. RS1 via SSF is of potential application in silver recovery from used X-ray films.

  12. IRF4 rs12203592 functional variant and melanoma survival.

    PubMed

    Potrony, Miriam; Rebollo-Morell, Aida; Giménez-Xavier, Pol; Zimmer, Lisa; Puig-Butille, Joan Anton; Tell-Marti, Gemma; Sucker, Antje; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Schadendorf, Dirk; Puig, Susana

    2017-04-15

    Inherited genetic factors may modulate clinical outcome in melanoma. Some low-to-medium risk genes in melanoma susceptibility play a role in melanoma outcome. Our aim was to assess the role of the functional IRF4 SNP rs12203592 in melanoma prognosis in two independent sets (Barcelona, N = 493 and Essen, N = 438). Genotype association analyses showed that the IRF4 rs12203592 T allele increased the risk of dying from melanoma in both sets (Barcelona: odds ratio [OR] = 6.53, 95% CI 1.38-30.87, Adj p = 0.032; Essen: OR = 1.68, 95% CI 1.04-2.72, Adj p = 0.035). Survival analyses only showed significance for the Barcelona set (hazard ratio = 4.58, 95% CI 1.11-18.92, Adj p = 0.036). This SNP was also associated with tumour localization, increasing the risk of developing melanoma in head or neck (OR = 1.79, 95% CI 1.07-2.98, Adj p = 0.032) and protecting from developing melanoma in the trunk (OR = 0.59, 95% CI 0.41-0.85, Adj p = 0.004). These findings suggest for the first time that IRF4 rs12203592 plays a role in the modulation of melanoma outcome and confirms its contribution to the localization of the primary tumour.

  13. PSCA rs2294008 Polymorphism with Increased Risk of Cancer

    PubMed Central

    Geng, Peiliang; Li, Jianjun; Wang, Ning; Ou, Juanjuan; Xie, Ganfeng; Liu, Chen; Zhao, Xiaoxin; Xiang, Lisha; Liao, Yunmei; Liang, Houjie

    2015-01-01

    Background Published data on the association between PSCA rs2294008 polymorphism and cancer risk have implicated inconclusive results. To determine the relationship and to precisely assess the effect size estimate of the association, we performed a meta-analysis. Methods We searched published literature in Embase and PubMed databases using the search terms “PSCA”, “prostate stem cell antigen”, “variants”, “polymorphism”, “polymorphisms”, and “cancer”. A total of 21 eligible articles were retrieved, with 27, 197 cancer cases and 48, 237 controls. Results On the whole, we found the association between PSCA rs2294008 polymorphism and cancer risk was statistically significant: TT vs CC: OR = 1.18, 95% CI, 1.10 to 1.27; TT + CT vs CC: OR = 1.08, 95% CI, 1.05 to 1.10; TT vs CT + CC: OR = 1.14, 95% CI, 1.07 to 1.21; T vs C: OR = 1.10, 95% CI, 1.06 to 1.14; CT vs CC: OR = 1.10, 95% CI, 1.06 to 1.13. Stratified analyses in cancer type and ethnicity showed similar results. Conclusions Based on the statistical evidence, we can draw a conclusion that the rs2294008 polymorphism of PSCA gene is likely to play a role in cancer carcinogenesis, especially in gastric cancer and bladder cancer. PMID:26308216

  14. A Three Dimensional Picture of RS CVN Stellar Atmospheres

    NASA Astrophysics Data System (ADS)

    Linsky, Jeffrey L.

    The ROSAT all-sky survey provides a unique opportunity to study an RS CVn system simultaneously at x-ray, EUV, UV, optical, and radio wavelengths at many phases throughout an orbital period. ROSAT can detect the x-ray flux of each candidate system during each 30 second viewing 16 times per day for at least 2 days. We request a block of 7 IUE shifts to obtain NEAR SIMULTANEOUS emission line fluxes (SWP-LO) and Mg IT line profiles (LWP-HI), and we will obtain contemporaneous optical photometry and spectroscopy and VLA radio fluxes (3.6, 6, and 20 cm). one objective of this PROPOSAL is to obtain the FIRST 3-D MODEL OF THE INHOMOGENEOUS PHOTOSPHERE, CHROMOSPHERE, AND CORONA OF A STAR OTHER THAN THE SUN. We will use optical photometry and spectroscopy to map the spotted photospheres of each star, and the Mg II line profiles to DOPPLERIMAGE their chromospheres, to determine the location, size, and surface flux of the active regions. We will then use the time variation of the UV emission line and x-ray fluxes to determine what fluxes are due to the quiet and active regions separately. These data will provide SURFACE FLUXES for the quiet and active regions separately. We will then will model BOTH REGIONS independently using an emission measure analysis. We will also model any flares observed. The second part of the program will be a simultaneous UV/X-ray SURVEY with the objective of DETERMINING THE RANGE OF PHYSICAL MODELS APPLICABLE TO THE CHROMOSPHERES AND CORONAE OF RS CVN SYSTEMS. We propose to obtain emission line fluxes (SWP-LO) and Mg II line profiles (LWP-HI) of all bright RS CVns observed by ROSAT from mid-July through September 1990 that meet the IUE observing constraints. About 17 systems in the Strassmeier catalog will likely be observed during this period. While many RS CVn systems have been observed separately by IUE and x-ray satellites, SIMULTANEOUS UV and x-ray observations are required to model these spatially inhomogenous and timevariable systems. This

  15. Different angiogenesis effect of mini-TyrRS/mini-TrpRS by systemic administration of modified siRNAs in rats with acute myocardial infarction.

    PubMed

    Zeng, Rui; Chen, Yu-Cheng; Zeng, Zhi; Liu, Wei-Qiang; Liu, Xiao-Xia; Liu, Rui; Qiang, Ou; Li, Xian

    2010-07-01

    We aimed to clarify the different angiogenesis effects of mini-tyrosyl-tRNA synthetase (TyrRS)/minitryptophanyl-tRNA synthetase (TrpRS) in rodent primates with acute myocardial infarction, by delivering small interfering RNAs (siRNAs) systemically in a liposomal formulation. Left coronary artery ligation was used to establish the model of acute myocardial infarction in rats; mini-TyrRS/mini-TrpRS-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP), and administered by intravenous injection to rats. Rats were divided into four experiment groups: sham operated group (no left anterior descending artery [LAD] occlusion); negative control group (LAD occlusion + saline injection); mock transfection group (LAD occlusion + mock transfected injection); experiment group (LAD occlusion + mini-TyrRS/mini-TrpRS-specific siRNAs injection). Silencing efficiency was assayed by Western blotting. To determine whether mini-TyrRS/mini-TrpRS affected the angiogenesis activity of rats with myocardial infarction, we measured the myocardial infarction size by TTC staining, and the capillary density using immunohistochemistry staining, to investigate the expression of factor VIII. The myocardial infarction size and the capillary density of mini-TyrRS-siRNA group were respectively 18.89% and 8.64/0.1 mm(2) 1 month after ligation, while in the mini-TrpRS-siRNA group these values were 7.33% and 17.32/0.1 mm(2), significantly different compared with the mock transfection group (14.19%; 13.56/0.1 mm(2)) and negative control group (14.28%; 13.89/0.1 mm(2)), P < 0.05. There were no significant changes between the mock transfection group and the negative control group, P > 0.05. These results indicated that angiogenesis is either stimulated by mini-TyrRS or inhibited by mini-TrpRS in rat models with acute myocardial infarction.

  16. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study

    PubMed Central

    2016-01-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout. PMID:27550484

  17. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study.

    PubMed

    Lee, Sung Won; Lee, Shin Seok; Oh, Dong Ho; Park, Dong Jin; Kim, Hyun Sook; Choi, Jung Ran; Chae, Soo Cheon; Yun, Ki Jung; Chung, Won Tae; Choe, Jung Yoon; Kim, Seong Kyu

    2016-10-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

  18. Physico-chemical, functional and structural properties of RS3/RS4 from kidney bean (Phaseolus vulgaris) cultivars.

    PubMed

    Gani, Adil; Jan, Amreen; Shah, Asima; Masoodi, F A; Ahmad, Mudasir; Ashwar, Bilal Ahmad; Akhter, Rehana; Wani, Idrees Ahmed

    2016-06-01

    Starch isolated from four kidney bean cultivars (Yellow bean, Red bean, Black bean and White bean) were physically and chemically modified in order to prepare resistant starch (RS3/RS4). Following the Heat-moisture treatment (HMT) and Citric acid modification (CT) of the native starch, the amylose content got decreased whereas bulk and tapped density (g/ml) increased. Both HMT and CT reduced the swelling power and the solubility of native starch. Pasting temperature increased and peak, breakdown, final, and set-back viscosity decreased after both the modifications. Fourier Transform Infrared Spectroscopy (FTIR) analysis displayed peaks at 1020cm(-1) in HMT and 1724cm(-1) in CT starches. Differential Scanning Calorimetry (DSC) analysis revealed that samples were more stable after modification. X-ray diffraction (XRD) analysis revealed reordering of chain segments to more crystalline structure. These results suggested modifications resulted in starch with improved properties and could be a possible method for the RS preparation with better thermal stability.

  19. TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population.

    PubMed

    Xu, Pengcheng; Guo, Wen; Jin, Tianbo; Wang, Jihong; Fan, Dongsheng; Hao, Zengtao; Jing, Shangfei; Han, ChaoQian; Du, Jieli; Jiang, Dong; Wen, Shuzheng; Wang, Jianzhong

    2017-01-03

    This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele "A" in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease.

  20. TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population

    PubMed Central

    Jin, Tianbo; Wang, Jihong; Fan, Dongsheng; Hao, Zengtao; Jing, Shangfei; Han, ChaoQian; Du, Jieli; Jiang, Dong; Wen, Shuzheng; Wang, Jianzhong

    2017-01-01

    This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele “A” in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease. PMID:27901480

  1. Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on Gastric Cancer Susceptibility

    PubMed Central

    Ni, Qing; Yin, Junfeng; Wang, Xiangjun; Liu, Xinnong

    2015-01-01

    Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk. Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI). Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model. Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect. PMID:25983750

  2. Exceptional longevity and muscle and fitness related genotypes: a functional in vitro analysis and case-control association replication study with SNPs THRH rs7832552, IL6 rs1800795, and ACSL1 rs6552828

    PubMed Central

    Fuku, Noriyuki; He, Zi-hong; Sanchis-Gomar, Fabian; Pareja-Galeano, Helios; Tian, Ye; Arai, Yasumichi; Abe, Yukiko; Murakami, Haruka; Miyachi, Motohiko; Zempo, Hirofumi; Naito, Hisashi; Yvert, Thomas; Verde, Zoraida; Venturini, Letizia; Fiuza-Luces, Carmen; Santos-Lozano, Alejandro; Rodriguez-Romo, Gabriel; Ricevuti, Giovanni; Hirose, Nobuyoshi; Emanuele, Enzo; Garatachea, Nuria; Lucia, Alejandro

    2015-01-01

    There are several gene variants that are candidates to influence functional capacity in long-lived individuals. As such, their potential association with exceptional longevity (EL, i.e., reaching 100+ years) deserves analysis. Among them are rs7832552 in the thyrotropin-releasing hormone receptor (TRHR) gene, rs1800795 in the interleukin-6 (IL6) gene and rs6552828 in the coenzyme A synthetase long-chain 1 (ACSL1) gene. To gain insight into their functionality (which is yet unknown), here we determined for the first time luciferase gene reporter activity at the muscle tissue level in rs7832552 and rs6552828. We then compared allele/genotype frequencies of the 3 abovementioned variants among centenarians [n = 138, age range 100–111 years (114 women)] and healthy controls [n = 334, 20–50 years (141 women)] of the same ethnic and geographic origin (Spain). We also studied healthy centenarians [n = 79, 100–104 years (40 women)] and controls [n = 316, 27–81 years (156 women)] from Italy, and centenarians [n = 742, 100–116 years (623 women)] and healthy controls [n = 499, 23–59 years (356 women)] from Japan. The THRH rs7832552 T-allele and ACSL1 rs6552828 A-allele up-regulated luciferase activity compared to the C and G-allele, respectively (P = 0.001). Yet we found no significant association of EL with rs7832552, rs1800795 or rs6552828 in any of the 3 cohorts. Further research is needed with larger cohorts of centenarians of different origin as well as with younger old people. PMID:25999849

  3. Polymorphism of rs7688672 and rs10033237 in cGKII/PRKG2 and gout susceptibility of Han population in northern China.

    PubMed

    Guo, Min; Cheng, Zhifeng; Li, Changgui; Li, Shanshan; Li, Ming; Wang, Mingli; Xu, Jinmei; Tang, Yingying; Wang, Yujing; Qiu, Wenli; Liu, Xiaomin

    2015-05-10

    Gout is a genetic or acquired metabolic disease caused by increase of uric acid synthesis resulted from purine metabolic abnormalities. Whether cGMP-dependent protein kinase 2 (cGKII/PRKG2) is correlated with gout remains controversial. The objective of the present study was to investigate whether there is a correlation between polymorphism of cGKII/PRKG2 and gout susceptibility of Han population in northern China. Four hundred and five male patients with gout in the case group and 429 controls in the control group were collected from the Department of Endocrinology and Metabolic Disease, the Fourth Affiliated Hospital of Harbin Medical University. A case-control study method was used to study the correlation between cGKII/PRKG2 polymorphism rs7688672 and rs10033237 and gout susceptibility. The genotype frequencies of rs7688672 and rs10033237 polymorphisms of cGKII/PRKG2 in the case group and the control group both were in accordance with Hardy-Weinberg equilibrium. There were significant differences of rs10033237 in the allele frequencies and genotype distributions (P<0.05) between the two groups, while no association was found between rs7688672 and gout. Combined mutation sites AA(*) from rs7688672 and rs10033237 were negatively correlated with gout susceptibility, whereas haplotype GG(*) was positively correlated with gout susceptibility. In conclusion, patients with rs10033237 polymorphism of cGKII/PRKG2 gene are more likely to suffer from gout. With regard to haplotypes of rs10033237 and rs7688672, both AA(*) and GG(*) are related to gout. AA(*) is a gout susceptible gene, whereas GG(*) is a protective gene.

  4. Genetic Polymorphisms of rs3077 and rs9277535 in HLA-DP associated with Systemic lupus erythematosus in a Chinese population

    PubMed Central

    Zhang, Junlong; Zhan, Wenli; Yang, Bin; Tian, Anning; Chen, Lin; Liao, Yun; Wu, Yongkang; Cai, Bei; Wang, Lanlan

    2017-01-01

    Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4+ T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE. In total, samples from 335 SLE patients and 635 healthy controls were collected and genotyped by a polymerase chain reaction-high resolution melting (PCR-HRM) assay. A significant positive correlation was observed between the SNP rs3077, rs9277535 of HLA-DP and SLE susceptibility (rs3077, OR = 0.74, 95%CI = 0.60–0.91, P = 0.004; rs9277535, OR = 0.72, 95%CI = 0.59–0.88, P = 0.001). Rs3077 polymorphism was corelated to IL-17, INF-γ and cutaneous vasculitis (P = 0.037, P = 0.020 and P = 0.006, respectively). Additionally, rs3077 AA genotype carriers showed lower concentration of inflammatory cytokines and lower cutaneous vasculitis incidence than did the other two genotype. No significant association was observed between rs9277535 and cytokines or any clinical features. In conclusion, HLA-DP polymorphisms (rs3077 and rs9277535) were associated with SLE susceptibility and the levels of some inflammatory cytokines in SLE patients. PMID:28094303

  5. Evolved expendable launch vehicle system: RS-68 main engine development

    NASA Astrophysics Data System (ADS)

    Conley, David; Lee, Norman Y.; Portanova, Peter L.; Wood, Byron K.

    2003-08-01

    Delta IV is one of two competing Evolved Expendable Launch Vehicle (EELV) systems being developed in an industry/United States Government partnership to meet the needs of the new era of space launch for the early decades of the 21 st Century. The Rocketdyne Division of The Boeing Company and the United States Air Force have developed a 650 Klbf sea-level (2.9 MN) class liquid hydrogen/liquid oxygen main engine for the Delta IV family of EELV. The purpose of this paper is to present the innovative approach to the design, development, testing and certification of the RS-68 engine.

  6. Radio polarization characteristics of two RS CVn binaries

    NASA Technical Reports Server (NTRS)

    Mutel, R. L.; Lestrade, J.-F.; Doiron, D. J.

    1985-01-01

    The results of multifrequency epoch VLA observations of polarized radio emission from the nearby active RS CVn binaries UX Arietis and HR 1099 are reported. For both systems, there is an excellent correlation between handedness of circular polarization and frequency. Helicity reversal is almost always seen between 1.4 and 5.0 GHz, possibly due to optical depth effects. There may also be an anticorrelation between total intensity and fractional circular polarization, especially at 5 GHz. This is consistent with models in which intense flares are associated with compact selfabsorbed synchrotron sources, while the quiescent emission arises from larger gyrosynchrotron-emitting plasma.

  7. RS CVn binaries: Testing the solar-stellar dynamo connection

    NASA Technical Reports Server (NTRS)

    Dempsey, R.

    1995-01-01

    We have used the Extreme Ultraviolet Explorer satellite to study the coronal emission from the EUV-bright RS CVn binaries Sigma2 CrB, observed February 10-21, 1994, and II Peg, observed October 1-5, 1993. We present time-resolved and integrated EUV short-, medium-, and long-wavelength spectra for these binaries. Sigma2 CrB shows significant first-order emission features in the long-wavelength region. The coronal emission distributions and electron densities are estimated for those active coronae dominated by high temperature plasma.

  8. RS INDI - A photometric analysis using the grid technique

    NASA Astrophysics Data System (ADS)

    Marton, S. F.; Grieco, A.; Lapasset, E.; Sistero, R. F.; Claria, J. J.

    1990-10-01

    Simultaneous solutions from 2484 UBV photelelectric observations of the EB-type system RS Indi has been obtained with the Wilson-Devinney code. Using the grid technique, families of solutions were found for all possible configurations. As different configurations gave similar quality of fit, the more probable configuration was suggested by physical criteria. New times of minimum light obtained in the years 1985 and 1986 confirm the decreasing period of the system. No interpretation was found for the asymmetries observed in the light curves.

  9. SEAC4RS Aerosol Radiative Effects and Heating Rates

    NASA Astrophysics Data System (ADS)

    Cochrane, S.; Schmidt, S.; Redemann, J.; Hair, J. W.; Ferrare, R. A.; Segal-Rosenhaimer, M.; LeBlanc, S. E.

    2015-12-01

    We will present (a) aerosol optical properties, (b) aerosol radiative forcing, (c) aerosol and gas absorption and heating rates, and (d) spectral surface albedo for cases from August 19th and 26th of the SEAC4RS mission. This analysis is based on irradiance data from the Solar Spectral Flux Radiometer (SSFR), spectral aerosol optical depth from the Sky-Scanning, Sun-Tracking Atmospheric Research (4STAR), and extinction profiles from the DIAL/High Spectral Resolution Lidar (HSRL). We derive spectrally resolved values of single scattering albedo, asymmetry parameter, and surface albedo from the data, and determine profiles of absorption and heating rate segregated by absorber (aerosol and gas).

  10. [Medication adherence of elderly in Porto Alegre, RS].

    PubMed

    Rocha, Cristiane Hoffmeister; de Oliveira, Ana Paula Sueiro; Ferreira, Caroline; Faggiani, Fabiana Tôrres; Schroeter, Guilherme; de Souza, Antônio Carlos Araújo; DeCarli, Geraldo Attilio; Morrone, Fernanda Bueno; Werlang, Maria Cristina

    2008-04-01

    Polipharmacy and medication non-adherence are problems faced frequently in the treatment of elderly patients. An exploratory cross-sectional study and quantitative approach were conducted to assess the frequency of treatment-adherence in elderly and how polipharmacy can affect adherence. Four hundred and sixty six elderly answered a questionnaire in Porto Alegre, RS in individual interviews. The adherence frequency found was 173 (37.1%) and was higher among those, who use less medication. These results indicate the need for implementing educational programs for the elderly in order to help them to follow their drug therapy.

  11. Role of IL-8 rs4073 and rs2227306 polymorphisms in the development of primary gouty arthritis in a Chinese population.

    PubMed

    Cui, Y X; Zhao, H; Guo, H Q

    2016-10-17

    In this study, we investigated the role of two single nucleotide polymorphisms in the promoter region of the interleukin-8 gene (IL-8; rs4073 and rs2227306) in the susceptibility to primary gouty arthritis in a Chinese population. Three hundred and twelve patients with primary gouty arthritis and 340 healthy controls were recruited from the Yan'an University Affiliated Hospital between January 2014 and March 2015. The IL-8 rs4073 and rs2227306 polymorphisms were genotyped by polymerase chain reaction combined with restriction fragment length polymorphism. Unconditional multiple-logistic regression analysis revealed that the TT genotype of rs4073 was correlated with primary gouty arthritis risk, compared to the AA genotype [adjusted odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.08-2.54; P = 0.02]. In addition, the IL-8 rs4073 T allele was associated with a significant elevated risk of primary gouty arthritis, in comparison to the A allele (OR = 1.34, 95%CI = 1.07-1.67; P = 0.01). However, we observed no significant relationship between the IL-8 rs2227306 polymorphism and primary gouty arthritis risk. The results of this study suggest that the IL-8 rs4073 polymorphism could be a marker for primary gouty arthritis development.

  12. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4...-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate as follows: (2) In or on food commodities in food handling establishments where food and food products are held, processed, prepared...

  13. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4...-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate as follows: (2) In or on food commodities in food handling establishments where food and food products are held, processed, prepared...

  14. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4...-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate as follows: (2) In or on food commodities in food handling establishments where food and food products are held, processed, prepared...

  15. The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis

    PubMed Central

    Liu, Rui; Mo, Yuan-Yuan; Wang, Hui-Li; Tan, Yan; Wen, Xiu-Jie; Deng, Man-Jing; Yan, Hong; Li, Lei

    2016-01-01

    Accumulating evidences have demonstrated that lipopolysaccharide (LPS) represents the important etiologic factor for sepsis. Some previous studies have reported the relationship between common polymorphisms rs4986790 and rs4986791 in the coding gene for this receptor and the susceptibility to sepsis, but there were distinct divergences between those findings. We therefore designed this meta-analysis incorporated 28 published articles containing 6,537 sepsis patients and 8,832 controls for a more comprehensive conclusion on this matter. Odds ratios (ORs) and 95% confidence interval (95% CIs) were calculated to evaluate the association of toll like receptor 4 gene polymorphisms rs4986790 and rs4986791 with sepsis risk. Heterogeneity between included studies was inspected using Q test, and sensitivity analysis was implemented via sequential deletion of each included study to investigate the stability of overall estimates. Funnel plot and Egger’s test were adopted to examine publication bias across selected studies. We found no significant association for either the polymorphism rs4986790 or rs4986791 with sepsis susceptibility in total analysis under any genetic models. Neither did we after combining these two polymorphisms. The results of this meta-analysis suggest that the rs4986790 and rs4986791 polymorphisms in toll like receptor 4 gene may have no statistically significant influence on sepsis susceptibility. PMID:27958344

  16. The FTO rs9939609 and LEPR rs1137101 mothers–newborns gene polymorphisms and maternal fat mass index effects on anthropometric characteristics in newborns

    PubMed Central

    Mărginean, Claudiu; Mărginean, Cristina Oana; Iancu, Mihaela; Meliţ, Lorena Elena; Tripon, Florin; Bănescu, Claudia

    2016-01-01

    Abstract The aim of this study was to assess the impact of mothers’ and newborns’ fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs1137101 gene polymorphisms on neonatal anthropometric parameters in order to identify a potential risk for developing obesity. We performed a cross-sectional study on 355 mother–newborn couples in an Obstetrics Gynecology Tertiary Hospital from Romania, evaluated with regard to anthropometric parameters, clinical and laboratory parameters besides 2 genetic polymorphisms (FTO rs9939609 and LEPR rs1137101). Newborns with mothers carrying variant AT or AA genotype for FTO rs9939609 presented lower BMI (P = 0.012) and lower MUAC (P = 0.029). There was a significant interaction effect between newborn and mother LEPR rs1137101 polymorphism on birth weight (P = 0.009) and BMI (P = 0.007). We noticed significantly increased birth weight and BMI in newborns carriers of AG + GG genotype, coming from mothers with AA genotype (P = 0.006). There was no evidence of significant interaction effect between newborn and mother FTO rs9939609 polymorphism on the studied anthropometrical data (P > 0.05). In addition, lower BMI scores (P = 0.042) were observed in newborns carriers of TT genotype whose mothers had AA + AT genotype. Lower MUAC scores (P = 0.041) were noticed in newborns carriers of AA + AT genotype whose mothers had AA + AT genotype for FTO rs9939609 gene polymorphism. Newborns carriers of the AG + GG genotype (P = 0.003) of LEPR rs1137101 coming from mothers with increased FMI (upper tertile) had significantly increased BMIs. Presence of the variant A allele of FTO rs9939609 polymorphism in mothers decreased BMI and MUAC in newborns. The impact of LEPR rs1137101 polymorphism on BMI and birth weight in newborns differed depending on the presence/absence of the dominant LEPR allele in mothers. In addition, we noticed that maternal FMI presented a significant positive effect on

  17. VIIRS Aerosol Products During the SEAC4RS Field Experiment

    NASA Astrophysics Data System (ADS)

    Remer, L. A.; Munchak, L. A.; Huang, J.; Martins, J. V.; Espinosa, R.; Orozco, D.

    2014-12-01

    The Studies of Emissions, Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field experiment that took place during August and September 2013 offered an in depth portrait of the aerosol system over much of the continental United States. Heavily instrumented aircraft, including the NASA DC-8 sampled a wide variety of aerosol types including transported Saharan dust, both fresh and aged smoke from western wildfires, urban pollution plumes and also biogenic aerosol produced by the "green volcano" in the vegetated Ozarks. Complementing these aircraft measurements was an enhanced array of AERONET stations sprinkled across the country and also concentrated in a mesoscale array near the home base of Houston Texas. This rich collection of suborbital aerosol information permits a more comprehensive evaluation of the VIIRS aerosol product that includes validation of the products across the mesoscale and choices of case studies in which we can delve deeper into the VIIRS retrieval to test algorithm assumptions. We will compare VIIRS retrievals during SEAC4RS with MODIS retrievals, with AERONET observations and retrievals, and with measurements and retrievals from the Polar Imaging Nephelometer (PI-Neph) that flew aboard the NASA DC-8.

  18. Enantioresolution of (RS)-baclofen by liquid chromatography: A review.

    PubMed

    Batra, Sonika; Bhushan, Ravi

    2017-01-01

    Baclofen is a commonly used racemic drug and has a simple chemical structure in terms of the presence of only one stereogenic center. Since the desirable pharmacological effect is in only one enantiomer, several possibilities exist for the other enantiomer for evaluation of the disposition of the racemic mixture of the drug. This calls for the development of enantioselective analytical methodology. This review summarizes and evaluates different methods of enantioseparation of (RS)-baclofen using both direct and indirect approaches, application of certain chiral reagents and chiral stationary phases (though very expensive). Methods of separation of diastereomers of (RS)-baclofen prepared with different chiral derivatizing reagents (under microwave irradiation at ease and in less time) on reversed-phase achiral columns or via a ligand exchange approach providing high-sensitivity detection by the relatively less expensive methods of TLC and HPLC are discussed. The methods may be helpful for determination of enantiomers in biological samples and in pharmaceutical formulations for control of enantiomeric purity and can be practiced both in analytical laboratories and industry for routine analysis and R&D activities.

  19. Association between three functional microRNA polymorphisms (miR-499 rs3746444, miR-196a rs11614913 and miR-146a rs2910164) and breast cancer risk: a meta-analysis

    PubMed Central

    Zhang, Hong; Zhang, Yafei; Yan, Wanjun; Wang, Wen; Zhao, Xixi; Ma, Xingcong; Gao, Xiaoyan; Zhang, Shuqun

    2017-01-01

    Three functional microRNA polymorphisms (miR-499 rs3746444 A > G, miR-196a rs11614913 C > T and miR-146a rs2910164 G > C) have been reported to be associated with breast cancer (BC) risk. However, the results of the published studies are inconsistent. In order to obtain a more credible result, we conducted this meta-analysis. We searched PubMed, EMBASE and Web of Science databases to identify relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Thirty-eight eligible studies with 17,417 cases and 18,988 controls were included in this meta-analysis. Our results showed that the rs3746444 was associated with an increased breast cancer risk in the four genetic models (G vs. A: OR = 1.17, P = 0.008; GG vs. AA: OR = 1.41, P < 0.001; AG vs. AA: OR = 1.10, P = 0.036; GG+AG vs. AA: OR = 1.16, P = 0.001). In the subgroup analysis by ethnicity, significant correlation remained in Asians but not in Caucasians. For rs11614913, obvious decreased breast cancer risk was observed in Caucasian populations (T vs. C: OR = 0.93, P = 0.044). However, we couldn't detect an association between rs2910164 and breast cancer risk. This meta-analysis demonstrates that rs3746444 could increase breast cancer risk in Asians and in general populations, while rs11614913 could decrease the risk of breast cancer in Caucasians. The rs2910164 polymorphism has no association with breast cancer risk. More multicenter studies with larger sample sizes are required to verify our results. PMID:27880723

  20. Impact of G-quadruplex structures and intronic polymorphisms rs17878362 and rs1642785 on basal and ionizing radiation-induced expression of alternative p53 transcripts

    PubMed Central

    Perriaud, Laury; Marcel, Virginie; Sagne, Charlotte; Favaudon, Vincent; Guédin, Aurore; De Rache, Aurore; Guetta, Corinne; Hamon, Florian; Teulade-Fichou, Marie-Paule; Hainaut, Pierre; Mergny, Jean-Louis; Hall, Janet

    2014-01-01

    G-quadruplex (G4) structures in intron 3 of the p53 pre-mRNA modulate intron 2 splicing, altering the balance between the fully spliced p53 transcript (FSp53, encoding full-length p53) and an incompletely spliced transcript retaining intron 2 (p53I2 encoding the N-terminally truncated Δ40p53 isoform). The nucleotides forming G4s overlap the polymorphism rs17878362 (A1 wild-type allele, A2 16-base pair insertion) which is in linkage disequilibrium with rs1642785 in intron 2 (c.74+38 G>C). Biophysical and biochemical analyses show rs17878362 A2 alleles form similar G4 structures as A1 alleles although their position is shifted with respect to the intron 2 splice acceptor site. In addition basal FSp53 and p53I2 levels showed allele specific differences in both p53-null cells transfected with reporter constructs or lymphoblastoid cell lines. The highest FSp53 and p53I2 levels were associated with combined rs1642785-GG/rs17878362-A1A1 alleles, whereas the presence of rs1642785-C with either rs17878362 allele was associated with lower p53 pre-mRNA, total TP53, FSp53 and p53I2 levels, due to the lower stability of transcripts containing rs1642785-C. Treatment of lymphoblastoid cell with the G4 binding ligands 360A or PhenDC3 or with ionizing radiation increased FSp53 levels only in cells with rs17878362 A1 alleles, suggesting that under this G4 configuration full splicing is favoured. These results demonstrate the complex effects of intronic TP53 polymorphisms on G4 formation and identify a new role for rs1642785 on mRNA splicing and stability, and thus on the differential expression of isoform-specific transcripts of the TP53 gene. PMID:25269805

  1. Angioqueratomas de fordyce múltiplos de vulva associados à cirrose hepática.

    PubMed

    Souza Teixeira, Marcelo; Dos Santos Lima, Caren; De Abreu Neves Salles1, Simone; Luz, Flávio Barbosa; Roberta Duarte Bezerra Pinto, Roberta; Pantaleão, Luciana

    2016-05-15

    Fordyce angiokeratoma is a benign skin neoplasm, characterized by erythematous-violet keratotic papules with mamillated surface, which follows a chronic and minimally symptomatic course. However, symptoms can be related such as itching, burning, bleeding, dyspareunia; aesthetic and social concerns may prompt request for treatment. The condition mainly affects men and usually occurs in the scrotum, but rarely may occur in women. A 30-year-old woman with liver cirrhosis and portal hypertension is described. Over a period of two years she developed multiple angiokeratomas of the vulva, complicated by frequent bleeding. Histopathologic analysis of the lesion confirmed the diagnosis of angiokeratoma and all lesions were surgically removed. The results of the treatment were very satisfactory, with no relapses or complications.Angioqueratoma de Fordyce é uma dermatose incomum que compõe o grupo das neoplasias cutâneas benignas, caracterizando-se pelo aparecimento de lesões papuloceratósicas, eritemato-violáceas de superfície mamilonada, que apresentam curso crônico e oligossintomático. No entanto, outros sintomas podem estar associados, como prurido, ardência, sangramento e dispareunia, além de problemas estéticos e de ordem social. Afeta principalmente homens, acometendo a região escrotal, sendo raro seu surgimento em mulheres. Relata-se caso de uma paciente com 30 anos de idade, portadora de cirrose hepática e hipertensão portal evoluindo há 2 anos com múltiplos angioqueratomas na vulva de sangramento frequente. A análise histopatológica confirmou o diagnóstico de angioqueratoma e a paciente foi submetida à exérese cirúrgica das lesões. Os resultados terapêuticos foram satisfatórios, sem recidivas ou complicações.

  2. Film coating of seeds with Bacillus cereus RS87 spores for early plant growth enhancement.

    PubMed

    Jetiyanon, Kanchalee; Wittaya-Areekul, Sakchai; Plianbangchang, Pinyupa

    2008-10-01

    The plant growth-promoting rhizobacterium Bacillus cereus RS87 was previously reported to promote plant growth in various crops in both greenhouse and field trials. To apply as a plant growth promoting agent with practical use, it is essential to ease the burden of routine preparation of a fresh suspension of strain RS87 in laboratory. The objectives of this study were to investigate the feasibility of film-coating seeds with B. cereus RS87 spores for early plant growth enhancement and to reveal the indoleacetic acid (IAA) production released from strain RS87. The experiment consisted of the following 5 treatments: nontreated seeds, water-soaked seeds, film-coated seeds, seeds soaked with vegetative cells of strain RS87, and film-coated seeds with strain RS87 spores. Three experiments were conducted separately to assess seed emergence, root length, and plant height. Results showed that both vegetative cells and spores of strain RS87 significantly promoted (P < or = 0.05) seed emergence, root length and plant height over the control treatments. The strain RS87 also produced IAA. In conclusion, the film coating of seeds with spores of B. cereus RS87 demonstrated early plant growth enhancement as well as seeds using their vegetative cells. IAA released from strain RS87 would be one of the mechanisms for plant growth enhancement.

  3. Creative Implementation of 3Rs Principles within Industry Programs: Beyond Regulations and Guidelines

    PubMed Central

    Bratcher, Natalie A; Reinhard, Gregory R

    2015-01-01

    The industry involved with using animals as an essential part of research has supported the theory and philosophy of the 3Rs for years. However, both the culture and approach surrounding the 3Rs is evolving rapidly, and many institutions are attempting to surpass the regulations and guidelines to implement the 3Rs for improved science and animal welfare. Regulatory documents and guidelines such as the Animal Welfare Act, the Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy on Humane Care and Use of Laboratory Animals, and the US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training clearly outline how the IACUC should address the 3Rs, but there are many additional paradigms and resources that an institution can use to promote the 3Rs creatively. We review the legal mandates and guidelines that institutions must or should follow, and we present some creative approaches toward their compliance, including the creation of full-time dedicated 3Rs roles as well as temporary 3Rs-focused positions such as visiting scientist and postdoctoral fellowships and internships. We also discuss how to creatively achieve 3Rs progress through internal committees and working groups, involvement in 3Rs consortia, recognizing 3Rs advances through awards programs, and creating 3Rs volunteer opportunities. Adherence to regulations and guidelines creates a solid foundation for good animal care and science, and creative 3Rs approaches enable the growth of a robust animal welfare culture that enhances the potential for 3Rs benefits to animals and science. PMID:25836958

  4. Creative implementation of 3Rs principles within industry programs: beyond regulations and guidelines.

    PubMed

    Bratcher, Natalie A; Reinhard, Gregory R

    2015-03-01

    The industry involved with using animals as an essential part of research has supported the theory and philosophy of the 3Rs for years. However, both the culture and approach surrounding the 3Rs is evolving rapidly, and many institutions are attempting to surpass the regulations and guidelines to implement the 3Rs for improved science and animal welfare. Regulatory documents and guidelines such as the Animal Welfare Act, the Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy on Humane Care and Use of Laboratory Animals, and the US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training clearly outline how the IACUC should address the 3Rs, but there are many additional paradigms and resources that an institution can use to promote the 3Rs creatively. We review the legal mandates and guidelines that institutions must or should follow, and we present some creative approaches toward their compliance, including the creation of full-time dedicated 3Rs roles as well as temporary 3Rs-focused positions such as visiting scientist and postdoctoral fellowships and internships. We also discuss how to creatively achieve 3Rs progress through internal committees and working groups, involvement in 3Rs consortia, recognizing 3Rs advances through awards programs, and creating 3Rs volunteer opportunities. Adherence to regulations and guidelines creates a solid foundation for good animal care and science, and creative 3Rs approaches enable the growth of a robust animal welfare culture that enhances the potential for 3Rs benefits to animals and science.

  5. Small interfering RNA knockdown of mini-TyrRS and mini-TrpRS effects angiogenesis in human umbilical vein endothelial cells in hypoxic culture.

    PubMed

    Zeng, Rui; Chen, Yu-Cheng; Zeng, Zhi; Liu, Rui; Qiang, Ou; Jiang, Xiao-Fei; Liu, Xiao-Xia; Li, Xian; Wang, Hao-Yu

    2008-03-01

    Aim We studied the role of mini-TyrRS and mini-TrpRS in angiogenesis by using small interfering RNA-mediated mini-TyrRS/mini-TrpRS knockout in hypoxic culture of human umbilical vein endothelial cells. Methods SiRNA was used as the main method to inhibited the gene function. Silencing efficiency was assayed by real-time reverse transcription-polymerase chain reaction and western blotting. The angiogenic activity in vitro was evaluated by transwell migration assay and Matrigel-induced capillary tube formation in hypoxic culture. Cell proliferation was determined by crystal violet staining. Results The results showed that levels of the mini-TyrRS/mini-TrpRS gene and protein in mock transfection group and negative control group were higher, but noticeably decreased in experimental group. However, no significant difference was detected between mock transfection group and negative control group, but there was a statistically significant difference compared with experimental group. For mini-TyrRS-siRNA group, the cell migration, tube formation and the rate of cell proliferation were respectively inhibited by (47.4, 56.3, 65.4, 73.7%), (60.5, 69.1, 75.9, 83.6%) and (40.4, 56.2, 61.2, 68.0%). For mini-TrpRS-siRNA, were respectively increased by (18.0, 33.8, 45.1, 56.4%), (18.3, 31.2, 40.3, 45.7%) and (8.4, 26.4, 38.2, 46.6%). Conclusion These results indicated that angiogenesis is either stimulated by mini-TyrRS or inhibited by mini-TrpRS in matrigel models in hypoxic culture, raising the possibility that mini-TyrRS stimulates a common downstream signaling event. Thus, naturally occurring fragments of two proteins involved in translation, TyrRS and TrpRS, have opposing activity on endothelial cell angiogenesis in the matrigel assays. The opposing activities of the two tRNA synthetases suggest tight regulation of the balance between pro- and anti-angiogenic stimuli.

  6. Relationships between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men – a preliminary study

    PubMed Central

    Rotter, Iwona; Skonieczna-Żydecka, Karolina; Kosik-Bogacka, Danuta; Adler, Grażyna; Rył, Aleksandra; Laszczyńska, Maria

    2016-01-01

    Purpose Metabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations. Subjects and methods This study involved 272 men of Caucasian descent aged 50–75 years. Lipid profile, including TCh, LDL, HDL, and TG, was evaluated by spectrophotometric method. Anthropometric measurements concerned WC and blood pressure. MetS was diagnosed according to the criteria of the IDF. Sex hormone profile, including TST, FTS, E2, DHEAS, and SHBG, was examined using enzyme-linked immunosorbent assay. Polymorphisms within FTO, MC4R, and PPARγ genes were identified using polymerase chain reaction-restriction fragments length polymorphism. Results This study did not show links between the analyzed genetic polymorphisms and the presence of MetS, T2DM, HT, and obesity. However, higher concentrations of TCh and LDL were found in men with the FTO rs9939609 polymorphism in the recessive mode of inheritance (P=0.03 and P=0.05, respectively). Lower WC was found to be associated with MC4R rs17782313 gene inherited in the same model (P=0.005). Conclusion FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms seem to have little effect on the incidence of metabolic malfunctions and no effect on androgen-related disorders in the examined middle-aged and elderly men. PMID:27920511

  7. Family-Based Association Study of rs17300539 and rs12495941 Polymorphism in Adiponectin Gene and Polycystic Ovary Syndrome in a Chinese Population

    PubMed Central

    Sun, Xianchang; Wu, Xingguo; Duan, Yunmin; Liu, Guanghai; Yu, Xinyan; Zhang, Wenjuan

    2017-01-01

    Backgriond Polycystic ovary syndrome (PCOS) is a complex disease that has both genetic and environmental components. Adiponectin plays an important role in the regulation of insulin sensitivity and insulin resistance (IR) in PCOS. The aim of this study was to determine 2 single-nucleotide polymorphisms (SNPs) variants (rs12495941 and rs17300539) of the adiponectin gene (ADIPOQ) in polycystic ovary syndrome (PCOS) families. Material/Methods We recruited 197 PCOS probands, their biological parents, and 192 controls. Anthropometric variables, including hip circumference (HC) and waist circumference (WC), were measured in all subjects during their first visit to the outpatient department. Serum T, FBG, FINS, TC, TG, LDL, and HDL levels were measured. PCOS patients were divided into 2 groups based on BMI: group A (BMI <25 kg/m2) and group B (BMI ≥25 kg/m2). Parents of PCOS were accordingly categorized into group C and group D (fathers), and group E and group F (mothers). The associations among ADIPOQ rs12495941, rs17300539, and PCOS were analyzed using the transmission disequilibrium test (TDT). Results A significant association was found between SNP rs17300539 and PCOS in our Chinese population. The levels of TG and FINS and the genotype frequencies of rs17300539 are significantly different between overweight and lean PCOS. No significant association was detected for rs12495941. Conclusions TDT confirms that rs17300539 of ADIPOQ is strongly associated with the risk of PCOS in a Chinese Han population, but rs12495941 of ADIPOQ is not associated with the occurrence of PCOS. PMID:28060790

  8. Interleukin-28B rs12979860C/T and rs8099917T/G contribute to spontaneous clearance of hepatitis C virus in Caucasians.

    PubMed

    Zheng, Ming-Hua; Li, Yu; Xiao, Dong-Dong; Shi, Ke-Qing; Fan, Yu-Chen; Chen, Li-Li; Liu, Wen-Yue; Luo, Ying-Wan; Chen, Yong-Ping

    2013-04-15

    Two single nucleotide polymorphisms rs12979860C/T and rs8099917T/G around interleukin-28B (IL28B) locus have been extensively investigated in their association with hepatitis C virus (HCV) spontaneous clearance. However, with the variable and even inconsistent results, it is necessary to conduct a meta-analysis. A literature search was conducted to seek articles about genetic variation of IL28B and spontaneous clearance of HCV. Odds ratio with 95% confidential interval were calculated to estimate their relationship. Furthermore, meta-regression analysis was performed to search for potential affective factors. A total of 8 studies including 2460 patients with chronic HCV infection and 1052 individuals with spontaneous HCV clearance met inclusion criteria, in which seven studies describing rs12979860 and three studies describing rs8099917. Analysis performed in Caucasian populations indicated that rs12979860CC and rs8099917TT contributed to HCV spontaneous clearance in both dominant model (CC vs. CT+TT, P<1×10(-4); TT vs. TG+GG, P<10(-4), respectively) and co-dominant model (CC vs. CT, P<1×10(-4), CC vs. TT, P<1×10(-4); TT vs. TG, P<10(-4), TT vs. GG, P=0.012, respectively). Meta-regression analysis suggested that male proportion (P=1×10(-5)) and mean age (P=1×10(-3)) might weaken the effect of rs12979860CC, but HCV genotype 1/4 (P=4×10(-4)) might contribute to it. IL28B rs12979860CC and rs8099917TT genotypes contribute to spontaneous HCV clearance in Caucasians.

  9. Associations between CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer risk: Proof from 26 case-control studies

    PubMed Central

    He, Jing; Wang, Weiye; Xue, Wenji; Wang, Yiwei; Zheng, Leizhen; Zhu, Mei-Ling

    2016-01-01

    Cytochrome P450 1A1 (CYP1A1) enzyme is one of the most important metabolizing enzymes responsible for the metabolism of numerous xenobiotics. Numerous individual case-control studies have investigated the associations between the CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer (CRC) risk, but the conclusions were controversial. To obtain a scientific conclusion, we performed a meta-analysis based on a total of 26 publications, including 20 studies with 8665 cases and 9953 controls on rs1048943 A > G and 19 studies with 6416 cases and 7551 controls on rs4646903 T > C, respectively. The pooled analysis indicated that rs1048943 A > G was associated with an increased risk of CRC (G vs. A: OR = 1.28, 95% CI = 1.08−1.52; GG vs. AA: OR = 1.54, 95% CI = 1.25−1.91; GA vs. AA: OR = 1.26, 95% CI = 1.00−1.60; GG/GA vs. AA: OR = 1.31, 95% CI = 1.05−1.64; GG vs. GA/AA: OR = 1.56, 95% CI = 1.26−1.91). Stratification analysis showed the association between rs1048943 A > G and CRC risk was more obvious in studies with the population-based (PB) design or high quality score. The association between rs4646903 T > C and CRC risk did not reach statistical significance in the pooled analysis as well as stratification analysis. This meta-analysis demonstrated CYP1A1 rs1048943 A > G may increase the susceptibility to CRC instead of rs4646903 T > C. This conclusion suggested CYP1A1 may contribute to the pathogenesis of CRC. PMID:27384991

  10. The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.

    PubMed

    Lurie, Galina; Gaudet, Mia M; Spurdle, Amanda B; Carney, Michael E; Wilkens, Lynne R; Yang, Hannah P; Weiss, Noel S; Webb, Penelope M; Thompson, Pamela J; Terada, Keith; Setiawan, Veronica Wendy; Rebbeck, Timothy R; Prescott, Jennifer; Orlow, Irene; O'Mara, Tracy; Olson, Sara H; Narod, Steven A; Matsuno, Rayna K; Lissowska, Jolanta; Liang, Xiaolin; Levine, Douglas A; Le Marchand, Loic; Kolonel, Laurence N; Henderson, Brian E; Garcia-Closas, Montserrat; Doherty, Jennifer Anne; De Vivo, Immaculata; Chen, Chu; Brinton, Louise A; Akbari, Mohammad R; Goodman, Marc T

    2011-02-08

    Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

  11. Post-bronchiolitis wheezing is associated with toll-like receptor 9 rs187084 gene polymorphism

    PubMed Central

    Nuolivirta, Kirsi; Törmänen, Sari; Teräsjärvi, Johanna; Vuononvirta, Juho; Koponen, Petri; Korppi, Matti; Helminen, Merja; Peltola, Ville; He, Qiushui

    2016-01-01

    Innate immunity receptors play a critical role in host defence, as well as in allergy and asthma. The aim of this exploratory study was to evaluate whether there are associations between TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or TLR10 rs4129009 polymorphisms and viral findings, clinical characteristics or subsequent wheezing in infants with bronchiolitis. In all, 135 full-term infants were hospitalized for bronchiolitis at age less than 6 months: 129 of them were followed-up until the age of 1.5 years. The outcome measures were repeated wheezing, use of inhaled corticosteroids, atopic dermatitis during the first 1.5 years of life and total serum immunoglobulin E (IgE). There were no significant associations between the genotypes or allele frequencies of TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or TLR10 rs4129009 polymorphisms and clinical characteristics or the severity of bronchiolitis during hospitalization. During follow-up, repeated wheezing was more common in children with TLR9 rs187084 variant genotype CC (30.5%) than in children with TLR9 wild-type genotype TT (12.2%) (p = 0.02, aOR 2.73, 95% CI 1.02–7.29). The TLR10 rs4129009 minor allele G was associated with elevated total serum IgE. TLR9 rs187084 gene polymorphism may be associated with post-bronchiolitis wheezing, and TLR10 rs4129009 gene polymorphism may be associated with atopy. PMID:27498757

  12. XPG rs2296147 T>C polymorphism predicted clinical outcome in colorectal cancer

    PubMed Central

    Zhu, Jin-Hong; Hua, Rui-Xi; Xue, Wen-Qiong; Li, Xi-Zhao; Wang, Tong-Min; He, Jing; Jia, Wei-Hua

    2016-01-01

    Xeroderma pigmentosum group G (XPG), one of key components of nucleotide excision repair pathway (NER), is involved in excision repair of UV-induced DNA damage. Single nucleotide polymorphisms (SNPs) in the XPG gene have been reported to associate with the clinical outcome of various cancer patients. We aimed to assess the impact of four potentially functional SNPs (rs2094258 C>T, rs2296147 T>C, rs751402 G>A, and rs873601 G>A) in the XPG gene on prognosis in colorectal cancer (CRC) patients. A total of 1901 patients diagnosed with pathologically confirmed CRC were genotyped for four XPG polymorphisms. Cox proportional hazards model analysis controlled for several confounding factors was conducted to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the four included SNPs, only rs2296147 was shown to significantly affect progression-free survival (PFS) in CRC. Patients carrying rs2296147 CT/TT genotype had a significantly shorter median 10 years PFS than those carrying CC genotype (88.5 months vs. 118.1 months), and an increased progression risk were observed with rs2296147 (HR = 1.324, 95% CI = 1.046–1.667). Moreover, none of the four SNPs were associated with overall survival. In conclusion, our study showed that XPG rs2296147 CT/TT variants conferred significant survival disadvantage in CRC patients in term of PFS. XPG rs2296147 polymorphism could be predictive of unfavorable prognosis of CRC patients. PMID:26887052

  13. rs3806268 of NLRP3 gene polymorphism is associated with the development of primary gout

    PubMed Central

    Deng, Jianping; Lin, Wen; Chen, Yunpeng; Wang, Xin; Yin, Zhong; Yao, Chunhong; Liu, Tangbing; Lv, Yonghong

    2015-01-01

    The aim of the present study was to investigate the association between seven functional SNPs in NALP3 gene and the susceptibility to primary gout. A total of 247 patients with primary gout and 247 controls were selected in this study. Genotyping of NALP3 rs4612666, rs3806268, rs12239046, rs10754558, rs7512998, rs12137901 and rs12565738 was performed using the Sequenom MassARRAY platform. Comparison analysis showed that primary gout patients were more likely to have a higher body mass index, DBP, SBP, TG, urea nitrogen and uric acid (P < 0.05). According to logistic regression analysis, individuals carrying with the GG genotype of rs3806268 were associated with increased risk of primary gout when compared with the AA genotype (OR=1.83, 95% CI=1.03-3.26). However, no significant associations were identified for the remaining SNPs. In conclusion, we found a significant association between rs3806268 in NLRP3 gene and the risk of primary gout in a Chinese population. Further clinical and genetic studies are required to investigate the mechanisms underlying the association between NALP3 polymorphisms and the development of primary gout. PMID:26722603

  14. rs3806268 of NLRP3 gene polymorphism is associated with the development of primary gout.

    PubMed

    Deng, Jianping; Lin, Wen; Chen, Yunpeng; Wang, Xin; Yin, Zhong; Yao, Chunhong; Liu, Tangbing; Lv, Yonghong

    2015-01-01

    The aim of the present study was to investigate the association between seven functional SNPs in NALP3 gene and the susceptibility to primary gout. A total of 247 patients with primary gout and 247 controls were selected in this study. Genotyping of NALP3 rs4612666, rs3806268, rs12239046, rs10754558, rs7512998, rs12137901 and rs12565738 was performed using the Sequenom MassARRAY platform. Comparison analysis showed that primary gout patients were more likely to have a higher body mass index, DBP, SBP, TG, urea nitrogen and uric acid (P < 0.05). According to logistic regression analysis, individuals carrying with the GG genotype of rs3806268 were associated with increased risk of primary gout when compared with the AA genotype (OR=1.83, 95% CI=1.03-3.26). However, no significant associations were identified for the remaining SNPs. In conclusion, we found a significant association between rs3806268 in NLRP3 gene and the risk of primary gout in a Chinese population. Further clinical and genetic studies are required to investigate the mechanisms underlying the association between NALP3 polymorphisms and the development of primary gout.

  15. Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia.

    PubMed

    Vargas-Torres, Sandra Liliana; Portari, Elyzabeth Avvad; Silva, Amanda Lima; Klumb, Evandro Mendes; da Rocha Guillobel, Heloísa Carneiro; de Camargo, Maria José; Santos-Rebouças, Cíntia Barros; Russomano, Fábio Bastos; Macedo, Jacyara Maria Brito

    2016-08-01

    The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions.

  16. The rs4646 and rs12592697 Polymorphisms in CYP19A1 Are Associated with Disease Progression among Patients with Breast Cancer from Different Racial/Ethnic Backgrounds

    PubMed Central

    Armamento-Villareal, Reina; Shah, Vallabh O.; Aguirre, Lina E.; Meisner, Angela L. W.; Qualls, Clifford; Royce, Melanie E.

    2016-01-01

    Given the racial/ethnic disparities in breast cancer, we evaluated the association between CYP19A1 single nucleotide polymorphisms (SNPs) on disease progression in women with breast cancer from different racial/ethnic backgrounds. This is a cross-sectional analysis of data from 327 women with breast cancer in the Expanded Breast Cancer Registry program of the University of New Mexico. Stored DNA samples were analyzed for CYP19A1 SNPs using a custom designed microarray panel. Genotype-phenotype correlations were analyzed. Of the 384 SNPs, 2 were associated with clinically significant outcomes, the rs4646 and rs12592697. The T allele for the rs4646 was associated with advanced stage of the disease at the time of presentation (odds ratio [OR]:1.8, confidence intervals [CI]: 1.05–3.13, p < 0.05) and a more progressive disease (OR: 2.1 [CI: 1.1–4.0], p = 0.04). For the rs12592697, the variant T allele was more frequent in Hispanic women and associated with a more progressive disease (OR: 2.05 [CI: 1.0–4.0], p = 0.04). However, further analysis according to menopausal status showed that the association between these 2 SNPs with disease progression or the stage at diagnosis are confined only to postmenopausal women. The odds ratios of disease progression among postmenopausal women carrying the T allele for the rs4646 and rs12592697 are 3.05 (1.21, 7.74, p = 0.02) and 3.80 (1.24, 11.6, p = 0.02), respectively. Regardless, differences in disease progression among the different genotypes for both SNPs disappeared after adjustment for treatment. In summary, the rs4646 and the rs12592697 SNPs in CYP19A1 are associated with differences in disease progression in postmenopausal women. However, treatment appears to mitigate the differences in genetic risk. PMID:27994616

  17. Muscle-Related Polymorphisms (MSTN rs1805086 and ACTN3 rs1815739) Are Not Associated with Exceptional Longevity in Japanese Centenarians

    PubMed Central

    Yvert, Thomas; Zempo, Hirofumi; Naito, Hisashi; Abe, Yukiko; Arai, Yasumichi; Murakami, Haruka; Miyachi, Motohiko; Pareja-Galeano, Helios; Emanuele, Enzo; Hirose, Nobuyoshi; Lucia, Alejandro

    2016-01-01

    Myostatin (MSTN) and α-actinin-3 (ACTN3) genes are potentially associated with preservation of muscle mass and oxidative capacity, respectively. To explore the possible role of these genes in exceptional longevity (EL), the allele/genotype frequency distribution of two polymorphisms in MSTN (rs1805086, K153R) and ACTN3 (rs1815739, R577X) was studied in Japanese centenarians of both sexes (n = 742) and healthy controls (n = 814). The rs1805086 R-allele (theoretically associated with muscle mass preservation at the expense of oxidative capacity) was virtually absent in the two groups, where genotype distributions were virtually identical. Likewise, no differences in allele (p = 0.838 (women); p = 0.193 (men); p = 0.587 (both sexes)) or genotype distribution were found between groups for ACTN3 rs1815739 (p = 0.975 (women), p = 0.136 (men), p = 0.752 (both sexes)). Of note, however, the frequency of the rs1805086 R-allele observed here is the lowest been reported to date whereas that of the ‘highly oxidative/efficient’ rs1815739 XX genotype in Japanese male centenarians (33.3%) or supercentenarians of both sexes (≥110 years) are the highest (32.6%), for a non-American population. No definite conclusions can be inferred in relation to EL owing to its lack of association with both rs1815739 and rs1805086. However, it cannot be excluded that these gene variants could eventually be related to a “healthy” metabolic phenotype in the Japanese population. Further research might determine if such metabolic profile is among the factors that can potentially predispose these individuals to live longer than Caucasians and what genetic variants might be actually involved. PMID:27861536

  18. Association between Insulin-Like Growth Factor 1 Gene rs12423791 or rs6214 Polymorphisms and High Myopia: A Meta-Analysis

    PubMed Central

    Guo, Lan; Du, Xueying; Lu, Ciyong; Zhang, Wei-Hong

    2015-01-01

    Objective To evaluate the association of insulin-like growth factor 1 gene rs12423791 and rs6214 polymorphisms with high myopia. Methods An electronic search was conducted on PubMed, Embase, the Cochrane Library and the Chinese Biological Abstract Database for articles published prior to May 6, 2014. A meta-analysis was performed using Revman 5.1 and Stata 12.0, and the odds ratios with 95% confidence intervals were calculated in fixed or random effects models based on the results of the Q test. The subgroup analysis was conducted on the basis of the various regions, the sensitivity analysis was also performed to evaluate the stability of the results, and the publication bias was evaluated by a funnel plot and Egger’s linear regression analysis. Results This comprehensive meta-analysis included 2808 high myopia patients and 2778 controls from five unrelated studies. The results demonstrated that the significant association was not present in any genetic models between IGF-1 rs12423791 or rs6214 and high myopia. However, subgroup analysis indicated that rs12423791 polymorphism was associated with high myopia in the Chinese populations in the allelic contrast model (C vs. G: OR=1.24, 95% CI=1.04-1.48 in the fixed-effects model), the dominant model (CC+CG vs. GG: OR=1.40, 95% CI=1.16-1.69 in the fixed-effects model), and the codominant model (CG vs. GG: OR=1.37, 95% CI= 1.12-1.68 in the fixed-effects model). Additionally, none of the individual studies significantly affected the association between IGF-1 rs12423791 and high myopia, according to sensitivity analysis. Conclusion This meta-analysis shows that IGF-1 rs12423791 or rs6214 gene polymorphism is not associated with high myopia. PMID:26076017

  19. Polymorphisms in TRPV1 and TAS2Rs associate with sensations from sampled ethanol

    PubMed Central

    Allen, Alissa L.; McGeary, John E.; Hayes, John E.

    2014-01-01

    Background Genetic variation in chemosensory genes can explain variability in individual’s perception of and preference for many foods and beverages. To gain insight into variable preference and intake of alcoholic beverages, we explored individual variability in the responses to sampled ethanol. In humans, ethanol elicits sweet, bitter and burning sensations. Here, we explore the relationship between variation in ethanol sensations and polymorphisms in genes encoding bitter taste receptors (TAS2Rs) and a polymodal nociceptor (TRPV1). Methods Caucasian participants (n=93) were genotyped for 16 SNPs in TRPV1, 3 SNPs in TAS2R38 and 1 SNP in TAS2R13. Participants rated sampled ethanol on a generalized Labeled Magnitude Scale. Two stimuli were presented: a 16% ethanol whole mouth sip-and-spit solution with a single time-point rating of overall intensity, and a cotton swab saturated with 50% ethanol on the circumvallate papillae (CV) with repeated ratings made over 3 minutes. Area under the curve (AUC) was calculated for the time-intensity data. Results The ethanol whole mouth solution had overall intensity ratings near ‘very strong’. Burning/stinging had the highest mean AUC values, followed by bitterness and sweetness. Whole mouth intensity ratings were significantly associated with burning/stinging and bitterness AUC values on the CV. Three TRPV1 SNPs (rs224547, rs4780521, rs161364) were associated with ethanol sensations on the CV, with two (rs224547 and rs4780521) exhibiting strong linkage disequilibrium. Additionally, the TAS2R38 SNPs rs713598, rs1726866, and rs10246939 formed a haplotype, and were associated with bitterness on the CV. Lastly, overall intensity for whole mouth ethanol associated with the TAS2R13 SNP rs1015443. Conclusions These data suggest genetic variations in TRPV1 and TAS2Rs influence sensations from sampled ethanol and may potentially influence how individuals initially respond to alcoholic beverages. PMID:25257701

  20. Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage

    PubMed Central

    Cao, Xuanye; Li, Chaoqun; Xiao, Siyu; Tang, Yunlan; Huang, Jing; Zhao, Shuan; Li, Xueyu; Li, Jixi; Zhang, Ruilin; Yu, Wei

    2017-01-01

    Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner. Oxidative stress increases the level of PCAF and decreases the level of SIRT1 and deacetylase activity, all of which promote the nuclear translocation of hyperacetylated TyrRS. Furthermore, TyrRS is primarily acetylated on the K244 residue near the nuclear localization signal (NLS), and acetylation inhibits the aminoacylation activity of TyrRS. Molecular dynamics simulations have shown that the in silico acetylation of K244 induces conformational changes in TyrRS near the NLS, which may promote the nuclear translocation of acetylated TyrRS. Herein, we show that the acetylated K244 residue of TyrRS protects against DNA damage in mammalian cells and zebrafish by activating DNA repair genes downstream of transcription factor E2F1. Our study reveals a previously unknown mechanism by which acetylation regulates an aminoacyl-tRNA synthetase, thus affecting the repair pathways for damaged DNA. PMID:28069943

  1. Association of the ACE rs4646994 and rs4341 polymorphisms with the progression of carotid atherosclerosis in slovenian patients with type 2 diabetes mellitus

    PubMed Central

    Merlo, S; Novák, J; Tkáčová, N; Nikolajević Starčević, J; Šantl Letonja, M; Makuc, J; Cokan Vujkovac, A; Letonja, J; Bregar, D; Zorc, M; Rojko, M; Mankoč, S; Kruzliak, P

    2015-01-01

    Abstract The current study was designed to reveal possible associations between the angiotensin-converting-enzyme (ACE) gene polymorphisms (rs4646994 and rs4341) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) in a 4-year-long follow-up study. Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. Genotyping of ACE polymorphisms was performed using KASPar assays, and ultrasound examinations were performed twice (at the enrollment and at follow-up). With regard to the progression of atherosclerosis in subjects with T2DM, statistically significant differences were demonstrated in the change of the sum of carotid plaques thickness for the rs4646994 polymorphism. We did not demonstrate an association between the tested polymorphisms (rs4646994 and rs4341) and either carotid intima media thickness (CIMT) or CIMT progression in a 3.8-year period. In our study, we demonstrated that subjects with T2DM with the DD genotype of the rs4646994 [ACE insertion/deletion (I/D)] polymorphism had faster progression of atherosclerosis in comparison to subjects with other genotypes. PMID:27785395

  2. Association between 8q24 (rs13281615 and rs6983267) polymorphism and breast cancer susceptibility: a meta-analysis involving 117,355 subjects.

    PubMed

    Zhang, Yafei; Zeng, Xianling; Lu, Hongwei; Ji, Hong; Zhao, Enfa; Li, Yiming

    2016-10-18

    Published data on the association between 8q24 polymorphism and breast cancer (BC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between 8q24 (rs13281615 and rs6983267) polymorphism and BC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to August 13, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Twenty-six studies published from 2008 to 2014, with a total of 52,683 cases and 64,672 controls, were included in this meta-analysis. The pooled results showed that there was significant association between 8q24 rs13281615 polymorphism and BC risk in any genetic model. In the subgroup analysis by ethnicity, the effects remained in Asians and Caucasians. However, no genetic models reached statistical association in Africans. There was no association in any genetic model in rs6983267. This meta-analysis suggests that 8q24 rs13281615 polymorphism is a risk factor for susceptibility to BC in Asians, Caucasians and in overall population, While, there was no association in Africans. The rs6983267 polymorphism has no association with BC risk in any genetic model. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

  3. Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus

    PubMed Central

    Sakiyama, Masayuki; Matsuo, Hirotaka; Nakaoka, Hirofumi; Yamamoto, Ken; Nakayama, Akiyoshi; Nakamura, Takahiro; Kawai, Sayo; Okada, Rieko; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-01-01

    Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping of 1,048 male gout patients and 1,334 male controls was performed by TaqMan method. Eight SNPs showed significant associations with gout after Bonferroni correction. rs671 (Glu504Lys) of ALDH2 had the most significant association with gout (P = 1.7 × 10−18, odds ratio = 0.53). After adjustment for rs671, the other 8 SNPs no longer showed a significant association with gout, while the significant association of rs671 remained. rs671 has been reportedly associated with alcohol drinking behavior, and it is well-known that alcohol drinking elevates serum uric acid levels. These data suggest that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the MYL2-CUX2 locus and that “A” allele (Lys) of rs671 plays a protective role in the development of gout. PMID:27181629

  4. Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility.

    PubMed

    Chen, Guangyuan; Fu, Xiuhua; Wang, Guangyu; Liu, Guiyou; Bai, Xiuping

    2015-05-21

    Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10-22, odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.22-1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10-53, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples.

  5. CLU rs9331888 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Caucasian But Not East Asian Populations.

    PubMed

    Zhang, Shuyan; Li, Xuling; Ma, Guoda; Jiang, Yongshuai; Liao, Mingzhi; Feng, Rennan; Zhang, Liangcai; Liu, Jiafeng; Wang, Guangyu; Zhao, Bin; Jiang, Qinghua; Li, Keshen; Liu, Guiyou

    2016-04-01

    Large-scale genome-wide association studies (GWAS) identified three single nucleotide polymorphisms rs11136000, rs2279590, and rs9331888 in CLU gene to be significantly associated with Alzheimer's disease (AD) in Caucasian ancestry. Both rs11136000 and rs2279590 variants were successfully replicated in Asian population. However, previous studies reported either a weak association or no association between rs9331888 polymorphism and AD in Asian population. Here, we searched the PubMed, AlzGene, and Google Scholar databases. We selected 12 independent studies that evaluated the association between the rs9331888 polymorphism and AD using a case-control design. Using an additive model, we did not identify significant heterogeneity among these 12 studies. We observed significant association between rs9331888 polymorphism and AD in pooled populations (P = 2.26E - 07, odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.06-1.14). In subgroup analysis, we did not identify significant heterogeneity in both Asian and Caucasian populations. We identified significant association in Caucasian population (P = 1.67E - 08, OR = 1.13, 95% CI 1.08-1.18) but not in East Asian population (P = 0.49, OR = 1.02, 95% CI 0.96-1.10).

  6. Stress-responsive gene RsICE1 from Raphanus sativus increases cold tolerance in rice.

    PubMed

    Man, Lili; Xiang, Dianjun; Wang, Lina; Zhang, Weiwei; Wang, Xiaodong; Qi, Guochao

    2017-03-01

    The ICE1 transcription factor plays a critical role in plant cold tolerance via triggering CBF/DREB1 cold-regulated signal networks. In this work, a novel MYC-type ICE1-like gene, RsICE1, was isolated from radish (Raphanus sativus L.), and its function in cold tolerance was characterized in rice. The RsICE1 gene was expressed constitutively with higher transcriptional levels in the roots and stems of radish seedlings. The NaCl, cold, and ABA treatments could significantly upregulate RsICE1 expression levels, but dehydration stress had a weak effect on its expression. Ectopic expression of the RsICE1 gene in rice conferred enhanced tolerance to low-temperature stress grounded on a higher survival rate, higher accumulation of soluble sugars and free proline content, a decline in electrolyte leakage and MDA levels, and higher chlorophyll levels relative to control plants. OsDREBL and OsTPP1, downstream cold-regulated genes, were remarkably upregulated at transcription levels in rice overexpressing RsICE1 under low-temperature stress, which indicated that RsICE1 was involved in CBF/DREB1 cold-regulated signal networks. Overall, the above data showed that RsICE1 played an active role in improving rice cold tolerance, most likely resulting from the upregulation of OsDREBL and OsTPP1 expression levels by interacting with the RsICE1 gene under low-temperature stress.

  7. Validation of the Official Slovak Version of the Unified Dyskinesia Rating Scale (UDysRS).

    PubMed

    Skorvanek, Matej; Minar, Michal; Grofik, Milan; Kracunova, Katarina; Han, Vladimir; Cibulcik, Frantisek; Necpal, Jan; Gurcik, Ladislav; Valkovic, Peter

    2015-01-01

    After successful clinimetric testing of the Unified Dyskinesia Rating Scale (UDysRS), a program for translation and validation of non-English versions of the UDysRS was initiated. The aim of this study was to validate and confirm the factor structure of the Slovak translation of the UDysRS. We examined 251 patients with Parkinson's disease and dyskinesia using the Slovak version of the UDysRS. The average age of our sample was 65.2 ± 9.2 years and average disease duration was 10.9 ± 5.0 years. Slovak data were compared using confirmatory factor analysis with the Spanish data. To be designated as the official Slovak UDysRS translation, the comparative fit index (CFI) had to be ≥0.90 relative to the Spanish language version. Exploratory factor analysis was performed to explore the underlying factor structure without the constraint of a prespecified factor structure. For all four parts of the Slovak UDysRS, the CFI, in comparison with the Spanish language factor structure, was ≥0.98. Isolated differences in the factor structure of the Slovak UDysRS were identified by exploratory factor analysis compared with the Spanish version. The Slovak version of the UDysRS was designated as an official non-English translation and can be downloaded from the website of the International Parkinson and Movement Disorder Society.

  8. Association between BDNF-rs6265 and obesity in the Boston Puerto Rican Health Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study is to examine a functional variant (rs6265) in the BDNF gene interacting with dietary intake modulate obesity traits in the Boston Puerto Rican Health Study population. BDNF rs6265 was genotyped in 1147 Puerto Ricans (aged 45-75 years), and examined for association with o...

  9. Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions

    PubMed Central

    Zhang, Wenji; Li, Xuedong; Ye, Tiantian; Chen, Fen; Yu, Shihui; Chen, Jianting; Yang, Xinggang; Yang, Na; Zhang, Jinsong; Liu, Jinlu; Pan, Weisan; Kong, Jun

    2014-01-01

    This study was carried out to evaluate the ocular performance of a cationic Eudragit (EDU) RS 100-coated nanostructured lipid carrier (NLC). The genistein encapsulated NLC (GEN-NLC) was produced using the melt-emulsification technique followed by surface absorption of EDU RS 100. The EDU RS 100 increased the surface zeta potential from −7.46 mV to +13.60 mV, by uniformly forming a spherical coating outside the NLC surface, as shown by transmission electron microscopy images. The EDU RS 100 on the NLC surface effectively improved the NLC stability by inhibiting particle size growth. The obtained EDU RS 100-GEN-NLC showed extended precorneal clearance and a 1.22-fold increase in AUC (area under the curve) compared with the bare NLC in a Gamma scintigraphic evaluation. The EDU RS 100 modification also significantly increased corneal penetration producing a 3.3-fold increase in apparent permeability coefficients (Papp) compared with references. Draize and cytotoxicity testing confirmed that the developed EDU RS 100-GEN-NLC was nonirritant to ocular tissues and nontoxic to corneal cells. These results indicate that the NLC surface modified by EDU RS 100 significantly improves the NLC properties and exhibits many advantages for ocular use. PMID:25246787

  10. Brush Seal Arrangement for the RS-68 Turbopump Set

    NASA Technical Reports Server (NTRS)

    Nunez, D.; Ransom, D.; Prueger, G.

    2006-01-01

    The nature of the RS-68 turbopumps requires that the hydrogen seals separating the pump from the turbine must have extremely low levels of leakage and be contained in small packages. Conventional seal technologies are not able to reasonably satisfy such design requirements. A review of experimental measurements and analysis publications suggests that brush seals are well suited for the design requirements. Brush seals are shown to have less leakage than conventional labyrinth and damper seals and have no adverse effects on the rotordynamics of the machine. The bulk-flow analysis presented by Hendricks et al. is used as a guideline to create a spreadsheet that provides mass flow through the seal and heat generated by the rubbing contact of the bristles on the shaft. The analysis is anchored to published data for LN2 and LH2 leakage tests. Finally, the analysis is used to design seals for both applications. It is observed that the most important analysis parameter is the thickness of the bristle pack and its relationship to seal clearance, lay angle and pressure drop.

  11. The axisymmetric envelopes of RS Cnc and EP Aqr

    NASA Astrophysics Data System (ADS)

    Le Bertre, T.; Hoai, D. T.; Nhung, P. T.; Winters, J. M.

    2016-12-01

    We report on observations obtained at IRAM on two semi-regular variable Asymptotic Giant Branch (AGB) stars, RS Cnc and EP Aqr, undergoing mass loss at an intermediate rate of ˜ 10^{-7} MȯMd. Interferometric data obtained with the Plateau-de-Bure interferometer (NOEMA) have been combined with On-The-Fly maps obtained with the 30-m telescope in the CO(1-0) and (2-1) rotational lines. The spectral maps of spatially resolved sources reveal an axisymmetric morphology in which matter is flowing out at a low velocity (˜ 2 kms) in the equatorial planes, and at a larger velocity (˜ 8 kms) along the polar axes. There are indications that this kind of morpho-kinematics is relatively frequent among stars at the beginning of their evolution on the Thermally-Pulsing AGB, in particular among those that show composite CO line profiles, and that it might be caused by the presence of a companion. We discuss the progress that could be expected for our understanding of the mass loss mechanisms in this kind of sources by increasing the spatial resolution of the observations with ALMA or NOEMA.

  12. An investment in the Three Rs can be very profitable.

    PubMed

    Curren, Rodger

    2009-12-01

    The Principles of Humane Experimental Technique by William Russell and Rex Burch provides exceptional value, both to practitioners of alternative methodologies and to bibliophiles who enjoy the pursuit of an out-of-print book. I was stimulated to find an original edition by my first visits to FRAME and its Chairman, Michael Balls. The search continued for several years, until I was able to find an edition suitable for presentation to him. During this hunt, I was able to learn a great deal about the Three Rs of Replacement, Reduction and Refinement, and the programmes that FRAME initiated to educate scientists and the general public about alternative approaches. Very importantly, I was able to use many of FRAME's successful strategies to build up a similar organisation in the United States, the Institute for In Vitro Sciences. The double value of this book is now revealed - not only are its concepts scientifically and ethically valuable, but the price now being charged by secondhand booksellers means a more than ten-fold increase in the value of my investment!

  13. RASSF1A and the rs2073498 Cancer Associated SNP

    PubMed Central

    Donninger, Howard; Barnoud, Thibaut; Nelson, Nick; Kassler, Suzanna; Clark, Jennifer; Cummins, Timothy D.; Powell, David W.; Nyante, Sarah; Millikan, Robert C.; Clark, Geoffrey J.

    2011-01-01

    RASSF1A is one of the most frequently inactivated tumor suppressors yet identified in human cancer. It is pro-apoptotic and appears to function as a scaffolding protein that interacts with a variety of other tumor suppressors to modulate their function. It can also complex with the Ras oncoprotein and may serve to integrate pro-growth and pro-death signaling pathways. A SNP has been identified that is present in approximately 29% of European populations [rs2073498, A(133)S]. Several studies have now presented evidence that this SNP is associated with an enhanced risk of developing breast cancer. We have used a proteomics based approach to identify multiple differences in the pattern of protein/protein interactions mediated by the wild type compared to the SNP variant protein. We have also identified a significant difference in biological activity between wild type and SNP variant protein. However, we have found only a very modest association of the SNP with breast cancer predisposition. PMID:22649770

  14. Can mothers rely on the Brazilian health system for their deliveries? An assessment of use of the public system and out-of-pocket expenditure in the 2004 Pelotas Birth Cohort Study, Brazil

    PubMed Central

    Barros, Aluísio JD; Santos, Iná S; Bertoldi, Andréa D

    2008-01-01

    Background In a country where comprehensive free health care is provided via a public health system (SUS), an unexpected high frequency of catastrophic out-of-pocket expenditure has been described. We studied how deliveries were financed among mothers of a birth cohort and whether they were an important source of household out-of-pocket expenditure. Methods All deliveries occurring in the city of Pelotas, Brazil, during 2004, were recruited for a birth cohort study. All mothers were interviewed just after birth and three months later. Comprehensive data on the pregnancy, delivery, birth conditions and newborn health were collected, along with detailed information on expenses related to the delivery. Results The majority of the deliveries (81%) were financed by the public health system, a proportion that increased to more than 95% among the 40% poorest mothers. Less than 1% of these mothers reported some out-of-pocket expenditure. Even among those mothers covered by a private health plan, nearly 50% of births were financed by the SUS. Among the 20% richest, a third of the deliveries were paid by the SUS, 50% by private health plans and 17% by direct payment. Conclusion The public health system offered services in quantity and quality enough to attract even beneficiaries of private health plans and spared mothers from the poorest strata of the population of practically any expense. PMID:18366672

  15. Accuracy Assessment and Correction of Vaisala RS92 Radiosonde Water Vapor Measurements

    NASA Technical Reports Server (NTRS)

    Whiteman, David N.; Miloshevich, Larry M.; Vomel, Holger; Leblanc, Thierry

    2008-01-01

    Relative humidity (RH) measurements from Vaisala RS92 radiosondes are widely used in both research and operational applications, although the measurement accuracy is not well characterized as a function of its known dependences on height, RH, and time of day (or solar altitude angle). This study characterizes RS92 mean bias error as a function of its dependences by comparing simultaneous measurements from RS92 radiosondes and from three reference instruments of known accuracy. The cryogenic frostpoint hygrometer (CFH) gives the RS92 accuracy above the 700 mb level; the ARM microwave radiometer gives the RS92 accuracy in the lower troposphere; and the ARM SurTHref system gives the RS92 accuracy at the surface using 6 RH probes with NIST-traceable calibrations. These RS92 assessments are combined using the principle of Consensus Referencing to yield a detailed estimate of RS92 accuracy from the surface to the lowermost stratosphere. An empirical bias correction is derived to remove the mean bias error, yielding corrected RS92 measurements whose mean accuracy is estimated to be +/-3% of the measured RH value for nighttime soundings and +/-4% for daytime soundings, plus an RH offset uncertainty of +/-0.5%RH that is significant for dry conditions. The accuracy of individual RS92 soundings is further characterized by the 1-sigma "production variability," estimated to be +/-1.5% of the measured RH value. The daytime bias correction should not be applied to cloudy daytime soundings, because clouds affect the solar radiation error in a complicated and uncharacterized way.

  16. LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography

    PubMed Central

    2014-01-01

    Background Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients. Methods 1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis. Results The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95% CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95% CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes. Conclusions We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association. PMID:24776095

  17. Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome.

    PubMed

    Li, Chao; Shi, Yuhua; You, Li; Wang, Laicheng; Chen, Zi-Jiang

    2011-03-01

    The aim of the present study was to determine whether or not the 'melatonin receptor (MTNR1B)' gene polymorphisms are associated with a predisposition for polycystic ovary syndrome (PCOS). The single-nucleotide polymorphisms (SNPs), rs10830963 and rs10830962, in the MTNR1B gene were detected in 526 patients with PCOS and 547 healthy Chinese Han women. The association between MTNR1B gene variants and plasma glucose and insulin levels during the oral glucose tolerance test (OGTT) and hormone levels was investigated. The frequencies of three genotypes and two allelotypes of the SNP, rs10830963, differed significantly between women with PCOS and healthy controls (P < 0.001 and P < 0.001, respectively). The SNP, rs10830963, was significantly associated with higher fasting plasma glucose concentrations (P < 0.001) and increased the area under the curve of plasma glucose levels during the OGTT (P < 0.001), as well as increased homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.027). No significant differences were observed in the genotypes and allele distributions of rs10830962 polymorphisms between the PCOS and the control groups (P = 0.311 and P = 0.178, respectively). There was no significant difference in the clinical and the metabolic characteristics in women with PCOS with different genotypes in the SNP, rs10830962 (all P > 0.005). The present study suggest that the SNP, rs10830963, in the MTNR1B gene is not only associated with susceptibility to PCOS, but also contributes to the PCOS phenotype.

  18. Association of genetic variants in INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) with type 2 diabetes (T2D): a case-control study in three ethnic groups from North-West India.

    PubMed

    Sokhi, Jasmine; Sikka, Ruhi; Raina, Priyanka; Kaur, Ramandeep; Matharoo, Kawaljit; Arora, Punit; Bhanwer, Ajs

    2016-02-01

    Genetic contributions towards Type 2 diabetes (T2D) have been assessed through association studies across different world populations with inconsistencies. The majority of the T2D susceptibility loci are common across different races or populations but show ethnicity-specific differences. The pathogenesis of T2D involves genetic variants in the candidate genes. The interactions between the genes involved in insulin signaling and secretory pathways are believed to play an important role in determining an individual's susceptibility towards T2D. Therefore, the present study was initiated to examine the differences, if any, in the contribution of polymorphisms towards T2D susceptibility in the background of different ethnic specifications. The present case-control study included a total of 1216 T2D cases and healthy controls from three ethnic groups (Jat Sikhs, Banias and Brahmins) of North-West India. Polymorphisms were selected on the basis of information available in the literature for INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) in context to T2D. The genotyping was done using PCR-RFLP method. Statistical analysis was done using SPSS 16.0. The analyses revealed that INS (rs689) polymorphism conferred risk towards T2D susceptibility in all the three ethnic groups whereas INSR (rs1799816) polymorphism conferred risk towards T2D in Brahmins only and PP1G.G (rs1799999) polymorphism indicated T2D risk in Jat Sikhs only. Furthermore, interaction analyses indicated the cumulative role of three genetic variants in modulating T2D susceptibility in the three ethnic groups. In conclusion, our results substantiated the evidences for the role of ethnicity in differential susceptibility to T2D in the background of same genetic variants.

  19. The Two-Component System GrvRS (EtaRS) Regulates ace Expression in Enterococcus faecalis OG1RF

    PubMed Central

    Singh, Kavindra V.; La Rosa, Sabina Leanti; Cohen, Ana Luisa V.; Murray, Barbara E.

    2014-01-01

    Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. PMID:25385790

  20. Cephalopods in neuroscience: regulations, research and the 3Rs.

    PubMed

    Fiorito, Graziano; Affuso, Andrea; Anderson, David B; Basil, Jennifer; Bonnaud, Laure; Botta, Giovanni; Cole, Alison; D'Angelo, Livia; De Girolamo, Paolo; Dennison, Ngaire; Dickel, Ludovic; Di Cosmo, Anna; Di Cristo, Carlo; Gestal, Camino; Fonseca, Rute; Grasso, Frank; Kristiansen, Tore; Kuba, Michael; Maffucci, Fulvio; Manciocco, Arianna; Mark, Felix Christopher; Melillo, Daniela; Osorio, Daniel; Palumbo, Anna; Perkins, Kerry; Ponte, Giovanna; Raspa, Marcello; Shashar, Nadav; Smith, Jane; Smith, David; Sykes, António; Villanueva, Roger; Tublitz, Nathan; Zullo, Letizia; Andrews, Paul

    2014-03-01

    Cephalopods have been utilised in neuroscience research for more than 100 years particularly because of their phenotypic plasticity, complex and centralised nervous system, tractability for studies of learning and cellular mechanisms of memory (e.g. long-term potentiation) and anatomical features facilitating physiological studies (e.g. squid giant axon and synapse). On 1 January 2013, research using any of the about 700 extant species of "live cephalopods" became regulated within the European Union by Directive 2010/63/EU on the "Protection of Animals used for Scientific Purposes", giving cephalopods the same EU legal protection as previously afforded only to vertebrates. The Directive has a number of implications, particularly for neuroscience research. These include: (1) projects will need justification, authorisation from local competent authorities, and be subject to review including a harm-benefit assessment and adherence to the 3Rs principles (Replacement, Refinement and Reduction). (2) To support project evaluation and compliance with the new EU law, guidelines specific to cephalopods will need to be developed, covering capture, transport, handling, housing, care, maintenance, health monitoring, humane anaesthesia, analgesia and euthanasia. (3) Objective criteria need to be developed to identify signs of pain, suffering, distress and lasting harm particularly in the context of their induction by an experimental procedure. Despite diversity of views existing on some of these topics, this paper reviews the above topics and describes the approaches being taken by the cephalopod research community (represented by the authorship) to produce "guidelines" and the potential contribution of neuroscience research to cephalopod welfare.

  1. Bone mineral density is associated with vitamin D related rs6013897 and estrogen receptor polymorphism rs4870044: The Tromsø study

    PubMed Central

    Jorde, Rolf; Emaus, Nina; Eggen, Anne Elise; Joakimsen, Ragnar Martin; Kamycheva, Elena

    2017-01-01

    Background Bone mineral density (BMD) is determined by bone remodeling processes regulated by endocrine, autocrine and genetic mechanisms. Thus, some studies have reported that BMD is associated with single nucleotide polymorphisms (SNPs) associated with vitamin D receptor (VDR), serum 25(OH)D levels and estrogen receptor 1 (ESR1), but without consensus. Therefore, we aimed to map and compare the risk genotypes for forearm and total hip low BMD. Methods and findings Data were derived from a population-based study in northern Norway; the Tromsø Study. Distal forearm BMD was measured with a single x-ray absorptiometric device, while total hip BMD was measured with a dual-energy x-ray absorptiometric device. There were 7,317 and 4,082 successful analyses of distal forearm and total hip BMD, respectively, and at least one SNP of interest. We evaluated plausible BMD modulating factors and associations of BMD and SNPs related to vitamin D metabolism (FokI, Cdx2, BsmI, rs2298850, rs10741657, rs3794060, rs6013897), ApaI-BsmI-TaqI haplotypes and ESR1 SNP rs4870044. Results Age, BMI, physical activity and smoking were significantly associated with BMD. In a linear regression model with adjustment for age and gender and with the major homozygote as reference, rs6013897 had a standardized beta coefficient (β) of –0.031 (P = 0.024) for total hip BMD. β for ESR1 SNP rs4870044 was –0.016 (P = 0.036) for forearm BMD and –0.034 (P = 0.015) for total hip BMD. The other SNPs nor serum 25(OH)D were significantly associated with BMD. Conclusions Both forearm and total hip BMD were associated with ESR1 SNP rs4870044. Of the vitamin D–related genes, only CYP24A1 gene rs6013897 was associated with total hip BMD, but the association was weak and needs confirmation in other studies. Serum 25(OH)D was not associated with BMD in our population, probably due to the generally sufficient vitamin D levels in the population. PMID:28253304

  2. Evaluation of interferon-induced transmembrane protein-3 (IFITM3) rs7478728 and rs3888188 polymorphisms and the risk of pulmonary tuberculosis

    PubMed Central

    Naderi, Mohammad; Hashemi, Mohammad; Abedipour, Fatemeh; Bahari, Gholamreza; Rezaei, Maryam; Taheri, Mohsen

    2016-01-01

    The current study aimed to examine the possible association between the interferon-induced transmembrane protein-3 (IFITM3) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample population. This case-control study was conducted on 188 PTB patients and 169 healthy subjects. The rs7478728 and rs3888188 variants of IFITM3 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The findings showed no significant association between rs7478728 polymorphism and risk of PTB. Regarding rs3888188 polymorphism, the TG genotype as well as G allele significantly increased the risk of PTB [odds ratio (OR)=2.48, 95% confidence interval (CI): 1.42–4.53; P=0.002, and OR=2.26, 95% CI: 1.33–3.86; P=0.003, respectively]. In conclusion, the findings revealed that rs3888188 polymorphism increased the risk of PTB in a sample of Iranian population. Additional investigation with larger sample sizes and different ethnicities are needed to verify our findings. PMID:27882230

  3. Two common functional catalase gene polymorphisms (rs1001179 and rs794316) and cancer susceptibility: evidence from 14,942 cancer cases and 43,285 controls

    PubMed Central

    Wang, Xijing; Kang, Huafeng; Lin, Shuai; Yang, Pengtao; Dai, Cong; Xu, Peng; Li, Shanli; Dai, Zhijun

    2016-01-01

    Recent studies have focused on the associations of catalase polymorphisms with various types of cancer, including cervical and prostate cancers. However, the results were inconsistent. To obtain a more reliable conclusion, we evaluated the relationship between the two common catalase gene polymorphisms (rs1001179 and rs794316) and cancer risk by a meta-analysis. Our meta-analysis included 37 published studies involving 14,942 cancer patients and 43,285 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the cancer risk. The results demonstrated that the rs1001179 polymorphism was associated with an increased cancer risk in the recessive and homozygote models (TT vs. CC: OR = 1.19, P = 0.01; TT vs. CT+CC: OR = 1.19, P <0.001). Furthermore, stratified analyses revealed a significant association between the rs1001179 polymorphism and prostate cancer in all models except the homozygote comparison. An association of the rs794316 polymorphism with cancer risk was detected in two genetic models (TT vs. AA: OR = 1.34, 95% CI = 1.03–1.74, P <0.001; TT vs. AT+AA: OR = 1.39, 95% CI = 1.09–1.77, P = 0.01). Additional well-designed studies with large samples should be performed to validate our results. PMID:27449288

  4. Pioneering better science through the 3Rs: an introduction to the national centre for the replacement, refinement, and reduction of animals in research (NC3Rs).

    PubMed

    Burden, Natalie; Chapman, Kathryn; Sewell, Fiona; Robinson, Vicky

    2015-03-01

    The National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is an independent scientific organization that is based in the United Kingdom, which was set up by the government to lead the discovery and application of new technologies and approaches that minimize the use of animals in research and improve animal welfare. The NC3Rs uses a range of strategies to improve and advance science through application of the 3Rs. These include funding basic research, open innovation (CRACK IT), and programs run by inhouse scientists. We present several case studies from the NC3Rs portfolio, featuring asthma research, the use of nonhuman primates in monoclonal antibody development, and CRACK IT. Finally, we anticipate the future, as we use our experience to move into new research fields and expand toward international collaboration. Here we highlight how equipping scientists with relevant and emerging 3Rs tools can help overcome the challenges and limitations of the use of animals in research to the benefit of the whole bioscience community.

  5. Pioneering Better Science through the 3Rs: An Introduction to the National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs)

    PubMed Central

    Burden, Natalie; Chapman, Kathryn; Sewell, Fiona; Robinson, Vicky

    2015-01-01

    The National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is an independent scientific organization that is based in the United Kingdom, which was set up by the government to lead the discovery and application of new technologies and approaches that minimize the use of animals in research and improve animal welfare. The NC3Rs uses a range of strategies to improve and advance science through application of the 3Rs. These include funding basic research, open innovation (CRACK IT), and programs run by inhouse scientists. We present several case studies from the NC3Rs portfolio, featuring asthma research, the use of nonhuman primates in monoclonal antibody development, and CRACK IT. Finally, we anticipate the future, as we use our experience to move into new research fields and expand toward international collaboration. Here we highlight how equipping scientists with relevant and emerging 3Rs tools can help overcome the challenges and limitations of the use of animals in research to the benefit of the whole bioscience community. PMID:25836967

  6. MAOA rs1137070 and heroin addiction interactively alter gray matter volume of the salience network

    PubMed Central

    Sun, Yan; Liu, Linwen; Feng, Jiajia; Yue, Weihua; Lu, Lin; Fan, Yong; Shi, Jie

    2017-01-01

    The rs1137070 polymorphism of monoamine oxidase A (MAOA) is associated with alcoholism and smoking behavior. However, the association between rs1137070 and heroin addiction remains unclear. In this study, we examined the allelic distribution of rs1137070 in 1,035 heroin abusers and 2,553 healthy controls and investigated the interactive effects of rs1137070 and heroin addiction on gray matter volume (GMV) based on 78 heroin abusers and 79 healthy controls. The C allele frequency of rs1137070 was significantly higher in heroin abusers. Heroin addiction and the rs1137070 variant interactively altered measures of GMV in the anterior cingulate cortex, orbital frontal cortex, temporal pole, and insula, which were correlated with cognitive function. Heroin abusers with the C allele had lower measures of GMV in these regions than the healthy controls with the same allele, whereas those with the T allele displayed a different trend. The altered brain regions were connected with white matter tracts, yielding a structural network that partially overlapped with the salience network. These findings suggest that the low activity-related C allele of MAOA rs1137070 is associated with an increase in the sensitivity to heroin addiction and the damaging effects of heroin abuse on cognition and the salience network. PMID:28345608

  7. A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria.

    PubMed

    Marquet, Sandrine; Conte, Ianina; Poudiougou, Belco; Argiro, Laurent; Dessein, Hélia; Couturier, Charlène; Burté, Florence; Oumar, Aboubacar A; Brown, Biobele J; Traore, Abdoualye; Afolabi, Nathaniel K; Barry, Abdoulaye; Omokhodion, Samuel; Shokunbi, Wuraola A; Sodeinde, Olugbemiro; Doumbo, Ogobara; Fernandez-Reyes, Delmiro; Dessein, Alain J

    2017-01-31

    Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali. Two SNPs of IL22, rs1012356 (P = 0.016, OR = 2.12) and rs2227476 (P = 0.007, OR = 2.08) were independently associated with CM in a sample of 115 Nigerian children with CM and 160 controls. The association with rs2227476 (P = 0.01) was replicated in 240 nuclear families with one affected child from Mali. SNP rs2227473, in linkage disequilibrium with rs2227476, was also associated with CM in the combined cohort for these two populations, (P = 0.004, OR = 1.55). SNP rs2227473 is located within a putative binding site for the aryl hydrocarbon receptor, a master regulator of IL-22 production. Individuals carrying the aggravating T allele of rs2227473 produced significantly more IL-22 than those without this allele. Overall, these findings suggest that IL-22 is involved in the pathogenesis of CM.

  8. Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis.

    PubMed

    Ojo, Kayode K; Ranade, Ranae M; Zhang, Zhongsheng; Dranow, David M; Myers, Janette B; Choi, Ryan; Nakazawa Hewitt, Steve; Edwards, Thomas E; Davies, Douglas R; Lorimer, Donald; Boyle, Stephen M; Barrett, Lynn K; Buckner, Frederick S; Fan, Erkang; Van Voorhis, Wesley C

    2016-01-01

    We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment.

  9. Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis

    PubMed Central

    Ranade, Ranae M.; Zhang, Zhongsheng; Dranow, David M.; Myers, Janette B.; Choi, Ryan; Nakazawa Hewitt, Steve; Edwards, Thomas E.; Davies, Douglas R.; Lorimer, Donald; Boyle, Stephen M.; Barrett, Lynn K.; Buckner, Frederick S.; Fan, Erkang; Van Voorhis, Wesley C.

    2016-01-01

    We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment. PMID:27500735

  10. Positive association between PPARD rs2016520 polymorphism and coronary heart disease in a Han Chinese population.

    PubMed

    Ye, H D; Li, Y R; Hong, Q X; Zhou, A N; Zhao, Q L; Xu, L M; Xu, M Q; Xu, X T; Tang, L L; Dai, D J; Jiang, D J; Huang, Y; Wang, D W; Duan, S W

    2015-06-11

    PPARD encodes peroxisome proliferator-activated re-ceptor delta, which has been shown to play an important role in control-ling lipid metabolism and atherosclerosis. In this case-control study, we explored the relationship between PPARD rs2016520 polymorphism and coronary heart disease (CHD) in a Han Chinese population. A to-tal of 657 CHD cases and 640 controls were included in the associa-tion study. rs2016520 polymorphism genotyping was performed using the melting temperature-shift polymerase chain reaction method. The PPARD rs2016520-G allele reduced CHD risk by 17.9% (χ(2) = 5.061, P = 0.025, OR = 0.821, 95%CI = 0.692-0.975). Furthermore, a signifi-cant difference in CHD risk was observed for the PPARD rs2016520 polymorphism in the dominant model (AG + GG vs AA: χ(2) = 4.751, degrees of freedom (df) = 1, P = 0.029, OR = 0.784, 95%CI = 0.631- 0.976). Analysis by age suggested that the G-allele decreased CHD risk by 14.8% in ages greater than 65 years (χ(2) = 4.446, P = 0.035, OR = 0.852, 95%CI = 0.684-1.060). In contrast, meta-analysis of PPARD rs2016520 among 3732 cases and 5042 controls revealed no associa-tion between PPARD rs2016520 and CHD (P = 0.19). We found that the PPARD rs2016520-GG genotype decreased CHD risk in a Han Chinese population. Moreover, we found an association between serum high-density lipoprotein cholesterol level and PPARD rs2016520 in senior individuals aged ≥ 65 years. The meta-analysis revealed no association between PPARD rs2016520 and CHD, suggesting ethnic differences in the association between the PPARD locus and CHD.

  11. LINGO1 rs9652490 is associated with essential tremor and Parkinson disease.

    PubMed

    Vilariño-Güell, Carles; Ross, Owen A; Wider, Christian; Jasinska-Myga, Barbara; Cobb, Stephanie A; Soto-Ortolaza, Alexandra I; Kachergus, Jennifer M; Keeling, Brett H; Dachsel, Justus C; Melrose, Heather L; Behrouz, Bahareh; Wszolek, Zbigniew K; Uitti, Ryan J; Aasly, Jan O; Rajput, Alex; Farrer, Matthew J

    2010-02-01

    Recently, a variant in LINGO1 (rs9652490) was found to associate with increased risk of essential tremor. We set out to replicate this association in an independent case-control series of essential tremor from North America. In addition, given the clinical and pathological overlap between essential tremor and Parkinson disease, we also evaluate the effect of LINGO1 rs9652490 in two case-control series of Parkinson disease. Our study demonstrates a significant association between LINGO1 rs9652490 and essential tremor (P = 0.014) and Parkinson disease (P = 0.0003), thus providing the first evidence of a genetic link between both diseases.

  12. Radio outbursts in RS Canum Venaticorum stars - coronal heating and electron runaway

    SciTech Connect

    Mullan, D.J.

    1985-08-01

    Radio outbursts of RS CVn stars are sometimes thought of as analogs of flares in red dwarf stars. The possibility is examined that the outbursts are not due to flares, but rather to a highly efficient case of coronal heating: mechanical energy reaching the corona from the convection zone of an RS CVn star gives rise to induced electric fields which may be so large that electron runaway becomes possible. It is proposed that gyrosynchrotron emission from fast electrons which are produced by this process are the source of radio outbursts from RS CVn stars. 31 references.

  13. RS-34 (Peacekeeper Post Boost Propulsion System) Orbital Debris Application Concept Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Burnside, Christopher G.

    2013-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) lead a study to evaluate the Rocketdyne produced RS-34 propulsion system as it applies to an orbital debris removal design reference mission. The existing RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper ICBM program; specifically the pressure-fed storable bi-propellant Stage IV Post Boost Propulsion System. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC is working closely with the USAF to obtain all the remaining RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Concept Study, preceded by a utilization study to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions, sought to further understand application for an orbital debris design reference mission as the orbital debris removal mission was found to closely mimic the heritage RS-34 mission. The RS-34 Orbital Debris Application Concept Study sought to identify multiple configurations varying the degree of modification to trade for dry mass optimization and propellant load for overall capability and evaluation of several candidate missions. The results of the RS-34 Phoenix Utilization Study show that the system is technically sufficient to successfully support all of the missions

  14. TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 gene polymorphisms as possible risk factor for rheumatoid arthritis: relation to activity and severity.

    PubMed

    Mosaad, Y M; El-Bassiony, S R; El-Ghaweet, A E; Elhindawy, M M; El-Deek, B S; Sultan, W A

    2015-08-01

    This study was aimed to evaluate the impact of both TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 polymorphisms on susceptibility to rheumatoid arthritis (RA) in a cohort of Egyptian population and to evaluate for the first time their relation to activity, severity, disease-related disability and erosion. TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 gene polymorphisms were typed by RFLP for 128 patients with RA and 125 healthy controls. The A allele, A-containing genotypes (GA and AA) of the TIM-4 and GA haplotype were present with significant higher frequency in patients with RA than healthy controls (Pc  < 0.001). These findings suggest that the A allele, A-containing genotypes (GA and AA) and GA haplotype may be a susceptibility risk factor for RA [OR = 5.83 (3.6-9.4), OR = 9.41 (5.0-17.6) and OR = 4.21 (1.07-19.2), respectively]. No associations were found between TIM genotypes and disease activity, severity or presence of erosion. However, the RA patients with GA genotype of TIM-4 have higher grade of rheumatoid factor (RF) positivity (P = 0.018), and have worse disease-related disability (P = 0.007) and worse pain (0.025). TIM-4 rs7700944 and not TIM-1 rs41297579 G>A (-1454) is associated with RA in the present cohort of Egyptian and may be a risk factor for development of RA in Egyptian. Both SNPs have no effect on disease activity, severity or erosion. However, TIM-4 GA genotype is associated with higher grade of RF positivity and worse disease-related disability and pain.

  15. Genome-wide association study-identified SNPs (rs3790844, rs3790843) in the NR5A2 gene and risk of pancreatic cancer in Japanese

    PubMed Central

    Ueno, Makoto; Ohkawa, Shinichi; Morimoto, Manabu; Ishii, Hiroshi; Matsuyama, Masato; Kuruma, Sawako; Egawa, Naoto; Nakao, Haruhisa; Mori, Mitsuru; Matsuo, Keitaro; Hosono, Satoyo; Nojima, Masanori; Wakai, Kenji; Nakamura, Kozue; Tamakoshi, Akiko; Takahashi, Mami; Shimada, Kazuaki; Nishiyama, Takeshi; Kikuchi, Shogo; Lin, Yingsong

    2015-01-01

    We genotyped 2 SNPs (rs3790844 T/C and rs3790843 G/A) in the NR5A2 gene that were identified in a genome-wide association study (GWAS) of pancreatic cancer in populations of mainly European ancestry, and we examined their associations with pancreatic cancer risk in a case-control study of 360 patients and 400 control subjects in Japan. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The SNPs were in linkage disequilibrium (r2 = 0.80). For rs3790843, the multivariable-adjusted OR was 0.75 (95% CI: 0.41–1.36) and 0.60 (95%CI: 0.33–1.08) for subjects with the AG and AA genotype, respectively, compared to subjects with the GG genotype. The per allele OR was 0.78 (0.62–0.99) (P = 0.046). For rs3790844, the multivariable-adjusted OR was 0.65 (95% CI: 0.37–1.14) and 0.47 (95%CI: 0.27–0.83) for subjects with the CT and CC genotype, respectively, compared to subjects with the TT genotype. The per allele OR was 0.70 (0.56–0.89) (P = 0.003). Our case-control study found that rs3790843 and rs3790844 in the NR5A2 gene are associated with pancreatic cancer risk in Japanese subjects. The direction of association is consistent with the prior findings from GWASs. PMID:26592175

  16. Role of TLR4  rs4986790A>G and rs4986791C>T Polymorphisms in the Risk of Inflammatory Bowel Disease

    PubMed Central

    Ao, Ran; Wang, Ying; Zhnag, Dao-Rong; Du, Ya-Qi

    2015-01-01

    Objective. The present meta-analysis investigated the contribution of TLR4 rs4986790A>G and rs4986791C>T genetic polymorphisms in increasing the risk of inflammatory bowel disease (IBD). Methods. Databases were searched using a combination of keywords related to TLR4 and IBD. Relevant studies were selected based on strict inclusion and exclusion criteria. Meta-analysis of the data extracted from the selected studies was performed using CMA 2.0 statistical analysis software. Results. Out of the 70 studies retrieved by database search, only 13 studies were eligible for inclusion in this meta-analysis and these 13 studies contained a total number of 4409 IBD patients and 5693 healthy controls. The meta-analysis results demonstrated that TLR4 rs4986790A>G polymorphism is associated with an increased risk of IBD (allele model: OR = 1.268, 95% CI = 1.124~1.431, and P < 0.001; dominant model: OR = 1.240, 95% CI = 1.090~1.409, and P = 0.001). Similarly, TLR4 rs4986791C>T polymorphism also conferred an increased risk of IBD (allele model: OR = 1.259, 95% CI = 1.092~1.453, and P = 0.002; dominant model: OR = 1.246, 95% CI = 1.072~1.447, and P = 0.004). Conclusion. Our meta-analysis results demonstrate that TLR4 rs4986790A>G and rs4986791C>T genetic polymorphisms are associated with the etiopathogenesis of IBD. PMID:26089865

  17. Construction, expression, and characterization of Arabidopsis thaliana 4CL and Arachis hypogaea RS fusion gene 4CL::RS in Escherichia coli.

    PubMed

    Zhang, Erhao; Guo, Xuefeng; Meng, Zhifen; Wang, Jin; Sun, Jia; Yao, Xi; Xun, Hang

    2015-09-01

    Resveratrol is an important antioxidant that confers several beneficial effects on human health. 4-coumarate coenzyme A ligase (4CL) and resveratrol synthase (RS) are key rate-limiting enzymes in the biosynthetic pathway of resveratrol. Using gene fusion technology, the fusion gene, 4CL::RS, was constructed by the 4CL gene from Arabidopsis thaliana and RS gene from Arachis hypogaea. DNAMAN analysis showed that the fusion gene encoded a 964-amino acid protein with an approximate weight of 104.7 kDa and a pI of 5.63. A prokaryotic expression vector containing Nco-I and EcoR-I restriction sites, pET-30a/4CL::RS, was identified by liquid culture bacterial PCR, enzyme digestion, and sequencing, and then used in the induction of expression. Subsequently, a biosynthetic pathway of resveratrol was constructed in Escherichia coli BL21(DE3) that harbored pET-30a/4CL::RS. The recombinant strains were induced to express the fusion protein at 28 °C for 8 h. After bacterial cells were disrupted by hypothermic ultrasonication, the 4CL::RS fusion protein was thoroughly separated from tags using Ni-NTA affinity chromatography, and then detected by SDS-PAGE analysis. When the recombinant strains expressed the fusion protein, the precursor, p-coumaric acid, was converted to resveratrol. In the present study, the final concentration of resveratrol derived from 1 mM p-coumaric acid was 80.524 mg/L, with a 35.28 % (mol/mol) conversion yield.

  18. 75 FR 44051 - Resolicitation of Applications for the Railroad Safety Technology Program Grant Program (RS-TEC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... Grant Program (RS-TEC-10-001) AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Notice of Funds Availability, Resolicitation of Applications (RS-TEC-10-001... Railroad Safety Technology Grant Program ] (Funding Opportunity RS-TEC-10-001), the Federal...

  19. The FTO gene polymorphism (rs9939609) is associated with metabolic syndrome in morbidly obese subjects from southern Italy.

    PubMed

    Liguori, Rosario; Labruna, Giuseppe; Alfieri, Andreina; Martone, Domenico; Farinaro, Eduardo; Contaldo, Franco; Sacchetti, Lucia; Pasanisi, Fabrizio; Buono, Pasqualina

    2014-08-01

    Gene variants in MC4R, SIRT1 and FTO are associated with severe obesity and metabolic impairment in Caucasians. We investigated whether common variants in these genes are associated with metabolic syndrome (MetS) in a large group of morbidly obese young adults from southern Italy. One thousand morbidly obese subjects (62% women, mean body mass index 46.5 kg/m(2), mean age 32.6 years) whose families had lived in southern Italy for at least 2 generations were recruited. Single-nucleotide polymorphisms (SNPs) rs12970134, rs477181, rs502933 (MC4R locus), rs3818292, rs7069102, rs730821, rs2273773, rs12413112 (SIRT1 locus) and rs1421085, rs9939609, 9930506, 1121980 (FTO locus) were genotyped by Taqman assay; blood parameters were assayed by routine methods; the Fat Mass, Fat Free Mass, Respiratory Quotient, Basal Metabolic Rate (BMR) and waist circumference were also determined. Binomial logistic regression showed that the TA heterozygous genotype of SNP rs9939609 in the FTO gene was associated with the presence of MetS in our population [OR (95% CI): 2.53 (1.16-5.55)]. Furthermore, the FTO rs9939609 genotype accounted for 21.3% of the MetS phenotype together with total cholesterol, BMR and age. Our results extend the knowledge on genotype susceptibility for MetS in relation to a specific geographical area of residence.

  20. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    NASA Astrophysics Data System (ADS)

    Anh, Nguyen Tuan; Chi, Nguyen T.; Khai Tran, T.; Tuyen Dao, T. P.; Nhan Le, N. T.; Mau Chien, Dang; Hoai, Nguyen To

    2012-12-01

    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid.

  1. Consideration and Checkboxes: Incorporating Ethics and Science into the 3Rs

    PubMed Central

    Landi, Margaret S; Shriver, Adam J; Mueller, Anne

    2015-01-01

    Members of the research community aim to both produce high-quality research and ensure that harm is minimized in animals. The primary means of ensuring these goals are both met is the 3Rs framework of replacement, reduction, and refinement. However, some approaches to the 3Rs may result in a ‘check box mentality’ in which IACUC members, researchers, administrators, and caretakers check off a list of tasks to evaluate a protocol. We provide reasons for thinking that the 3Rs approach could be enhanced with more explicit discussion of the ethical assumptions used to arrive at an approved research protocol during IACUC review. Here we suggest that the notion of moral considerability, and all of the related issues it gives rise to, should be incorporated into IACUC discussions of 3Rs deliberations during protocol review to ensure that animal wellbeing is enhanced within the constraints of scientific investigation. PMID:25836970

  2. The gender-specific association of rs334558 in GSK3β with major depressive disorder

    PubMed Central

    Liu, Sha; Wang, Le; Sun, Ning; Yang, Chunxia; Liu, Zhifen; Li, Xinrong; Cao, Xiaohua; Xu, Yong; Zhang, Kerang

    2017-01-01

    Abstract Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with a heritability ranging from 40% to 50%. The single nucleotide polymorphism (SNP) rs334558 on the glycogen synthase kinase-3β (GSK3β) gene has been identified as a genetic risk loci associated with schizophrenia and bipolar disorder. However, results from replication studies examining the association between rs334558 and MDD remain inconsistent. In the present study, first, we conducted a meta-analysis of the association between rs334558 and MDD by combining 5 available case-control samples totaling 2311 cases and 2535 controls. Second, genotyping data from patients with MDD at our institution, after further stratification by gender, were analyzed to determine the association between rs334558 and MDD. All studies retrieved and included in the meta-analysis were from Korea and China. The meta-analysis suggested that the functional polymorphism rs334558 within the GSK3β promoter region was associated with MDD risk (P < 0.05). The associations were observed both in the allelic and genetic models. Analysis of the genotyping data extracted from our hospital database revealed that rs334558 exhibited exclusive association with MDD in female patients (P=0.015). Our findings suggest that GSK3β rs334558 polymorphisms might be a potential risk for MDD, and females with GSK3β rs334558 polymorphisms might have higher penetrance of MDD. If validated in larger scale samples and in different ethnic populations, these findings might be of value as diagnostic references for MDD. PMID:28099358

  3. Association between MC4R rs17782313 Polymorphism and Overeating Behaviours

    PubMed Central

    Yilmaz, Zeynep; Davis, Caroline; Loxton, Natalie J.; Kaplan, Allan S.; Levitan, Robert D.; Carter, Jacqueline C.; Kennedy, James L.

    2014-01-01

    Background/Objectives Melanocortins play a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behaviour, and depressed mood. Subjects/Methods We genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviours was obtained during the in-person assessment. Results BMI was associated with rs17782313 C allele; however this finding did not survive correction for multiple testing (p=0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviours, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n=152). Conclusions To our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behaviour, as well as to demonstrate possible mechanisms behind MC4R’s influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating. PMID:24827639

  4. Survey of Canadian animal-based researchers' views on the Three Rs: replacement, reduction and refinement.

    PubMed

    Fenwick, Nicole; Danielson, Peter; Griffin, Gilly

    2011-01-01

    The 'Three Rs' tenet (replacement, reduction, refinement) is a widely accepted cornerstone of Canadian and international policies on animal-based science. The Canadian Council on Animal Care (CCAC) initiated this web-based survey to obtain greater understanding of 'principal investigators' and 'other researchers' (i.e. graduate students, post-doctoral researchers etc.) views on the Three Rs, and to identify obstacles and opportunities for continued implementation of the Three Rs in Canada. Responses from 414 participants indicate that researchers currently do not view the goal of replacement as achievable. Researchers prefer to use enough animals to ensure quality data is obtained rather than using the minimum and potentially waste those animals if a problem occurs during the study. Many feel that they already reduce animal numbers as much as possible and have concerns that further reduction may compromise research. Most participants were ambivalent about re-use, but expressed concern that the practice could compromise experimental outcomes. In considering refinement, many researchers feel there are situations where animals should not receive pain relieving drugs because it may compromise scientific outcomes, although there was strong support for the Three Rs strategy of conducting animal welfare-related pilot studies, which were viewed as useful for both animal welfare and experimental design. Participants were not opposed to being offered "assistance" to implement the Three Rs, so long as the input is provided in a collegial manner, and from individuals who are perceived as experts. It may be useful for animal use policymakers to consider what steps are needed to make replacement a more feasible goal. In addition, initiatives that offer researchers greater practical and logistical support with Three Rs implementation may be useful. Encouragement and financial support for Three Rs initiatives may result in valuable contributions to Three Rs knowledge and improve

  5. Fatty acid translocase gene CD36 rs1527483 variant influences oral fat perception in Malaysian subjects.

    PubMed

    Ong, Hing-Huat; Tan, Yen-Nee; Say, Yee-How

    2017-01-01

    We determined whether single nucleotide polymorphisms (SNPs; rs1761667 and rs1527483) in the fatty acid translocase CD36 gene - a receptor for fatty acids - is associated with oral fat perception (OFP) of different fat contents in custards and commercially-available foods, and obesity measures in Malaysian subjects (n=313; 118 males, 293 ethnic Chinese; 20 ethnic Indians). A 170-mm visual analogue scale was used to assess the ratings of perceived fat content, oiliness and creaminess of 0%, 2%, 6% and 10% fat content-by-weight custards and low-fat/regular versions of commercially-available milk, mayonnaise and cream crackers. Overall, the subjects managed to significantly discriminate the fat content, oiliness and creaminess between low-fat/regular versions of milk and mayonnaise. Females rated the perception of fat content and oiliness of both milks higher, but ethnicity, obesity and adiposity status did not seem to play a role in influencing most of OFP. The overall minor allele frequencies for rs1761667 and rs1527483 were 0.30 and 0.26, respectively. Females and individuals with rs1527483 TT genotype significantly perceived greater creaminess of 10% fat-by-weight custard. Also, individuals with rs1527483 TT genotype and T allele significantly perceived greater fat content of cream crackers, independent of fat concentration. rs1761667 SNP did not significantly affect OFP, except for cream crackers. Both gene variants were also not associated with obesity measures. Taken together, this study supports the notion that CD36 - specifically rs1527483, plays a role in OFP, but not in influencing obesity in Malaysian subjects. Besides, gender is an important factor for OFP, where females had higher sensitivity.

  6. Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

    PubMed Central

    Zhang, Peijin; Zhang, Yanyan; Zhang, Jing; Wang, Hui; Ma, He; Wang, Wei; Gao, Xiuyin; Xu, Hao; Lu, Zhaojun

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are the leading cause of Budd-Chiari syndrome (BCS), and the C allele of JAK2 rs4495487 was reported to be an additional candidate locus that contributed to MPNs. In the present study, we examined the role of JAK2 rs4495487 in the etiology and clinical presentation of Chinese BCS patients. 300 primary BCS patients and 311 healthy controls were enrolled to evaluate the association between JAK2 rs4495487 polymorphism and risk of BCS. All subjects were detected for JAK2 rs4495487 by real-time PCR. Results. The JAK2 rs4495487 polymorphism was associated with JAK2 V617F-positive BCS patients compared with controls (P < 0.01). The CC genotype increased the risk of BCS in patients with JAK2 V617F mutation compared with individuals presenting TT genotype (OR = 13.60, 95% CI = 2.04–90.79) and non-CC genotype (OR = 12.00, 95% CI = 2.07–69.52). We also observed a significantly elevated risk of combined-type BCS associated with CC genotype in the recessive model (OR = 4.44, 95% CI = 1.31–15.12). This study provides statistical evidence that the JAK2 rs4495487 polymorphism is susceptibility factor JAK2 V617F positive BCS and combined BCS in China. Further larger studies are required to confirm these findings. PMID:26557140

  7. Smoking attenuated the association between IκBα rs696 polymorphism and defective spermatogenesis in humans.

    PubMed

    Yu, B; Ding, Q; Zheng, T; Jiang, L; Li, Q; Sun, X; Bai, C; Huang, Z

    2015-11-01

    Defective spermatogenesis is prevalent in infertile men, but the molecular mechanisms underlying its aetiology are largely unknown. In this study, a proposed association between IκBα SNPs, smoking-related ROS and sperm quality was investigated. Two polymorphisms in the IκBα gene, rs2233406 and rs696 were genotyped in 342 controls and 338 patients with defective spermatogenesis from a southern Chinese population. The results showed the rs696 AA genotype to be significantly more common (21.60% versus 14.33%, P = 0.013) and the rs696 GG genotype to be significantly rarer (28.99% versus 37.13%, P = 0.024) in the cases than in the controls. After subjects were stratified into smokers and nonsmokers, these differences were only observed in nonsmokers. Further analysis showed the rs696 AA genotype to be significantly closely associated with defective spermatogenesis in all subjects (P = 0.014, OR = 1.647) and in nonsmokers (P = 0.036, OR = 1.889). In a TM3 cell model, exposure to cigarette smoke condensate was found to activate NF-κB luciferase activity and altered transcriptional level of NF-κB pathway genes. In conclusion, this study demonstrates an association between functional polymorphisms of the IκBα rs696 and cigarette smoking with the risk of defective spermatogenesis, suggesting some interaction between the NF-κB signalling pathway and smoking-related ROS in human spermatogenesis.

  8. The Use of Systematic Reviews and Reporting Guidelines to Advance the Implementation of the 3Rs

    PubMed Central

    Avey, Marc T; Fenwick, Nicole; Griffin, Gilly

    2015-01-01

    In 1959, Russell and Burch published The Principles of Humane Experimental Technique, which included concrete advice on factors that they considered would govern progress in the implementation of these principles (enunciated as the 3Rs [Replacement, Reduction, and Refinement in animal-based studies]). One challenge to the implementation of the 3Rs was identified as information retrieval. Here, we further explore this challenge—the need for ‘research on research’—and the role that systematic reviews and reporting guidelines can play in implementation of the 3Rs. First, we examine the 2-fold nature of the challenge of information retrieval: 1) the identification of relevant publications spread throughout a large population of nonrelevant publications and 2) the incomplete reporting of relevant details within those publications. Second, we evaluate how systematic reviews and reporting guidelines can be used generally to address this challenge. Third, we assess the explicit reporting of the 3Rs in a cohort of preclinical animal systematic reviews. Our results show that Reduction methods are the most commonly reported by authors of systematic reviews but that, in general, reporting on how findings relate to the 3Rs is limited at best. Although systematic reviews are excellent tools for resolving the challenge of information retrieval, their utility for making progress in implementation of the 3Rs may be limited unless authors improve their reporting of these principles. PMID:25836961

  9. Association Between MIF-AS rs755622 and Nephrolithiasis Risk in a Chinese Population.

    PubMed

    Ma, Gaoxiang; Yuan, Qinbo; Wang, Qiangdong; Du, Mulong; Chu, Haiyan; Dong, Zhenjia; Xiao, Xu; Wang, Meilin; Qin, Chao; Yin, Changjun; Zhang, Zhengdong; Zhang, Wei

    2016-02-20

    BACKGROUND Single-nucleotide polymorphisms (SNPs) located at lncRNA may affect the stability and splicing processes of mRNA formation, which result in the alteration of its interacting partners. The SNP rs755622 within exon of antisense lncRNA MIF- AS and promoter of MIF was implicated in renal disease risk. MATERIAL AND METHODS In this case-control study, we genotyped the SNP rs755622 in 230 patients diagnosed with nephrolithiasis and 250 controls in a Chinese population. RESULTS We found that the rs755622 CG and CC genotypes had a significantly increased nephrolithiasis risk (adjusted OR=1.52, 95% CI=1.03-2.25; OR=2.63, 95% CI=1.21-5.72, P=0.015), compared with GG genotype in the additive model. The rs755622 C carriers (GC/CC) had an adjusted OR (95% CI) of 1.65 (1.14-2.39, P=0.016), compared with the GG genotype in the dominant model. This hazardous effect was more pronounced in subgroup age >46, BMI >24, hypertension, ever smoking, and ever drinking subjects. Moreover, we found that rs755622 could modulate the function of MIF-AS by influencing its folding. CONCLUSIONS These results indicate that the MIF-AS rs755622 polymorphism may have a crucial role in the development of nephrolithiasis.

  10. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4... operation provided exposed food has been covered or removed from the area being treated prior to...

  11. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4... operation provided exposed food has been covered or removed from the area being treated prior to...

  12. CIITA rs4774 and rs6498122 polymorphisms are associated with oral lichen planus in Chinese people: a case-control study.

    PubMed

    Wu, Dan; Wang, Lifeng; Sun, Mao; Wang, Guoxia; Fu, Shanmin; Dong, Guangying; Wu, Yuanming

    2013-04-01

    Oral lichen planus (OLP) is a common autoimmune inflammatory disorder that is difficult to cure, and its pathogenesis is still largely unknown. The major histocompatibility complex (MHC) class II transactivator (CIITA) gene has been reported to be an important candidate in some classical autoimmune diseases, and certain single nucleotide polymorphisms (SNPs) in CIITA have been confirmed to be associated with susceptibility to some autoimmune diseases. We conducted this research to investigate the existence of any correlation between OLP and SNPs in CIITA. A case-control study was performed to genotype 15 SNPs in the CIITA gene from 42 patients with OLP and from 86 controls; this was carried out by the PCR and then by a locus-specific single-base extension reaction. Allele detection was performed using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The SNP rs4774 variant in exon 11 (+1614G/C, Gly500Ala) of CIITA is significantly associated with OLP in healthy persons, both in genotype frequency and in allele frequency. Another intronic SNP, rs6498122, showed significant differences only in allele frequency. In conclusion, our data show that the two SNPs rs4774 and rs6498122 are associated with OLP and could also indicate the autoimmune characteristics of OLP.

  13. A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria

    PubMed Central

    Marquet, Sandrine; Conte, Ianina; Poudiougou, Belco; Argiro, Laurent; Dessein, Hélia; Couturier, Charlène; Burté, Florence; Oumar, Aboubacar A.; Brown, Biobele J.; Traore, Abdoualye; Afolabi, Nathaniel K.; Barry, Abdoulaye; Omokhodion, Samuel; Shokunbi, Wuraola A.; Sodeinde, Olugbemiro; Doumbo, Ogobara; Fernandez-Reyes, Delmiro; Dessein, Alain J.

    2017-01-01

    Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali. Two SNPs of IL22, rs1012356 (P = 0.016, OR = 2.12) and rs2227476 (P = 0.007, OR = 2.08) were independently associated with CM in a sample of 115 Nigerian children with CM and 160 controls. The association with rs2227476 (P = 0.01) was replicated in 240 nuclear families with one affected child from Mali. SNP rs2227473, in linkage disequilibrium with rs2227476, was also associated with CM in the combined cohort for these two populations, (P = 0.004, OR = 1.55). SNP rs2227473 is located within a putative binding site for the aryl hydrocarbon receptor, a master regulator of IL-22 production. Individuals carrying the aggravating T allele of rs2227473 produced significantly more IL-22 than those without this allele. Overall, these findings suggest that IL-22 is involved in the pathogenesis of CM. PMID:28139719

  14. RS-25 for the NASA Crew Launch Vehicle: The Evolution of SSME for Space Exploration

    NASA Technical Reports Server (NTRS)

    Kynard, Michael H.; Genge, Gary G.; Greene, William D.; Jacobs, William; McArthur, J. Craig; Mims, Michael J.; Tepool, J. Eric; Wofford, Steven J.

    2006-01-01

    As a first step towards the fulfillment of the National Vision for Space Exploration, NASA has begun development of the Crew Launch Vehicle (CLV). The CLV will act, in conjunction with the Crew Exploration Vehicle, as the next generation human launch system to first support missions to the International Space Station (ISS), then later to support the lunar return missions, and then after that to exploration missions to Mars and beyond. The CLV is a two-stage launch vehicle with the first stage based upon the Space Shuttle solid rocket booster. The newly designed, expendable second stage is powered by a single RS-25 liquid hydrogen/liquid oxygen rocket engine. The RS-25 is essentially the Space Shuttle Main Engine (SSME) evolved for a new mission, new environments, and new conditions. The CLV Upper-Stage Engine (USE) office has been established to develop the RS-25 in support of the CLV Project. This paper presents an outline and discussion of the risks associated with this endeavor of transforming the SSME into the upper-stage, altitude-start RS-25 and the plans being undertaken to understand and mitigate these risks. In addition, to meet the long-term requirements of the CLV launch manifest, it will be necessary to redevelop the RS-25, with its long history as the reusable SSME for the Space Shuttle Program, as an expendable engine. While the first flights of CLV will be using heritage SSME hardware, beyond that a new version of RS-25 as an expendable engine is being pursued by the CLV USE element. The goals of this work include the need to make the hardware more producible while maintaining the inherent and inherited reliability of the basic design. This paper will also discuss the risks and present the plans for developing both this next generation version of the RS-25 and for developing the manufacturing capacity necessary to support the CLV Project.

  15. Biocompatibility of rapidly solidified magnesium alloy RS66 as a temporary biodegradable metal.

    PubMed

    Willbold, Elmar; Kalla, Katharina; Bartsch, Ivonne; Bobe, Katharina; Brauneis, Maria; Remennik, Sergei; Shechtman, Dan; Nellesen, Jens; Tillmann, Wolfgang; Vogt, Carla; Witte, Frank

    2013-11-01

    Biodegradable magnesium-based alloys are very promising materials for temporary implants. However, the clinical use of magnesium-based alloys is often limited by rapid corrosion and by insufficient mechanical stability. Here we investigated RS66, a magnesium-based alloy with extraordinary physicochemical properties of high tensile strength combined with a high ductility and a homogeneous grain size of ~1 μm which was obtained by rapid solidification processing and reciprocal extrusion. Using a series of in vitro and in vivo experiments, we analyzed the biodegradation behavior and the biocompatibility of this alloy. In vitro, RS66 had no cytotoxic effects in physiological concentrations on the viability and the proliferation of primary human osteoblasts. In vivo, RS66 cylinders were implanted into femur condyles, under the skin and in the muscle of adult rabbits and were monitored for 1, 2, 3, 4 and 8 weeks. After explantation, the RS66 cylinders were first analyzed by microtomography to determine the remaining RS66 alloy and calculate the corrosion rates. Then, the implantation sites were examined histologically for healing processes and foreign body reactions. We found that RS66 was corroded fastest subcutaneously followed by intramuscular and bony implantation of the samples. No clinical harm with transient gas cavities during the first 6 weeks in subcutaneous and intramuscular implantation sites was observed. No gas cavities were formed around the implantation site in bone. The corrosion rates in the different anatomical locations correlated well with the local blood flow prior to implantation. A normal foreign body reaction occurred in all tissues. Interestingly, no enhanced bone formation could be observed around the corroding samples in the condyles. These data show that RS66 is biocompatible, and due to its interesting physicochemical properties, this magnesium alloy is a promising material for biodegradable implants.

  16. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer

    PubMed Central

    Ou, Jingxing; Vijayasarathy, Camasamudram; Ziccardi, Lucia; Chen, Shan; Zeng, Yong; Marangoni, Dario; Pope, Jodie G.; Bush, Ronald A.; Wu, Zhijian; Li, Wei; Sieving, Paul A.

    2015-01-01

    Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor–depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1–signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology. PMID:26098217

  17. Research on texture feature of RS image based on cloud model

    NASA Astrophysics Data System (ADS)

    Wang, Zuocheng; Xue, Lixia

    2008-10-01

    This paper presents a new method applied to texture feature representation in RS image based on cloud model. Aiming at the fuzziness and randomness of RS image, we introduce the cloud theory into RS image processing in a creative way. The digital characteristics of clouds well integrate the fuzziness and randomness of linguistic terms in a unified way and map the quantitative and qualitative concepts. We adopt texture multi-dimensions cloud to accomplish vagueness and randomness handling of texture feature in RS image. The method has two steps: 1) Correlativity analyzing of texture statistical parameters in Grey Level Co-occurrence Matrix (GLCM) and parameters fuzzification. GLCM can be used to representing the texture feature in many aspects perfectly. According to the expressive force of texture statistical parameters and by Correlativity analyzing of texture statistical parameters, we can abstract a few texture statistical parameters that can best represent the texture feature. By the fuzziness algorithm, the texture statistical parameters can be mapped to fuzzy cloud space. 2) Texture multi-dimensions cloud model constructing. Based on the abstracted texture statistical parameters and fuzziness cloud space, texture multi-dimensions cloud model can be constructed in micro-windows of image. According to the membership of texture statistical parameters, we can achieve the samples of cloud-drop. By backward cloud generator, the digital characteristics of texture multi-dimensions cloud model can be achieved and the Mathematical Expected Hyper Surface(MEHS) of multi-dimensions cloud of micro-windows can be constructed. At last, the weighted sum of the 3 digital characteristics of micro-window cloud model was proposed and used in texture representing in RS image. The method we develop is demonstrated by applying it to texture representing in many RS images, various performance studies testify that the method is both efficient and effective. It enriches the cloud

  18. The 8q24 rs6983267G variant is associated with increased thyroid cancer risk.

    PubMed

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Polanco Echeverry, Guadalupe; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carmona, Luis G Carvajal

    2015-10-01

    The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11-1.27, P=4.03×10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23×10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by ∼13%.

  19. 8q24 rs6983267G variant is associated with increased thyroid cancer risk

    PubMed Central

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Echeverry, Guadalupe Polanco; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carvajal Carmona, Luis G.

    2015-01-01

    The G allele of the rs6983267 single nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in thyroid cancer susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3,067 cases and 8,575 controls. We detected significant associations between rs6983267G and thyroid cancer in the British Isles (Odds Ratio, OR= 1.19, 95% confidence interval, CI: 1.11–1.27, P= 4.03 × 10−7), Japan (OR= 1.20, 95% CI: 1.03–1.41, P= 0.022) and a borderline significant association of similar effect direction and size in Colombia (OR= 1.19, 95% CI: 0.99–1.44, P= 0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5,484 cases and 12,594 controls, confirmed the association between rs6983267G and thyroid cancer (P= 1.23 × 10−7, OR= 1.13, 95% CI: 1.07–1.18). Our results therefore support the notion that rs6983267G is a bona fide thyroid cancer risk variant that increases the risk of disease by ~13%. PMID:26290501

  20. Basigin rs8259 Polymorphism Confers Decreased Risk of Chronic Heart Failure in a Chinese Population

    PubMed Central

    Li, Mu-Peng; Hu, Xiao-Lei; Yang, Yong-Long; Zhang, Yan-Jiao; Zhou, Ji-Peng; Peng, Li-Ming; Tang, Jie; Chen, Xiao-Ping

    2017-01-01

    Left ventricular remodeling is an essential risk factor contributing to the pathogenesis of chronic heart failure (CHF). Basigin (BSG) promotes cardiovascular inflammation and myocardial remodeling processes by induction of extracellular matrix metalloproteinases and inflammatory cytokines. BSG rs8259 polymorphism was associated with BSG expression and risk of acute coronary syndrome. Therefore, we investigated whether rs8259 polymorphism contributes to risk and prognosis of CHF in Chinese patients. In total 922 adult patients with CHF and 1107 matched healthy controls were enrolled. BSG rs8259 polymorphism was genotyped using PCR-restriction fragment length polymorphism. Whole blood BSG mRNA expression data from Genotype-Tissue Expression project was accessed. Evaluation of follow-up data was performed in only 15.2% (140) of the patients with CHF. BSG rs8259 TT genotype was associated with a decreased risk of CHF (OR = 0.83, 95% CI = 0.72–0.96, p = 0.010), especially in patients with hypertension (OR = 0.80, 95% CI = 0.68–0.95, p = 0.011) and coronary heart disease (OR = 0.81, 95% CI = 0.69–0.96, p = 0.013) after adjustment for multiple cardiovascular risk factors. Rs8259 T allele was associated with decreased BSG mRNA in whole blood from 338 healthy normal donors (p = 1.31 × 10−6). However, rs8259 polymorphism failed to exhibit an association with cardiovascular mortality (p = 0.283). BSG rs8259 polymorphism may contribute to decreased risk of CHF in a Chinese Han population. PMID:28230811

  1. Effect of IAA produced by Klebsiella oxytoca Rs-5 on cotton growth under salt stress.

    PubMed

    Liu, Yan; Shi, Zaiqiang; Yao, Lixia; Yue, Haitao; Li, Hui; Li, Chun

    2013-01-01

    Klebsiella oxytoca Rs-5 isolated with ACC (1-aminocyclopropane-1-carboxylate) deaminase activity as the sole nitrogen source could obviously promote cotton seedling growth under salt stress and produce phytohormone indole-3-acetic acid (IAA). The amount of IAA produced by the strain Rs-5 was measured, and the effect of IAA on cotton growth under salt stress was studied. Different treatments were set to treat cotton seeds with fermentation broth containing strain Rs-5 (FB), strain Rs-5, fermentation broth with bacteria removed (FB-NB), fermentation broth without bacteria or IAA (FB-NB-NI) and single IAA solutions (SI) according to the IAA concentration after strain Rs-5 culturing of 48, 72 and 120 h. The germination rate, dry weight, plant height, root length and malondialdehyde (MDA), proline and endogenous IAA content in roots were determined. The results showed that both IAA produced by strain Rs-5 and the strain were effective in promoting cotton growth under salt stress. The growth and ability to resist salt stress of cotton seedlings were increased with the enhancement of IAA concentration. The treatment of FB containing bacteria and IAA at 120 h obtained the best state of cotton growth, when the IAA content was the highest in the fermentation broth (42.14 μg·L(-1)). The germination rate, dry weight, plant height and root length were increased by 29.4%, 24.3%, 27.2% and 27.2% , respectively, compared to the saline control. The strain Rs-5 and/or IAA could obviously reduce the MDA and proline content and increase the endogenous IAA content in cotton seedlings. However, the efficacy of other components in the fermentation broth was inconspicuous.

  2. Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population

    PubMed Central

    2013-01-01

    Background Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. Methods We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. Results We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10-4). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10-4). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. Conclusions To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data

  3. Association of methionine synthase rs1801394 and methionine synthase reductase rs1805087 polymorphisms with meningioma in adults: A meta-analysis

    PubMed Central

    ZENG, XIAN-TAO; LU, JUN-TI; TANG, XIANG-JUN; WENG, HONG; LUO, JIE

    2014-01-01

    Several epidemiological studies suggested that methionine synthase (MTRR) rs1801394 and methionine synthase reductase (MTR) rs1805087 polymorphisms may be involved in the risk of meningioma in adults; however, the results from different case-control studies have been inconsistent. Therefore, we performed a meta-analysis to investigate the association of MTRR and MTR polymorphisms with meningioma. PubMed, Web of Knowledge, China National Knowledge Infrastructure and Wanfang databases were searched up to October 30, 2013 and 3 publications, involving 7 case-control studies, were finally included. Following data extraction, a meta-analysis was conducted using Stata 12.0 software. The pooled results based on the fixed effects model demonstrated that the MTRR rs1801394 polymorphism was associated with an increased risk of meningioma [odds ratio (OR)=1.18, 95% confidence interval (CI): 1.05–1.32 for G vs. A; OR=1.41, 95% CI: 1.12–1.77 for GG vs. AA; OR=1.08, 95% CI: 0.94–1.33 for AG vs. AA; OR=1.19, 95% CI: 1.01–1.40 for (AG+GG) vs. AA; and OR=1.32, 95% CI: 1.07–1.63 for GG vs. (AG+AA)]; however, an association between the MTR rs1805087 polymorphism and the risk of meningioma was not identified [OR=0.99, 95% CI: 0.88–1.12 for G vs. A; OR=1.09, 95% CI: 0.80–1.48 for GG vs. AA; OR=0.95, 95% CI: 0.82–1.11 for AG vs. AA; OR=0.97, 95% CI: 0.84–1.13 for (AG+GG) vs. AA; and OR=1.09, 95% CI: 0.80–1.48 for GG vs. (AG+AA)]. Therefore, the currently available evidence suggests that the MTRR rs1801394 polymorphism may increase the risk of meningioma, whereas the MTRR rs1801394 polymorphism is not associated with meningioma. PMID:24748989

  4. Effects of PSCA rs2294008 (C/T) and c-MYC rs9642880 (G/T) polymorphisms on bladder cancer: evidence from a meta-analysis

    PubMed Central

    Gao, Jie; Yang, Peng-Tao; Diao, Yan; Kang, Hua-Feng; Zhao, Yang; Lin, Shuai; Wang, Zi-Ming; Wang, Meng; Wang, Xi-Jing; Dai, Zhi-Jun

    2015-01-01

    Previous studies have investigated the associations between the two polymorphisms (prostate stem cell antigen (PSCA) rs2294008 C/T and c-MYC rs9642880 G/T) and bladder cancer (BC) risk. However, the results are inconsistent. We therefore carried out a meta-analysis to estimate the relationship between PSCA/c-MYC polymorphisms and BC risk. We searched PubMed up to November 2014 to identify potentially eligible literatures. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations, the data were further stratified by ethnicity. Heterogeneity was evaluated by Q test and I2 statistics. Begg’s funnel plot and Egger’s test were used to assess the publication bias. 11 studies from 9 articles were identified, including a total of 16,814 cancer cases and 52,868 case-free controls. We found a significant association between PSCA rs2294008 polymorphism and BC risk (the allele contrast model: OR = 1.14, 95% CI = 1.11-1.18; homozygote comparison: OR = 1.28, 95% CI = 1.20-1.37; heterozygote comparison: OR = 1.23, 95% CI = 1.17-1.30; dominant model: OR = 1.25, 95% CI = 1.19-1.31 and recessive model: OR = 1.13, 95% CI = 1.07-1.20). Moreover, a significant increased risk of BC was confirmed both in Caucasian and in Asians. For c-MYC rs9642880 polymorphism, significant increased BC risk was detected under the following genetic models (the allele contrast model: OR = 1.20, 95% CI = 1.13-1.27; homozygote comparison: OR = 1.37, 95% CI = 1.21-1.55; heterozygote comparison: OR = 1.20, 95% CI = 1.09-1.32; dominant model: OR = 1.25, 95% CI = 1.14-1.37 and recessive model: OR = 1.26, 95% CI = 1.13-1.40). Further stratified analysis by ethnicity also observed the same results. This meta-analysis suggested that PSCA rs2294008 and c-MYC rs9642880 polymorphisms may increase the BC risk. Further studies are needed to clarify the effects. PMID:25932146

  5. The CYP7A1 gene rs3808607 variant is associated with susceptibility of tuberculosis in Moroccan population

    PubMed Central

    Qrafli, Mounia; Amar, Youssef; Bourkadi, Jamaleddine; Ben Amor, Jouda; Iraki, Ghali; Bakri, Youssef; Amzazi, Saaîd; Lahlou, Ouafae; Seghrouchni, Fouad; El Aouad, Rajae; Sadki, Khalid

    2014-01-01

    Introduction Despite the medical progress in treatment. Tuberculosis (TB) continues to be a serious global health problem. A genome-wide linkage study identified a major susceptibility locus on chromosomal region 8q12-q13 in Moroccan TB patients. The CYP7A1 gene is located in this region and codes for cholesterol 7a-hydroxylase, an enzyme involved in cholesterol catabolism. Methods We selected three SNPs (rs3808607, rs8192875 and rs8192879) and studied their genotype and allele frequencies distribution in patients with pulmonary (PTB) or pleural TB (pTB), and compared them to Healthy Controls (HC). Genotyping of rs8192875 and rs8192879 SNPs was carried out using the Taq Man SNP genotyping Assay while rs3808607 was investigated by PCR-RFLP. Results We reported here for the first time a statistically significant increase in the AA homozygote genotype frequency of rs3808607 in PTB patients compared to HC (p = 0.02, OR = 1.93, 95% CI: 1.93 (1.07;3.49). The increased risk of developing TB was maintained when we combined the groups of patients (PTB-pTB) (p = 0.01, OR= 1.91, 95% CI = (1.07 - 3.42). In contrast, no genetic association was observed between the rs8192875 or rs8192879 polymorphisms and TB. Conclusion Our investigations suggest that rs3808607 may play a role in susceptibility to TB in a Moroccan population. PMID:25360185

  6. p15RS Attenuates Wnt/β-Catenin Signaling by Disrupting β-Catenin·TCF4 Interaction*

    PubMed Central

    Wu, Yinyuan; Zhang, Yanquan; Zhang, Haiwei; Yang, Xi; Wang, Yinyin; Ren, Fangli; Liu, Huitu; Zhai, Yonggong; Jia, Baoqing; Yu, Jun; Chang, Zhijie

    2010-01-01

    The formation of a β-catenin·TCF4 complex in the nucleus of cells is well known as a prerequisite for the transcription of Wnt target genes. Although many co-factors have been identified to regulate the activity of the β-catenin·TCF4 complex, it remains unclear how the complex association is negatively regulated. In this study, we report that p15RS, a negative regulator of the cell cycle, blocks β-catenin·TCF4 complex formation and inhibits Wnt signaling. We observed that p15RS interacts with β-catenin and TCF4. Interestingly, whereas the interaction of p15RS with β-catenin is increased, its interaction with TCF4 is decreased upon Wnt1 stimulation. Moreover, overexpression of p15RS reduces the interaction of β-catenin with TCF4, whereas the depletion of p15RS enhances their interaction. We further demonstrate that overexpression of p15RS suppresses canonical Wnt signaling and results in retarded cell growth, whereas depletion of p15RS shows an enhanced effect on Wnt signaling. We analyzed that inhibition of Wnt signaling by p15RS leads to decreased expression of CYCLIN D1 and c-MYC, two Wnt targeted genes critical for cell growth. Our data suggest that p15RS inhibits Wnt signaling by interrupting β-catenin·TCF4 complex formation and that Wnt signaling initiates downstream gene expression by removing p15RS from promoters. PMID:20739273

  7. DeAnnIso: a tool for online detection and annotation of isomiRs from small RNA sequencing data

    PubMed Central

    Zhang, Yuanwei; Zang, Qiguang; Zhang, Huan; Ban, Rongjun; Yang, Yifan; Iqbal, Furhan; Li, Ao; Shi, Qinghua

    2016-01-01

    Small RNA (sRNA) Sequencing technology has revealed that microRNAs (miRNAs) are capable of exhibiting frequent variations from their canonical sequences, generating multiple variants: the isoforms of miRNAs (isomiRs). However, integrated tool to precisely detect and systematically annotate isomiRs from sRNA sequencing data is still in great demand. Here, we present an online tool, DeAnnIso (Detection and Annotation of IsomiRs from sRNA sequencing data). DeAnnIso can detect all the isomiRs in an uploaded sample, and can extract the differentially expressing isomiRs from paired or multiple samples. Once the isomiRs detection is accomplished, detailed annotation information, including isomiRs expression, isomiRs classification, SNPs in miRNAs and tissue specific isomiR expression are provided to users. Furthermore, DeAnnIso provides a comprehensive module of target analysis and enrichment analysis for the selected isomiRs. Taken together, DeAnnIso is convenient for users to screen for isomiRs of their interest and useful for further functional studies. The server is implemented in PHP + Perl + R and available to all users for free at: http://mcg.ustc.edu.cn/bsc/deanniso/ and http://mcg2.ustc.edu.cn/bsc/deanniso/. PMID:27179030

  8. RS-34 Phoenix In-Space Propulsion System Applied to Active Debris Removal Mission

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Burnside, Christopher G.

    2014-01-01

    In-space propulsion is a high percentage of the cost when considering Active Debris Removal mission. For this reason it is desired to research if existing designs with slight modification would meet mission requirements to aid in reducing cost of the overall mission. Such a system capable of rendezvous, close proximity operations, and de-orbit of Envisat class resident space objects has been identified in the existing RS-34 Phoenix. RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper program; specifically the pressure-fed storable bi-propellant Stage IV Post Boost Propulsion System. The National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC has obtained permission from the USAF to obtain all the remaining RS-34 stages for re-use opportunities. The MSFC Advanced Concepts Office (ACO) was commissioned to lead a study for evaluation of the Rocketdyne produced RS-34 propulsion system as it applies to an active debris removal design reference mission for resident space object targets including Envisat. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy payloads at multiple orbital locations. The RS-34 Concept Study lead by sought to further understand application for a similar orbital debris design reference mission to provide propulsive capability for rendezvous, close proximity operations to support the capture phase of the mission, and deorbit of single or multiple large class resident space objects. Multiple configurations varying the degree of modification were identified to trade for dry mass optimization and

  9. Prediction of solubilities for ginger bioactive compounds in hot water by the COSMO-RS method

    NASA Astrophysics Data System (ADS)

    Zaimah Syed Jaapar, Syaripah; Azian Morad, Noor; Iwai, Yoshio

    2013-04-01

    The solubilities in water of four main ginger bioactives, 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol, were predicted using a conductor-like screening model for real solvent (COSMO-RS) calculations. This study was conducted since no experimental data are available for ginger bioactive solubilities in hot water. The σ-profiles of these selected molecules were calculated using Gaussian software and the solubilities were calculated using the COSMO-RS method. The solubilities of these ginger bioactives were calculated at 50 to 200 °C. In order to validate the accuracy of the COSMO-RS method, the solubilities of five hydrocarbon molecules were calculated using the COSMO-RS method and compared with the experimental data in the literature. The selected hydrocarbon molecules were 3-pentanone, 1-hexanol, benzene, 3-methylphenol and 2-hydroxy-5-methylbenzaldehyde. The calculated results of the hydrocarbon molecules are in good agreement with the data in the literature. These results confirm that the solubilities of ginger bioactives can be predicted using the COSMO-RS method. The solubilities of the ginger bioactives are lower than 0.0001 at temperatures lower than 130 °C. At 130 to 200 °C, the solubilities increase dramatically with the highest being 6-shogaol, which is 0.00037 mole fraction, and the lowest is 10-gingerol, which is 0.000039 mole fraction at 200 °C.

  10. Anti Pneumococcal Activity of Azithromycin-Eudragit RS100 Nano-Formulations

    PubMed Central

    Adibkia, Khosro; Khorasani, Golrokh; Payab, Shahriar; Lotfipour, Farzaneh

    2016-01-01

    Purpose: Bacterial pneumonia is a common lung infection caused by different types of bacteria. Azithromycin (AZI), an azalide antibiotic, is widely used to manage pneumococcal infections. Studies have shown that antibiotics in nanocarriers may lead to increased antibacterial activity and reduced toxicity. The aim of this work was to valuate in vitro antibacterial performance azithromycin-Eudragit RS100 nano-formulations against Streptococcus pneumoniae and Staphylococcus aureus. Methods: AZI-Eudragit RS100 nanoparticles were prepared via electrospinning technique and the in vitro antibacterial performance against S. pneumoniae and S. aureus were assessed using agar dilution method. Results: Nanofibers in the sizes about 100-300 nm in diameter and micro scale in length and nanobeads in the range of 100-500 nm were achieved. The Minimum Inhibitory Concentrations (MIC) showed an enhancement in the antimicrobial effect of AZI-Eudragit RS100 nanofibers (40 µg/ml) compare to untreated AZI solution (>160 µg/ml) against S. pneumonia. The MIC value for AZI-Eudragit RS100 nanofibers against S. aureus was >128 µg/ml, same as that of the untreated AZI solution. Conclusion: The enhanced efficiency of AZI in nanofibers could be related to the more adsorption opportunity of nanofibers to S. pneumonia capsulated cell wall which provides an antibiotic depot on the bacterial surface compared to S. aureus. AZI-Eudragit RS100 nanofibers with enhanced antimicrobial effect against S. pneumonia can be considered as a candidate for in vivo evaluations in antibiotic therapy of Pneumococcal infections. PMID:27766231

  11. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    PubMed Central

    Ognjenović, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonović, Miljan

    2016-01-01

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. This report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. PMID:26869582

  12. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    DOE PAGES

    Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; ...

    2016-02-10

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

  13. Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population.

    PubMed

    Mačeková, Soňa; Bernasovský, Ivan; Gabriková, Dana; Bôžiková, Alexandra; Bernasovská, Jarmila; Boroňová, Iveta; Behulová, Regina; Svíčková, Petra; Petrejčíková, Eva; Soták, Miroslav; Sovičová, Adriana; Carnogurská, Jana

    2012-01-01

    The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.

  14. CLU rs2279590 polymorphism contributes to Alzheimer's disease susceptibility in Caucasian and Asian populations.

    PubMed

    Zhang, Shuyan; Zhang, Donghui; Jiang, Yongshuai; Wu, Lina; Shang, Hong; Liu, Jiafeng; Feng, Rennan; Liao, Mingzhi; Zhang, Liangcai; Liu, Yong; Liu, Guiyou; Li, Keshen

    2015-03-01

    It is reported that CLU rs2279590 polymorphism is significantly associated with Alzheimer's disease (AD) in European ancestry. Recent studies investigated rs2279590 polymorphism in Asian population (Chinese, Japanese and Korean). Four studies showed negative association and two studies showed weak association between rs2279590 and AD. We believe that the weak association or no association may be caused by the relatively small sample size in Asian population. Here, we reinvestigated the association in Asian population. Meanwhile, to investigate the genetic heterogeneity of the rs2279590 polymorphism in Asian and Caucasian populations, we searched the PubMed and AlzGene databases and selected 11 independent studies (6 studies in Asian population and 5 studies in Caucasian population) including 20,655 individuals (8,605 cases and 12,050 controls) for meta-analysis. Our results showed significant association between rs2279590 polymorphism and AD in Asian population with P = 2.00E-04 and P = 2.00E-04 using additive and recessive models, respectively. We observed no significant heterogeneity between Asian and Caucasian populations. We believe that our results may be helpful to understand the mechanisms of CLU in AD pathogenesis and will be useful for future genetic studies in AD.

  15. The TP53 gene rs1042522 C>G polymorphism and neuroblastoma risk in Chinese children.

    PubMed

    He, Jing; Wang, Fenghua; Zhu, Jinhong; Zhang, Zhuorong; Zou, Yan; Zhang, Ruizhong; Yang, Tianyou; Xia, Huimin

    2017-03-08

    TP53, a tumor suppressor gene, plays a critical role in cell cycle control, apoptosis, and DNA damage repair. Previous studies have indicated that the TP53 gene Arg72Pro (rs1042522 C>G) polymorphism is associated with susceptibility to various types of cancer. We evaluated the association of the TP53 gene rs1042522 C>G polymorphism with neuroblastoma susceptibility in a hospital-based study among the Chinese Han population. Enrolled were 256 patients and 531 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) generated using logistic regression models were used to determine the strength of the association of interest. No association was detected between rs1042522 C>G polymorphism and neuroblastoma risk. In our stratification analysis of age, gender, sites of origin, and clinical stages, we observed that subjects with rs1042522 CG/GG genotypes had a lower risk of developing neuroblastoma in the mediastinum (Adjusted OR=0.52, 95% CI=0.33-0.82, P=0.005) than those carrying the CC genotype. These results indicate that TP53 gene rs1042522 C>G polymorphism may exert a weak and site-specific effect on neuroblastoma risk in Southern Chinese children and warrant further confirmation.

  16. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    SciTech Connect

    Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonovic, Miljan

    2016-02-10

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords

  17. FIRE, A Test Bed for ARIES-RS/AT Advanced Physics and Plasma Technology

    SciTech Connect

    Dale M. Meade

    2004-10-21

    The overall vision for FIRE [Fusion Ignition Research Experiment] is to develop and test the fusion plasma physics and plasma technologies needed to realize capabilities of the ARIES-RS/AT power plant designs. The mission of FIRE is to attain, explore, understand and optimize a fusion dominated plasma which would be satisfied by producing D-T [deuterium-tritium] fusion plasmas with nominal fusion gains {approx}10, self-driven currents of {approx}80%, fusion power {approx}150-300 MW, and pulse lengths up to 40 s. Achieving these goals will require the deployment of several key fusion technologies under conditions approaching those of ARIES-RS/AT. The FIRE plasma configuration with strong plasma shaping, a double null pumped divertor and all metal plasma-facing components is a 40% scale model of the ARIES-RS/AT plasma configuration. ''Steady-state'' advanced tokamak modes in FIRE with high beta, high bootstrap fraction, and 100% noninductive current drive are suitable for testing the physics of the ARIES-RS/A T operating modes. The development of techniques to handle power plant relevant exhaust power while maintaining low tritium inventory is a major objective for a burning plasma experiment. The FIRE high-confinement modes and AT-modes result in fusion power densities from 3-10 MWm{sup -3} and neutron wall loading from 2-4 MWm{sup -2} which are at the levels expected from the ARIES-RS/AT design studies.

  18. The atypical antipsychotic olanzapine disturbs depotentiation by modulating mAChRs and impairs reversal learning.

    PubMed

    Song, Woo Seok; Cha, Jin Hee; Yoon, Sang Ho; Cho, Young Seon; Park, Kyeong-Yeol; Kim, Myoung-Hwan

    2017-03-01

    Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown. Here we show that Olz interrupts depotentiation (reversal of long-term potentiation) without disturbing de novo LTP (long-term potentiation) and LTD (long-term depression). At hippocampal SC-CA1 synapses, inhibition of NMDARs (N-methyl-d-aspartate receptors), mGluRs (metabotropic glutamate receptors), or mAChRs (muscarinic acetylcholine receptors) disrupted depotentiation. In addition, co-activation of NMDARs, mGluRs, and mAChRs reversed stably expressed LTP. Olz inhibits the activation of mAChRs, which amplifies glutamate signaling through enhanced NMDAR opening and Gq (Gq class of G protein)-mediated signal transduction. Behaviorally, Olz impairs spatial reversal learning of mice in the Morris water maze test. Our results uncover a novel mechanism underpinning the cognitive modulation of Olz and show that the anticholinergic property of Olz affects glutamate signaling and synaptic plasticity.

  19. NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis

    PubMed Central

    2014-01-01

    Background A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population. Methods We analyzed allelic and genotypic frequency of NQO1 rs1800566 in 290 patients with MS and 310 healthy controls, using TaqMan Assays. Results NQO1 rs1800566 allelic and genotypic frequencies did not differ significantly between MS patients and controls, and were unrelated with age of onset of MS, gender, and clinical type of MS. Conclusions Our results indicate that NQO1 rs1800566 does not have an effect on MS disease risk. PMID:24755231

  20. Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis

    PubMed Central

    Li, Jingguang; Zhao, Yajun; Li, Rena; Broster, Lucas S.; Zhou, Chenglin; Yang, Suyong

    2015-01-01

    A common variant in the oxytocin receptor gene (OXTR), rs53576, has been broadly linked to socially related personality traits and behaviors. However, the pattern of published results is inconsistent. Here, we performed a meta-analysis to comprehensively evaluate the association. The literature was searched for relevant studies and effect sizes between individuals homozygous for the G allele (GG) and individuals with A allele carriers (AA/AG). Specifically, two indices of sociality were evaluated independently: i) general sociality (24 samples, n = 4955), i.e., how an individual responds to other people in general; and ii) close relationships (15 samples, n = 5262), i.e., how an individual responds to individuals with closed connections (parent-child or romantic relationship). We found positive association between the rs53576 polymorphism and general sociality (Cohen’s d = 0.11, p = .02); G allele homozygotes had higher general sociality than the A allele carriers. However, the meta-analyses did not detect significant genetic association between rs53576 and close relationships (Cohen’s d = 0.01, p = .64). In conclusion, genetic variation in the rs53576 influences general sociality, which further implies that it is worthy to systematically examine whether the rs53576 is a valid genetic marker for socially related psychiatric disorders. PMID:26121678

  1. An Xp22.1-p22.2 YAC contig encompassing the disease loci for RS, KFSD, CLS, HYP and RP15: refined localization of RS.

    PubMed

    Van de Vosse, E; Bergen, A A; Meershoek, E J; Oosterwijk, J C; Gregory, S; Bakker, B; Weissenbach, J; Coffey, A J; van Ommen, G J; Den Dunnen, J T

    1996-01-01

    To facilitate the positional cloning of the genes involved in retinoschisis (RS), keratosis follicularis spinulosa decalvans (KFSD), Coffin-Lowry syndrome (CLS), X-linked hypophosphatemic rickets (XLH, locus name HYP) and X-linked dominant cone-rod degeneration (locus name RP15), we have extended the molecular map of the Xp22 region. Screening of several YAC libraries allowed us to identify 156 YACs, 52 of which localize between markers DXS414 (P90) and DXS451 (kQST80H1). Analysis of their marker content facilitated the construction of a YAC contig from the region spanning (in this order): DXS414 - DXS987 - DXS207 - DXS1053 - DXS197 - DXS 43 - DXS1195 - DXS418 - DXS999 - PDHA1 - DXS7161 - DXS443 - DXS 7592 - DXS1229 - DXS365 - DXS7101 - DXS7593 - DXS1052 - DXS274 - DXS989 - DXS451. The region between DXS414 and DXS451 covers about 4.5-5 Mb. Two additional markers (DXS7593 and DXS7592) were placed in the region, thereby increasing the genetic resolution. Using the deduced marker order, the analysis of key recombinants in families segregating RS allowed us to refine the critical region for RS to 0.6 Mb, between DXS418 and DXS7161.

  2. The SaeRS Two-Component System of Staphylococcus aureus

    PubMed Central

    Liu, Qian; Yeo, Won-Sik; Bae, Taeok

    2016-01-01

    In the Gram-positive pathogenic bacterium Staphylococcus aureus, the SaeRS two-component system (TCS) plays a major role in controlling the production of over 20 virulence factors including hemolysins, leukocidins, superantigens, surface proteins, and proteases. The SaeRS TCS is composed of the sensor histidine kinase SaeS, response regulator SaeR, and two auxiliary proteins SaeP and SaeQ. Since its discovery in 1994, the sae locus has been studied extensively, and its contributions to staphylococcal virulence and pathogenesis have been well documented and understood; however, the molecular mechanism by which the SaeRS TCS receives and processes cognate signals is not. In this article, therefore, we review the literature focusing on the signaling mechanism and its interaction with other global regulators. PMID:27706107

  3. Polymorphism of MDM2 promoter 309 (rs 2279744) and the risk of PCOS.

    PubMed

    Chan, Ying; Jiang, Hongguo; Yang, Xiaoling; Li, Dongya; Ma, Lan; Luo, Ying; Tang, Wenru

    2016-01-01

    This study aimed at evaluating possible association between MDM2 SNP309 polymorphism (rs 2279744) and polycystic ovary syndrome (PCOS). One hundred and twenty-five women with PCOS and two hundred and fifty women without PCOS were collected from the department of reproductive medicine of college hospital in this case-control study. Peripheral blood samples were collected from all participants and DNA was extracted, MDM2 SNP309 polymorphism (rs 2279744) was determined from the 125 cases and 250 controls. Women were grouped into PCOS (n = 125) group and control group (n = 250). Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the association between MDM2 SNP309 polymorphism (rs 2279744) and PCOS. The distribution of T allele was significant higher in PCOS cases than controls. MDM2 SNP 309 T allele is associated with PCOS.

  4. High-resolution optical spectroscopy of RS Ophiuchi during 2008-2009

    NASA Astrophysics Data System (ADS)

    Somero, A.; Hakala, P.; Wynn, G. A.

    2017-01-01

    RS Ophiuchi (RS Oph) is a symbiotic variable and a recurrent nova (RN). We have monitored it with the Nordic Optical Telescope and obtained 30 high-resolution (R = 46 000) optical spectra over one orbital cycle during quiescence. To our knowledge, this is the best-sampled high-resolution spectroscopic data set of RS Oph over one orbital period. We do not detect any direct signatures of an accretion disc such as double peaked emission lines, but many line profiles are complex consisting of superimposed emission and absorption components. We measure the spin of the red giant and conclude that it is tidally locked to the binary orbit. We observe Na I absorption features, probably arising from the circumbinary medium, that has been shaped by previous RN outbursts. We do not detect any intrinsic polarization in the optical wavelengths.

  5. Genomic characterization of Ralstonia solanacearum phage ϕRS138 of the family Siphoviridae.

    PubMed

    Van Truong Thi, Bich; Pham Khanh, Nguyen Huan; Namikawa, Ryuta; Miki, Kaito; Kondo, Akihiro; Dang Thi, Phuong Thao; Kamei, Kaeko

    2016-02-01

    ϕRS138, a bacteriophage of the family Siphoviridae that lyses Ralstonia solanacearum, was isolated. The genomic DNA of ϕRS138 was 41,941 bp long with a GC content of 65.1 % and contained 56 putative open reading frames. The ϕRS138 genome could be divided into three regions based on similarities to other genomes: (1) a region containing genes encoding a putative transcriptional regulator and an integrase, similar to the prophage genes in Ralstonia solanacearum K60-1; (2) a region encoding proteins related to structural modules and virion morphogenesis, similar to genes in the Pseudomonas phages of the family Siphoviridae; and (3) a region highly similar to the genomes of other Ralstonia solanacearum strains.

  6. Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Merlo, Sebastjan; Starčević, Jovana Nikolajević; Mankoč, Sara; Šantl Letonja, Marija; Cokan Vujkovac, Andreja; Zorc, Marjeta; Petrovič, Daniel

    2016-01-01

    Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM. PMID:26881237

  7. Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Merlo, Sebastjan; Starčević, Jovana Nikolajević; Mankoč, Sara; Šantl Letonja, Marija; Cokan Vujkovac, Andreja; Zorc, Marjeta; Petrovič, Daniel

    2016-01-01

    Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.

  8. Association of GDF1 rs4808863 with fetal congenital heart defects: a case–control study

    PubMed Central

    Zhang, Juan; Wu, Qingqing; Wang, Li; Li, Xiaofei; Ma, Yuqing; Yao, Ling

    2015-01-01

    Background Congenital heart defects (CHDs) are the most common fetal defects and the most important cause of child mortality and morbidity. Objective To investigate the association between growth/differentiation factor 1 (GDF1) polymorphisms and fetal CHDs, by evaluating the association of GDF1 rs4808863 with fetal CHDs. Design A case–control study. Setting Beijing, China. Participants We selected 124 fetuses with a CHD and a normal karyotype and normal array-based comparative genomic hybridisation analysis and compared them with 124 normal fetuses matched for gestational age and sex. Fetuses with a CHD, from 20 to 32 weeks of gestation were included. Fetuses with any chromosomal abnormalities, and fetuses from multiple pregnancies and those carried by pregnant women with chronic diseases, were excluded from this research. DNA extraction and genotyping were carried out for all cases to investigate the genotype distributions of GDF1 rs4808863. Results A significant difference was noted for the CT phenotype of GDF1 rs4808863 between the controls and the fetuses with CHDs using homozygote and heterozygote comparisons. The minor allele (T allele) of GDF1 rs4808863 was associated with an increased risk of CHD (p<0.05). A statistically significant difference between controls and fetuses with CHDs was noted in a comparison with the mutation genotype CT+TT and wild-type genotype CC (p<0.05) using dominant modal analysis. After stratification analysis, the CT phenotype, the minor allele (T allele) and the mutation genotype CT+TT of the rs4808863 polymorphism were associated with atrioventricular septal defect (AVSD), left ventricular outflow tract obstruction (LVOTO) and left–right laterality defects (p<0.05). Conclusions Our results suggest that the GDF1 rs4808863 polymorphism contributes to an increased risk of fetal CHDs, especially the subtypes of AVSD, LVOTO and left–right laterality defects. PMID:26656983

  9. Analyzing large-scale samples highlights significant association between rs10411210 polymorphism and colorectal cancer.

    PubMed

    He, Dongfeng; Ma, Lihong; Feng, Rennan; Zhang, Liangcai; Jiang, Yongshuai; Zhang, Yanqiao; Liu, Guiyou

    2015-08-01

    Colorectal cancer (CRC) is the third most common form of cancer and the second leading cause of cancer-related death in the Western countries. In order to detect common CRC genetic variants, genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. RHPN2 is located on 9q13.11, which encodes a member of the rhophilin family of Ras-homologous (Rho)-GTPase binding proteins. RHPN2 gene rs10411210 polymorphism was identified to be significantly associated with CRC in European ancestry. GWAS and candidate studies investigate whether rs10411210 polymorphism is associated with CRC risk in European, Asian and American populations. However, most studies reported no association. Evidence shows that RHPN2 rs10411210 variant may be a prognostic biomarker for patients with surgically resected CRC. Here we reevaluated this association using large-scale samples from 15 studies (131580 samples including 53564 CRC cases and 78016 controls) using meta-analysis method by searching the PubMed and Google Scholar databases. We did not identify significant heterogeneity among these 15 studies (P=0.4201 and I(2)=2.8%). Our results showed significant association between rs10411210 and CRC (P=9.17E-14, odds ratio (OR)=1.10, 95% confidence interval (CI) 1.07-1.13). In subgroup analysis, we found significant association between rs10411210 and CRC in European population with P=5.70E-09, OR=1.14, 95% CI 1.10-1.20 and Asian population with P=3.36E-07, OR=1.11, 95% CI 1.07-1.16, but not American population with P=0.0576, OR=1.05, 95% CI 1.00-1.09. Collectively, our analysis further highlights significant association between rs10411210 polymorphism and colorectal cancer.

  10. SHBG Gene Polymorphism (rs1799941) Associates with Metabolic Syndrome in Children and Adolescents

    PubMed Central

    White, Marquitta J.; Eren, Fatih; Agirbasli, Deniz; Williams, Scott M.; Agirbasli, Mehmet

    2015-01-01

    Background Metabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents. Methods Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls). Results Logistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006). The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963). Conclusions The significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children. PMID:25647406

  11. Novel CC chemokine receptor 4 antagonist RS-1154 inhibits ovalbumin-induced ear swelling in mice.

    PubMed

    Nakagami, Yasuhiro; Kawashima, Kayo; Yonekubo, Kazuki; Etori, Maki; Jojima, Takaaki; Miyazaki, Shojiro; Sawamura, Ryoko; Hirahara, Kazuki; Nara, Futoshi; Yamashita, Makoto

    2009-12-10

    CC chemokine ligand 17 (CCL17/thymus and activation-regulated chemokine: TARC) and CCL22 (macrophage-derived chemokine: MDC) selectively bind to CC chemokine receptor 4 (CCR4). The CCR4 system is considered to be responsible for the pathology of allergic diseases such as atopic dermatitis. To find and develop potential medicines against allergic diseases, we screened an in-house library to search for compounds having a profile as a CCR4 antagonist. From among the screening hits, we focused on 3-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}quinazoline-2,4(1H,3H)-dione (named RS-1154), which had been newly synthesized in our laboratory. This compound inhibited the binding of [(125)I]CCL17 to human CCR4-expressing CHO cells with an IC(50) value of 27.7 nM and moreover inhibited CCL17-induced migration of DO11.10 mice-derived T helper 2 cells with an IC(50) value of 1.5 nM in vitro. We then examined the effect of RS-1154 in an ovalbumin-induced ear swelling assay. The ear thickness was decreased by intravenous administration of anti-CCL17 or anti-CCL22 antibodies, suggesting that the CCR4 system is involved in the ear swelling. Though partially, the oral administration of RS-1154 also significantly ameliorated the ear swelling at the doses of 30 and 100 mg/kg. Furthermore, the serum level of interleukin-4 decreased after the administration of RS-1154. In this study, we succeeded in obtaining a newly-synthesized compound, RS-1154, which has a potential to inhibit the chemotaxis of T helper 2 cells in vitro and to ameliorate ovalbumin-induced ear swelling in vivo. These results raise the possibility that RS-1154 or one of derivatives might become a therapeutic agent for atopic dermatitis patients.

  12. Association between Tourette Syndrome and the Dopamine D3 Receptor Gene Rs6280

    PubMed Central

    He, Fan; Zheng, Yi; Huang, Huan-Huan; Cheng, Yu-Hang; Wang, Chuan-Yue

    2015-01-01

    Background: Tourette syndrome (TS) is a complex, heterozygous genetic disorder. The number of molecular genetic studies have investigated several candidate genes, particularly those implicated in the dopamine system. The dopamine D3 receptor (DRD3) gene has been considered as a candidate gene in TS. There was not any report about the association study of TS and DRD3 gene in Han Chinese population. We combined a case–control genetic association analysis and nuclear pedigrees transmission disequilibrium test (TDT) analysis to investigate the association between DRD3 gene rs6280 single nucleotide polymorphisms (SNPs) and TS in a Han Chinese population. Methods: A total of 160 TS patients was diagnosed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The DRD3 gene rs6280 SNPs were genotyped by TaqMan SNP genotyping assay technique in all subjects. We used a case–control genetic association analysis to compare the difference in genotype and allele frequencies between 160 TS patients and 90 healthy controls. At the same time, we used TDT analysis to identify the DRD3 gene rs6280 transmission disequilibrium among 101 nuclear pedigrees. Results: The genotype and allele frequency of DRD3 gene rs6280 SNPs had no statistical difference between control group (90) and TS group (160) (χ2 = 3.647, P = 0.161; χ2 = 0.643, P = 0.423) using Chi-squared test. At the basis of the 101 nuclear pedigrees, TDT analysis showed no transmission disequilibrium of DRD3 gene rs6280 SNPs (χ2 = 0; P = 1). Conclusions: Our findings provide no evidence for an association between DRD3 gene rs6280 and TS in the Han Chinese population. PMID:25698199

  13. MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

    PubMed

    Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

    2016-01-01

    Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

  14. Sigma receptors [σRs]: biology in normal and diseased states

    PubMed Central

    Rousseaux, Colin G.; Greene, Stephanie F.

    2016-01-01

    Abstract This review compares the biological and physiological function of Sigma receptors [σRs] and their potential therapeutic roles. Sigma receptors are widespread in the central nervous system and across multiple peripheral tissues. σRs consist of sigma receptor one (σ1R) and sigma receptor two (σ2R) and are expressed in numerous regions of the brain. The sigma receptor was originally proposed as a subtype of opioid receptors and was suggested to contribute to the delusions and psychoses induced by benzomorphans such as SKF-10047 and pentazocine. Later studies confirmed that σRs are non-opioid receptors (not an µ opioid receptor) and play a more diverse role in intracellular signaling, apoptosis and metabolic regulation. σ1Rs are intracellular receptors acting as chaperone proteins that modulate Ca2+ signaling through the IP3 receptor. They dynamically translocate inside cells, hence are transmembrane proteins. The σ1R receptor, at the mitochondrial-associated endoplasmic reticulum membrane, is responsible for mitochondrial metabolic regulation and promotes mitochondrial energy depletion and apoptosis. Studies have demonstrated that they play a role as a modulator of ion channels (K+ channels; N-methyl-d-aspartate receptors [NMDAR]; inositol 1,3,5 triphosphate receptors) and regulate lipid transport and metabolism, neuritogenesis, cellular differentiation and myelination in the brain. σ1R modulation of Ca2+ release, modulation of cardiac myocyte contractility and may have links to G-proteins. It has been proposed that σ1Rs are intracellular signal transduction amplifiers. This review of the literature examines the mechanism of action of the σRs, their interaction with neurotransmitters, pharmacology, location and adverse effects mediated through them. PMID:26056947

  15. FTO at rs9939609, Food Responsiveness, Emotional Control and Symptoms of ADHD in Preschool Children

    PubMed Central

    Velders, Fleur P.; De Wit, Jolanda E.; Jansen, Pauline W.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tiemeier, Henning

    2012-01-01

    The FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)2) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural phenotypes, such as impulsivity and control. We examined the effect of the FTO minor allele (A) at rs9939609 on eating behaviour, impulsivity and control in young children, thus before the BMI effect becomes apparent. This study was embedded in the Generation R Study, a population-based cohort from fetal life onwards. 1,718 children of European descent were genotyped for FTO at rs9939609. With logistic regression assuming an additive genetic model, we examined the association between the FTO minor allele and eating behaviour, impulsivity and control in preschool children. There was no relation between FTO at rs9939609 and child BMI at this age. The A allele at rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03). Also, children with the A allele were less likely to have symptoms of ADHD (OR 0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to children without the A allele. Our findings suggest that before the association between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to increased food responsiveness, a decreased risk for symptoms of ADHD and better emotional control. Future studies are needed to investigate whether these findings represent one single mechanism or reflect pleiotropic effects of FTO. PMID:23155456

  16. Prostate stem cell antigen variation rs2294008 associated with the risk of bladder cancer

    PubMed Central

    Li, Maomao; Yu, Xi; Cheng, Liangliang; Huang, Yi; Weng, Guobin

    2015-01-01

    Several studies reported Prostate stem cell antigen (PSCA) rs2294008 was susceptibly associated with bladder cancer (BC) risk. However, the results were not entirely consistent. The aim of this study was to investigate the association between rs2294008 and BC risk. Comprehensive meta-analysis was preformed to provide a more precise assessment of the association between rs2294008 and BC risk. Twenty five studies involving 14,244 BC patients and 53,963 controls were included in our meta-analysis. The crude odds ratios (ORs) and the 95% confidence intervals (95% CIs) were used to evaluate the strength of the association. Pooled results indicated that the PSCA variant rs2294008-T was significantly connected with an increased risk of BC (OR = 1.15, 95% CI = 1.12-1.18, P(z) < 0.0001). Moreover, stratified analyses showed that rs2294008 significantly increased BC risk in European (OR = 1.10, 95% CI = 1.05-1.15, P(z) < 0.0001), North American (OR = 1.18, 95% CI = 1.12-1.24, P(z) < 0.0001), and Asian (OR = 1.17, 95% CI = 1.13-1.22, P(z) < 0.0001). In conclusion, our meta-analysis demonstrated that the PSCA rs2294008 is a risk factor for BC in European, Asian and North American. Further large case-control studies are needed to assess the relationship in other populations. Biologically functional studies are needed to verify the molecular mechanisms in the pathogenesis of BC. PMID:26550251

  17. rsEGFP2 enables fast RESOLFT nanoscopy of living cells

    PubMed Central

    Grotjohann, Tim; Testa, Ilaria; Reuss, Matthias; Brakemann, Tanja; Eggeling, Christian; Hell, Stefan W; Jakobs, Stefan

    2012-01-01

    The super-resolution microscopy called RESOLFT relying on fluorophore switching between longlived states, stands out by its coordinate-targeted sequential sample interrogation using low light levels. While RESOLFT has been shown to discern nanostructures in living cells, the reversibly photoswitchable green fluorescent protein (rsEGFP) employed in these experiments was switched rather slowly and recording lasted tens of minutes. We now report on the generation of rsEGFP2 providing faster switching and the use of this protein to demonstrate 25–250 times faster recordings. DOI: http://dx.doi.org/10.7554/eLife.00248.001 PMID:23330067

  18. E. coli RS2GFP Retention Mechanisms in Laboratory-Scale Fractured Rocks: A Statistical Model

    NASA Astrophysics Data System (ADS)

    Rodrigues, S. N.; Qu, J.; Dickson, S. E.

    2011-12-01

    With billions of gallons of groundwater being withdrawn every day in the US and Canada, it is imperative to understand the mechanisms which jeopardize this resource and the health of those who rely on it. Porous media aquifers have typically been considered to provide significant filtration of particulate matter (e.g. microorganisms), while the fractures in fractured rock aquifers and aquitards are considered to act as contaminant highways allowing a large fraction of pathogens to travel deep into an aquifer relatively quickly. Recent research results indicate that fractured rocks filter out more particulates than typically believed. The goal of the research presented here is to quantify the number of E. coli RS2GFP retained in a single, saturated, laboratory-scale fracture, and to relate the retention of E. coli RS2GFP to the aperture field characteristics and groundwater flow rate. To achieve this goal, physical experiments were conducted at the laboratory-scale to quantify the retention of E. coli RS2GFP through several single, saturated, dolomitic limestone fractures under a range of flow rates. These fractures were also cast with a transparent epoxy in order to visualize the transport mechanisms in the various different aperture fields. The E. coli RS2GFP is tagged with a green-fluorescent protein (GFP) that is used to obtain visualization data when excited by ultraviolet light. A series of experiments was conducted, each of which involved the release of a known number of E. coli RS2GFP at the upstream end of the fracture and measuring the effluent concentration profile. These experiments were conducted using both the natural rock and transparent cast of several different aperture fields, under a range of flow rates. The effects of different aperture field characteristics and flow rates on the retention of E. coli RS2GFP will be determined by conducting a statistical analysis of the retention data under different experimental conditions. The images captured

  19. Implementation of RS-485 Communication between PLC and PC of Distributed Control System Based on VB

    NASA Astrophysics Data System (ADS)

    Lian Zhang, Chuan; Da Huang, Zhi; Qing Zhou, Gui; Chong, Kil To

    2015-05-01

    This paper focuses on achieving RS-485 communication between programmable logical controller (PLC) and PC based on visual basic 6.0 (VB6.0) on an experimental automatic production line. Mitsubishi FX2N PLCs and a PC are chosen as slave stations and main station, respectively. Monitoring software is developed using VB6.0 for data input/output, flow control and online parameters setting. As a result, all functions are fulfilled with robust performance. It is concluded from results that one PC can monitor several PLCs using RS-485 communication.

  20. rsEGFP2 enables fast RESOLFT nanoscopy of living cells.

    PubMed

    Grotjohann, Tim; Testa, Ilaria; Reuss, Matthias; Brakemann, Tanja; Eggeling, Christian; Hell, Stefan W; Jakobs, Stefan

    2012-12-31

    The super-resolution microscopy called RESOLFT relying on fluorophore switching between longlived states, stands out by its coordinate-targeted sequential sample interrogation using low light levels. While RESOLFT has been shown to discern nanostructures in living cells, the reversibly photoswitchable green fluorescent protein (rsEGFP) employed in these experiments was switched rather slowly and recording lasted tens of minutes. We now report on the generation of rsEGFP2 providing faster switching and the use of this protein to demonstrate 25-250 times faster recordings.DOI:http://dx.doi.org/10.7554/eLife.00248.001.

  1. A light-curve distortion-wave analysis of eight RS Canum Venaticorum systems

    NASA Astrophysics Data System (ADS)

    Caton, D. B.

    1986-01-01

    A program of differential U,B,V photometry of 14 RS CVn systems carried out at Rosemary Hill Observatory in 1978 - 1981 is described, and an analysis of the light curves for the characteristic distortion wave for eight of the systems is presented. The V light curves of the systems are shown. Significant waves were observed in RS CVn, RZ Eri, and RW UMa. No significant waves were found in UX Com, GK Hya, AR Lac, LX Per, or TY Pyx. Unusual light curve distortions were observed in UX Com and AR Lac.

  2. Association of GABRA6 1519 T>C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy.

    PubMed

    Prasad, D K V; Shaheen, Uzma; Satyanarayana, U; Prabha, T Surya; Jyothy, A; Munshi, Anjana

    2014-10-01

    The idiopathic generalized epilepsy (IGE) is a neurological disorder which accounts for approximately 30% of all epilepsy cases. Patients identified with IGE syndromes have pharmacoresponsive epilepsies without abnormal neurological symptoms, structural brain lesions and are of unknown origin. A genetic etiology to IGEs has been proposed. Gamma amino butyric acid (GABA), a major inhibitory neurotransmitter acts by binding to transmembrane GABAA and GABAB receptors of both pre- and postsynaptic neurons. Synapsin II (SynII), a neuron specific phosphoprotein plays a major role in synaptogenesis and neurotransmitter release. The present study was carried out with an aim to evaluate the association of GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G gene polymorphisms with IGE. Molecular analysis revealed that the frequency of 'CC' genotype and 'C'allele of GABRA6 (rs3219151) T>C gene polymorphism was significantly higher in IGE patients compared to healthy controls [CC vs. TT, χ2=26; p<0.001; Odds ratio=3.6 (95% CI; 2.1-5.9); C vs T, χ2=24.7; p<0.001; Odds ratio=1.78 (95% CI; 1.4-2.2)]. The frequency of 'GG' genotype and 'G' allele of the intronic polymorphism A>G in Syn II gene was also found to be significantly associated with the disease when compared to controls [GG vs AA, χ2=64.52; p<0.001; Odds ratio=7.37 (95% CI; 4.4-12.3); G vs. A, χ2=65.78; p<0.001; Odds ratio=2.57 (95% CI; 2.0-3.2)]. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. The gene-gene interaction at two loci involving GABRA6 and Syn II revealed a significant association [χ2=36.6, p<0.001, Odds ratio=3.17 (95% CI; 2.2-4.6)] with IGE. Therefore, the present study clearly indicates that both GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh. The gene-gene interaction studies demonstrated significant interactive effects

  3. Genetic association of rs1344706 in ZNF804A with bipolar disorder and schizophrenia susceptibility in Chinese populations

    PubMed Central

    Rao, Shuquan; Yao, Yao; Ryan, Joanne; Jin, Chunhui; Xu, Yong; Huang, Xinhe; Guo, Jianxiu; Wen, Yueqiang; Mao, Canquan; Meyre, David; Zhang, Fuquan

    2017-01-01

    Rs1344706 in the the zinc finger protein 804A (ZNF804A) gene has been identified to be associated with schizophrenia and bipolar disorder (BD) in Europeans. However, whether rs1344706 is associated with schizophrenia in Chinese populations remains inconclusive; furthermore, the association between rs1344706 and BD in Chinese populations has been rarely explored. To explore the association between rs1344706 and schizophrenia/BD in Chinese populations, we genotyped rs1344706 among 1128 Chinese subjects (537 patients with BD and 591 controls) and found that rs1344706 showed marginal allelic association with BD (P = 0.028) with T-allele being more prevalent in cases than that in controls (OR = 1.19, 95% CI 1.03–1.37). Meta-analysis of rs1344706 by pooling all available data showed that rs1344706 was significantly associated with BD (P = 0.001). Besides, positive association of rs1344706 with schizophrenia was observed in Northern Chinese (P = 0.005). Furthermore, ZNF804A is highly expressed in human and mouse brains, especially in prenatal stage. PMID:28120939

  4. PCSK1 rs6232 Is Associated with Childhood and Adult Class III Obesity in the Mexican Population

    PubMed Central

    Villalobos-Comparán, Marisela; Villamil-Ramírez, Hugo; Villarreal-Molina, Teresa; Larrieta-Carrasco, Elena; León-Mimila, Paola; Romero-Hidalgo, Sandra; Jacobo-Albavera, Leonor; Liceaga-Fuentes, Adriana E.; Campos-Pérez, Francisco J.; López-Contreras, Blanca E.; Tusié-Luna, Teresa; del Río-Navarro, Blanca E.; Aguilar-Salinas, Carlos A.; Canizales-Quinteros, Samuel

    2012-01-01

    Background Common variants rs6232 and rs6235 in the PCSK1 gene have been associated with obesity in European populations. We aimed to evaluate the contribution of these variants to obesity and related traits in Mexican children and adults. Methodology/Principal Findings Rs6232 and rs6235 were genotyped in 2382 individuals, 1206 children and 1176 adults. Minor allele frequencies were 0.78% for rs6232 and 19.99% for rs6235. Rs6232 was significantly associated with childhood obesity and adult class III obesity (OR = 3.01 95%CI 1.64–5.53; P = 4×10−4 in the combined analysis). In addition, this SNP was significantly associated with lower fasting glucose levels (P = 0.01) and with increased insulin levels and HOMA-B (P = 0.05 and 0.01, respectively) only in non-obese children. In contrast, rs6235 showed no significant association with obesity or with glucose homeostasis parameters in any group. Conclusion/Significance Although rs6232 is rare in the Mexican population, it should be considered as an important risk factor for extreme forms of obesity. PMID:22737226

  5. Surviving as a Postmodern Social Worker: Two Ps and Three Rs of Direct Practice

    ERIC Educational Resources Information Center

    Ungar, Michael

    2004-01-01

    Social workers interested in postmodernism have been provided an abundance of theory, but little to guide them in direct practice in diverse child welfare roles. In this article, two Ps and three Rs of practice based on postmodernist principles are discussed: positioning, power, resource sharing, resistance, and reflection. Professionals working…

  6. Genome Sequence of Penicillium solitum RS1, Which Causes Postharvest Apple Decay

    PubMed Central

    Wu, Guangxi; Jurick, Wayne M.; Gaskins, Verneta L.; Yin, Yanbin; Bennett, Joan W.; Shelton, Daniel R.

    2016-01-01

    Penicillium species cause postharvest decay, commonly known as blue mold, in pome fruits, such as apples and pears. To devise novel strategies to prevent and reduce economic losses during storage, the genome sequence of Penicillium solitum RS1 is reported here for the first time. PMID:27174276

  7. Predictive value of XPG rs2296147T>C polymorphism on clinical outcomes of cancer patients

    PubMed Central

    Wang, Yuhan; Han, Yingying; Weng, Qiang; Yuan, Zhengrong

    2016-01-01

    The Xeroderma pigmentosum complementation group G (XPG) rs2296147T>C polymorphism is suspected to associate with the clinical outcomes of cancer patients. However, the results are inconsistent. This meta-analysis aimed to evaluate the reliable predictive value of XPG rs2296147T>C polymorphism on clinical outcomes of cancer patients. A total of 11 eligible studies were enrolled in this meta-analysis. Our results indicated that the cancer patients with TT and CT genotypes were significantly associated with better respond rates when compared with the CC genotype (TT versus (vs.) CC: odds ratio (OR) = 2.05, 95% confidence intervals (CIs), 1.32-3.20, P = 0.002; TT+CT vs. CC: OR= 1.57, 95% CI, 1.14-2.17, P = 0.005). The TT genotype and/or T allele might be associated with higher survival time for cancer patients than the CC genotype and/or C allele. The cumulative meta-analyses showed an apparent beneficial objective response of TT genotype on cancer patients. In conclusion, this meta-analysis suggests that the XPG rs2296147T>C polymorphism is associated with the clinical outcomes of cancer patients. The XPG rs2296147T>C polymorphism might be a predictive factor of prognosis in cancers patients and contribute to individual treatment in the future. PMID:27588464

  8. rs965513 polymorphism as a common risk marker is associated with papillary thyroid cancer

    PubMed Central

    Han, Jun; Chen, Meijun; Qiao, Hong; Zhang, Shaojun

    2016-01-01

    Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. With the rapid development of genome-wide association studies (GWAS), many genome variants associated with susceptibility to PTC have been identified, including the single nucleotide polymorphism rs965513 (9q22.33) near FOXE1. To evaluate the association between rs965513 and PTC in different ethnicities and countries, we conducted a meta-analysis using relatively large-scale samples from 23 studies (N = 163,136; 20,736 cases and 142,400 controls) by searching the PubMed and Google Scholar databases. Significant heterogeneity caused by different populations among the selected studies was observed. The A allele of rs965513 polymorphism was shown to be highly associated with risk of thyroid cancer, with odds ratios of 1.58 (95% CI 1.32–1.90) in all populations, 1.65 (95% CI 1.31–2.07)) in Caucasian populations and 1.49 in Asian populations. Compared to the dominant and recessive models, we observed the highest odds ratio (OR = 2.80, 95% CI 2.12–3.69) in the homozygous model. These results revealed that the rs965513 polymorphism is a risk factor for thyroid cancer PMID:27191655

  9. Does company compliance with RS-17 influence the characterization of a casual nexus in expert testimony?

    PubMed Central

    Ribeiro, Manuela; Guimarães, Bruno; Sampaio, Breno

    2015-01-01

    Objective: To examine whether company compliance with RS-17 influences the characterization of the casual nexus in physical therapists' expert reports of cumulative trauma disorders in the labor court of Pernambuco, Brazil. Method: The sample was composed of seven physical therapists who provided expert testimony regarding cumulative trauma disorder cases in the labor court of Pernambuco, Brazil. Data collection was performed across two stages. In the first stage, the experts answered a sociodemographic survey and requested the identification numbers of recent cases where expert testimony was provided to characterize the causal nexus. In the second stage, the researchers went to the labor court to collect expert testimony data. These experts indicated that of 75 total cases, 31% (N=23) of the companies fulfilled RS-17, whereas 69% (N=52) did not comply with the law. Results: Among the organizations that complied with legislation, 30% of the analyzed expert testimonies showed a positive causal nexus. However, of the companies that did not comply with RS-17, 71% of the expert testimonies revealed a causal nexus. These results indicate that the breach of the law increases the probability that a causal nexus will be determined by 54.8%. Conclusion: The results showed that failure to comply with RS-17 significantly increases the probability that a causal nexus will be determined in physical therapists' expert testimony of cumulative trauma disorders. PMID:25714436

  10. Research on agricultural ecology and environment analysis and modeling based on RS and GIS

    NASA Astrophysics Data System (ADS)

    Zhang, Wensheng; Chen, Hongfu; Wang, Mingsheng

    2009-07-01

    Analysis of agricultural ecology and environment is based on the data of agricultural resources, which are obtained by RS monitoring. The over-exploitation of farmlands will cause structural changes of the soil composition, and damage the planting environment and the agro-ecosystem. Through the research on the dynamic monitoring methods of multitemporal RS images and GIS technology, the crop growth status, crop acreage and other relevant information in agricultural production are extracted based on the monitor and analysis of the conditions of the fields and crop growth. The agro-ecological GIS platform is developed with the establishment of the agricultural resources management database, which manages spatial data, RS data and attribute data of agricultural resources. Using the RS, GIS analysis results, the reasons of agro-ecological destruction are analyzed and the evaluation methods are established. This paper puts forward the concept of utilization capacity of farmland, which describes farmland space for development and utilization that is influenced by the conditions of the land, water resources, climate, pesticides and chemical fertilizers and many other agricultural production factors. Assessment model of agricultural land use capacity is constructed with the help of Fuzzy. Assessing the utilization capacity of farmland can be helpful to agricultural production and ecological protection of farmland. This paper describes the application of the capacity evaluation model with simulated data in two aspects, namely, in evaluating the status of farmland development and utilization and in optimal planting.

  11. Variability of multilevel switching in scaled hybrid RS/CMOS nanoelectronic circuits: theory

    NASA Astrophysics Data System (ADS)

    Heittmann, Arne; Noll, Tobias G.

    2013-07-01

    A theory is presented which describes the variability of multilevel switching in scaled hybrid resistive-switching/CMOS nanoelectronic circuits. Variability is quantified in terms of conductance variation using the first two moments derived from the probability density function (PDF) of the RS conductance. For RS, which are based on the electrochemical metallization effect (ECM), this variability is - to some extent - caused by discrete events such as electrochemical reactions, which occur on atomic scale and are at random. The theory shows that the conductance variation depends on the joint interaction between the programming circuit and the resistive switch (RS), and explicitly quantifies the impact of RS device parameters and parameters of the programming circuit on the conductance variance. Using a current mirror as an exemplary programming circuit an upper limit of 2-4 bits (dependent on the filament surface area) is estimated as the storage capacity exploiting the multilevel capabilities of an ECM cell. The theoretical results were verified by Monte Carlo circuit simulations on a standard circuit simulation environment using an ECM device model which models the filament growth by a Poisson process. Contribution to the Topical Issue “International Semiconductor Conference Dresden-Grenoble - ISCDG 2012”, Edited by Gérard Ghibaudo, Francis Balestra and Simon Deleonibus.

  12. DHPG Activation of Group 1 mGluRs in BLA Enhances Fear Conditioning

    ERIC Educational Resources Information Center

    Rudy, Jerry W.; Matus-Amat, Patricia

    2009-01-01

    Group 1 metabotropic glutamate receptors are known to play an important role in both synaptic plasticity and memory. We show that activating these receptors prior to fear conditioning by infusing the group 1 mGluR agonist, (R.S.)-3,5-dihydroxyphenylglycine (DHPG), into the basolateral region of the amygdala (BLA) of adult Sprague-Dawley rats…

  13. The Eclipsing Binary Pulsar PSR B1718-19: a Clean RS CVN System?

    NASA Astrophysics Data System (ADS)

    Kaspi, Victoria

    1996-07-01

    We request WFPC2 observations of the eclipsing binary pulsarPSR B1718-19. This slowly-rotating pulsar lies in thedirection of the globular cluster NGC 6342, and defiesstandard binary pulsar formation models in which the pulsar is``spun-up'' via mass accretion. Furthermore, the observedeclipses cannot be explained with standard models. Thispulsar's unusual properties can be explained elegantly if itscompanion is an active, non-degenerate star like thoseobserved in RS CVn systems, but in this case, subject only togravity. Following Keck observations of the field, we proposeHST observations of PSR B1718-19 to detect and studyvariability in the companion, in order to answer the followingquestions. 1- Are the eclipses seen in PSR B1718-19 indeed aresult of RS CVn-type activity in the companion, and what isthe evolutionary history of the binary? 2- Is the activity inRS CVn systems purely a tidal effect? 3- How are mass loss,rotation, and surface activity related in RS CVn stars? 4- IsPSR B1718-19 in NGC 6342?

  14. X-ray crystal structure of divalent metal-activated ß-xyloisdase, RS223BX

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report the first X-ray structure of a glycoside hydrolase family 43 ß-xylosidase, RS223BX, which is strongly activated by the addition of divalent metal cations. The 2.69 Å structure reveals that the Ca2+ cation is located at the back of the active site pocket. The Ca2+ coordinates to H274 to sta...

  15. Mapping the mouse brain with rs-fMRI: An optimized pipeline for functional network identification.

    PubMed

    Zerbi, Valerio; Grandjean, Joanes; Rudin, Markus; Wenderoth, Nicole

    2015-12-01

    The use of resting state fMRI (rs-fMRI) in translational research is a powerful tool to assess brain connectivity and investigate neuropathology in mouse models. However, despite encouraging initial results, the characterization of consistent and robust resting state networks in mice remains a methodological challenge. One key reason is that the quality of the measured MR signal is degraded by the presence of structural noise from non-neural sources. Notably, in the current pipeline of the Human Connectome Project, a novel approach has been introduced to clean rs-fMRI data, which involves automatic artifact component classification and data cleaning (FIX). FIX does not require any external recordings of physiology or the segmentation of CSF and white matter. In this study, we evaluated the performance of FIX for analyzing mouse rs-fMRI data. Our results showed that FIX can be easily applied to mouse datasets and detects true signals with 100% accuracy and true noise components with very high accuracy (>98%), thus reducing both within- and between-subject variability of rs-fMRI connectivity measurements. Using this improved pre-processing pipeline, maps of 23 resting state circuits in mice were identified including two networks that displayed default mode network-like topography. Hierarchical clustering grouped these neural networks into meaningful larger functional circuits. These mouse resting state networks, which are publicly available, might serve as a reference for future work using mouse models of neurological disorders.

  16. rs621554 single nucleotide polymorphism of DLC1 is associated with breast cancer susceptibility and prognosis.

    PubMed

    Ding, Xia; Gao, Sumei; Yang, Qifeng

    2016-05-01

    Deleted in liver cancer 1 (DLC1) on chromosome 8p22, is an important tumor suppressor gene originally identified to be deleted in hepatocellular carcinoma. It can regulate the structure of the actin cytoskeleton and inhibit cell proliferation, motility and angiogenesis, which predominantly depends on its homology to rat RhoGAP. There are many genetic variants in DLC1, which may influence its antitumor efficacy. The rs621554 (IVS19+108C>T) polymorphism is a synonymous single nucleotide polymorphism (SNP) previously found to be associated with hepatocellular carcinoma. In the present study, 453 patients with breast cancer and 330 healthy females were analyzed using a cycling probe method. It was determined that the rs621554 polymorphism of DLC1 was associated with breast cancer susceptibility, with the CC and CT genotypes resulting in a higher risk of developing breast cancer. In regard to clinicopathological variables, it was demonstrated that the CT and CC genotype were associated with tumor size, lymph node metastasis and progesterone receptor status. Patients with the CT and CC genotype had shorter disease-free survival and overall survival rates compared with those with the TT genotype. Additionally, it was demonstrated that the rs621554 polymorphism was correlated with DLC1 expression at the mRNA level. These results suggested that the rs621554 polymorphism is associated with breast cancer susceptibility and prognosis, and may serve as a biomarker for breast cancer development and progression.

  17. RS-Forest: A Rapid Density Estimator for Streaming Anomaly Detection

    PubMed Central

    Wu, Ke; Zhang, Kun; Fan, Wei; Edwards, Andrea; Yu, Philip S.

    2015-01-01

    Anomaly detection in streaming data is of high interest in numerous application domains. In this paper, we propose a novel one-class semi-supervised algorithm to detect anomalies in streaming data. Underlying the algorithm is a fast and accurate density estimator implemented by multiple fully randomized space trees (RS-Trees), named RS-Forest. The piecewise constant density estimate of each RS-tree is defined on the tree node into which an instance falls. Each incoming instance in a data stream is scored by the density estimates averaged over all trees in the forest. Two strategies, statistical attribute range estimation of high probability guarantee and dual node profiles for rapid model update, are seamlessly integrated into RS-Forest to systematically address the ever-evolving nature of data streams. We derive the theoretical upper bound for the proposed algorithm and analyze its asymptotic properties via bias-variance decomposition. Empirical comparisons to the state-of-the-art methods on multiple benchmark datasets demonstrate that the proposed method features high detection rate, fast response, and insensitivity to most of the parameter settings. Algorithm implementations and datasets are available upon request. PMID:25685112

  18. A Simple Method for Specifying the R/S Configuration about a Chiral Center.

    ERIC Educational Resources Information Center

    Idoux, John P.

    1982-01-01

    Describes a method for specifying R/S (clockwise/counterclockwise) configuration about a chiral center which does not require the use of a three-dimensional physical model, the mental visualization of the molecule, or the memorization of a recently reported arbitrary number system. (Author/JN)

  19. A fast technique for computing syndromes of BCH and RS codes. [deep space network

    NASA Technical Reports Server (NTRS)

    Reed, I. S.; Truong, T. K.; Miller, R. L.

    1979-01-01

    A combination of the Chinese Remainder Theorem and Winograd's algorithm is used to compute transforms of odd length over GF(2 to the m power). Such transforms are used to compute the syndromes needed for decoding CBH and RS codes. The present scheme requires substantially fewer multiplications and additions than the conventional method of computing the syndromes directly.

  20. rs657075 (CSF2) Is Associated with the Disease Phenotype (BAS-G) of Ankylosing Spondylitis

    PubMed Central

    Chen, Wei-Chiao; Wei, James Cheng-Chung; Lu, Hsing-Fang; Wong, Henry Sung-Ching; Woon, Peng Yeong; Hsu, Yu-Wen; Huang, Jin-Ding; Chang, Wei-Chiao

    2017-01-01

    Ankylosing spondylitis (AS) is a systemic autoimmune disease mainly affecting the lumbar spine and sacroiliac joints, and exhibits peripheral inflammatory arthropathy. More than 25 loci have been identified as associated with AS. Because both AS and rheumatoid arthritis (RA) are autoimmune diseases that may share some common genetic factors, we therefore examined if the newly identified RA genetic polymorphisms were associated with AS in a Taiwanese population. In this study, we enrolled 475 AS patients and 11,301 healthy subjects from a Taiwanese biobank as controls. Although none of single-nucleotide polymorphisms (SNPs) were associated with the susceptibility to AS, the AS disease index Bath AS Global (BAS-G) clinical phenotype was observed as significantly correlated to the AA genotype of rs657075 (CSF2). The significance remains after gender/age/disease duration adjustment and after group categorization by human leukocyte antigen-B 27 (HLA-B27) genotype. We further investigated the possible functions of rs657075 through bioinformatics approaches. Results revealed that polymorphism of rs657075 is able to influence the expression of acyl-CoA synthetase long-chain family member 6 (ACSL6). In conclusion, our study indicated that rs657075 (CSF2) is strongly associated with the AS disease index Bath AS Global (BAS-G) clinical phenotype. PMID:28054948

  1. The CASP8 rs3834129 polymorphism and breast cancer risk in BRCA1 mutation carriers.

    PubMed

    Catucci, Irene; Verderio, Paolo; Pizzamiglio, Sara; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Roversi, Gaia; Ripamonti, Carla B; Pasini, Barbara; Barile, Monica; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Varesco, Liliana; Martayan, Aline; Riboni, Mirko; Volorio, Sara; Radice, Paolo; Peterlongo, Paolo

    2011-02-01

    The rs3834129 polymorphism, in the promoter of CASP8 gene, has been recently reported as associated with breast cancer risk in the general population, with the minor allele del having a protective effect. Some of the genetic variants found associated with breast cancer risk were reported as risk modifiers in individuals with mutations in BRCA1 and BRCA2 genes. Here, we tested the effect of the rs3834129 del allele on breast cancer risk in BRCA mutation carriers. The rs3834129 was genotyped in a total of 1,207 Italian female BRCA mutation carriers. Of these, 740 carried a BRCA1 mutation and 467 a BRCA2 mutation. Overall, 699 were affected with breast cancer and 508 were unaffected. When considering class 1 (loss-of-function) BRCA mutations, hazard ratios estimated by weighted multivariable Cox regression model, for individuals with at least one copy of the del allele, were 1.46 (95% confidence interval (CI): 1.08-1.99) for BRCA1 and BRCA2 mutation carriers combined, 1.74 (95% CI: 1.24-2.46) for BRCA1 mutation carriers, and 1.09 (95% CI: 0.66-1.80) for BRCA2 mutation carriers. These results suggest that the minor allele del of rs3834129 is associated under a dominant model with increased breast cancer risk in carriers of BRCA1 mutations but not in carriers of BRCA2 mutations.

  2. Face and emotion expression processing and the serotonin transporter polymorphism 5-HTTLPR/rs22531.

    PubMed

    Hildebrandt, A; Kiy, A; Reuter, M; Sommer, W; Wilhelm, O

    2016-06-01

    Face cognition, including face identity and facial expression processing, is a crucial component of socio-emotional abilities, characterizing humans as highest developed social beings. However, for these trait domains molecular genetic studies investigating gene-behavior associations based on well-founded phenotype definitions are still rare. We examined the relationship between 5-HTTLPR/rs25531 polymorphisms - related to serotonin-reuptake - and the ability to perceive and recognize faces and emotional expressions in human faces. For this aim we conducted structural equation modeling on data from 230 young adults, obtained by using a comprehensive, multivariate task battery with maximal effort tasks. By additionally modeling fluid intelligence and immediate and delayed memory factors, we aimed to address the discriminant relationships of the 5-HTTLPR/rs25531 polymorphisms with socio-emotional abilities. We found a robust association between the 5-HTTLPR/rs25531 polymorphism and facial emotion perception. Carriers of two long (L) alleles outperformed carriers of one or two S alleles. Weaker associations were present for face identity perception and memory for emotional facial expressions. There was no association between the 5-HTTLPR/rs25531 polymorphism and non-social abilities, demonstrating discriminant validity of the relationships. We discuss the implications and possible neural mechanisms underlying these novel findings.

  3. Reactor Statics Module, RS-9: Multigroup Diffusion Program Using an Exponential Acceleration Technique.

    ERIC Educational Resources Information Center

    Macek, Victor C.

    The nine Reactor Statics Modules are designed to introduce students to the use of numerical methods and digital computers for calculation of neutron flux distributions in space and energy which are needed to calculate criticality, power distribution, and fuel burnup for both slow neutron and fast neutron fission reactors. The last module, RS-9,…

  4. Design of vancomycin RS-100 nanoparticles in order to increase the intestinal permeability

    PubMed Central

    Loveymi, Badir Delf; Jelvehgari, Mitra; Zakeri-Milani, Parvin; Valizadeh, Hadi

    2012-01-01

    Purpose: The purpose of this work was to preparation of vancomycin (VCM) biodegradable nanoparticles to improve the intestinal permeability, using water-in-oil-in-water (W/O/W) multiple emulsion method. Methods: The vancomycin-loaded nanoparticles were created using double-emulsion solvent evaporation method. Using Eudragit RS100 as a coating material. The prepared nanoparticles were identifyed for their micromeritic and crystallographic properties, drug loading, particle size, drug release, Zeta potential, effective permeability (Peff) and oral fractional absorption. Intestinal permeability of VCM nanoparticles was figured out, in different concentrations using SPIP technique in rats. Results: Particle sizes were between 362 and 499 nm for different compositions of VCM-RS-100 nanoparticles. Entrapment efficiency expansed between 63%-94.76%. The highest entrapment efficiency 94.76% was obtained when the ratio of drug to polymer was 1:3. The in vitro release studies were accomplished in pH 7.4. The results showed that physicochemical properties were impressed by drug to polymer ratio. The FT-IR, XRPD and DSC results ruled out any chemical interaction betweenthe drug and RS-100. Effective intestinal permeability values of VCM nanoparticles in concentrations of 200, 300 and 400 μg/ml were higher than that of solutions at the same concentrations. Oral fractional absorption was achieved between 0.419-0.767. Conclusion: Our findings suggest that RS-100 nanoparticles could provide a delivery system for VCM, with enhanced intestinal permeability. PMID:24312770

  5. Design and realization of RS application system for earthquake emergency based on digital earth

    NASA Astrophysics Data System (ADS)

    Yuan, Xiaoxiang; Wang, Xiaoqing; Guo, Jianxing; Dou, Aixia; Ding, Xiang

    2016-11-01

    The current RS-based earthquake emergency system is mainly based on stand-alone software which cannot meet the requirements of massive remote sensing data and parallel seismic damage information extraction after a devastating earthquake. Taking Shaanxi Province as an example, this paper explored firstly the network-based working mode of seismic damage information extraction and data management strategy for multi-user cooperative operation based on analysing work flow of the RS application to earthquake emergency. Then, using WorldWind java SDK, the RS application system for earthquake emergency based on digital earth platform was brought out in CS architecture. Finally, spatial data tables of classification and grade of seismic damage were designed and the system was developed. This system realized functions including 3D display, management of seismic RS image and GIS data obtained before and after earthquake for different user levels and cooperative extraction and publish of such seismic information as building damage, traffic damage and seismo-geological disasters caused by earthquake in real time. Some application to earthquake cases such as 2014 M s6.5 Ludian earthquake show that this system can improve the efficiency of seismic damage information interpretation and data sharing, and provide import disaster information for decision making of earthquake emergency rescue and disaster relief.

  6. A functional SNP rs1892901 in FOSL1 is associated with gastric cancer in Chinese population

    PubMed Central

    Liu, Wenjie; Tian, Tian; Liu, Li; Du, Jiangbo; Gu, Yayun; Qin, Na; Yan, Caiwang; Wang, Zhaoming; Dai, Juncheng; Fan, Zhining

    2017-01-01

    FOSL1 (FOS like antigen 1) is one kind of proto-oncogene, and may play a vital role in carcinogenesis of multiple cancers. However, studies about the relationship between SNPs in FOSL1 and gastric cancer are still lacking. Thus, we investigated the association of seven SNPs in FOSL1 with gastric cancer using case-control design in a two-stage strategy (Screening stage: 1,140 gastric cancer cases and 1,547 controls; Replication stage: 1,006 cases and 2,273 controls). We found that rs1892901 was significantly associated with increased risk of gastric cancer in additive model (adjusted OR = 1.25, 95%CI: 1.06–1.47, P = 0.008) in first stage. Following replication results revealed that the relationship between rs1892901 and gastric cancer risk was consistent with our primary results. In silico analysis showed that rs1892901 might alter multiple regulatory motifs, disturb protein binding, and affect the expression of FOSL1 and other important gastric cancer-related genes such as EGR1, CHD, EP300, FOS, JUN and FOSL2. Our findings indicated that functional SNP rs1892901 in FOSL1 might affect the expression of FOSL1, and ultimately increase the risk of gastric cancer. Further functional studies and large-scale population studies are warranted to confirm our findings. PMID:28169308

  7. Growth phase-dependent activation of the DccRS regulon of Campylobacter jejuni

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two-component systems are widespread prokaryotic signal transduction devices which allow the regulation of cellular functions in response to changing environmental conditions. The two-component system DccRS (Cj1223-Cj1222) of Campylobacter jejuni is important for the colonization of chickens. Here w...

  8. Main Engine Prototype Development for 2nd Generation RLV RS-83

    NASA Technical Reports Server (NTRS)

    Vilja, John; Fisher, Mark; Lyles, Garry M. (Technical Monitor)

    2002-01-01

    This presentation reports on the NASA project to develop a prototype for RS-83 engine designed for use on reusable launch vehicles (RLV). Topics covered include: program objectives, overview schedule, organizational chart, integrated systems engineering processes, requirement analysis, catastrophic engine loss, maintainability analysis tools, and prototype design analysis.

  9. The COMT (rs165599) gene polymorphism contributes to chemotherapy-induced cognitive impairment in breast cancer patients

    PubMed Central

    Cheng, Huaidong; Li, Wen; Gan, Chen; Zhang, Bo; Jia, Qianqian; Wang, Kai

    2016-01-01

    The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before and after chemotherapy. Six single-nucleotide polymorphisms (SNPs), including COMT (rs165599, rs4680, rs737865), APOE (rs429358, rs7412), and BDNF (rs6265), were evaluated. The scores of breast cancer patients after chemotherapy were poorer in comparison to those before chemotherapy (t = -5.317, z = -3.372, respectively, P < 0.01), and the scores of TNBC patients were poorer than those of NTNBC patients were after chemotherapy (t = -5.997, z = -5.284, respectively, P < 0.01). Patients with the COMT (rs165599) genotype had a significantly lower chance of developing cognitive decline than the patients with the G/G genotype, and this was linear with the retrospective memory (RM) questionnaires (β = -1.441, CI (95%) = -2.781~-0.101). However, there was no significant difference between the memory scores of APOE (rs429358, rs7412) and BDNF (rs6265) carriers before or after chemotherapy. This study suggests that CICI in TNBC patients was more prominent than that in NTNBC patients after chemotherapy, and the COMT (rs165599) polymorphism was linear to the retrospective memory (RM) questionnaires, and may be a potential genetic marker for increased vulnerability to CICI in TNBC patients. PMID:27904710

  10. RS-25 for the NASA Cargo Launch Vehicle: The Evolution of SSME for Space Exploration

    NASA Technical Reports Server (NTRS)

    Kynard, Michael H.; McArthur, J. Craig; Ise, Dayna S.

    2006-01-01

    A key element of the National Vision for Space Exploration is the development of a heavy-lift Cargo Launch Vehicle (CaLV). Missions to the Moon, Mars, and beyond are only possible with the logistical capacity of putting large payloads in low-earth orbit. However, beyond simple logistics, there exists the need for this capability to be as cost effective as possible to ensure mission sustainability. An element of the CaLV project is, therefore, the development of the RS-25, which represents the evolution of the proven Space Shuttle Main Engine (SSME) into a high-performance, cost-effective expendable rocket engine. The development of the RS-25 will be built upon the foundation of over one million seconds of accumulated hot-fire time on the SSME. Yet in order to transform the reusable SSME into the more cost-effective, expendable RS-25 changes will have to be made. Thus the project will inevitably strive to maintain a balance between demonstrated heritage products and processes and the utilization of newer technology developments. Towards that end, the Core Stage Engine Office has been established at the NASA Marshall Space Flight Center to initiate the design and development of the RS-25 engine. This paper is being written very early in the formulation phase of the RS-25 project. Therefore the focus of this paper will be to present the scope, challenges, and opportunities for the RS-25 project. Early schedules and development decisions and plans will be explained. For not only must the RS-25 project achieve cost effectiveness through the development of new, evolved components such as a channel-wall nozzle, a new HIP-bonded main combustion chamber, and several others, it must simultaneously develop the means whereby this engine can be manufactured on a scale never envisioned for the SSME. Thus, while the overall project will span the next eight to ten years, there is little doubt that even this schedule is aggressive with a great deal of work to accomplish.

  11. The rs5934505 single nucleotide polymorphism (SNP) is associated with low testosterone and late-onset hypogonadism, but the rs10822184 SNP is associated with overweight and obesity in a Chinese Han population: a case-control study.

    PubMed

    Chen, Y-P; Nie, L-L; Li, H-G; Liu, T-H; Fang, F; Zhao, K; Yang, R-F; Ma, X-L; Kong, X-B; Zhang, H-P; Guan, H-T; Xia, W; Hong, W-X; Duan, S; Zeng, X-C; Shang, X-J; Zhou, Y-Z; Gu, Y-Q; Wu, W-X; Xiong, C-L

    2016-01-01

    Low testosterone is associated with late-onset hypogonadism (LOH) and obesity. Recently, studies have shown that four single nucleotide polymorphisms (SNPs), rs12150660, rs727428, rs5934505, and rs10822184, are associated with testosterone levels in populations of European descent. Therefore, we investigated whether the SNP loci are related to low testosterone, LOH, or obesity in a Chinese Han population. Ruling out co-morbidities, DNA was prepared from 409 men (aged 40-65 years) with low serum testosterone (defined as total testosterone <11.6 nmol/L) and 1 : 1 normal controls (matched age, body mass index (BMI), and the same living area) who were selected from 6898 males. According to the same standards, 310 men with LOH and 1 : 1 normal controls were selected from 6898 males. Excluding the cases with an unreliable sequencing result, genetic analyses were performed. The minor allele frequencies of the SNP loci rs12150660, rs727428, rs5934505, and rs10822184 were 0.1%, 44.6%, 18.7%, and 38.9%, respectively. rs5934505 was associated with the serum total testosterone and calculated free testosterone (CFT) levels (p = 0.045 and p = 0.021). rs5934505 (C>T) was associated with an increased risk of low total testosterone, low CFT, and LOH and adjusted for other factors, with an odds ratio (OR) of 2.01 (1.34-3.01), 2.14 (1.42-3.20), and 1.64 (1.04-2.58). rs10822184 was significantly correlated with weight and BMI (p = 0.035 and p = 0.027). rs10822184 (T>C) was associated with an increased risk of overweight and obesity. We adjusted for other factors, with odds ratios (ORs) of 1.94 (1.36-2.78) and 1.56 (1.00-2.43). In summary, our study provided convincing evidence that rs5934505 (C>T) was associated with the risk of low testosterone and LOH in Chinese populations. We were the first to find that rs10822184 (T>C) was significantly correlated with the risk of overweight and obesity in Chinese populations. However, further large and functional studies are warranted to confirm

  12. Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222

    PubMed Central

    Enciso-Mora, V; Hosking, F J; Di Stefano, A L; Zelenika, D; Shete, S; Broderick, P; Idbaih, A; Delattre, J-Y; Hoang-Xuan, K; Marie, Y; Labussière, M; Alentorn, A; Ciccarino, P; Rossetto, M; Armstrong, G; Liu, Y; Gousias, K; Schramm, J; Lau, C; Hepworth, S J; Schoemaker, M; Strauch, K; Müller-Nurasyid, M; Schreiber, S; Franke, A; Moebus, S; Eisele, L; Swerdlow, A; Simon, M; Bondy, M; Lathrop, M; Sanson, M; Houlston, R S

    2013-01-01

    Background: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. Methods: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. Results: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10−24, minor allele frequency ∼0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. Conclusion: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3′-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma. PMID:23571737

  13. High affinity group III mGluRs regulate mossy fiber input to CA3 interneurons.

    PubMed

    Cosgrove, Kathleen E; Meriney, Stephen D; Barrionuevo, Germán

    2011-12-01

    Stratum lacunosum-moleculare interneurons (L-Mi) in hippocampal area CA3 target the apical dendrite of pyramidal cells providing feedforward inhibition. Here we report that selective activation of group III metabotropic glutamate receptors (mGluRs) 4/8 with L(+)-2-amino-4-phosphnobytyric acid (L-AP4; 10 μM) decreased the probability of glutamate release from the mossy fiber (MF) terminals synapsing onto L-Mi. Consistent with this interpretation, application of L-AP4 in the presence of 3 mM strontium decreased the frequency of asynchronous MF EPSCs in L-Mi. Furthermore, the dose response curve showed that L-AP4 at 400 μM produced no further decrease in MF EPSC amplitude compared with 20 μM L-AP4, indicating the lack of mGluRs 7 at these MF terminals. We also found that one mechanism of mGluRs 4/8-mediated inhibition of release is linked to N-type voltage gated calcium channels at MF terminals. Application of the group III mGluR antagonist MSOP (100 μM) demonstrated that mGluRs 4/8 are neither tonically active nor activated by low and moderate frequencies of activity. However, trains of stimuli to the MF at 20 and 40 Hz delivered during the application of MSOP revealed a relief of inhibition of transmitter release and an increase in the overall probability of action potential firing in the postsynaptic L-Mi. Interestingly, the time to first action potential was significantly shorter in the presence of MSOP, indicating that mGluR 4/8 activation delays L-Mi firing in response to MF activity. Taken together, our data demonstrate that the timing and probability of action potentials in L-Mi evoked by MF synaptic input is regulated by the activation of presynaptic high affinity group III mGluRs.

  14. Expanding the three Rs to meet new challenges in humane animal experimentation.

    PubMed

    Schuppli, Catherine A; Fraser, David; McDonald, Michael

    2004-11-01

    The Three Rs are the main principles used by Animal Ethics Committees in the governance of animal experimentation, but they appear not to cover some ethical issues that arise today. These include: a) claims that certain species should be exempted on principle from harmful research; b) increased emphasis on enhancing quality of life of research animals; c) research involving genetically modified (GM) animals; and d) animals bred as models of disease. In some cases, the Three Rs can be extended to cover these developments. The burgeoning use of GM animals in science calls for new forms of reduction through improved genetic modification technology, plus continued attention to alternative approaches and cost-benefit analyses that include the large numbers of animals involved indirectly. The adoption of more expanded definitions of refinement that go beyond minimising distress will capture concerns for enhancing the quality of life of animals through improved husbandry and handling. Targeting refinement to the unpredictable effects of gene modification may be difficult; in these cases, careful attention to monitoring and endpoints are the obvious options. Refinement can also include sharing data about the welfare impacts of gene modifications, and modelling earlier stages of disease, in order to reduce the potential suffering caused to disease models. Other issues may require a move beyond the Three Rs. Certain levels of harm, or numbers and use of certain species, may be unacceptable, regardless of potential benefits. This can be addressed by supplementing the utilitarian basis of the Three Rs with principles based on deontological and relational ethics. The Three Rs remain very useful, but they require thoughtful interpretation and expansion in order for Animal Ethics Committees to address the full range of issues in animal-based research.

  15. Minor variant of rs 16827043 in the iron regulator hemojuvelin gene (HJV) contributes to hypertension

    PubMed Central

    Nikkari, Seppo T.; Visto, Anni-Laura; Määttä, Kirsi M.; Kunnas, Tarja A.

    2017-01-01

    Abstract It is known that iron overload may lead to an increased risk for many diseases. According to GWAS studies, iron regulatory protein HFE gene variant H63D (rs1799945) was associated with hypertension, an observation which we were able to confirm also in our TAMRISK cohort. Thus, it is possible that abnormalities in iron homeostasis may predispose to hypertension. This prompted us to study whether there is an association between hypertension and another iron overload-associated gene, hemojuvelin (HJV), which has 2 common polymorphic sites (rs 16827043, rs7536827). The study included 336 hypertensive cases and 480 controls. All participants were 50- year-old Finnish men and women, and the data was collected from the Tampere adult population cardiovascular risk study (TAMRISK). Genotypes were determined using Competitive Allelic Specific PCR (KASP). We found that the minor variant of the HJV polymorphic site rs16827043 (G-allele) is a statistically significant factor associated with hypertension among 50 year-old individuals compared with the AA genotype carriers (OR = 1.66, 95% CI: 1.06 – 2.60, P = 0.03). The risk was even higher when overweight subjects (BMI>30) were excluded from the analyses. For the other polymorphic variant rs7536827, association with hypertension was found only among normal or slightly overweight A-allele carriers. In conclusion, HJV genetic variants were associated with essential hypertension in Finnish subjects from the TAMRISK cohort. Previous studies together with the present one indicate that individuals with possible dysregulation of iron metabolism may have higher risk for hypertension than those with normal iron homeostasis. PMID:28151915

  16. Synchronization, TIGoRS, and Information Flow in Complex Systems: Dispositional Cellular Automata.

    PubMed

    Sulis, William H

    2016-04-01

    Synchronization has a long history in physics where it refers to the phase matching of two identical oscillators. This notion has been extensively studied in physics as well as in biology, where it has been applied to such widely varying phenomena as the flashing of fireflies and firing of neurons in the brain. Human behavior, however, may be recurrent but it is not oscillatory even though many physiological systems do exhibit oscillatory tendencies. Moreover, much of human behaviour is collaborative and cooperative, where the individual behaviours may be distinct yet contemporaneous (if not simultaneous) and taken collectively express some functionality. In the context of behaviour, the important aspect is the repeated co-occurrence in time of behaviours that facilitate the propagation of information or of functionality, regardless of whether or not these behaviours are similar or identical. An example of this weaker notion of synchronization is transient induced global response synchronization (TIGoRS). Previous work has shown that TIGoRS is a ubiquitous phenomenon among complex systems, enabling them to stably parse environmental transients into salient units to which they stably respond. This leads to the notion of Sulis machines, which emergently generate a primitive linguistic structure through their dynamics. This article reviews the notion of TIGoRS and its expression in several complex systems models including tempered neural networks, driven cellular automata and cocktail party automata. The emergent linguistics of Sulis machines are discussed. A new class of complex systems model, the dispositional cellular automaton is introduced. A new metric for TIGoRS, the excess synchronization, is introduced and applied to the study of TIGoRS in dispositional cellular automata. It is shown that these automata exhibit a nonlinear synchronization response to certain perturbing transients.

  17. Genetic Association Between CDKN1B rs2066827 Polymorphism and Susceptibility to Cancer

    PubMed Central

    Lu, Yongchao; Gao, Kejian; Zhang, Miao; Zhou, Aiyan; Zhou, Xiaoming; Guan, Zhongan; Shi, Xuewen; Ge, Shujian

    2015-01-01

    Abstract Much attention has been directed to the association between cancer risk and rs2066827 polymorphism of the CDKN1B gene. However, the results are indefinitive and inconclusive. This study was devised to evaluate the hypothesis that rs2066827 polymorphism is associated with the risk of cancer. Computer-based databases (EMBASE, PubMed, and CNKI) were used to seek all case–control studies evaluating rs2066827 polymorphism and susceptibility to cancer. The genetic risk was assessed by calculating pooled odds ratio (OR) with its corresponding 95% confidence interval (CI). Fixed-effects pooled ORs were calculated by the Mantel–Haenszel method (Ph > 0.05), and random-effects pooled ORs were estimated by the DerSimonian–Laird method (Ph < 0.05). Data on rs2066827 polymorphism and cancer risk were available for 9038 cancer cases and 11,596 controls participating in 17 studies. Carriage of a TG genotype was associated with a minor but significant decrease in the risk of cancer (pooled OR 0.92, 95% CI: 0.86–0.99; model, TG vs. TT). We observed a moderately decreased risk of ovarian cancer based on 1829 cases and 2868 controls (pooled OR 0.85, 95% CI: 0.74–0.97; model, TG vs. TT). A slightly deceased risk of cancer was also indicated in Caucasians consisting of 6707 cases and 8279 controls (pooled OR 0.91, 95% CI: 0.85–0.98; model, TG vs. TT). These data suggest that carriage of a TG genotype at rs2066827 polymorphism may be associated with decreased susceptibility to cancer, ovarian cancer in particular. PMID:26579796

  18. RS-61443--a phase I clinical trial and pilot rescue study.

    PubMed

    Sollinger, H W; Deierhoi, M H; Belzer, F O; Diethelm, A G; Kauffman, R S

    1992-02-01

    RS-61443, a morpholinoethyl ester of mycophenolic acid, inhibits the synthesis of guanosine monophosphate, which plays a pivotal role in lymphocyte metabolism. The drug blocks proliferative responses of T and B lymphocytes, and inhibits antibody formation and the generation of cytotoxic T cells. In vivo, RS-61443 prolongs the survival of islet allografts in mice, heart allografts in rats, and kidney allografts in dogs. Reversal of ongoing acute rejection was demonstrated in rat heart allografts and kidney allografts in dogs. Preliminary evidence suggests that the drug prevents chronic rejection. The purpose of this study was to test the safety and tolerance in patients receiving primary cadaver kidneys. RS-61443 in doses from 100 mg/day p.o. to 3500 mg/day p.o. was given to patients in combination with cyclosporine and prednisone. Further study goals were to evaluate the pharmacokinetics of RS-61443, watch for the occurrence of opportunistic infections and acute rejection, and establish dosages for further clinical trials. Forty-eight patients were entered, with six patients in each dose group. RS-61443 was well tolerated in all dose groups, with only one adverse event possibly related to the drug (hemorrhagic gastritis). There was a statistically significant correlation between rejection episodes and dose (P = 0.022), patients with rejection episodes versus dose (P = 0.038), and number of OKT3/prednisone courses versus dose (P = 0.008). There was no overt nephrotoxicity or hepatotoxicity. Preliminary results of a rescue trial in 20 patients with kidney transplants will also be presented.

  19. The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men

    PubMed Central

    Tejedor, M. Teresa; Garcia-Sobreviela, Maria Pilar; Ledesma, Marta; Arbones-Mainar, Jose M.

    2014-01-01

    Background The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined. Methods We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease. Results The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI>30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01–1.59). Conclusions This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males. PMID:25268647

  20. Association of adenylyl cyclase 6 rs3730070 polymorphism and hemolytic level in patients with sickle cell anemia.

    PubMed

    Cita, Kizzy-Clara; Ferdinand, Séverine; Connes, Philippe; Brudey, Laura; Tressières, Benoit; Etienne-Julan, Maryse; Lemonne, Nathalie; Tarer, Vanessa; Elion, Jacques; Romana, Marc

    2016-05-01

    A recent study suggested that adenosine signaling pathway could promote hemolysis in patients with sickle cell anemia (SCA). This signaling pathway involves several gene coding enzymes for which variants have been described. In this study, we analyzed the genotype-phenotype relationships between functional polymorphisms or polymorphisms associated with altered expression of adenosine pathway genes, namely adenosine deaminase (ada; rs73598374), adenosine A2b receptor (adora2b; rs7208480), adenylyl cyclase6 (adcy6; rs3730071, rs3730070, rs7300155), and hemolytic rate in SCA patients. One hundred and fifty SCA patients were genotyped for adcy6, ada, and adora2b variants as well as alpha-globin gene, a genetic factor known to modulate hemolytic rate. Hematological and biochemical data were obtained at steady-state. Lactate dehydrogenase, aspartate aminotransferase, reticulocytes and total bilirubin were used to calculate a hemolytic index. Genotype-phenotype relationships were investigated using parametric tests and multivariate analysis. SCA patients carrying at least one allele of adcy6 rs3730070-G exhibited lower hemolytic rate than non-carriers in univariate analysis (p=0.006). The presence of adcy6 rs3730070-G variant was associated with a decreased hemolytic rate in adjusted model for age and alpha-thalassemia (p=0.032). Our results support a protective effect of adcy6 rs3730070-G variant on hemolysis in SCA patients.

  1. The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans

    PubMed Central

    Thevissen, Karin; de Mello Tavares, Patricia; Xu, Deming; Blankenship, Jill; Vandenbosch, Davy; Idkowiak-Baldys, Jolanta; Govaert, Gilmer; Bink, Anna; Rozental, Sonia; de Groot, Piet W.J.; Davis, Talya R.; Kumamoto, Carol A.; Vargas, Gabriele; Nimrichter, Leonardo; Coenye, Tom; Mitchell, Aaron; Roemer, Terry; Hannun, Yusuf A.; Cammue, Bruno P.A.

    2012-01-01

    Summary The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2,868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes was involved in cell wall integrity and hyphal growth/septin ring formation. Consistent with these genetic data, we demonstrated that RsAFP2 interacts with the cell wall of C. albicans, which also contains glucosylceramides, and activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces mislocalization of septins and blocks the yeast-to-hypha transition in C. albicans. Increased ceramide levels have previously been shown to result in apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans membranes were analyzed following RsAFP2 treatment and, as expected, increased accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans cells was detected. This is the first report on the interaction of a plant defensin with glucosylceramides in the fungal cell wall, causing cell wall stress, and on the effects of a defensin on septin localization and ceramide accumulation. PMID:22384976

  2. RS-1748, a novel CC chemokine receptor 4 antagonist, inhibits ovalbumin-induced airway inflammation in guinea pigs.

    PubMed

    Nakagami, Yasuhiro; Kawase, Yumi; Yonekubo, Kazuki; Nosaka, Emi; Etori, Maki; Takahashi, Sakiko; Takagi, Nana; Fukuda, Takeshi; Kuribayashi, Takeshi; Nara, Futoshi; Yamashita, Makoto

    2010-01-01

    CC chemokine receptor 4 (CCR4) is generally recognized as a preferential marker for T helper 2 cells, and we have previously reported morpholine-derivative CCR4 antagonists, RS-1154 and RS-1269. Here, we investigate the pharmacological profiles of a novel pyrimidine-derivative CCR4 antagonist, 2-{4-[2-(diethylamino)ethoxy]phenyl}-N-(2,4-difluorobenzyl)-5-fluoropyrimidin-4-amine (RS-1748), which showed potency to inhibit the bindings of [(125)I]CCL17 and [(35)S]GTPgammaS to human CCR4-expressing Chinese hamster ovary (CHO) cells with IC(50) values of 59.9 nM and 18.4 nM, respectively. Furthermore, RS-1748 inhibited ovalbumin-induced airway inflammation in guinea pigs at a dose of 10 mg/kg. These results indicate that RS-1748 would be a promising lead compound for developing a therapeutic agent against asthma.

  3. Genomic characterization of ϕRS603, a filamentous bacteriophage that is infectious to the phytopathogen Ralstonia solanacearum.

    PubMed

    Van, Truong Thi Bich; Yoshida, Shohei; Miki, Kaito; Kondo, Akihiro; Kamei, Kaeko

    2014-12-01

    A filamentous bacteriophage (ϕ), ϕRS603, which is infectious to the phytopathogen Ralstonia solanacearum was isolated. ϕRS603 was found to have a circular single-stranded DNA genome composed of 7679 nucleotides and to contain 13 putative open reading frames (ORFs). The ϕRS603 genome showed strong similarity with those of Ralstonia phages ϕRSM1 and ϕRSM3, as reported by Askora et al. The ϕRS603 genome had no ORFs corresponding to ORFs 2, 3, 13 and 14 (integrase) of ϕRSM3. ϕRS603 had an ORF that was homologous to other Ralstonia phages ϕRSS0 and ϕRSS1; however, ϕRSM1 and ϕRSM3 did not.

  4. Polymorphism rs7278468 is associated with Age-related cataract through decreasing transcriptional activity of the CRYAA promoter.

    PubMed

    Ma, Xiaoyin; Jiao, Xiaodong; Ma, Zhiwei; Hejtmancik, J Fielding

    2016-03-17

    CRYAA plays critical functional roles in lens transparency and opacity, and polymorphisms near CRYAA have been associated with age-related cataract (ARC). This study examines polymorphisms in the CRYAA promoter region for association with ARC and elucidates the mechanisms of this association. Three SNPs nominally associated with ARC were identified in the promoter region of CRYAA: rs3761382 (P = 0.06, OR (Odds ratio) = 1.5), rs13053109 (P = 0.04, OR = 1.6), rs7278468 (P = 0.007, OR = 0.6). The C-G-T haplotype increased the risk for ARC overall (P = 0.005, OR = 1.8), and both alleles and haplotypes show a stronger association with cortical cataract (rs3761382, P = 0.002, OR = 2.1; rs13053109, P = 0.002, OR = 2.1; rs7278468, P = 0.0007, OR = 0.5; C-G-T haplotype, P = 0.0003, OR = 2.2). The C-G-T risk haplotype decreased transcriptional activity through rs7278468, which lies in a consensus binding site for the transcription repressor KLF10. KLF10 binding inhibited CRYAA transcription, and both binding and inhibition were greater with the T rs7278468 allele. Knockdown of KLF10 in HLE cells partially rescued the transcriptional activity of CRYAA with rs7278468 T allele, but did not affect activity with the G allele. Thus, our data suggest that the T allele of rs7278468 in the CRYAA promoter is associated with ARC through increasing binding of KLF-10 and thus decreasing CRYAA transcription.

  5. The Three Rs--opportunities for improving animal welfare and the quality of scientific research.

    PubMed

    Combes, Robert D; Balls, Michael

    2014-09-01

    In 2013, an undercover investigation by the BUAV raised serious concerns about the use, treatment and care of laboratory animals involved in regulated procedures at Imperial College, London. This led to an inquiry, set up by the college, which found deficiencies in the local ethical review process and a general lack of focus on the implementation of the Three Rs (Replacement, Refinement and Reduction). The Three Rs concept is the foundation of UK and EU legislation, but surveys of the published literature show that lack of its adoption is widespread. In spite of numerous guidelines, publications and publicity material extolling the benefits of the Three Rs to both animals and science, as well as substantial advances in the development, validation, and deployment of mechanistically-based non-animal methods, many scientists prefer to use traditional animal-based approaches. In addition, such scientists tend to pay less attention than they should to strategic planning, experimental design and the choice of appropriate statistical procedures. They are often unaware of the existence of replacement test methods to address all or some of their objectives, and are reluctant to develop and use new replacement methods. We explore some possible reasons for these shortcomings. We summarise the welfare and scientific effects of each of the Three Rs, and argue that: a) there is an urgent need for evidence to be made readily accessible to prospective licensees, which directly demonstrates the beneficial effects on animal welfare of the implementation of the Three Rs, separately and in combination, and the direct link this has with the quality of the scientific data obtained; b) a detailed systematic review of this evidence should be undertaken to augment the inadequate content of the prescribed Module 5 licensee training offered currently in the UK; c) such training (including that suggested in new EU-wide proposals) should be much more comprehensive, with stronger emphasis on

  6. Preliminary Evidence for cue-induced Alcohol Craving Modulated by Serotonin Transporter Gene Polymorphism rs1042173

    PubMed Central

    Ait-Daoud, Nassima; Seneviratne, Chamindi; Smith, Justin B.; Roache, John D.; Dawes, Michael A.; Liu, Lei; Wang, Xin-Qun; Johnson, Bankole A.

    2012-01-01

    We previously have shown that cue-induced alcohol craving and propensity for higher drinking are modulated by allelic differences in SLC6A4 associated with serotonin transporter (5-HTT) expression level alterations. In an independent study, we characterized another polymorphism, SNP rs1042173, in 3′-untranslated region (3′-UTR) of the same gene, which also altered 5-HTT expression levels; the T allele of rs1042173 was associated with lower mRNA and protein levels. In subsequent analyses, the TT genotype was found to be associated with higher drinking intensity in alcohol-dependent (AD) individuals of Caucasian descent. Building upon these findings, we hypothesized that the low-expressing TT genotype associated with intense drinking would predict higher craving for alcohol in AD individuals. In this pilot study, we sought to test our hypothesis by examining 34 Hispanic AD volunteers (mean age, 34.8 years) for rs1042173 genotype-based [i.e., TT versus TG/GG (Gx)] differences in subjective response to alcohol. We employed a human laboratory paradigm and analyzed the data using a linear mixed-effects model (SAS® PROC MIXED) to assess treatment, cue procedures, and genotype main effects as well as the two-way interaction effects between them. On subjective “urge to drink” and “crave for a drink,” we found a significant main effect of the cue experiment (p ≤ 0.01) and an interaction effect between genotype and cue effects (p < 0.05). TT genotype was associated with higher urge to drink (p = 0.002) and crave for a drink (p = 0.005) when exposed to alcohol cue. Our results not only support the hypothesis that rs1042173 is a genetic marker for cue-induced alcohol craving among AD males but also are suggestive of a neurobiological mechanism associated with the rs1042173-TT genotype that triggers a disproportionate craving in response to alcohol consumption, which in turn may lead to more intense drinking. Future studies with larger sample

  7. The Shape of Near-Earth Asteroid 275677 (2000 RS11) From Inversion of Arecibo and Goldstone Radar Images

    NASA Astrophysics Data System (ADS)

    Brauer, Kaley; Busch, Michael W.; Benner, Lance A. M.; Brozovic, Marina; Howell, Ellen S.; Nolan, Michael C.; Springmann, Alessondra; Giorgini, Jon D.; Taylor, Patrick A.; Jao, Joseph S.

    2015-11-01

    We observed near-Earth asteroid 2000 RS11 with the Arecibo and Goldstone planetary radars during a 0.035 au approach in March 2014, obtaining delay-Doppler images between March 13 and March 17. The finest-resolution images have range resolution of 7.5 m/pixel and show that RS11 is a contact binary with complex topography. We used the SHAPE software package (Magri et al., Icarus 186, 156-160 2007) to create a physical model of RS11 and its spin state from these delay-Doppler images.The rotation period of RS11 is well constrained from optical lightcurves, P = 4.444 ± 0.001 h (Warner et al., Minor Planet Bulletin 41, 160; 2014 and Benishek, Minor Planet Bulletin 41, 257; 2014). We found two possible pole directions and corresponding shape models, mirror images of one another, which provide equally good fits to the radar data. RS11’s pole direction is either (λ , β) = (155°, 30°) ± 10° or (335°, -30°) ± 10° in J2000 ecliptic coordinates. The most likely pole directions of RS11 are not aligned with the heliocentric orbit normal and instead have an obliquity within 10° of 56° or 124°.Our best-fit shape models are 1400-vertex polyhedra comprising two lobes in contact. The lengths of RS11’s principal axes are 698 ± 71 m, 578 ± 59 m, and 758 ± 77 m. RS11 has a volume of 0.086 ± 0.026 km^3. The long axis of RS11’s larger lobe is 751 ± 77 m and the long axis of the smaller lobe is 398 ± 41 m; the volume ratio between these lobes is roughly 2.7 ± 10%. Spectral data informs us that RS11 is an S-class object (Lazzarin et al., Icarus 169, 379; 2004).RS11's shape is unusual compared with those of other contact binary NEAs imaged by radar. Its larger lobe is flattened. Additionally, while the neck between the smaller and larger lobes of most contact binaries is located near the larger lobe's longest principal axis (such as in the cases of 25143 Itokawa and 4179 Toutatis), RS11's neck is near its larger lobe's shortest principal axis. RS11 is the first

  8. Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area.

    PubMed

    Hotta, Kikuko; Kitamoto, Takuya; Kitamoto, Aya; Mizusawa, Seiho; Matsuo, Tomoaki; Nakata, Yoshio; Hyogo, Hideyuki; Ochi, Hidenori; Kamohara, Seika; Miyatake, Nobuyuki; Kotani, Kazuaki; Komatsu, Ryoya; Itoh, Naoto; Mineo, Ikuo; Wada, Jun; Yoneda, Masato; Nakajima, Atsushi; Funahashi, Tohru; Miyazaki, Shigeru; Tokunaga, Katsuto; Masuzaki, Hiroaki; Ueno, Takato; Chayama, Kazuaki; Hamaguchi, Kazuyuki; Yamada, Kentaro; Hanafusa, Toshiaki; Oikawa, Shinichi; Yoshimatsu, Hironobu; Sakata, Toshiie; Tanaka, Kiyoji; Matsuzawa, Yuji; Nakao, Kazuwa; Sekine, Akihiro

    2011-10-01

    Visceral fat accumulation has an important role in increasing morbidity and mortality rate by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of obesity have been identified by genome-wide association studies in Caucasian populations. We genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography (CT) for measuring visceral fat area (VFA) and subcutaneous fat area (SFA), for the following single-nucleotide polymorphisms (SNPs): NEGR1 rs2815752, SEC16B rs10913469, TMEM18 rs6548238, ETV5 rs7647305, GNPDA2 rs10938397, BDNF rs6265 and rs925946, MTCH2 rs10838738, SH2B1 rs7498665, MAF rs1424233, and KCTD15 rs29941 and rs11084753. In the additive model, none of the SNPs were significantly associated with body mass index (BMI). The SH2B1 rs7498665 risk allele was found to be significantly associated with VFA (P=0.00047) but not with BMI or SFA. When the analysis was performed in men and women separately, no significant associations with VFA were observed (P=0.0099 in men and P=0.022 in women). None of the other SNPs were significantly associated with SFA. Our results suggest that there is a VFA-specific genetic factor and that a polymorphism in the SH2B1 gene influences the risk of visceral fat accumulation.

  9. Asymmetric photolysis of /RS/-leucine with circularly polarized ultraviolet light

    NASA Technical Reports Server (NTRS)

    Flores, J. J.; Bonner, W. A.; Massey, G. A.

    1977-01-01

    (RS)-leucine in 0.1 M HCl solution has been subjected to photolysis with 212.8-nm right (R-) and left circularly polarized light (LCPL) obtained from a laser source. RCPL preferentially photolyzed the (R)-leucine component and LCPL the (S)-leucine component of the RS substrate. The enantiomeric excess produced were 1.98% for the 59% conversion with RCPL and 2.50% for the 75% conversion with LCPL. These 'equal and opposite' effects represent the second highest enantiomeric enrichments yet reported for an asymmetric photolysis and the first ever reported for a prebiotically important substrate - an amino acid. Implications regarding the origin of optical activity are briefly discussed.

  10. Reprogrammable multiplexed detection of circulating oncomiRs using hybridization chain reaction.

    PubMed

    Rana, Muhit; Balcioglu, Mustafa; Kovach, Maya; Hizir, Mustafa Salih; Robertson, Neil M; Khan, Irfan; Yigit, Mehmet V

    2016-02-28

    In this study, we have coupled the DNA polymerization capability of hybridization chain reaction (HCR) with the plasmonic properties of gold nanoparticles to develop a reprogrammable and multiplexed detection of three circulating oncomiRs (miR-10b, miR-21 and miR-141) dysregulated in various disease states of breast cancer. We have demonstrated that by simply changing the initiator (label-free short single stranded DNA) content of the HCR, while keeping everything else unchanged, the same nanoparticle assembly can be reprogrammed for the detection of the target oncomiRs individually or simultaneously in all possible combinations. We have shown that as little as 20 femtomoles of each oncomiR can be detected visually without using any analytical instrument. Furthermore, we demonstrated that the target oncomiR can be detected in an RNA pool isolated from a liquid biopsy mimic of breast cancer.

  11. Crystallization of lysozyme with (R)-, (S)- and (RS)-2-methyl-2,4-pentanediol

    PubMed Central

    Stauber, Mark; Jakoncic, Jean; Berger, Jacob; Karp, Jerome M.; Axelbaum, Ariel; Sastow, Dahniel; Buldyrev, Sergey V.; Hrnjez, Bruce J.; Asherie, Neer

    2015-01-01

    Chiral control of crystallization has ample precedent in the small-molecule world, but relatively little is known about the role of chirality in protein crystallization. In this study, lysozyme was crystallized in the presence of the chiral additive 2-methyl-2,4-pentanediol (MPD) separately using the R and S enantiomers as well as with a racemic RS mixture. Crystals grown with (R)-MPD had the most order and produced the highest resolution protein structures. This result is consistent with the observation that in the crystals grown with (R)-MPD and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there is preferential interaction between lysozyme and this enantiomer. These findings suggest that chiral interactions are important in protein crystallization. PMID:25760593

  12. Russell and Burch's 3Rs then and now: the need for clarity in definition and purpose.

    PubMed

    Tannenbaum, Jerrold; Bennett, B Taylor

    2015-03-01

    Russell and Burch's The Principles of Humane Experimental Technique was first published in 1959. A Special Edition containing the original text was reissued in 1992, after its ideas had gained widespread interest in the scientific community. In the Principles, Russell and Burch proposed a new applied science that would improve the treatment of laboratory animals while advancing the quality of science in studies that use animals. They introduced and defined the terms replacement, reduction, and refinement, which subsequently have become known as 'alternatives' or 'alternative methods' for minimizing the potential for animal pain and distress in biomedical research. Here we describe and explain the original definitions of the 3Rs in the Principles, examine how current definitions differ among themselves and from Russell and Burch's definitions, and suggest relevant considerations for evaluating all definitions of the 3Rs.

  13. Crystallization of lysozyme with (R)-, (S)- and (RS)-2-methyl-2,4-pentanediol

    DOE PAGES

    Stauber, Mark; Jakoncic, Jean; Berger, Jacob; ...

    2015-03-01

    Chiral control of crystallization has ample precedent in the small-molecule world, but relatively little is known about the role of chirality in protein crystallization. In this study, lysozyme was crystallized in the presence of the chiral additive 2-methyl-2,4-pentanediol (MPD) separately using the R and S enantiomers as well as with a racemic RS mixture. Crystals grown with (R)-MPD had the most order and produced the highest resolution protein structures. This result is consistent with the observation that in the crystals grown with (R)-MPD and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there is preferential interaction between lysozymemore » and this enantiomer. These findings suggest that chiral interactions are important in protein crystallization.« less

  14. FibromiRs: translating molecular discoveries into new anti-fibrotic drugs.

    PubMed

    Pottier, Nicolas; Cauffiez, Christelle; Perrais, Michael; Barbry, Pascal; Mari, Bernard

    2014-03-01

    Fibrosis, or tissue scarring, is defined as excessive and persistent accumulation of extracellular matrix components in response to chronic tissue injury. Fibrosis is a pathological feature characterizing nearly all forms of chronic organ failure. Fibroproliferative disorders of liver, kidney, heart, and lung are frequently associated with considerable morbidity and mortality worldwide. Limited therapeutic options are available; none is yet effective in stopping the ultimate progression of the disease. This has prompted investigations for new molecular targets. Recent studies have shown aberrant expression of miRNAs (fibromiRs) during the development of fibrosis. The challenge now is to understand how these aberrantly expressed miRNAs collaborate to drive fibrogenesis. Progress in understanding how fibromiRs contribute to tissue fibrosis is necessary to translate molecular discoveries into new therapeutics for fibroproliferative diseases.

  15. Association study between the Taq1A (rs1800497) polymorphism and schizophrenia in a Brazilian sample.

    PubMed

    Cordeiro, Quirino; Vallada, Homero

    2014-08-01

    Schizophrenia is a severe psychotic disorder with recurrent relapse and functional impairment. It results from a poorly understood gene-environment interaction. The Taq1A polymorphism (located in the gene cluster NTAD) is a likely candidate for schizophrenia. Its rs1800497 polymorphism was shown to be associated with DRD2 gene expression. Therefore the present work aims to investigate a possible association between schizophrenia and such polymorphism. The compared distribution of the alleles and genotypes of the studied polymorphism was investigated in a Brazilian sample of 235 patients and 834 controls. Genotypic frequencies were in Hardy-Weinberg equilibrium. There was a trend of allelic association between the Taq1A polymorphism (rs1800497) with schizophrenia in the studied sample. However no statistically differences were found between cases and controls when analyzed by gender or schizophrenia subtypes.

  16. SSME to RS-25: Challenges of Adapting a Heritage Engine to a New Vehicle Architecture

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2015-01-01

    A key constituent of the NASA Space Launch System (SLS) architecture is the RS-25 engine, also known as the Space Shuttle Main Engine (SSME). This engine was selected largely due to the maturity and extensive experience gained through 30-plus years of service. However, while the RS-25 is a highly mature system, simply unbolting it from the Space Shuttle and mounting it on the new SLS vehicle is not a "plug-and-play" operation. In addition to numerous technical integration and operational details, there were also hardware upgrades needed. While the magnitude of effort is less than that needed to develop a new clean-sheet engine system, this paper describes some of the expected and unexpected challenges encountered to date on the path to the first flight of SLS.

  17. MetastamiRs: Non-Coding MicroRNAs Driving Cancer Invasion and Metastasis

    PubMed Central

    Lopez-Camarillo, Cesar; Marchat, Laurence A.; Arechaga-Ocampo, Elena; Perez-Plasencia, Carlos; del Moral-Hernandez, Oscar; Castaneda-Ortiz, Elizabeth J.; Rodriguez-Cuevas, Sergio

    2012-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression. PMID:22408395

  18. Observations of Lower Stratospheric Water Vapor Injected by Overshooting Convection During SEAC4RS

    NASA Astrophysics Data System (ADS)

    Herman, R. L.; Ray, E. A.; Schwartz, M. J.; Read, W. G.; Troy, R. F.; Christensen, L. E.; Chin, K. B.; Stachnik, R. A.; Rosenlof, K. H.; Bedka, K. M.; Bui, T. V.

    2015-12-01

    Several NASA ER-2 aircraft flights during the 2013 NASA Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field mission sampled the UTLS region heavily influenced by the North American Monsoon (NAM). Enhanced water vapor was measured in the lower stratosphere between 160 hPa and 80 hPa over the continental United States. Here we present in-situ water vapor measurements from the improved JPL Laser Hygrometer (JLH Mark2) to characterize the NAM water vapor field during August and September 2013. Overshooting cloud tops are identified from a SEAC4RS overshooting top (OT) detection product that is based on infrared satellite imagery. Back-trajectory analysis ties enhanced water to overshooting cloud tops 1 to 7 days prior to the intercept by the aircraft. Regional context is provided by water observations from the Aura Microwave Limb Sounder (MLS).

  19. Vitamin D3 Receptor (VDR) Gene rs2228570 (Fok1) and rs731236 (Taq1) Variants Are Not Associated with the Risk for Multiple Sclerosis: Results of a New Study and a Meta-Analysis

    PubMed Central

    García-Martín, Elena; Agúndez, José A. G.; Martínez, Carmen; Benito-León, Julián; Millán-Pascual, Jorge; Calleja, Patricia; Díaz-Sánchez, María; Pisa, Diana; Turpín-Fenoll, Laura; Alonso-Navarro, Hortensia; Ayuso-Peralta, Lucía; Torrecillas, Dolores; Plaza-Nieto, José Francisco; Jiménez-Jiménez, Félix Javier

    2013-01-01

    Background Some epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the VDR gene and HLADRB1*1501 in the risk for MS. Objectives The aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the VDR gene in the risk for MS. A secondary objective was to address the possible interactions between VDR genes and HLADRB1*1501. Methods We analyzed the allelic and genotype frequency of VDR rs2228570, rs731236, and HLADRB1*1501 (rs3135388) in 303 patients with MS and 310 healthy controls, using TaqMan Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (http://www.hrc.es/investigacion/metadisc.html; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic. Results VDR rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. HLADRB1*1501 showed a high association with the risk of developing MS 4.76(95% C.I.  = 3.14–7.27; p<0.0001). The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. HLADRB1*1501 showed lack of interaction with VDR rs2228570 and rs731236 in increasing MS risk. Conclusions These results suggest that VDR rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these VDR SNPs and HLADRB1 in the risk for MS

  20. CYP4F2 (rs2108622) Gene Polymorphism Association with Age-Related Macular Degeneration

    PubMed Central

    Kriauciuniene, Loresa; Balciuniene, Vilma Jurate; Buteikiene, Dovile; Miniauskiene, Goda; Liutkeviciene, Rasa

    2016-01-01

    Background. Age-related macular degeneration is the leading cause of blindness in elderly individuals where aetiology and pathophysiology of age-related macular degeneration are not absolutely clear. Purpose. To determine the frequency of the genotype of rs2108622 in patients with early and exudative age-related macular degeneration. Methods. The study enrolled 190 patients with early age-related macular degeneration, 181 patients with exudative age-related macular degeneration (eAMD), and a random sample of 210 subjects from the general population (control group). The genotyping of rs2108622 was carried out using the real-time polymerase chain reaction method. Results. The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the early AMD group, the eAMD group, and the control group. The CYP4F2 (1347C>T) T/T genotype was more frequent in males with eAMD compared to females (10.2% versus 0.8%; p = 0.0052); also T/T genotype was less frequently present in eAMD females compared to healthy control females (0.8% versus 6.2%; p = 0.027). Conclusion. Rs2108622 gene polymorphism had no predominant effect on the development of early AMD and eAMD. The T/T genotype was more frequent in males with eAMD compared to females and less frequently present in eAMD females compared to healthy females. PMID:27652291

  1. mGluRs modulate strength and timing of excitatory transmission in hippocampal area CA3.

    PubMed

    Cosgrove, Kathleen E; Galván, Emilio J; Barrionuevo, Germán; Meriney, Stephen D

    2011-08-01

    Excitatory transmission within hippocampal area CA3 stems from three major glutamatergic pathways: the perforant path formed by axons of layer II stellate cells in the entorhinal cortex, the mossy fiber axons originating from the dentate gyrus granule cells, and the recurrent axon collaterals of CA3 pyramidal cells. The synaptic communication of each of these pathways is modulated by metabotropic glutamate receptors that fine-tune the signal by affecting both the timing and strength of the connection. Within area CA3 of the hippocampus, group I mGluRs (mGluR1 and mGluR5) are expressed postsynaptically, whereas group II (mGluR2 and mGluR3) and III mGluRs (mGluR4, mGluR7, and mGluR8) are expressed presynaptically. Receptors from each group have been demonstrated to be required for different forms of pre- and postsynaptic long-term plasticity and also have been implicated in regulating short-term plasticity. A recent observation has demonstrated that a presynaptically expressed mGluR can affect the timing of action potentials elicited in the postsynaptic target. Interestingly, mGluRs can be distributed in a target-specific manner, such that synaptic input from one presynaptic neuron can be modulated by different receptors at each of its postsynaptic targets. Consequently, mGluRs provide a mechanism for synaptic specialization of glutamatergic transmission in the hippocampus. This review will highlight the variability in mGluR modulation of excitatory transmission within area CA3 with an emphasis on how these receptors contribute to the strength and timing of network activity within pyramidal cells and interneurons.

  2. MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

    PubMed Central

    Miao, Hui-Kai; Chen, Li-Ping; Cai, Dong-Ping; Kong, Wei-Ju; Xiao, Li; Lin, Jie

    2015-01-01

    Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer. PMID:26617824

  3. IUE spectra of a flare in HR 5110: A flaring RS CVn or Algol system?

    NASA Technical Reports Server (NTRS)

    Simon, T.; Linsky, J. L.; Schiffer, F. H., III

    1981-01-01

    Ultraviolet spectra of the RS CVn type binary system HR 5110 were obtained with IUE on May 31, 1979 during a period of intense radio flaring of this star. High temperature transition region lines are present, but are not enhanced above observed quiescent strengths. The similarities of HR 5110 to the Algol system, As Eri, suggest that the 1979 May to June flare may involve mass exchange rather than annihilation of coronal magnetic fields.

  4. The hallmarks of cancer and the radiation oncologist: updating the 5Rs of radiobiology.

    PubMed

    Good, J S; Harrington, K J

    2013-10-01

    A comprehensive, mechanistic understanding of radiobiological phenomena that can be integrated within the broader context of cancer biology offers the prospect of transforming clinical practice in radiation oncology. In this review, we revisit the six established biological hallmarks of cancer and examine how they have provided insights into novel therapeutic strategies. In addition, we discuss the potential of two emerging hallmarks to continue to expand our understanding beyond the narrow confines of the traditional 5Rs of radiobiology.

  5. The human rs1050286 polymorphism alters LOX-1 expression through modifying miR-24 binding.

    PubMed

    Morini, Elena; Rizzacasa, Barbara; Pucci, Sabina; Polidoro, Chiara; Ferrè, Fabrizio; Caporossi, Daniela; Helmer Citterich, Manuela; Novelli, Giuseppe; Amati, Francesca

    2016-01-01

    The up-regulation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR1 polymorphisms were associated with increased susceptibility to acute myocardial infarction (AMI) and coronary artery diseases (CAD). In these pathologies, the identification of therapeutic approaches that can inhibit or reduce LOX-1 overexpression is crucial. Predictive analysis showed a putative hsa-miR-24 binding site in the 3'UTR of OLR1, 'naturally' mutated by the presence of the rs1050286 single nucleotide polymorphism (SNP). Luciferase assays revealed that miR-24 targets OLR1 3'UTR-G, but not 3'UTR-A (P < 0.0005). The functional relevance of miR-24 in regulating the expression of OLR1 was established by overexpressing miR-24 in human cell lines heterozygous (A/G, HeLa) and homozygous (A/A, HepG2) for rs1050286 SNP. Accordingly, HeLa (A/G), but not HepG2 (A/A), showed a significant down-regulation of OLR1 both at RNA and protein level. Our results indicate that rs1050286 SNP significantly affects miR-24 binding affinity to the 3'UTR of OLR1, causing a more efficient post-transcriptional gene repression in the presence of the G allele. On this basis, we considered that OLR1 rs1050286 SNP may contribute to modify OLR1 susceptibility to AMI and CAD, so ORL1 SNPs screening could help to stratify patients risk.

  6. The single nucleotide polymorphism Rs12817488 is associated with Parkinson's disease in the Chinese population.

    PubMed

    Yu, Ri-li; Guo, Ji-feng; Wang, Ya-qin; Liu, Zhen-hua; Sun, Zhan-fang; Su, Li; Zhang, Yuan; Yan, Xin-xiang; Tang, Bei-sha

    2015-06-01

    A recent meta-analysis of datasets from five of the published Parkinson's disease (PD) genome-wide association studies implicated the single nucleotide polymorphism (SNP) rs12817488 in coiled-coil domain containing 62 (CCDC62)/huntingtin interacting protein 1 related (HIP1R) as a risk factor for PD. We conducted a case-control study to evaluate the possible association between rs12817488 and PD in Chinese people. All patients (515 PD patients and 518 age and sex-matched controls) were successfully genotyped using polymerase chain reaction restriction fragment length polymorphism analysis. We observed that the rs12817488 polymorphism is associated with PD (p=0.003) and that the genotype and allele frequencies showed a difference between late-onset PD patients and male controls (p=0.025 and p=0.007, respectively). However, there was no difference in the early-onset PD patients and controls. We found a difference in the genotype and allele frequencies between the male PD patients and the male controls (p=0.034 and p=0.017, respectively). However, there was no difference in females. Patients with the A allele were susceptible to PD in both dominant (GA+AA versus GG; odds ratio [OR] 1.365, 95% confidence interval [CI] 1.041-1.788) and recessive (AA versus GG+GA; OR 1.606, 95% CI 1.194-2.158) models. Therefore, our findings support the conclusion that the rs12817488 in CCDC62/HIP1R polymorphism may increase the risk of PD in the Chinese Han population.

  7. HMGCR rs17671591 SNP Determines Lower Plasma LDL-C after Atorvastatin Therapy in Chilean Individuals.

    PubMed

    Cuevas, Alejandro; Fernández, César; Ferrada, Luis; Zambrano, Tomás; Rosales, Alexy; Saavedra, Nicolás; Salazar, Luis A

    2016-04-01

    Lipid-lowering response to statin therapy shows large interindividual variability. At a genome-wide significance level, single nucleotide polymorphisms (SNPs) in PCSK9 and HMGCR have been implicated in this differential response. However, the influence of these variants is uncertain in the Chilean population. Hence, we aimed to evaluate the contribution of PCSK9 rs7552841 and HMGCR rs17671591 SNPs as genetic determinants of atorvastatin response in Chilean hypercholesterolaemic individuals. One hundred and one hypercholesterolaemic patients received atorvastatin 10 mg/day for 4 weeks. Plasma lipid profile (TC, HDL-C, LDL-C and TG) was determined before and after statin treatment, and SNPs were identified by allelic discrimination using TaqMan(®) SNP Genotyping Assays. Adjusted univariate and multivariate analyses' models were used for statistical analyses, and a p-value <0.05 was considered significant. From baseline (week 0) to the study end-point (week 4), significant reductions were observed in plasma TC, LDL-C and TG (p < 0.001), while HDL-C levels were increased (p < 0.001). Multivariate analysis showed no association between lipid levels and atorvastatin therapy for the PCSK9 variant. However, the HMGCR rs17671591 T allele contributed to basal HDL-C concentration variability along with a higher increase in this lipid fraction after statin medication. In addition, this allele determined greater plasma LDL-C reductions after therapy with atorvastatin. Our data suggest that the HMGCR rs17671591 polymorphism can constitute a genetic marker of lower plasma LDL-C and enhanced HDL-C concentration after atorvastatin therapy in the Chilean population.

  8. An Analysis of Light Variations of RS Canum Venaticorum Binary Systems.

    NASA Astrophysics Data System (ADS)

    Caton, Daniel Bruce

    Photoelectric data for fourteen RS Canum Venaticorum binary systems were obtained by the author from 1978 through 1981, at Rosemary Hill Observatory. These data are presented in the form of light curves and tabulated magnitudes and heliocentric Julian Dates. The outside-of-eclipse points for eight systems were Fourier analyzed for measurement of any distortion wave in the light curve. The wave in RS Canum Venaticorum itself was found to have moved half a phase unit in only two years. A wave was discovered in the light curve of RZ Eridani, and was found to have changed in a manner consistent with the starspot model for RS CVn systems. The light curve for UX Comae Bernices was found to have a large amount of intrinsic scatter, and the system was found to be anomalously bright on one night. These characteristics suggest that some type of flare activity may be present in that system. The other five systems analyzed were found to have waves consistent with other published results, or to have no definite wave at all. The possibility of detecting spots and deriving spot sizes from secondary eclipse observations was also explored. For this purpose the Wilson-Devinney computer program for light curve synthesis was modified to allow spots on the secondary star. Comparison of computer synthesized secondary eclipses of spotted stars to actual observations showed that there is little chance of detecting fluctuations due to individual spots. It was found that there is even less chance for discriminating between a few large spots and a large number of smaller spots. However, the program did produce good fits to RS CVn light curves, using reasonable spot parameters.

  9. The Method and Key Technology of Dynamic RS-GIS Environment Monitoring

    NASA Astrophysics Data System (ADS)

    Chen, Jianping; Xiang, Jie; Tarolli, Paolo; Lai, Zili

    2016-04-01

    Demographic growth, socio-economic development and urbanization have resulted in excessive exploitation and exerted increasing pressure on limited resources and the fragile ecological environment in China. There is an urgent need for theory and technology to achieve the comprehensive evaluation of environment. Remote sensing is one of the most important technology to monitor and evaluate environment. This study summed up dynamic RS (Remote Sensing)-GIS (Geographic Information System) environment monitoring theory, and established a dynamic monitoring system, adopting comprehensive methods of multi-source, multi-scale and multi-temporal remote sensing data acquisition. A software system is developed based on RS-GIS analysis method to support the whole dynamic monitoring and evaluation theory. The main work and results obtained are as follows: 1)Summarized the evaluation theory of dynamic RS-GIS environment monitoring, using remote sensing technology as the main method to monitor environment; 2) established an advanced space-air-ground digital terrain data acquisition and processing technology (advanced satellite constellations, airborne and terrestrial laser scanner, low-cost Structure from Motion (SfM), photogrammetry, Unmanned Aerial Vehicle (UAV) and ground camera surveys); 3) Deeply study the application of quantitative digital terrain analysis in the assessment of environment, which successfully position geological disaster information and automatically extracted information; 4) Developed the RESEE software to support the whole dynamic monitoring and evaluation theory based on 4D-GIS; 5) A demonstration study of the dynamic monitoring environment is carried out in Beijing Miyun Iron Mine. Results show that the space-air-ground integrated and dynamic RS-GIS environment monitoring method and key technology can realize the positioning and quantitative monitoring the environment problem, and realize the risk assessment of the geological hazard.

  10. Galectin-3 and Its Genetic Variation rs4644 Modulate Enterovirus 71 Infection

    PubMed Central

    Huang, Wen-Chan; Chen, Hung-Lin; Chen, Huan-Yuan; Peng, Kuan-Po; Lee, Yungling; Huang, Li-Min; Chang, Luan-Yin; Liu, Fu-Tong

    2016-01-01

    Galectin-3, a chimeric type β-galactoside-binding protein, is known to modulate viral infection; however, its role in enterovirus 71 (EV71) infection has not been investigated. We generated galectin-3 null rhabdomyosarcoma (RD) cells and evaluated whether EV71 infection would be affected. In galectin-3 null cells, the released and intracellular EV71 viral loads were suppressed after 24 h of infection, and cell death rates were significantly lower, while cell proliferation remained unaltered. In addition, RD cells expressing a nonsynonymous genetic variant of galectin-3, rs4644 (LGALS3 +191C/A, P64H), produced lower virus titers than those with wild-type galectin-3 (C allele). To clarify whether the in vitro viral load reduction correlates with clinical severity, we enrolled children with laboratory-confirmed EV71 infection. Since hyperglycemia is an indicator of severe EV71 infection in children, 152 of 401 enrolled children had glucose examinations at admission, and 59 subjects had serum glucose levels ≥ 150 mg/dL. In comparison to the rs4644 AA genotype (2.2 ± 0.06 log10 mg/dL), serum glucose levels during EV71 infection were higher in patients with CC (2.4 ± 0.17 log10 mg/dL, p = 0.03) and CA (2.4 ± 0.15 log10 mg/dL, p = 0.02) genotypes, respectively. These findings suggest that the rs4644 AA genotype of galectin-3 might exert a protective effect. In summary, galectin-3 affects EV71 replication in our cellular model and its variant, rs4644, is associated with hyperglycemia in the clinical setting. The underlying mechanism and its potential therapeutic application warrant further investigation. PMID:28002441

  11. Polymorphisms in prostate stem cell antigen gene rs2294008 increase gastric cancer risk in Chinese.

    PubMed

    Zeng, Zhirong; Wu, Xiaoqin; Chen, Fanggen; Yu, Jun; Xue, Ling; Hao, Yuantao; Wang, Yiming; Chen, Minhu; Sung, Joseph J Y; Hu, Pinjin

    2011-05-01

    A recent genome-wide study identified a strong association between polymorphisms in the prostate stem cell antigen (PSCA) gene and the risk of diffuse-type of gastric cancer in Japanese and Korean population. In this case-control study, we aimed to investigate the possible association between PSCA rs2294008 C/T with clinicopathological features and the prognosis of gastric cancer in a Southern Chinese population. Genotypes of 460 gastric cancer patients and 549 controls were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. We found that individuals with at least one copy of the rs2294008T allele (CT or TT genotype) had an increased risk for gastric cancer compared with CC genotype (OR = 1.42, 95% CI = 1.10-1.82, P = 0.006). Further stratification analyses indicated that the effect of PSCA rs2294008T carriers was noteworthy in intestinal type (OR = 1.55, 95% CI = 1.18-2.04, P = 0.002), poorly differentiated (OR = 1.59, 95% CI = 1.19-2.13, P = 0.002), noncardia (OR = 1.55, 95% CI = 1.17-2.04, P = 0.002) subtypes of gastric cancer. Cox proportional hazards analyses demonstrated that TT genotype (HR = 2.12, 95% CI = 1.22-3.69, P = 0.008) as well as TNM staging were prognostic factors of gastric cancer patients. In conclusion, The T allele of PSCA rs2294008 is associated with increased risk of gastric cancer, especially intestinal type, poorly differentiated, early onset, and noncardia gastric cancer in Chinese population. TNM staging and TT genotype might be involved in the prognosis of gastric cancer patients.

  12. PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk

    PubMed Central

    Wang, Meng; Wang, Xi-Jing; Ma, Yun-Feng; Ma, Xiao-Bin; Dai, Zhi-Ming; Lv, Ye; Lin, Shuai; Liu, Xing-Han; Yang, Peng-Tao; Dai, Zhi-Jun

    2015-01-01

    Background Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case–control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. Methods The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. Results Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08–1.28; TT vs CC, OR: 1.36, 95% CI: 1.14–1.62; TC vs CC, OR: 1.29, 95% CI: 1.17–1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18–1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02–1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. Conclusion Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer. PMID:25709466

  13. A Role for σRs in Stimulant Self-administration and Addiction

    PubMed Central

    Katz, Jonathan L.; Hong, Weimin C.; Hiranita, Takato; Su, Tsung-Ping

    2015-01-01

    Sigma-1 receptors (σ1Rs) are structurally unique intracellular proteins that function as chaperones. σ1Rs translocate from the mitochondria-associated membrane to other sub-cellular compartments, and can influence a host of targets, including ion channels, G-protein-coupled receptors, lipids, and other signaling proteins. Drugs binding to σRs can induce or block the actions of σRs. Studies indicate that stimulant self-administration induces reinforcing effects of σR agonists, due to dopamine transporter actions. Once established the reinforcing effects of σR agonists are independent of dopaminergic mechanisms traditionally thought to be critical in the reinforcing effects of stimulants. Self-administered doses of σR agonists do not increase dopamine concentrations in the nucleus accumbens shell, a transmitter and brain region considered important for reinforcing effects of abused drugs. However, the self-administration of σR agonists is blocked by σR antagonists. Several effects of stimulants have been blocked by σR antagonists, including reinforcing effects assessed by a place-conditioning procedure. However, the self-administration of stimulants is largely unaffected by σR antagonists, indicating fundamental differences in the mechanisms underlying these two procedures used to assess reinforcing effects. When σR antagonists are administered in combination with dopamine uptake inhibitors an effective and specific blockade of stimulant self-administration is obtained. Actions of stimulant drugs related to their abuse induce unique changes in σR activity and the changes induced potentially create redundant, and once established, independent reinforcement pathways. Concomitant targeting of both dopaminergic pathways and σR proteins produces a selective antagonism of stimulant self-administration, suggesting new avenues for combination chemotherapies to specifically combat stimulant abuse. PMID:26650253

  14. Rotational modulation and flares on RS Canum Venaticorum and BY Draconis stars. 18: Coordinated VLA, ROSAT, and IUE observations of RS CVn binaries

    NASA Technical Reports Server (NTRS)

    Fox, David C.; Linsky, Jeffrey L.; Veale, Anthony; Dempsey, Robert C.; Brown, Alex; Neff, James E.; Pagano, Isabella; Rodono, Marcello; Bromage, Gordon E.; Kuerster, Martin

    1994-01-01

    As part of a coordinated program of multi-wavelength observations of RS CVn close binary systems, we observed 15 systems with the Very Large Array (VLA) and 10 systems with IUE, simultaneously or nearly simultaneously with the ROSAT All Sky Survey observations of these stars. Of the 22 systems observed with ROSAT, three were observed both by IUE and the VLA. Radio observations were made at 3.6, 6 and 20 cm. Of the 15 observed RS CVn systems, we detected 11 with greater than 4 sigma confidence at one or more wavelengths. The IUE observations were made within the RIASS (ROSAT-IUE All Sky Survey) program. We present the results of the VLA observations, along with the corresponding subsets of the ROSAT Position Sensitive Proportional Counter (PSPC) X-ray and Wide Field Camera (WFC) XUV survey, and RIASS IUE observations. We obtained an extended VLA/IUE/ROSAT simultaneous coverage of one system, TY Pyx, covering more than one orbital period. These observations reveal that the quiescent radio flux of TY Pyx is relatively constant over time scales of up to 7 hours, but that it did change by a factor of 3 over 24 hours, probably due to a flare on 1990 Nov. 12. The UV, XUV and X-ray fluxes do not show large day-to-day or phase-related variability. The observation of the decay phase of a radio flare on EI Eri, with no accompanying X-ray or XUV flare, suggests that the lack of a strong correlation between X-ray and radio flares previously noted for dMe flare stars holds for RS CVn systems as well. We suggest that the radio flare may have been due to a coherent emission process such as electron cyclotron emission. The simultaneous measurements presented here provide a unique test of the general correlation between radio and soft X-ray luminosities, L(sub radio) approximately L(sub x exp m) (Drake et al. 1989) with a power-law slope close to unity, which was previously derived using data obtained years apart. Our derived slopes are consistent with and thus support the general

  15. A genetic polymorphism (rs17251221) in the calcium-sensing receptor is associated with ovarian cancer susceptibility.

    PubMed

    Yan, Shi; Yuan, Cunzhong; Yang, Qifeng; Li, Xiaoyan; Yang, Ning; Liu, Xiaoyan; Dong, Ruihua; Zhang, Xi; Yuan, Zeng; Zhang, Ning; Kong, Beihua

    2015-10-01

    Calcium-sensing receptor (CaSR) is a G-protein‑ coupled receptor that senses blood calcium. In vivo, CaSR is required for normal epidermal differentiation by mediating calcium signaling. CaSR was confirmed to be a tumor suppressor in colon and breast cancer. The single-nucleotide polymorphism (SNP) rs17251221, located on the intron, is a genetic variation of the CaSR gene. We analyzed rs17251221 in ovarian cancer using an allelic discrimination assay. Cycling probes were used for genotyping 290 ovarian cancer patients and 312 age-matched cancer-free females. rs17251221 and clinicopathological characteristics of ovarian cancer were analyzed statistically. The AG and GG genotypes were confirmed to appear in fewer cancer cases than in controls and the genotype distribution between cases and controls was statistically significant. The AG+GG genotype was correlated with low ovarian cancer risk, while rs17251221 was not associated with clinicopathological variables including age at diagnosis, tumor size, histologic type, pathological subtype, lymph node metastasis, CA-125 expression, clinical stage, or degree of differentiation. The rs17251221 polymorphism genotype was not correlated with survival in ovarian cancer. These results suggest that the G allele of the CaSR rs17251221 polymorphism is protective against ovarian cancer and the homozygous GG genotype may be a protective genotype as well. The rs17251221 may play an important role in the development of ovarian cancer and could be used as a biomarker for predicting ovarian cancer.

  16. TNFAIP3 rs2230926 polymorphisms in rheumatoid arthritis of southern Chinese Han population: a case-control study.

    PubMed

    Hao, Guifeng; Li, Yasong; Liu, Jinlin; Wo, Mingyi

    2014-01-01

    Polymorphism of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) has been be related to various auto-immune diseases. Based on previous studies that the single nucleotide polymorphism (SNP) of rs2230926 was association with rheumatoid arthritis (RA) of Japanese, Caucasian population and the northern Chinese Han population, we tested the alleles and geno-type frequencies of rs2230926 in TNFAIP3 to investigate whether rs2230926 is susceptible to RA of southern Chinese Han population. In our case-control association study, 207 RA patients fulfilling the American College of Rheumatology (ACR) 1987 criteria were compared with 199 unrelated healthy subjects. After testing the alleles and genotype frequencies of rs2230926, the airwise linkage disequilibrium (LD) was computed and odd ration (OR) and 95% confidence intervals (95% CI) were used for evaluating the susceptibility to RA. The SNP of rs2230926 of the cases and control subjects were conformed to the Hardy-Weinberg equilibrium (P = 0.02257). The significantly statistical differences in alleles of T, G were founded in the cases and controls (P = 0.0027, OR 0.417, 95% CI 0.232-0.749); the genetic types of rs2230926 were associated with a susceptibility to RA, with OR 0.375 (95% CI 0.198-0.707, P = 0.0018). In the present study, our results indicated that the genetic polymorphism of rs2230926 in TNFAIP3 may be a susceptible factor conferring risk for RA in southern Chinese Han population.

  17. HIWI2 rs508485 Polymorphism Is Associated with Non-obstructive Azoospermia in Iranian Patients

    PubMed Central

    Kamaliyan, Zeeba; Pouriamanesh, Sara; Amin-beidokhti, Mona; Rezagholizadeh, Amir; Mirfakhraie, Reza

    2017-01-01

    Background: The PIWI-interacting RNA (piRNA) pathway has an essential role in transposon silencing, meiosis progression, spermatogenesis, and germline maintenance. HIWI genes are critical for piRNA biogenesis and function. Therefore, polymorphisms in HIWI genes contribute to spermatogenesis defects and can be considered as risk factors for male infertility. The aim of the present study was to investigate the association between the HIWI2 gene rs508485 polymorphism and non-obstructive azoospermia. Methods: A total of 121 Iranian men with idiopathic azoospermia and 100 fertile controls were genotyped for HIWI2 rs508485 (T>C) polymorphism using Tetra-ARMS PCR. The presence of eight sequence-tagged site (STS) markers from the Y chromosome AZF region was also investigated by Multiplex PCR (M-PCR). Results: Thirteen (10.74%) patients showed Y chromosome microdeletions and therefore were excluded from the study. rs508485 in the 3’UTR of HIWI2 was associated with increased risk of azoospermia in our studied population with a P-value of 0.035 and odds ratio of 2.00 (CI 95%: 1.04-3.86). Conclusions: We provide evidence for an association between genetic variation in the HIWI2 gene involved in the piRNA pathway and idiopathic non-obstructive azoospermia in Iranian patients. Therefore, piRNA pathway gene variants can be considered as risk factors for male infertility. PMID:28367472

  18. [Wetland landscape pattern change based on GIS and RS: a review].

    PubMed

    Kong, Fan-Ting; Xi, Min; Li, Yue; Kong, Fan-Long; Chen, Wan

    2013-04-01

    Wetland is an ecological landscape with most biodiversity in nature, which has unique ecological structure and function, and contains abundant natural resources to provide material guarantee for human's living and development. Wetland landscape pattern is the comprehensive result of various ecological processes, and has become a hot issue in wetland ecological study. At present, the combination of geographic information system (GIS) and remote sensing (RS) technologies is an important way to study the wetland landscape pattern change. This paper reviewed the research progress in the wetland landscape change based on GIS and RS from the aspects of the research methods of wetland landscape pattern, index of wetland landscape pattern, and driving forces of wetland landscape pattern evolution, and discussed the applications of the combination of GIS and RS in monitoring the wetland landscape pattern change, the index selection of wetland landscape pattern, and the driving mechanisms of the combined action of human and nature. Some deficiencies in the current studies were put forward, and the directions of the future-studies were prospected.

  19. SSME to RS-25: Challenges of Adapting a Heritage Engine to a New Vehicle Architecture

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2015-01-01

    Following the cancellation of the Constellation program and retirement of the Space Shuttle, NASA initiated the Space Launch System (SLS) program to provide next-generation heavy lift cargo and crew access to space. A key constituent of the SLS architecture is the RS-25 engine, also known as the Space Shuttle Main Engine (SSME). The RS-25 was selected to serve as the main propulsion system for the SLS core stage in conjunction with the solid rocket boosters. This selection was largely based on the maturity and extensive experience gained through 135 missions, 3000+ ground tests, and over a million seconds total accumulated hot-fire time. In addition, there were also over a dozen functional flight assets remaining from the Space Shuttle program that could be leveraged to support the first four flights. However, while the RS-25 is a highly mature system, simply unbolting it from the Space Shuttle boat-tail and installing it on the new SLS vehicle is not a "plug-and-play" operation. In addition to numerous technical integration details involving changes to significant areas such as the environments, interface conditions, technical performance requirements, operational constraints and so on, there were other challenges to be overcome in the area of replacing the obsolete engine control system (ECS). While the magnitude of accomplishing this effort was less than that needed to develop and field a new clean-sheet engine system, the path to the first flight of SLS has not been without unexpected challenges.

  20. Building a Human Health Risk Assessment Ontology (RsO): A Proposed Framework.

    PubMed

    McKone, Thomas E; Feng, Lydia

    2015-11-01

    Over the last decade the health and environmental research communities have made significant progress in collecting and improving access to genomic, toxicology, exposure, health, and disease data useful to health risk assessment. One of the barriers to applying these growing volumes of information in fields such as risk assessment is the lack of informatics tools to organize, curate, and evaluate thousands of journal publications and hundreds of databases to provide new insights on relationships among exposure, hazard, and disease burden. Many fields are developing ontologies as a way of organizing and analyzing large amounts of complex information from multiple scientific disciplines. Ontologies include a vocabulary of terms and concepts with defined logical relationships to each other. Building from the recently published exposure ontology and other relevant health and environmental ontologies, this article proposes an ontology for health risk assessment (RsO) that provides a structural framework for organizing risk assessment information and methods. The RsO is anchored by eight major concepts that were either identified by exploratory curations of the risk literature or the exposure-ontology working group as key for describing the risk assessment domain. These concepts are: (1) stressor, (2) receptor, (3) outcome, (4) exposure event, (5) dose-response approach, (6) dose-response metric, (7) uncertainty, and (8) measure of risk. We illustrate the utility of these concepts for the RsO with example curations of published risk assessments for ionizing radiation, arsenic in drinking water, and persistent pollutants in salmon.

  1. Bitter peptides activate hTAS2Rs, the human bitter receptors

    PubMed Central

    Maehashi, Kenji; Matano, Mami; Wang, Hong; Vo, Lynn A.; Yamamoto, Yasushi; Huang, Liquan

    2008-01-01

    Fermented food contains numerous peptides derived from material proteins. Bitter peptides formed during the fermentation process are responsible for the bitter taste of fermented food. We investigated whether human bitter receptors (hTAS2Rs) recognize bitterness of peptides with a heterologous expression system. HEK293 cells expressing hTAS2R1, hTAS2R4, hTAS2R14, and hTAS2R16 responded to bitter casein digests. Among those cells, the hTAS2R1-expressing cell was most strongly activated by the synthesized bitter peptides Gly-Phe and Gly-Leu, and none of the cells was activated by the non-bitter dipeptide Gly-Gly. The results showed that these bitter peptides, as well as many other bitter compounds, activate hTAS2Rs, suggesting that humans utilize these hTAS2Rs to recognize and perceive the structure and bitterness of peptides. PMID:18037373

  2. SerRS-tRNASec complex structures reveal mechanism of the first step in selenocysteine biosynthesis

    PubMed Central

    Wang, Caiyan; Guo, Yu; Tian, Qingnan; Jia, Qian; Gao, Yuanzhu; Zhang, Qinfen; Zhou, Chun; Xie, Wei

    2015-01-01

    Selenocysteine (Sec) is found in the catalytic centers of many selenoproteins and plays important roles in living organisms. Malfunctions of selenoproteins lead to various human disorders including cancer. Known as the 21st amino acid, the biosynthesis of Sec involves unusual pathways consisting of several stages. While the later stages of the pathways are well elucidated, the molecular basis of the first stage—the serylation of Sec-specific tRNA (tRNASec) catalyzed by seryl-tRNA synthetase (SerRS)—is unclear. Here we present two cocrystal structures of human SerRS bound with tRNASec in different stoichiometry and confirm the formation of both complexes in solution by various characterization techniques. We discovered that the enzyme mainly recognizes the backbone of the long variable arm of tRNASec with few base-specific contacts. The N-terminal coiled-coil region works like a long-range lever to precisely direct tRNA 3′ end to the other protein subunit for aminoacylation in a conformation-dependent manner. Restraints of the flexibility of the coiled-coil greatly reduce serylation efficiencies. Lastly, modeling studies suggest that the local differences present in the D- and T-regions as well as the characteristic U20:G19:C56 base triple in tRNASec may allow SerRS to distinguish tRNASec from closely related tRNASer substrate. PMID:26433229

  3. (R,S)-2-chlorophenoxyl pyrazolides as novel substrates for improving lipase-catalyzed hydrolytic resolution.

    PubMed

    Kao, Min-fang; Lu, Pei-yu; Kao, Jou-yan; Wang, Pei-yun; Wu, An-chi; Tsai, Shau-Wei

    2012-01-01

    The best reaction condition of Candida antartica lipase B as biocatalyst, 3-(2-pyridyl)pyrazole as leaving azole, and water-saturated methyl t-butyl ether as reaction medium at 45°C were first selected for performing the hydrolytic resolution of (R,S)-2-(4-chlorophenoxyl) azolides (1-4). In comparison with the kinetic resolution of (R,S)-2-phenylpropionyl 3-(2-pyridyl)pyrazolide or (R,S)-α-methoxyphenylacetyl 3-(2-pyridyl)pyrazolide at the same reaction condition, excellent enantioselectivity with more than two order-of-magnitudes higher activity for each enantiomer was obtained. The resolution was then extended to other (R,S)-3-(2-pyridyl)pyrazolides (5-7) containing 2-chloro, 3-chloro, or 2,4-dichloro substituent, giving good (E > 48) to excellent (E > 100) enantioselectivity. The thermodynamic analysis for 1, 2, and 4-7 demonstrates profound effects of the acyl or leaving moiety on varying enthalpic and entropic contributions to the difference of Gibbs free energies. A thorough kinetic analysis further indicates that on the basis of 6, the excellent enantiomeric ratio for 4 and 7 is due to the higher reactivity of (S)-4 and lower reactivity of (R)-7, respectively.

  4. PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing

    PubMed Central

    Wilkening, Reid V.; Chang, Jennifer C.; Federle, Michael J.

    2016-01-01

    Summary Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg2+ and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles. PMID:26418177

  5. Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.

    PubMed

    Guo, Min; Chong, Yeeting E; Shapiro, Ryan; Beebe, Kirk; Yang, Xiang-Lei; Schimmel, Paul

    2009-12-10

    Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.

  6. Increased risk of pneumonia associated with angiotensin-converting enzyme (CD143) rs4340 polymorphism.

    PubMed

    Zhang, Xiaofang; Liu, Fangzhu

    2016-08-01

    The study aims to investigate the genetic association between rs4340 polymorphism at intron 16 of the angiotensin-converting enzyme (CD143) gene and pneumonia predisposition. Electronic database of PubMed, Embase, and CNKI (China National Knowledge Infrastructure) was searched for the studies addressing the association between CD143 rs4340 genotypes and pneumonia risk. The odds ratio (OR) with its 95 % confidence interval (CI) was employed to estimate the association. In total, ten case-control studies, including 1239 pneumonia cases and 2400 healthy controls, met the inclusion criteria. Our results showed a significant association between rs4340 SNP and pneumonia risk using the recessive model (OR 1.43, 95 % CI 1.20-1.70). A significantly increased risk was also indicated under the recessive model in Asian populations (OR 1.63, 95 % CI 1.16-2.30), Caucasian populations (OR 1.34, 95 % CI 1.09-1.65), community-acquired pneumonia (OR 1.42, 95 % CI 1.16-1.75) rather than nosocomial pneumonia (OR 1.47, 95 % CI 0.97-2.23). However, further studies with gene-gene and gene-environmental interactions should be considered to confirm this association.

  7. Pulsations and metallicity of the pre-main sequence eclipsing spectroscopic binary RS Cha

    NASA Astrophysics Data System (ADS)

    Alecian, E.; Catala, C.; van't Veer-Menneret, C.; Goupil, M.-J.; Balona, L.

    2005-11-01

    We present new spectroscopic observations of the pre-main sequence eclipsing spectroscopic binary RS Cha. A sample of 174 spectra were obtained with the GIRAFFE spectrograph at the SAAO at 32 000 resolution. The radial velocity curves derived from these spectra were combined with previous observations spanning a period of about 30 years to correct the ephemeris of the system, and the result indicates that the orbital period is not constant. Residuals of the binary radial velocity curve for both components with amplitudes up to a few km s-1 and periods on the order of 1 h are clearly seen in our data, which we interpret as the signatures of delta-Scuti type pulsations. We revisited the masses of both components and determined the surface metallicity Z of both components of the RS Cha system by fitting synthetic spectra to observed spectra in a set of selected spectral regions. The synthetic spectra are calculated with the SYNTH code using stellar atmosphere models computed with the Kurucz ATLAS 9 code, along with a list of lines obtained from the VALD database. A selection of the best spectra and the most relevant spectral regions allowed us to determine Z = 0.028 ± 0.005. We also derived new values of v sin i: 64 ± 6 km s-1 and 70 ± 6 km s-1 for the primary and the secondary star, respectively. Finally, we observationally confirm that the RS Cha system is a synchronized and circularized system.

  8. The Evolution of Animal Welfare and the 3Rs in Brazil, China, and India

    PubMed Central

    Bayne, Kathryn; Ramachandra, Gudde S; Rivera, Ekaterina A; Wang, Jianfei

    2015-01-01

    Increasingly, scientific collaborations and contracts cross country borders. The need for assurance that the quality of animal welfare and the caliber of animal research conducted are equivalent among research partners around the globe is of concern to the scientific and laboratory animal medicine communities, the general public, and other key stakeholders. Therefore, global harmonization of animal care and use standards and practices, with the welfare of the animals as a cornerstone, is essential. In the evolving global landscape of enhanced attention to animal welfare, a widely accepted path to achieving this goal is the successful integration of the 3Rs in animal care and use programs. Currently, awareness of the 3Rs, their implementation, and the resulting animal care and use standards and practices vary across countries. This variability has direct effects on the animals used in research and potentially the data generated and may also have secondary effects on the country's ability to be viewed as a global research partner. Here we review the status of implementation of the 3Rs worldwide and focus on 3 countries–Brazil, China and India–with increasing economic influence and an increasing footprint in the biomedical research enterprise. PMID:25836965

  9. ANIMAL WELFARE FROM MOUSE TO MOOSE--IMPLEMENTING THE PRINCIPLES OF THE 3RS IN WILDLIFE RESEARCH.

    PubMed

    Lindsjö, Johan; Fahlman, Åsa; Törnqvist, Elin

    2016-04-01

    The concept of the 3Rs (replacement, reduction, and refinement) was originally developed for improving laboratory animal welfare and is well known in biomedical and toxicologic research. The 3Rs have so far gained little attention in wildlife research, and there could be several reasons for this. First, researchers may prioritize the welfare of populations and ecosystems over the welfare of individual animals. The effects of research on individual animals can, however, impact welfare and research quality at group and population levels. Second, researchers may find it difficult to apply the 3Rs to studies of free-living wildlife because of the differences between laboratory and wild animals, species, research environment, and purpose and design of the studies. There are, however, several areas where it is possible to transfer the 3R principles to wildlife research, including replacement with noninvasive research techniques, reduction with optimized experimental design, and refinement with better methods of capture, anesthesia, and handling. Third, researchers may not have been trained in applying the 3Rs in wildlife research. This training is needed since ethics committees, employers, journal publishers, and funding agencies increasingly require researchers to consider the welfare implications of their research. In this paper, we compare the principles of the 3Rs in various research areas to better understand the possibilities and challenges of the 3Rs in wildlife research. We emphasize the importance of applying the 3Rs systematically throughout the research process. Based on experiences from laboratory research, we suggest three key factors to enhance implementation of the 3Rs in wildlife research: 1) organizational structure and management, 2) 3R awareness, and 3) research innovation, validation, and implementation. Finally, we encourage an interdisciplinary approach to incorporate the 3R principles in wildlife research. For improved animal welfare and increased

  10. A Nematode Calreticulin, Rs-CRT, Is a Key Effector in Reproduction and Pathogenicity of Radopholus similis

    PubMed Central

    Li, Yu; Wang, Ke; Xie, Hui; Wang, Yan-Tao; Wang, Dong-Wei; Xu, Chun-Lin; Huang, Xin; Wang, De-Sen

    2015-01-01

    Radopholus similis is a migratory plant-parasitic nematode that causes severe damage to many agricultural and horticultural crops. Calreticulin (CRT) is a Ca2+-binding multifunctional protein that plays key roles in the parasitism, immune evasion, reproduction and pathogenesis of many animal parasites and plant nematodes. Therefore, CRT is a promising target for controlling R. similis. In this study, we obtained the full-length sequence of the CRT gene from R. similis (Rs-crt), which is 1,527-bp long and includes a 1,206-bp ORF that encodes 401 amino acids. Rs-CRT and Mi-CRT from Meloidogyne incognita showed the highest similarity and were grouped on the same branch of the phylogenetic tree. Rs-crt is a multi-copy gene that is expressed in the oesophageal glands and gonads of females, the gonads of males, the intestines of juveniles and the eggs of R. similis. The highest Rs-crt expression was detected in females, followed by juveniles, eggs and males. The reproductive capability and pathogenicity of R. similis were significantly reduced after treatment with Rs-crt dsRNA for 36 h. Using plant-mediated RNAi, we confirmed that Rs-crt expression was significantly inhibited in the nematodes, and resistance to R. similis was significantly improved in transgenic tomato plants. Plant-mediated RNAi-induced silencing of Rs-crt could be effectively transmitted to the F2 generation of R. similis; however, the silencing effect of Rs-crt induced by in vitro RNAi was no longer detectable in F1 and F2 nematodes. Thus, Rs-crt is essential for the reproduction and pathogenicity of R. similis. PMID:26061142

  11. Molecular cloning of AtRS4, a seed specific multifunctional RFO synthase/galactosylhydrolase in Arabidopsis thaliana

    PubMed Central

    Gangl, Roman; Behmüller, Robert; Tenhaken, Raimund

    2015-01-01

    Stachyose is among the raffinose family oligosaccharides (RFOs) one of the major water-soluble carbohydrates next to sucrose in seeds of a number of plant species. Especially in leguminous seeds, e.g. chickpea, stachyose is reported as the major component. In contrast to their ambiguous potential as essential source of carbon for germination, RFOs are indigestible for humans and can contribute to diverse abdominal disorders. In the genome of Arabidopsis thaliana, six putative raffinose synthase genes are reported, whereas little is known about these putative raffinose synthases and their biochemical characteristics or their contribution to the RFO physiology in A. thaliana. In this paper, we report on the molecular cloning, functional expression in Escherichia coli and purification of recombinant AtRS4 from A. thaliana and the biochemical characterisation of the putative stachyose synthase (AtSTS, At4g01970) as a raffinose and high affinity stachyose synthase (Km for raffinose 259.2 ± 21.15 μM) as well as stachyose and galactinol specific galactosylhydrolase. A T-DNA insertional mutant in the AtRS4 gene was isolated. Only semi-quantitative PCR from WT siliques showed a specific transcriptional AtRS4 PCR product. Metabolite measurements in seeds of ΔAtRS4 mutant plants revealed a total loss of stachyose in ΔAtRS4 mutant seeds. We conclude that AtRS4 is the only stachyose synthase in the genome of A. thaliana that AtRS4 represents a key regulation mechanism in the RFO physiology of A. thaliana due to its multifunctional enzyme activity and that AtRS4 is possibly the second seed specific raffinose synthase beside AtRS5, which is responsible for Raf accumulation under abiotic stress. PMID:26483807

  12. A Nematode Calreticulin, Rs-CRT, Is a Key Effector in Reproduction and Pathogenicity of Radopholus similis.

    PubMed

    Li, Yu; Wang, Ke; Xie, Hui; Wang, Yan-Tao; Wang, Dong-Wei; Xu, Chun-Lin; Huang, Xin; Wang, De-Sen

    2015-01-01

    Radopholus similis is a migratory plant-parasitic nematode that causes severe damage to many agricultural and horticultural crops. Calreticulin (CRT) is a Ca2+-binding multifunctional protein that plays key roles in the parasitism, immune evasion, reproduction and pathogenesis of many animal parasites and plant nematodes. Therefore, CRT is a promising target for controlling R. similis. In this study, we obtained the full-length sequence of the CRT gene from R. similis (Rs-crt), which is 1,527-bp long and includes a 1,206-bp ORF that encodes 401 amino acids. Rs-CRT and Mi-CRT from Meloidogyne incognita showed the highest similarity and were grouped on the same branch of the phylogenetic tree. Rs-crt is a multi-copy gene that is expressed in the oesophageal glands and gonads of females, the gonads of males, the intestines of juveniles and the eggs of R. similis. The highest Rs-crt expression was detected in females, followed by juveniles, eggs and males. The reproductive capability and pathogenicity of R. similis were significantly reduced after treatment with Rs-crt dsRNA for 36 h. Using plant-mediated RNAi, we confirmed that Rs-crt expression was significantly inhibited in the nematodes, and resistance to R. similis was significantly improved in transgenic tomato plants. Plant-mediated RNAi-induced silencing of Rs-crt could be effectively transmitted to the F2 generation of R. similis; however, the silencing effect of Rs-crt induced by in vitro RNAi was no longer detectable in F1 and F2 nematodes. Thus, Rs-crt is essential for the reproduction and pathogenicity of R. similis.

  13. A Structural Basis for Reversible Photoswitching of Absorbance Spectra in Red Fluorescent Protein rsTagRFP

    PubMed Central

    Pletnev, Sergei; Subach, Fedor V.; Dauter, Zbigniew; Wlodawer, Alexander; Verkhusha, Vladislav V.

    2012-01-01

    rsTagRFP the first monomeric red fluorescent protein with reversibly photoswitchable absorbance spectra. The switching is realized by irradiation of rsTagRFP with blue (440 nm) and yellow (567 nm) light, turning the protein fluorescence ON and OFF, respectively. It is perhaps the most useful probe in this color class that has yet been reported. Because of the photoswitchable absorbance, rsTagRFP can be used as an acceptor in photochromic Förster resonance energy transfer (pcFRET). Yellow fluorescent proteins YPet and mVenus have been demonstrated to be excellent pcFRET donors for the rsTagRFP acceptor in its fusion constructs. Analysis of X-ray structures has shown that photoswitching of rsTagRFP is accompanied by cis-trans isomerization and protonation/deprotonation of the chromophore, with the deprotonated cis- and protonated trans- isomers corresponding to its ON and OFF states. Unlike in other photoswitchable fluorescent proteins, both conformers of rsTagRFP chromophore are essentially coplanar. Two other peculiarities of the rsTagRFP chromophore are an essentially hydrophobic environment of its p-hydroxyphenyl site and the absence of direct hydrogen bonding between this moiety and the protein scaffold. The influence of the immediate environment on rsTagRFP chromophore was probed by site-directed mutagenesis. Residues Glu145 and His197 were found to participate in protonation/deprotonation of the chromophore accompanying the photoswitching of rsTagRFP fluorescence, whereas the residues Met160 and Leu174 were shown to spatially restrict chromophore isomerization, favoring its radiative decay. PMID:22310052

  14. Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population

    PubMed Central

    Chen, Shanshan; Wang, Chuchu; Wang, Xiaojing; Xu, Chengqi; Wu, Manman; Wang, Pengxia; Tu, Xin; Wang, Qing K

    2015-01-01

    Background Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies. Methods and Results Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF (Padj=4.77×10−5), and the finding was replicated in 2 other independent populations with 709 cases and 2175 controls, 463 cases and 644 controls, and the combined population with a total of 2113 cases and 3381 controls (Padj=2.20×10−9; odds ratio [OR]=1.34 for major allele G). Meta-analysis, together with data from previous reports in Chinese and Japanese populations, also showed a significant association between rs3807989 and AF (P=3.40×10−4; OR=1.24 for allele G). We also found that rs3807989 showed a significant association with lone AF in 3 independent populations and in the combined population (Padj=3.85×10−8; OR=1.43 for major allele G). Conclusions The data in this study revealed a significant association between rs3807989 and AF in the Chinese Han population. Together with the findings that caveolin-1 interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF across different ethnic populations. This study is the first to show a significant association between rs3807989 and lone AF. PMID:25953654

  15. Genetic Polymorphism of the Serotonin Transporter Gene, SLC6A4 rs16965628, Is Associated with Obsessive Compulsive Disorder.

    PubMed

    Cengiz, Mujgan; Okutan, Saide Nur; Bayoglu, Burcu; Sakalli Kani, Ayse; Bayar, Reha; Kocabasoglu, Nese

    2015-05-01

    Obsessive compulsive disorder (OCD) is a psychiatric disorder characterized by obsessive ideas and compulsive behaviors. Genetic studies have centered on candidate genes involved in OCD etiology related to serotonergic and dopaminergic systems. In this study, the relationship between cathechol-O-methyltransferase (COMT) -287A/G (rs2097063), serotonin transporters 5-HTTLPR I/D, and SLC6A4 rs16965628 polymorphisms in 80 OCD patients and 100 healthy controls was determined. Patients and controls were genotyped for COMT rs2097063 and SLC6A4 rs16965628 polymorphisms by real-time polymerase chain reaction (PCR). The 5-HTTLPR I/D polymorphism was genotyped using PCR and agarose gel electrophoresis. Severity of symptoms was checked with a Yale-Brown Obsession Compulsion Scale (Y-BOCS). When the OCD group and controls were compared, no significant difference was found between COMT -287A/G (rs2097063), 5-HTTLPR I/D polymorphisms, and OCD. However, a significant difference was found between 5-HTT rs16965628 polymorphism and OCD (p=0.025, OR=3.43, 95% CI 1.41-10.35). In addition, the G allele frequency was found to be higher for rs16965628 in the OCD group. No significant difference was observed between COMT -287A/G (rs2097063), SLC6A4 rs16965628, and 5-HTTLPR I/D polymorphisms and Y-BOCS scores (p>0.05). There was also lack of correlation between Yale-Brown scores and gender of OCD patients. On the other hand, combined genotypes of SLC6A4 rs16965628 GG+GC were found to be risk factors for OCD development (p=0.02, OR=3.464; 95% CI 1.214-9.883) in logistic regression analysis adjusted for age and gender. Our findings suggest that subjects carrying the G allele of rs16965628 have genetic susceptibility to OCD. These data are the first to suggest that polymorphism in serotonin transporter (rs16965628) is associated with the development of OCD in the Turkish population.

  16. Stressful life events increase aggression and alcohol use in young carriers of the GABRA2 rs279826/rs279858 A-allele.

    PubMed

    Kiive, Evelyn; Laas, Kariina; Vaht, Mariliis; Veidebaum, Toomas; Harro, Jaanus

    2017-02-23

    Research of GABRA2 gene in alcohol use and impulse control suggests its role in aggressive behaviour. The purpose of the present study was to examine the effects of GABRA2 genotype and stressful life events on aggressive behaviour, alcohol use frequency and occurrence of alcohol use disorder in a population representative sample of adolescents followed up from third grade to 25 years of age. The sample consisted of the younger cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study. Aggressive behaviour was rated with the activity scale of af Klinteberg, Illinois Bully Scale and Buss-Perry Aggression Questionnaire. Stressful life events and alcohol use were self-reported. Life history of aggression and lifetime occurrence of psychiatric disorders were estimated in a structured interview. The sample was genotyped for GABRA2 rs279826 and rs279858 polymorphisms that are in strong linkage disequilibrium and yielded very similar findings: Higher number of stressful life events reported at age 15 was associated with increased fighting in A-allele carriers, but not in GG homozygotes. At age 25, A-allele carriers with more stressful life events scored higher on physical aggression than those with less stress, and this was also observed regarding life history of aggression. A-allele carriers exposed to higher stress had consumed alcoholic beverages more frequently at age 15, and by age 25, they had alcohol use disorder with higher prevalence. The results of the present study suggest that the GABRA2 genotype interacts with stress in young people with impact on the development of alcohol use and aggressive behaviour.

  17. Study of Association between Pre-Senile Cataracts and the Polymorphisms rs2228000 in XPC and rs1042522 in p53 in Spanish Population

    PubMed Central

    López Valverde, Gloria; Garcia Martin, Elena; Larrosa Povés, José M.; Polo Llorens, Vicente; Pablo Júlvez, Luis E.

    2016-01-01

    Purpose To determine if the presence of certain polymorphisms in the DNA repair gene XPC and the apoptosis inductor gene p53 is associated with pre-senile cataract development. Methods We have performed a retrospective study over three groups of patients. The group with pre-senile cataract formed by 72 patients younger than 55 with cataract surgery. The group with senile cataract formed by 101 patients older than 55 with cataract surgery. The group without cataract was formed by 42 subjects older than 55 without lens opacities. We analyzed the presence of SNP rs2228000 from XPC and rs1042522 from p53; and the relationship between risk factors such as smoking, alcohol intake, hypertension or diabetes. Results The comparison of the genotype distribution in XPC, within the different groups, did not show any statistically significant association in any of our analysis (p>0,05). The comparison of the genotype distribution in p53 within the different groups did not show any statistically significant association (p>0,05); except for the comparison between the pre-senile cataract group and the group with senile cataract where the genotype Pro/Pro (C/C) in the recessive inheritance model showed a higher risk for developing pre-senile cataract (p = 0,031; OR = 1.04–15.97). This association decreased when we performed the analysis adjusting by the studied risk factors (p = 0.056). Conclusions Allelic variants in the gene XPC are not associated with an increased risk for developing pre-senile cataract. The presence of the genotype Pro/Pro in p53 might be associated with a major risk for developing pre-senile cataract. PMID:27248495

  18. Association between SERPING1 rs2511989 polymorphism and age-related macular degeneration: Meta-analysis

    PubMed Central

    Dong, Yi; Li, Ze-Dong; Fang, Xin-Yu; Shi, Xue-Feng; Chen, Song; Tang, Xin

    2015-01-01

    AIM To investigate the association between SERPING1 rs2511989 (G>A) polymorphism and age-related macular degeneration (AMD). METHODS A number of electronic databases (up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE) were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038). However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25). CONCLUSION This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future. PMID:25938061

  19. Reference quality upper-air measurements: GRUAN data processing for the Vaisala RS92 radiosonde

    NASA Astrophysics Data System (ADS)

    Dirksen, R. J.; Sommer, M.; Immler, F. J.; Hurst, D. F.; Kivi, R.; Vömel, H.

    2014-12-01

    The GCOS (Global Climate Observing System) Reference Upper-Air Network (GRUAN) data processing for the Vaisala RS92 radiosonde was developed to meet the criteria for reference measurements. These criteria stipulate the collection of metadata, the use of well-documented correction algorithms, and estimates of the measurement uncertainty. An important and novel aspect of the GRUAN processing is that the uncertainty estimates are vertically resolved. This paper describes the algorithms that are applied in version 2 of the GRUAN processing to correct for systematic errors in radiosonde measurements of pressure, temperature, humidity, and wind, as well as how the uncertainties related to these error sources are derived. Currently, the RS92 is launched on a regular basis at 13 out of 15 GRUAN sites. An additional GRUAN requirement for performing reference measurements with the RS92 is that the manufacturer-prescribed procedure for the radiosonde's preparation, i.e. heated reconditioning of the sensors and recalibration during ground check, is followed. In the GRUAN processing however, the recalibration of the humidity sensors that is applied during ground check is removed. For the dominant error source, solar radiation, laboratory experiments were performed to investigate and model its effect on the RS92's temperature and humidity measurements. GRUAN uncertainty estimates are 0.15 K for night-time temperature measurements and approximately 0.6 K at 25 km during daytime. The other uncertainty estimates are up to 6% relative humidity for humidity, 10-50 m for geopotential height, 0.6 hPa for pressure, 0.4-1 m s-1 for wind speed, and 1° for wind direction. Daytime temperature profiles for GRUAN and Vaisala processing are comparable and consistent within the estimated uncertainty. GRUAN daytime humidity profiles are up to 15% moister than Vaisala processed profiles, of which two-thirds is due to the radiation dry bias correction and one-third is due to an additional

  20. RS-Predictor models augmented with SMARTCyp reactivities: Robust metabolic regioselectivity predictions for nine CYP isozymes

    PubMed Central

    Zaretzki, Jed; Rydberg, Patrik; Bergeron, Charles; Bennett, Kristin P.; Olsen, Lars

    2012-01-01

    RS-Predictor is a tool for creating pathway-independent, isozyme-specific site of metabolism (SOM) prediction models using any set of known cytochrome P450 substrates and metabolites. Until now, the RS-Predictor method was only trained and validated on CYP 3A4 data, but in the present study we report on the versatility the RS-Predictor modeling paradigm by creating and testing regioselectivity models for substrates of the nine most important CYP isozymes. Through curation of source literature, we have assembled 680 substrates distributed among CYPs 1A2, 2A6, 2B6, 2C19, 2C8, 2C9, 2D6, 2E1 and 3A4, which we believe is the largest publicly accessible collection of P450 ligands and metabolites ever released. A comprehensive investigation into the importance of different descriptor classes for predicting the regioselectivity of each isozyme is made through the generation of multiple independent RS-Predictor models for each set of isozyme substrates. Two of these models include a DFT reactivity descriptor derived from SMARTCyp. Optimal combinations of RS-Predictor and SMARTCyp are shown to have stronger performance than either method alone, while also exceeding the accuracy of the commercial regioselectivity prediction methods distributed by StarDrop and Schrödinger, correctly identifying a large proportion of the metabolites in each substrate set within the top two rank-positions: 1A2(83.0%), 2A6(85.7%), 2B6(82.1%), 2C19(86.2%), 2C8(83.8%), 2C9(84.5%), 2D6(85.9%), 2E1(82.8%), 3A4(82.3%) and merged(86.0%). Comprehensive datamining of each substrate set and careful statistical analyses of the predictions made by the different models revealed new insights into molecular features that control metabolic regioselectivity and enable accurate prospective prediction of likely SOMs. PMID:22524152

  1. Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation

    PubMed Central

    Servetas, Stephanie L.; Carpenter, Beth M.; Haley, Kathryn P.; Gilbreath, Jeremy J.; Gaddy, Jennifer A.

    2016-01-01

    ABSTRACT Helicobacter pylori must be able to rapidly respond to fluctuating conditions within the stomach. Despite this need for constant adaptation, H. pylori encodes few regulatory proteins. Of the identified regulators, the ferric uptake regulator (Fur), the nickel response regulator (NikR), and the two-component acid response system (ArsRS) are each paramount to the success of this pathogen. While numerous studies have individually examined these regulatory proteins, little is known about their combined effect. Therefore, we constructed a series of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS. A growth curve analysis revealed minor variation in growth kinetics across the strains; these were most pronounced in the triple mutant and in strains lacking ArsS. Visual analysis showed that strains lacking ArsS formed large aggregates and a biofilm-like matrix at the air-liquid interface. Biofilm quantification using crystal violet assays and visualization via scanning electron microscopy (SEM) showed that all strains lacking ArsS or containing a nonphosphorylatable form of ArsR (ArsR-D52N mutant) formed significantly more biofilm than the wild-type strain. Molecular characterization of biofilm formation showed that strains containing mutations in the ArsRS pathway displayed increased levels of cell aggregation and adherence, both of which are key to biofilm development. Furthermore, SEM analysis revealed prevalent coccoid cells and extracellular matrix formation in the ArsR-D52N, ΔnikR ΔarsS, and Δfur ΔnikR ΔarsS mutant strains, suggesting that these strains may have an exacerbated stress response that further contributes to biofilm formation. Thus, H. pylori ArsRS has a previously unrecognized role in biofilm formation. IMPORTANCE Despite a paucity of regulatory proteins, adaptation is key to the survival of H. pylori within the stomach. While prior studies have focused on individual

  2. RS-Predictor models augmented with SMARTCyp reactivities: robust metabolic regioselectivity predictions for nine CYP isozymes.

    PubMed

    Zaretzki, Jed; Rydberg, Patrik; Bergeron, Charles; Bennett, Kristin P; Olsen, Lars; Breneman, Curt M

    2012-06-25

    RS-Predictor is a tool for creating pathway-independent, isozyme-specific, site of metabolism (SOM) prediction models using any set of known cytochrome P450 (CYP) substrates and metabolites. Until now, the RS-Predictor method was only trained and validated on CYP 3A4 data, but in the present study, we report on the versatility the RS-Predictor modeling paradigm by creating and testing regioselectivity models for substrates of the nine most important CYP isozymes. Through curation of source literature, we have assembled 680 substrates distributed among CYPs 1A2, 2A6, 2B6, 2C19, 2C8, 2C9, 2D6, 2E1, and 3A4, the largest publicly accessible collection of P450 ligands and metabolites released to date. A comprehensive investigation into the importance of different descriptor classes for identifying the regioselectivity mediated by each isozyme is made through the generation of multiple independent RS-Predictor models for each set of isozyme substrates. Two of these models include a density functional theory (DFT) reactivity descriptor derived from SMARTCyp. Optimal combinations of RS-Predictor and SMARTCyp are shown to have stronger performance than either method alone, while also exceeding the accuracy of the commercial regioselectivity prediction methods distributed by Optibrium and Schrödinger, correctly identifying a large proportion of the metabolites in each substrate set within the top two rank-positions: 1A2 (83.0%), 2A6 (85.7%), 2B6 (82.1%), 2C19 (86.2%), 2C8 (83.8%), 2C9 (84.5%), 2D6 (85.9%), 2E1 (82.8%), 3A4 (82.3%), and merged (86.0%). Comprehensive datamining of each substrate set and careful statistical analyses of the predictions made by the different models revealed new insights into molecular features that control metabolic regioselectivity and enable accurate prospective prediction of likely SOMs.

  3. Compressive Creep Response of T1000G/RS-14 Graphite/Polycyanate Composite Materials

    SciTech Connect

    Starbuck, J.M.

    1998-01-01

    The response of a T1000G/RS-14 graphite/polycyanate composite material system to transverse compressive loads is quantified via experimentation. The primary objective of the work was to quantify the effects of process environment and test environment on the T1000G/RS-14 compressive creep response. Tests were conducted on both the neat resin and the composite material system. In addition to the creep tests, static compressive strength tests were conducted to define the stress-strain response. The creep behavior for the RS-14 resin was quantified by conducting a series of tests to study the effects of different process environments (air and nitrogen), different cure temperatures, and different test environments (air and vacuum). The combined effect on the RS-14 resin compressive creep of processing in nitrogen and testing under vacuum versus processing in air and testing in air was a 47% decrease in the creep strain after 2177 hr. The test environment appeared to have a greater effect on the resin creep than the process environment. Following the conclusion of the resin creep tests, composite transverse compressive creep tests were conducted. The composite creep test cylinder was post-cured in a nitrogen environment prior to machining test specimens and all tests were conducted in a vacuum environment. The series of tests investigated the effects of initial stress level and test temperature on the creep behavior. At the end of the 2000-hr tests at 275{degrees}F on specimens stressed at 10,000 psi, the nitrogen-processed and vacuum-tested conditions reduced the composite transverse compressive creep strain by 19% compared to processing in air and testing in air. The effects of process and test environment on the creep behavior are not as great for the composite system as they were for the neat resin, primarily because of the low resin content in the composite material system. At the 275{degrees}F test temperature there was a significant increase in the composite

  4. The interferon lambda 4 rs368234815 predicts treatment response to pegylated-interferon alpha and ribavirin in hemophilic patients with chronic hepatitis C

    PubMed Central

    Keshvari, Maryam; Alavian, Seyed Moayed; Behnava, Bita; Pouryasin, Ali; Sharafi, Heidar

    2016-01-01

    Background: A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-α) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC). Materials and Methods: In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-α/RBV were investigated. Single-nucleotide polymorphisms (SNPs) in IFNL genomic region including rs368234815, rs12979860, and rs8099917 were analyzed by DNA sequencing. Results: Of the 92 patients, 63 (68.5%) achieved sustained virological response (SVR). Of the 43 patients with rs368234815 TT/TT genotype, 36 (83.7%) achieved SVR, while in 49 patients with non-TT/TT genotypes, 27 (55.1%) achieved SVR. Other pretreatment parameters predicted SVR were patients’ body mass index, HCV genotype, rs12979860, and rs8099917 SNPs. In multivariate analysis, all above-mentioned parameters except rs8099917 remained as predictors of SVR. IFNL4 rs368234815 was a strong predictor of SVR; however, the prediction power of this SNP was the same as that of rs12979860 SNP in the patients of the current study. Conclusion: IFNL4 rs368234815 SNP can be considered for decision-making in the treatment of HCV-infected patients. PMID:27904617

  5. An Association Study between INSR/NsiI (rs2059806) and INSR/PmlI (rs1799817) SNPs in Women with Polycystic Ovary Syndrome from West Azerbaijan Province, Iran

    PubMed Central

    Bagheri, Morteza; Abdi-Rad, Isa; Hosseini-Jazani, Nima; Zarrin, Rasoul; Nanbakhsh, Fariba; Mohammadzaie, Nauman

    2015-01-01

    Background It has been demonstrated that insulin signaling pathway related genes have important roles in polycystic ovary syndrome (PCOS) risk. The goal of present investigation was to assess the potential association between INSR/NsiI (rs2059806) and INSR/PmlI (rs1799817) SNPs and PCOS. Methods 50 women with PCOS and 47 normal controls entered the study. NsiI and PmlI SNPs in the INSR gene were determined by RFLP-PCR. Results INSR/NsiI (rs2059806) SNP GG, GA, AA, G and A genotypic and allelic frequencies were 45(90%), 5(10%), 0(0%), 95(95%) and 5(5%) in cases and 41 (87.2%), 6(12.8%), 0(0%), 88(93.6%) and 6(6.38%) in controls, respectively. INSR/ PmlI (rs1799817) SNPs resulted in three genotypes of CC, CT, and TT with C and T alleles. The frequencies of PmlI (rs1799817) SNPs in the INSR gene were 37(37%) and 63(63%) in cases, also 39(41.49%) and 55 (58.51%) in controls regarding T and C alleles. The frequencies of PmlI (rs1799817) SNPs in the INSR gene were 4(8%), 29(58%), and 17(34%) in cases, also 5(10.64%), 29(61.7%), and 13(27.66%) in controls regarding TT, TC, and CC genotypes, respectively. Conclusion The present study as the first investigation of its own kind in Iranian Azeri Turkish women, reported no association between NsiI (rs2059806) and PmlI (rs1799817) SNPs in the INSR gene and PCOS risk. PMID:25927028

  6. Lack of association between interleukin 28B gene polymorphisms (rs8099917G/T, rs12979860 C/T) and susceptibility to chronic hepatitis C virus infection, Tehran, Iran

    PubMed Central

    Karkhane, Maryam; Mohebbi, Seyed Reza; Azimzadeh, Pedram; Saeedi Niasar, Mahsa; Sarbazi, Mohamad Reza; Sharifian, Afsaneh; Alizadeh, Afshin Mohammad

    2016-01-01

    Aim: Chronic Hepatitis C infection is a critical health problem worldwide, which caused by hepatitis C virus (HCV). Interleukin 28B (IL28B) is a determinant factor in disease progression and also susceptibility to chronic HCV infection. Background: The most significant aim of this study is to analyze the association between IL28B gene polymorphisms with susceptibility to chronic HCV infection in Iranian population. Methods: This study follows a case- control study design, in which, 288 patients with chronic hepatitis C and 250 healthy individuals were genotyped for IL28B polymorphisms (rs12979860 C/T and rs8099917 G/T). Studied population collected from Taleghani Haospital, Tehran. Genotyping of IL28B gene polymorphisms were performed using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) method. 10 percent of the studied population was sequenced to validate the results. Results: rs8099917 G/T and rs12979860 C/T were differently distributed in hepatitis C patients and healthy controls in the female gender. TT, TG and GG genotypes distribution in the female gender were 56.7%, 39.8% and 4.5% in cases and 67%, 31.6% and 1.4% in controls (p=0.54). Also CC, CT and TT genotypes distribution were 31.8%, 61.4% and 6.8% in cases and 51.7%, 44.9% and 3.4% in controls (p=0.2). However, there was no significant difference in the allelic frequency and genotype distribution of rs12979860 C/T and rs8099917 T/G in both HCV patients with genotype 1a and 3a. Conclusion: It seems that rs8099917 G/T polymorphism plays a significant role in susceptibility to chronic HCV infection in Iranian population. On the other hand, no association was found between rs12979860 C/T polymorphisms and chronic hepatitis C. PMID:28224025

  7. ESR1 gene polymorphisms PvuII (rs2234693T>C) and XbaI (rs9340799A>G) may not be directly correlated with cardiovascular disease risk.

    PubMed

    Jiang, N; Yang, G; Peng, C L

    2015-10-30

    The aim of this meta-analysis was to evaluate the correlations between the estrogen receptor 1 (ESR1) gene polymorphisms PvuII (rs2234693T>C) and XbaI (rs9340799A>G) and the risk of cardiovascular disease (CVD). Case-control studies were screened and selected from a larger group of studies that were retrieved through a comprehensive search of scientific literature databases, which was complemented by manual searches. Data from studies selected were analyzed using the Comprehensive Meta-analysis 2.0 software. A total of 240 studies were initially retrieved and 10 studies were eventually included in the meta-analysis. These 10 case-control studies involved 7029 CVD patients (5001 myocardial infarction patients, 1223 coronary artery disease patients, 805 acute coronary syndromes patients) and 6901 healthy controls. We found no significant association between the PvuII (rs2234693T>C) and XbaI (rs9340799A>G) polymorphisms and CVD risk. We detected no significant associations under all genetic inheritance models tested, including the allele, dominant, homozygous, heterozygous, and recessive models, or for comparisons between the case group and control group (all P > 0.05). Our meta-analysis results strongly suggest that the ESR1 gene polymorphisms PvuII (rs2234693T>C) and XbaI (rs9340799A>G) are not associated with CVD risk.

  8. [Improvement of natamycin production in an industrial strain by heterologous expression of the afsRS(cla) global regulatory genes].

    PubMed

    Tao, Zhengsheng; Wang, Yemin; Zheng, Hualiang; Tao, Meifeng

    2015-05-01

    The afsRS(cla) global regulatory genes from Streptomyces clavuligerus activate the production of two antibiotics in Streptomyces lividans. In this study, we gained an increase of 38% in the production of natamycin (3.56 g/L) in an industrial strain Streptomyces gilvosporeus TZ1401 through the integration of pHL851 that bears the afsRS(cla) global regulatory genes into its genome. We discovered by quantitive real-time reverse transcription PCR (qRT-PCR) that the expression of 6 genes of the natamycin biosynthetic gene cluster were improved from 1.9 to 2.7 times. This suggests that afsRS(cla) improve the production of natamycin through increased transcription. This study provides a good example for applying afsRS(cla) in high yield breeding of industrial antibiotic producers.

  9. Two-component signal transduction system SaeRS is involved in competence and penicillin susceptibility in Staphylococcus epidermidis.

    PubMed

    Lou, Qiang; Ma, Yuanfang; Qu, Di

    2016-04-01

    Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, the S. epidermidis SaeRS was identified to negatively regulate the expression of genes involved in competence (comF, murF), cytolysis (lrgA), and autolysis (lytS) by DNA microarray or real-time RT-PCR analysis. In addition, saeRS mutant showed increased competence and higher susceptibility to antibiotics such as penicillin and oxacillin than the wild-type strain. The study will be helpful for understanding the characterization of the SaeRS in S. epidermidis.

  10. RS-WebPredictor: a server for predicting CYP-mediated sites of metabolism on drug-like molecules

    PubMed Central

    Zaretzki, Jed; Bergeron, Charles; Huang, Tao-wei; Rydberg, Patrik; Swamidass, S. Joshua; Breneman, Curt M.

    2013-01-01

    Summary: Regioselectivity-WebPredictor (RS-WebPredictor) is a server that predicts isozyme-specific cytochrome P450 (CYP)-mediated sites of metabolism (SOMs) on drug-like molecules. Predictions may be made for the promiscuous 2C9, 2D6 and 3A4 CYP isozymes, as well as CYPs 1A2, 2A6, 2B6, 2C8, 2C19 and 2E1. RS-WebPredictor is the first freely accessible server that predicts the regioselectivity of the last six isozymes. Server execution time is fast, taking on average 2s to encode a submitted molecule and 1s to apply a given model, allowing for high-throughput use in lead optimization projects. Availability: RS-WebPredictor is accessible for free use at http://reccr.chem.rpi.edu/Software/RS-WebPredictor/ Contact: brenec@rpi.edu PMID:23242264

  11. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    PubMed Central

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  12. The rs2071559 AA VEGFR-2 genotype frequency is significantly lower in neovascular age-related macular degeneration patients.

    PubMed

    Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Cascio, Elisa; Di Desidero, Teresa; Agosta, Elisa; Canu, Bastianina; Sartini, Maria Sole; Danesi, Romano; Nardi, Marco; Bocci, Guido

    2012-01-01

    In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; P(corr) = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  13. The rs2071559 AA VEGFR-2 Genotype Frequency Is Significantly Lower in Neovascular Age-Related Macular Degeneration Patients

    PubMed Central

    Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Cascio, Elisa; Di Desidero, Teresa; Agosta, Elisa; Canu, Bastianina; Sartini, Maria Sole; Danesi, Romano; Nardi, Marco; Bocci, Guido

    2012-01-01

    In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; Pcorr = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs. PMID:22919317

  14. 5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus.

    PubMed

    Kruschwitz, J D; Walter, M; Varikuti, D; Jensen, J; Plichta, M M; Haddad, L; Grimm, O; Mohnke, S; Pöhland, L; Schott, B; Wold, A; Mühleisen, T W; Heinz, A; Erk, S; Romanczuk-Seiferth, N; Witt, S H; Nöthen, M M; Rietschel, M; Meyer-Lindenberg, A; Walter, H

    2015-07-01

    The s/s-genotype of the 5-HTTLPR polymorphism and the personality trait of neuroticism have both been associated with experiences of negative affect, anxiety and mood disorders, as well as an emotional processing bias towards negative facial emotions. On a neural level, this bias can be characterized by altered amygdala and fusiform gyrus (FFG) activity during perception of negative facial expressions. Using resting-state functional magnetic resonance imaging in a multi-center-sample of 178 healthy subjects of European descent, this study investigated the association of 5-HTTLPR (short s- and long l-allele) including the genotype of the single nucleotide polymorphism (SNP) rs25531 (A/G) within this region polymorphism, and trait neuroticism on resting-state functional connectivity (rs-FC) between amygdala and the FFG. Moreover, we aimed to identify additional brain regions with associations of 5-HTTLPR/rs25531 (combined according to its expression; low: s/s; high: l(A)/l(A); intermediate: s/l(A), s/l(G), l(G)/l(G), l(A)/l(G)) and trait neuroticism to amygdala rs-FC. Separate analyses for 5-HTTLPR/rs25531 and neuroticism (controlling for age, gender, handedness, and research site) revealed that s/s-homozygotes and individuals high in neuroticism obtained altered amygdala rs-FC in the right occipital face area, which is considered to be a "core component" of the face processing system. Importantly, effects of neuroticism were replicated across three independent research sites. Additionally, associations of 5-HTTLPR/rs25531 genotype and amygdala rs-FC were observed in the anterior and posterior cingulate cortex, whereas neuroticism was not related to rs-FC in these areas. The presented data implies that 5-HTTLPR/rs25531 variants and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus and suggests that variants of 5-HTTLPR/rs25531 genotype and different levels of neuroticism may partly account for altered processing of

  15. Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

    PubMed Central

    Robustillo-Villarino, Montserrat; García-Bermúdez, Mercedes; Llorca, Javier; Corrales, Alfonso; González-Juanatey, Carlos; Ubilla, Begoña; Miranda-Filloy, José A.; Mijares, Verónica; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J.; Ramírez Huaranga, Marco A.; Mínguez Sánchez, María D.; Tejera Segura, Beatriz; Ferraz-Amaro, Iván; Vicente, Esther; Carmona, F. David; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A.

    2015-01-01

    Objectives To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Methods A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). Results RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. Conclusions In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA. PMID:26571131

  16. The functional serotonin 1a receptor promoter polymorphism, rs6295, is associated with psychiatric illness and differences in transcription

    PubMed Central

    Donaldson, Z R; le Francois, B; Santos, T L; Almli, L M; Boldrini, M; Champagne, F A; Arango, V; Mann, J J; Stockmeier, C A; Galfalvy, H; Albert, P R; Ressler, K J; Hen, R

    2016-01-01

    The G/C single-nucleotide polymorphism in the serotonin 1a receptor promoter, rs6295, has previously been linked with depression, suicide and antidepressant responsiveness. In vitro studies suggest that rs6295 may have functional effects on the expression of the serotonin 1a receptor gene (HTR1A) through altered binding of a number of transcription factors. To further explore the relationship between rs6295, mental illness and gene expression, we performed dual epidemiological and biological studies. First, we genotyped a cohort of 1412 individuals, randomly split into discovery and replication cohorts, to examine the relationship between rs6295 and five psychiatric outcomes: history of psychiatric hospitalization, history of suicide attempts, history of substance or alcohol abuse, current posttraumatic stress disorder (PTSD), current depression. We found that the rs6295G allele is associated with increased risk for substance abuse, psychiatric hospitalization and suicide attempts. Overall, exposure to either childhood or non-childhood trauma resulted in increased risk for all psychiatric outcomes, but we did not observe a significant interaction between rs6295 and trauma in modulating psychiatric outcomes. In conjunction, we also investigated the potential impact of rs6295 on HTR1A expression in postmortem human brain tissue using relative allelic expression assays. We found more mRNA produced from the C versus the G-allele of rs6295 in the prefrontal cortex (PFC), but not in the midbrain of nonpsychiatric control subjects. Further, in the fetal cortex, rs6295C allele exhibited increased relative expression as early as gestational week 18 in humans. Finally, we found that the C:G allelic expression ratio was significantly neutralized in the PFC of subjects with major depressive disorder (MDD) who committed suicide as compared with controls, indicating that normal patterns of transcription may be disrupted in MDD/suicide. These data provide a putative biological

  17. Fermentation RS3 derived from sago and rice starch with Clostridium butyricum BCC B2571 or Eubacterium rectale DSM 17629.

    PubMed

    Purwani, Endang Yuli; Purwadaria, Tresnawati; Suhartono, Maggy Thenawidjaja

    2012-02-01

    Resistant starch type 3 (RS3) is retrograded starch which is not digested by human starch degrading enzyme, and will thus undergo bacterial degradation in the colon. The main fermentation products are the Short Chain Fatty Acid (SCFA): acetate, propionate and butyrate. SCFA has significant benefit impact on the metabolism of the host. The objectives of this research were to study the SCFA profile produced by colonic butyrate producing bacteria grown in medium containing RS3. RS3 was made from sago or rice starch treated with amylase, pullulanase and the combination of amylase and pullulanase. Fermentation study was performed by using Clostridium butyricum BCC B2571 or Eubacterium rectale DSM 17629, which has been identified as capable of degradation of starch residue and also regarded as beneficial bacteria. Experimental result revealed that enzyme hydrolysis of retrograded sago or rice starch was beneficial to RS formation. RS3 derived from sago contained higher RS (31-38%) than those derived from rice starch (21-26%). This study indicated that C. butyricum BCC B2571 produced acetate, propionate and butyrate at molar ratio of 1.8 : 1 : 1, when the medium was supplemented with RSSA at concentration 1%. In the medium containing similar substrate, E. rectale DSM 17629 produced acetate, propionate and butyrate at molar ratio of 1.7 : 1 : 1.2. High levels of acetate, propionate and butyrate at molar ratio of 1.8 : 1 : 1.1 was also produced by E. rectale DSM 17629 in medium supplemented with RSSP at concentration 1%. The results showed that both bacteria responded differently to the RS3 supplementation. Such result provided insight into the possibility of designing RS3 as prebiotic with featured regarding SCFA released in the human colon with potential health implication.

  18. Religiosity/spirituality of German doctors in private practice and likelihood of addressing R/S issues with patients.

    PubMed

    Voltmer, Edgar; Bussing, Arndt; Koenig, Harold G; Al Zaben, Faten

    2014-12-01

    This study examined the self-assessed religiosity and spirituality (R/S) of a representative sample of German physicians in private practice (n = 414) and how this related to their addressing R/S issues with patients. The majority of physicians (49.3 %)reported a Protestant denomination, with the remainder indicating mainly either Catholic(12.5 %) or none (31.9 %). A significant proportion perceived themselves as either religious(42.8 %) or spiritual (29.0 %). Women were more likely to rate themselves R/S than did men. Women (compared to men) were also somewhat more likely to attend religious services (7.4 vs. 2.1 % at least once a week) and participate in private religious activities(14.9 vs. 13.7 % at least daily), although these differences were not statistically significant.The majority of physicians (67.2 %) never/seldom addressed R/S issues with a typical patient. Physicians with higher self-perceived R/S and more frequent public and private religious activity were much more likely to address R/S issues with patients. Implications for patient care and future research are discussed.

  19. IL-16 rs4778889 polymorphism contribution to the development of renal cell cancer in a Chinese population.

    PubMed

    Yang, S X; Chen, F; Zhang, J W; Sun, Z Q; Chen, B P

    2016-06-10

    IL-16 plays an important role in affect the secretion of tumor-related inflammatory cytokines. We aimed to assess the role of interleukin-16 (IL-16) rs4778889 T/C and rs11556218 T/G polymorphisms in the occurrence of renal cell cancer (RCC). This study is composed of 274 RCC patients and 274 control subjects. Genotyping of polymorphisms was performed using polymerase chain reaction combined with restriction fragment length polymorphism analysis. All statistical analysis was carried out by the SPSS statistical software package, version 16.0 (SPSS Inc., Chicago, IL, USA). Using conditional logistic regression analysis, the TC and CC genotypes of rs4778889 exhibited a higher risk of RCC, with adjusted ORs (and 95%CIs) of 1.79 (1.23-2.62) and 2.67 (1.29-5.69), respectively. Moreover, under dominant and recessive models, individuals carried the rs4778889 polymorphism was exhibited elevated RCC risk, with adjusted ORs (and 95%CI) of 1.93 (1.35-2.76) and 2.11 (1.05-4.45), respectively. No significant differences were observed in rs11556218 genotype frequencies between the study groups. In conclusion, the results of our study reveal an association between the IL-16 rs4778889 polymorphism and heightened risk of RCC.

  20. Arterial and venous vasodilator actions of RS-1893, a novel cardiotonic agent, in the hindlimb preparation of the dog.

    PubMed

    Miyake, S; Shiga, H; Koike, H

    1989-10-01

    RS-1893, an orally active cardiotonic agent, has been suggested to dilate venous blood vessels, because it markedly decreases central venous pressure in anesthetized dogs. In order to evaluate venous vasodilator action of the agent, we measured hindlimb volume (HLV) in anesthetized dogs using a plethysmographic technique. RS-1893 (1-10 micrograms/kg, i.v.) produced dose-dependent increases in HLV, femoral blood flow, and left ventricular (LV)dP/dt, and a decrease in central venous pressure (CVP). In another series of experiments, we autoperfused the hindlimb with a constant flow and injected the drugs intraarterially (i.a.) to separately evaluate arterial and venous vasodilator actions. In this preparation, a decrease in perfusion pressure and an increase in HLV were considered to reflect arterial vasodilatation and venous vasodilatation, respectively. RS-1893 (0.3-3 micrograms i.a.) produced a dose-dependent increase in HLV and a decrease in perfusion pressure. Comparison of doses which increased HLV by 0.3 ml revealed that RS-1893 was about 20 times more potent than milrinone. The arterial vasodilator action of RS-1893 was about 15 times more potent than that of milrinone. We conclude that RS-1893 is a potent venous and arterial vasodilator with cardiotonic activity.

  1. Analysis of the association between the LUM rs3759223 variant and high myopia in a Japanese population

    PubMed Central

    Okui, Shintaro; Meguro, Akira; Takeuchi, Masaki; Yamane, Takahiro; Okada, Eiichi; Iijima, Yasuhito; Mizuki, Nobuhisa

    2016-01-01

    Purpose Many studies have investigated the relationship of the lumican gene (LUM) rs3759223 variant with the risk of high myopia, but the results have been inconsistent and inconclusive. In this study, we investigated whether LUM rs3759223 is associated with high myopia in a Japanese population. Methods We recruited 1,585 Japanese patients with high myopia (spherical equivalent [SE] <−9.00 diopters [D]) and 1,011 Japanese healthy controls (SE ≥−1.00 D). The rs3759223 variant was genotyped using the TaqMan assay, and the allelic and genotypic diversity among cases and controls was analyzed according to the SE level. Results In the allelic tests, the odds ratio (OR) for the T allele of rs3759223 tended to increase with the progression of SE, and the highest OR (1.56) was found in patients with SE <−15 D in both eyes. The OR of the T allele tended to increase with the progression of SE in the additive, dominant, and recessive inheritance models. However, we found no significant associations for any of the alleles or genotype models. Conclusion These data support the possibility that the LUM rs3759223 T allele accelerates the progression of SE in the Japanese population, although no significant associations were observed in this study. Additional genetic studies with larger samples that take into account the degree of SE are needed to clarify the contribution of rs3759223 to the risk of high myopia. PMID:27826181

  2. CD33 rs3865444 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese, European, and North American Populations.

    PubMed

    Li, Xingwang; Shen, Ning; Zhang, Shuyan; Liu, Jiafeng; Jiang, Qinghua; Liao, Mingzhi; Feng, Rennan; Zhang, Liangcai; Wang, Guangyu; Ma, Guoda; Zhou, Haihong; Chen, Zugen; Jiang, Yongshuai; Zhao, Bin; Li, Keshen; Liu, Guiyou

    2015-08-01

    The CD33 rs3865444 polymorphism was first identified to be associated with Alzheimer's disease (AD) in European population. However, the following studies reported weak or no significant association in Chinese, Japanese, Korean, American, and Canadian populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs3865444 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from previous 27 studies (N = 86,759; 31,106 cases and 55,653 controls) by searching the PubMed, AlzGene, and Google Scholar databases. We identified significant heterogeneity and observed no significant association between the rs3865444 polymorphism and AD in pooled populations (P = 0.264, odds ratio (OR) = 0.97, 95% confidence interval (CI) 0.93-1.02). In subgroup analysis, we identified significant heterogeneity only in East Asian population and observed no significant association between the rs3865444 polymorphism and AD. We further identified significant heterogeneity and observed significant association between the rs3865444 polymorphism and AD in Chinese population. We identified no significant heterogeneity and significant association in North American and European populations. Collectively, our analysis shows that the CD33 rs3865444 polymorphism is associated with AD susceptibility in Chinese, European, and North American populations. We believe that our findings will be very useful for future genetic studies on AD.

  3. Can rs3767140 SNP of the perlecan (HSPG2) gene affect the diabetes mellitus through the dyslipidemia?

    PubMed

    Kurnaz-Gömleksiz, Ö; Tokat, B; Aslan, E I; Yanar, F; Ermiş-Karaali, Z; Öztürk, O; Yilmaz-Aydoğan, H

    2016-07-31

    Perlecan (HSPG2) play an important role in the lipoprotein metabolisms. The G allele of the HSPG2-rs3767140 may affect the binding of heparan sulfate (HS) chains and hence cause loss of HS from the basement membrane. HSPG2-rs3767140 was studied in 60 T2DM patients and 109 healthy controls. In diabetic patients HSPG2-rs3767140 T variant allele carriers (TT+GT) have decreased fasting plasma glucose (FPG) and serum LDL-C levels (p=0.071 and p=0.060, respectively) versus GG genotype carriers. Moreover, in both of the two groups in which the T allele carriers HDL-cholesterol levels tend to be high. We investigated that the HSPG2-rs3767140 promoted to the dyslipidemic phenotype in the type 2 diabetes mellitus (T2DM) patients. We suggest that the HSPG2-rs3767140 might be associated with the decreased FPG and LDL-C and with the increased HDL-C in diabetics. Therefore, the HSPG2-rs3767140 might be a protective for the diabetes mellitus due to its ameliorating effect on the dyslipidemic phenotype.

  4. Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population

    PubMed Central

    Kimura, Hiroki; Tanaka, Satoshi; Kushima, Itaru; Koide, Takayoshi; Banno, Masahiro; Kikuchi, Tsutomu; Nakamura, Yukako; Shiino, Tomoko; Yoshimi, Akira; Oya-Ito, Tomoko; Xing, Jingrui; Wang, Chenyao; Takasaki, Yuto; Aleksic, Branko; Okada, Takashi; Ikeda, Masashi; Inada, Toshiya; Iidaka, Tetsuya; Iwata, Nakao; Ozaki, Norio

    2015-01-01

    B-cell CLL/lymphoma 9 (BCL9) is located within the schizophrenia (SCZ) suspected locus chr1q21.1. A recent study reported that a single nucleotide polyphormism (SNP) within BCL9 (rs583583) is associated with negative symptoms of Schizophrenia, as measured by the Positive and Negative Syndrome Scale (PANSS), in the Caucasian population. We therefore investigated genetic association of rs583583, and its effect on negative symptoms in the Japanese patients. For association analysis, we used a Japanese sample set comprising 1089 SCZ and 950 controls (CON). Analysis of the effect of rs586586 on negative symptoms as examined by PANSS was investigated using 280 SCZ. Furthermore, for analysis of cognitive performance, we investigated 90 SCZ and 51 CON using the Continuous Performance Test (CPT-IP) and the Wisconsin Card Sorting Test (WCST) Keio version. We did not detect association between rs583583 and SCZ. Furthermore, rs583583 was not associated with PANSS negative scores or with CPT-IT or WCST cognitive tests. Considering the results of our previous study, combined with the results of the current study of rs583583, we argue that BCL9 most likely does not harbor a common genetic variant that can increase the risk for SCZ in the Japanese population. PMID:26494551

  5. BRDT gene sequence in human testicular pathologies and the implication of its single nucleotide polymorphism (rs3088232) on fertility.

    PubMed

    Barda, S; Yogev, L; Paz, G; Yavetz, H; Lehavi, O; Hauser, R; Doniger, T; Breitbart, H; Kleiman, S E

    2014-07-01

    Bromodomain testis-specific (BRDT) protein is essential for the normal process of spermatogenesis. Mutant mice that expressed truncated BRDT had impaired testicular histology with severely reduced sperm concentration and abnormal sperm morphology, while a model of knockout Brdt mice with no BRDT protein had complete meiotic arrest. A BRDT single nucleotide polymorphism (SNP) (rs3088232) was reported as being associated with infertility in men. We assessed testicular specimens of 276 azoospermic men who underwent testicular sperm extraction to search for specimens that showed spermatogenic impairments similar to those of mutant BRDT mice. Ten similar specimens were selected for BRDT gene sequencing and they revealed three NCBI-reported SNPs (rs10783071, rs3088232 and rs10747493) variously distributed among them. Bioinformatics analysis predicted that they would not affect protein activity. Further assessment of rs3088232 frequency in a large group of non-obstructive azoospermia men and fertile controls demonstrated no significant difference between them (27.2 and 21.7% respectively; p = 0.122, Fisher's exact test). We conclude that the testicular impairments observed in the 10 specimens were not a consequence of BRDT gene mutation. The association between BRDT rs3088232 and infertility that had been reported in other studies was not supported.

  6. The Role of CzcRS Two-Component Systems in the Heavy Metal Resistance of Pseudomonas putida X4

    PubMed Central

    Liu, Pulin; Chen, Xi; Huang, Qiaoyun; Chen, Wenli

    2015-01-01

    The role of different czcRS genes in metal resistance and the cross-link between czcRS and czcCBA in Pseudomonas putida X4 were studied to advance understanding of the mechanisms by which P. putida copes with metal stress. Similar to P. putida KT2440, two complete czcRS1 and czcRS2 two-component systems, as well as a czcR3 without the corresponding sensing component were amplified in P. putida X4. The histidine kinase genes czcS1 and czcS2 were inactivated and fused to lacZ by homologous recombination. The lacZ fusion assay revealed that Cd2+ and Zn2+ caused a decrease in the transcription of czcRS1, whereas Cd2+ treatment enhanced the transcription of czcRS2. The mutation of different czcRSs showed that all czcRSs are necessary to facilitate full metal resistance in P. putida X4. A putative gene just downstream of czcR3 is related to metal ion resistance, and its transcription was activated by Zn2+. Data from quantitative real-time polymerase chain reaction (qRT-PCR) strongly suggested that czcRSs regulate the expression of czcCBA, and a cross-link exists between different czcRSs. PMID:26225958

  7. 'Abnormal' angle response curves of TW/Rs for near zero tilt and high tilt channeling implants

    SciTech Connect

    Guo Baonian; Gossmann, Hans-Joachim; Toh, Terry; Colombeau, Benjamin; Todorov, Stan; Sinclair, Frank; Shim, Kyu-Ha; Henry, Todd

    2012-11-06

    Angle control has been widely accepted as the key requirement for ion implantation in semiconductor device processing. From an ion implanter point of view, the incident ion direction should be measured and corrected by suitable techniques, such as XP-VPS for the VIISta implanter platform, to ensure precision ion placement in device structures. So called V-curves have been adopted to generate the wafer-based calibration using channeling effects as the Si lattice steer ions into a channeling direction. Thermal Wave (TW) or sheet resistance (Rs) can be used to determine the minimum of the angle response curve. Normally it is expected that the TW and Rs have their respective minima at identical angles. However, the TW and Rs response to the angle variations does depend on factors such as implant species, dose, and wafer temperature. Implant damage accumulation effects have to be considered for data interpretation especially for some 'abnormal' V-curve data. In this paper we will discuss some observed 'abnormal' angle responses, such as a) TW/Rs reverse trend for Arsenic beam, 2) 'W' shape of Rs Boron, and 3) apparent TW/Rs minimum difference for high tilt characterization, along with experimental data and TCAD simulations.

  8. In Silico Identification of OncomiRs in Different Cancer Types

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Malay; Bandyopadhyay, Sanghamitra

    2012-03-01

    The diagnosis, prognosis and therapeutics of various kinds of cancers are challenging domains of research. Current landmark of cancer research at the molecular level mainly focuses on the regulation of genes for studying cancer pathways. Recent investigations highlight that there is a significant association of a class of short RNAs in the progression of different types of cancer. In this paper, the involvement of microRNAs (miRNAs), a type of small endogenous RNAs, is explored in two categories of cancers in human, one tumor-based and another non-tumorous. A new approach of in silico identification of the miRNAs that might be associated with these cancer types is proposed. The oncomiRs, miRNAs associated with cancer, are identified by analyzing the differentially co-expressed miRNAs and further exploring how they cooperate with each other. Extensive computational analysis on miRNA expression profiles for the discovery of novel oncomiRs is pursued. The results are found to be promising by going deep into the regulatory information available on oncogenes from the up-to-date literature. Some of the miRNAs as oncogenic are identified by the approach like hsa-miR-186 and hsa-miR-154 for leukemia and prostate cancer, respectively, which are not included in standard databases. However, some of the emerging studies give evidences to these findings. Statistical and biological studies, on the other hand, strengthen the effectiveness of the proposed method in futuristic investigations for the exploration of undiscovered oncomiRs. On the whole, these analyses provide insight into the discovery of miRNA markers.

  9. Screening and optimization of low-cost medium for Pseudomonas putida Rs-198 culture using RSM.

    PubMed

    Peng, Yanjie; He, Yanhui; Wu, Zhansheng; Lu, Jianjiang; Li, Chun

    2014-01-01

    The plant growth-promoting rhizobacterial strain Pseudomonas putida Rs-198 was isolated from salinized soils from Xinjiang Province. We optimized the composition of the low-cost medium of P. putida Rs-198 based on its bacterial concentration, as well as its phosphate-dissolving and indole acetic acid (IAA)-producing capabilities using the response surface methodology (RSM), and a mathematical model was developed to show the effect of each medium component and its interactions on phosphate dissolution and IAA production. The model predicted a maximum phosphate concentration in medium containing 63.23 mg/L inorganic phosphate with 49.22 g/L corn flour, 14.63 g/L soybean meal, 2.03 g/L K₂HPO₄, 0.19 g/L MnSO₄ and 5.00 g/L NaCl. The maximum IAA concentration (18.73 mg/L) was predicted in medium containing 52.41 g/L corn flour, 15.82 g/L soybean meal, 2.40 g/L K₂HPO₄, 0.17 g/L MnSO₄ and 5.00 g/L NaCl. These predicted values were also verified through experiments, with a cell density of 10(13) cfu/mL, phosphate dissolution of 64.33 mg/L, and IAA concentration of 18.08 mg/L. The excellent correlation between predicted and measured values of each model justifies the validity of both the response models. The study aims to provide a basis for industrialized fermentation using P. putida Rs-198.

  10. Television food advertisement exposure and FTO rs9939609 genotype in relation to excess consumption in children

    PubMed Central

    Gilbert-Diamond, Diane; Emond, Jennifer A.; Lansigan, Reina K.; Rapuano, Kristina M.; Kelley, William M.; Heatherton, Todd F.; Sargent, James D.

    2016-01-01

    BACKGROUND/OBJECTIVE Exposure to food advertisements may cue overeating among children, especially among those genetically predisposed to respond to food cues. We aimed to assess how television food advertisements affect eating in the absence of hunger among children in a randomized trial. We hypothesized that the Fat Mass and Obesity Associated Gene (FTO) rs9939609 single nucleotide polymorphism would modify the effect of food advertisements. SUBJECTS/METHODS In this randomized experiment, 200 children aged 9–10 years old were served a standardized lunch and then shown a 34-minute television show embedded with either food or toy advertisements. Children were provided with snack food to consume ad libitum while watching the show and we measured caloric intake. Children were genotyped for rs9939609 and analyses were conducted in the overall sample and stratified by genotype. A formal test for interaction of the food ad effect on consumption by rs9939609 was conducted. RESULTS 172 unrelated participants were included in this analysis. Children consumed on average 453 (SD=185) kCals during lunch and 482 (SD=274) kCals during the experimental exposure. Children who viewed food advertisements consumed an average of 48 kCals (95% CI: 10, 85; P=0.01) more of a recently advertised food than those who viewed toy advertisements. There was a statistically significant interaction between genotype and food advertisement condition (P for interaction = 0.02), where the difference in consumption of a recently advertised food related to food advertisement exposure increased linearly with each additional FTO risk allele, even after controlling for BMI percentile. CONCLUSIONS Food advertisement exposure was associated with greater caloric consumption of a recently advertised food, and this effect was modified by an FTO genotype. Future research is needed to understand the neurological mechanism underlying these associations. PMID:27654143

  11. Lepton flavour violation in RS models with a brane- or nearly brane-localized Higgs

    NASA Astrophysics Data System (ADS)

    Beneke, M.; Moch, P.; Rohrwild, J.

    2016-05-01

    We perform a comprehensive study of charged lepton flavour violation in Randall-Sundrum (RS) models in a fully 5D quantum-field-theoretical framework. We consider the RS model with minimal field content and a "custodially protected" extension as well as three implementations of the IR-brane localized Higgs field, including the non-decoupling effect of the KK excitations of a narrow bulk Higgs. Our calculation provides the first complete result for the flavour-violating electromagnetic dipole operator in Randall-Sundrum models. It contains three contributions with different dependence on the magnitude of the anarchic 5D Yukawa matrix, which can all be important in certain parameter regions. We study the typical range for the branching fractions of μ → eγ, μ → 3 e, μN → eN as well as τ → μγ, τ → 3 μ and the electron electric dipole moment by a numerical scan in both the minimal and the custodial RS model. The combination of μ → eγ and μN → eN currently provides the most stringent constraint on the parameter space of the model. A typical lower limit on the KK scale T is around 2 TeV in the minimal model (up to 4 TeV in the bulk Higgs case with large Yukawa couplings), and around 4 TeV in the custodially protected model, which corresponds to a mass of about 10 TeV for the first KK excitations, far beyond the lower limit from the non-observation of direct production at the LHC.

  12. Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons

    PubMed Central

    Yang, Bo; Rajput, Padmesh S.; Kumar, Ujendra; Sastry, Bhagavatula R.

    2015-01-01

    The equilibrium potential for GABA-A receptor mediated currents (EGABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2) but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary. PMID:26389591

  13. The NOAA Microwave Integrated Retrieval System (MiRS): Recent Science Improvements and Validation Results

    NASA Astrophysics Data System (ADS)

    Grassotti, C.; Zhan, X.; Boukabara, S. A.; Chattopadhyay, M.; Smith, C. K.; Islam, T.; Davies, J. E.

    2015-12-01

    The Microwave Integrated Retrieval System (MiRS) has been the NOAA official operational microwave retrieval algorithm since 2007 and is currently run operationally on microwave data from NOAA-18, NOAA-19, MetopA, MetopB/AMSU-MHS, DMSP F-17, F-18/SSMIS, Suomi-NPP/ATMS, and Megha-Tropics/SAPHIR. It has also been run experimentally on data from TRMM/TMI, Aqua/AMSR-E, GCOM-W1/AMSR2, and GPM/GMI. Future plans include operational processing of JPSS-1/ATMS, DMSP F-19/SSMIS, and GPM/GMI data. The inversion within MiRS follows a 1D-variational methodology, in which the fundamental physical attributes affecting the microwave observations are retrieved physically, including the profile of atmospheric temperature, water vapor, liquid and frozen hydrometeors, as well as surface emissivity and temperature. The community radiative transfer model (CRTM) is used as the forward and Jacobian operator to simulate the radiances at each iteration prior to fitting the measurements to within the noise level. The retrieved surface properties are then used to determine surface physical characteristics, including, when appropriate, cryospheric parameters such as sea ice concentration, ice age, and snow water amount, using pre-determined relationships that link emissivity and effective skin temperature to these parameters. We present a review of science improvements included in the recently released MiRS v11.1 that have led to higher quality atmospheric and surface parameter retrievals, with the improvements quantified by comparison with relevant atmospheric and surface reference data.

  14. The impact of mineralocorticoid receptor ISO/VAL genotype (rs5522) and stress on reward learning.

    PubMed

    Bogdan, R; Perlis, R H; Fagerness, J; Pizzagalli, D A

    2010-08-01

    Research suggests that stress disrupts reinforcement learning and induces anhedonia. The mineralocorticoid receptor (MR) determines the sensitivity of the stress response, and the missense iso/val polymorphism (Ile180Val, rs5522) of the MR gene (NR3C2) has been associated with enhanced physiological stress responses, elevated depressive symptoms and reduced cortisol-induced MR gene expression. The goal of these studies was to evaluate whether rs5522 genotype and stress independently and interactively influence reward learning. In study 1, participants (n = 174) completed a probabilistic reward task under baseline (i.e. no-stress) conditions. In study 2, participants (n = 53) completed the task during a stress (threat-of-shock) and no-stress condition. Reward learning, i.e. the ability to modulate behavior as a function of reinforcement history, was the main variable of interest. In study 1, in which participants were evaluated under no-stress conditions, reward learning was enhanced in val carriers. In study 2, participants developed a weaker response bias toward a more frequently rewarded stimulus under the stress relative to no-stress condition. Critically, stress-induced reward learning deficits were largest in val carriers. Although preliminary and in need of replication due to small sample size, findings indicate that psychiatrically healthy individuals carrying the MR val allele, gene, which has been recently linked to depression, showed a reduced ability to modulate behavior as a function of reward when facing an acute, uncontrollable stressor. Future studies are warranted to evaluate whether rs5522 genotype interacts with naturalistic stressors to increase the risk of depression and whether stress-induced anhedonia might moderate such risk.

  15. Modelling the circumstellar medium in RS Ophiuchi and its link to Type Ia supernovae

    NASA Astrophysics Data System (ADS)

    Booth, R. A.; Mohamed, S.; Podsiadlowski, Ph.

    2016-03-01

    Recent interpretations of narrow, variable absorption lines detected in some Type Ia supernovae suggest that their progenitors are surrounded by dense, circumstellar material. Similar variations detected in the symbiotic recurrent nova system RS Oph, which undergoes thermonuclear outbursts every 20 years, making it an ideal candidate to investigate the origin of these lines. To this end, we present simulations of multiple mass transfer-nova cycles in RS Oph. We find that the quiescent mass transfer produces a dense, equatorial outflow, i.e. concentrated towards the binary orbital plane, and an accretion disc forms around the white dwarf. The interaction of a spherical nova outburst with these aspherical circumstellar structures produces a bipolar outflow, similar to that seen in Hubble Space Telescope imaging of the 2006 outburst. In order to produce an ionization structure that is consistent with observations, a mass-loss rate of 5 × 10-7 M⊙ yr-1 from the red giant is required. The simulations also produce a polar accretion flow, which may explain the broad wings of the quiescent H line and hard X-rays. By comparing simulated absorption line profiles to observations of the 2006 outburst, we are able to determine which components arise in the wind and which are due to the novae. We explore the possible behaviour of absorption line profiles as they may appear should a supernova occur in a system like RS Oph. Our models show similarities to supernovae like SN 2006X, but require a high mass-loss rate, dot{M} ˜ 10^{-6}-10-5 M⊙ yr-1, to explain the variability in SN 2006X.

  16. Rs3842530 Polymorphism in MicroRNA-205 Host Gene in Lung and Breast Cancer Patients

    PubMed Central

    Zou, Fan; Li, Jizhu; Jie, Xiaohua; Peng, Xiong; Fan, Ruiqi; Wang, Mengmeng; Wang, Jiangjie; Liu, Zhuoqi; Li, Hua; Deng, Huan; Yang, Xiaohong; Luo, Daya

    2016-01-01

    Background The expression of miR-205 is closely related to the occurrence, development, and prognosis of lung cancer and breast cancer. However, studies show that it plays opposite roles in different tumor types. Because the expression and regulation of miR-205 are primarily confined to epigenetic areas, whether genetic variation of miR-205 is related to the occurrence or to the development of tumors has not been reported. The aim of this study was to screen genetic variation of miR-205 gene and to investigate its association with the risk and development of lung and breast cancer. Material/Methods Genomic DNA was extracted from cultured tumor cell lines and formalin-fixed and paraffin-embedded lung and breast tissue samples. Bisulfite Clone Sequencing (BCS) and qRT-PCR were employed to detect the DNA methylation status and gene expression of the miR-205 gene, respectively. Genetic variation of miR-205 and miR-205HG were genotyped with PCR-sequencing method. Immunohistochemical analysis for ER, PR, and HER2 was performed on breast tissue samples. Results A polymorphism, rs3842530, located downstream of the miR-205 gene and in the fourth exon of the miR-205 host gene (miR-205HG), was screened. rs3842530 had no correlation with the risk of breast cancer, but was associated with the risk of lung cancer (P<0.05). Conclusions These results indicate that the functional association of rs3842530 in miR-205HG and lung cancer might provide a possible explanation for the tissue-dependent function of miR-205 in different tumors. PMID:27885248

  17. Inflamma-miRs in Aging and Breast Cancer: Are They Reliable Players?

    PubMed Central

    Cătană, Cristina Sorina; Calin, George A.; Berindan-Neagoe, Ioana

    2015-01-01

    Human aging is characterized by chronic low-grade inflammation known as “inflammaging.” Persistent low-level inflammation also plays a key role in all stages of breast cancer since “inflammaging” is the potential link between cancer and aging through NF-kB pathways highly influenced by specific miRs. Micro-RNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at a posttranscriptional level. Inflamma-miRs have been implicated in the regulation of immune and inflammatory responses. Their abnormal expression contributes to the chronic pro-inflammatory status documented in normal aging and major age-related diseases (ARDs), inflammaging being a significant mortality risk factor in both cases. Nevertheless, the correct diagnosis of inflammaging is difficult to make and its hidden contribution to negative health outcomes remains unknown. This methodological work flow was aimed at defining crucial unanswered questions about inflammaging that can be used to clarify aging-related miRNAs in serum and cell lines as well as their targets, thus confirming their role in aging and breast cancer tumorigenesis. Moreover, we aim to highlight the links between the pro-inflammatory mechanism underlying the cancer and aging processes and the precise function of certain miRNAs in cellular senescence (CS). In addition, miRNAs and cancer genes represent the basis for new therapeutic findings indicating that both cancer and ARDs genes are possible candidates involved in CS and vice versa. Our goal is to obtain a focused review that could facilitate future approaches in the investigation of the mechanisms by which miRNAs control the aging process by acting as efficient ARDs inflammatory biomarkers. An understanding of the sources and modulation of inflamma-miRs along with the identification of their specific target genes could enhance their therapeutic potential. PMID:26697428

  18. TERT rs2853676 polymorphisms correlate with glioma prognosis in Chinese population

    PubMed Central

    He, Xue; Wei, Yahui; Chen, Zhengshuai; Zhu, Xikai; Ma, Lifeng; Zhang, Ning; Zhang, Yuan; Kang, Longli; Yuan, Dongya; Zhang, Zongyong; Jin, Tianbo

    2016-01-01

    High rates of recurrence and the lack of effective treatments contribute to the poor prognosis of patients with glioma. There is therefore an urgent need for an easily detectable biomarker to facilitate early detection. In this study, we explored the association between TERT rs2853676 genetic polymorphisms and the prognosis of Chinese glioma patients. A total of 481 glioma patients at the Tangdu Hospital of the Fourth Military Medical University in China were included in this study. The overall survival rates were calculated using the Kaplan-Meier method. Prognostic factors were determined through multivariate Cox regression analysis. The overall survival (OS) rates of one, two, and three years were 31%, 10.3%, and 7.5%, respectively. The progress-free survival (PFS) rates of one, two, and three years were 15.7%, 7.3%, and 4.7%, respectively. The genotype “A/G” of TERT rs2857676 decreased the PFS rate (hazard ratios [HR] = 0.824; P = 0.059). The genotype “A/G (HR = 0.803; 95% CI, 0.656 – 0.982; P = 0.032)” and “A/A + A/G” decreased the recurrence rate compared to the genotype G/G (HR = 0.818; 95% CI, 0.675-0.99; P = 0.040). Our study indicates that TERT rs2853676 polymorphisms correlate with glioma survival and recurrence rates in a Chinese population, which suggests that they could potentially serve as prognostic markers in glioma patients. PMID:27655710

  19. Screening and optimization of low-cost medium for Pseudomonas putida Rs-198 culture using RSM

    PubMed Central

    Peng, Yanjie; He, Yanhui; Wu, Zhansheng; Lu, Jianjiang; Li, Chun

    2014-01-01

    The plant growth-promoting rhizobacterial strain Pseudomonas putida Rs-198 was isolated from salinized soils from Xinjiang Province. We optimized the composition of the low-cost medium of P. putida Rs-198 based on its bacterial concentration, as well as its phosphate-dissolving and indole acetic acid (IAA)-producing capabilities using the response surface methodology (RSM), and a mathematical model was developed to show the effect of each medium component and its interactions on phosphate dissolution and IAA production. The model predicted a maximum phosphate concentration in medium containing 63.23 mg/L inorganic phosphate with 49.22 g/L corn flour, 14.63 g/L soybean meal, 2.03 g/L K2HPO4, 0.19 g/L MnSO4 and 5.00 g/L NaCl. The maximum IAA concentration (18.73 mg/L) was predicted in medium containing 52.41 g/L corn flour, 15.82 g/L soybean meal, 2.40 g/L K2HPO4, 0.17 g/L MnSO4 and 5.00 g/L NaCl. These predicted values were also verified through experiments, with a cell density of 1013 cfu/mL, phosphate dissolution of 64.33 mg/L, and IAA concentration of 18.08 mg/L. The excellent correlation between predicted and measured values of each model justifies the validity of both the response models. The study aims to provide a basis for industrialized fermentation using P. putida Rs-198. PMID:25763026

  20. CYP7A1 (-204 A>C; rs3808607 and -469 T>C; rs3824260) promoter polymorphisms and risk of gallbladder cancer in North Indian population.

    PubMed

    Srivastava, Anvesha; Choudhuri, Gourdas; Mittal, Balraj

    2010-06-01

    Cholesterol 7-alpha hydroxylase (CYP7A1), which is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis, may affect cholesterol homeostasis and result in gallstone formation that is a major risk factor for gallbladder cancer (GBC) pathogenesis. Genetic variations in CYP7A1 may influence its expression and thus may affect the risk of gallstone disease and GBC. We aimed to study the association of 2 promoter polymorphisms of CYP7A1 (-204 A>C [rs3808607] and -469 T>C [rs3824260]) in gallstone and GBC susceptibility in North Indian population. The study included 185 GBC patients, 195 symptomatic gallstone patients, and 200 healthy controls. Genotyping for both polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism method. Although the CC genotype of CYP7A1 -204 A>C was not significantly associated with gallstone disease (P = .083, odds ratio [OR] = 1.69, 95% confidence interval [CI] = 0.9-3.0), it was conferring higher risk for GBC (P = .018, OR = 2.05, 95% CI = 1.1-3.7). However, CYP7A1 -469 T>C was not associated with gallstone disease and GBC risk in our population. After subgroup stratifications on the basis of sex and gallstone status, CC genotype and variant allele of CYP7A1 -204 A>C imparted higher risk for GBC in women (P = .003, OR = 3.30, 95% CI = 1.5-7.2) and patients without gallstones (P = .045, OR = 1.91, 95% CI = 1.2-3.6). Haplotype analysis of the 2 polymorphisms showed that C,T (P = .045, OR = 1.84, 95% CI = 1.0-3.3) and C,C (P = .0001, OR = 3.10, 95% CI = 1.6-6.0) haplotypes had elevated risk of GBC predisposition. CYP7A1 -469 T>C is not associated with gallstone disease or GBC risk. Although CYP7A1 -204 A>C might play a modest role in gallstone susceptibility, it is an independent risk factor for GBC in North Indian population. Underlying mechanism for GBC susceptibility by CYP7A1 (-204 A>C and -469 T>C) haplotype appears to be independent of gallstone pathway and is believed to involve

  1. Matrix Metalloproteinase-9 Polymorphism 1562 C > T (rs3918242) Associated with Protection against Placental Malaria

    PubMed Central

    Apoorv, Thittayil Suresh; Babu, Phanithi Prakash; Meese, Stefanie; Gai, Prabhanjan P.; Bedu-Addo, George; Mockenhaupt, Frank P.

    2015-01-01

    Phagocytosis of malaria pigment (hemozoin) induces increased activity of matrix metalloproteinase (MMP)-9, an endopeptidase involved in cytokine regulation. In this study, we examined whether a common functional MMP-9 promoter polymorphism (rs3918242) affects Plasmodium falciparum infection in pregnancy. Eighteen percent of Ghanaian primiparae carried the minor T allele. It was associated with reduced odds of placental hemozoin and of placental as well as peripheral blood parasitemia. The results indicate that a common MMP-9 polymorphism protects against placental malaria indicating that this endopeptidase is involved in susceptibility to P. falciparum. PMID:26013370

  2. Digital forest implementation based on integration of GPS, GIS and RS

    NASA Astrophysics Data System (ADS)

    Liu, Shuo; Qiao, Yanyou; Wen, Qingke

    2008-10-01

    Forest plays an important part in the sustainable development. Digital forest implementation will be helpful in cognizing and managing the forest. The paper discusses the programming theory of digital forest construction, and constructs the basic framework of digital forest using a series of modern information technologies, including integration of GPS, GIS and RS, software development and computer network. Taking monitoring of forestry biological pest as a thematic application case and adopting a series of successfully developed systems, this paper validates that it is feasible to implement digital forest with this method.

  3. Association between BHMT gene rs3733890 polymorphism and cancer risk: evidence from a meta-analysis

    PubMed Central

    Xu, Yue; Yan, Cunye; Hao, Zongyao; Zhou, Jun; Fan, Song; Tai, Sheng; Yang, Cheng; Zhang, Li; Liang, Chaozhao

    2016-01-01

    Background and objective The gene betaine-homocysteine methyltransferase (BHMT) has drawn much attention during the past decades. An increasing number of clinical and genetic investigations have supposed that BHMT rs3733890 polymorphism might be associated with risk of breast cancer and ovarian cancer. As no consistent conclusion has been achieved, we conducted an up-to-date summary of BHMT rs3733890 polymorphism and cancer risk through a meta-analysis. Materials and methods The articles were collected from PubMed, Google Scholar, and CNKI (Chinese) databases up to December 2015. Then, the correlations were determined by reading the titles and abstracts and by further reading the full text to filter the unqualified articles. Odds ratio (OR) and the corresponding 95% confidence intervals (CI) were used to assess the results. Results Among 187 articles collected in the analysis, seven studies with a total of 2,832 cases and 3,958 controls were included for evaluation of the association between BHMT rs3733890 polymorphism and susceptibility of cancer risk. The heterogeneity test showed no significant differences. Furthermore, we found that BHMT −742G>A polymorphism in case and control groups showed no statistically significant association with susceptibility in various cancer types except for uterine cervical cancer (A vs G: OR =0.641, 95% CI =0.445–0.923, P=0.017; AA+AG vs GG: OR =0.579, 95% CI =0.362–0.924, P=0.022). In addition, no statistically significant association was uncovered when stratification analyses were conducted by ethnicity and genotyping methods. Conclusion Our results have shown no obvious evidence that rs3733890 polymorphism in BHMT gene affected the susceptibility of head and neck squamous cell carcinoma, breast cancer, ovarian cancer, colorectal adenoma, and liver cancer. In contrast, we found the protective role of BHMT −742G>A polymorphism in uterine cervical cancer incidence. Future well-designed studies comprising larger sample size

  4. Southern RS CVn systems - Candidate list. [spectral catalog of variable binary stars

    NASA Technical Reports Server (NTRS)

    Weiler, E. J.; Stencel, R. E.

    1979-01-01

    A list of 43 candidate RS CVn binary systems in the far southern hemisphere of the sky (south of -40 deg declination) is presented. The candidate systems were selected from the first two volumes of the Michigan Spectral Catalog (1975, 1978), which provides MK classifications for southern HD stars and identifies any unusual characteristics noted for individual stellar spectra. The selection criteria used were: (1) the occurrence of Ca II H and K emission; (2) known or suspected binary nature; (3) regular light variations of zero to one magnitude; and (4) spectral type between F0 and K2 and luminosity less than bright giant (II).

  5. SaeRS-Dependent Inhibition of Biofilm Formation in Staphylococcus aureus Newman

    PubMed Central

    Lei, Mei G.; Blevins, Jon S.; Smeltzer, Mark S.; Lee, Chia Y.

    2015-01-01

    The SaeRS two-component regulatory system of Staphylococcus aureus is known to affect the expression of many genes. The SaeS protein is the histidine kinase responsible for phosphorylation of the response regulator SaeR. In S. aureus Newman, the sae system is constitutively expressed due to a point mutation in saeS, relative to other S. aureus strains, which results in substitution of proline for leucine at amino acid 18. Strain Newman is unable to form a robust biofilm and we report here that the biofilm-deficient phenotype is due to the saeSP allele. Replacement of the Newman saeSP with saeSL, or deletion of saeRS, resulted in a biofilm-proficient phenotype. Newman culture supernatants were observed to inhibit biofilm formation by other S. aureus strains, but did not affect biofilm formation by S. epidermidis. Culture supernatants of Newman saeSL or Newman ΔsaeRS had no significant effect on biofilm formation. The inhibitory factor was inactivated by incubation with proteinase K, but survived heating, indicating that the inhibitory protein is heat-stable. The inhibitory protein was found to affect the attachment step in biofilm formation, but had no effect on preformed biofilms. Replacement of saeSL with saeSP in the biofilm-proficient S. aureus USA300 FPR3757 resulted in the loss of biofilm formation. Culture supernatants of USA300 FPR3757 saeSP, did not inhibit biofilm formation by other staphylococci, suggesting that the inhibitory factor is produced but not secreted in the mutant strain. A number of biochemical methods were utilized to isolate the inhibitory protein. Although a number of candidate proteins were identified, none were found to be the actual inhibitor. In an effort to reduce the number of potential inhibitory genes, RNA-Seq analyses were done with wild-type strain Newman and the saeSL and ΔsaeRS mutants. RNA-Seq results indicated that sae regulates many genes that may affect biofilm formation by Newman. PMID:25853849

  6. The polymorphism rs763780 in the IL-17F gene is associated with response to biological drugs in patients with psoriasis.

    PubMed

    Prieto-Pérez, Rocío; Solano-López, Guillermo; Cabaleiro, Teresa; Román, Manuel; Ochoa, Dolores; Talegón, María; Baniandrés, Ofelia; López Estebaranz, José Luis; de la Cueva, Pablo; Daudén, Esteban; Abad-Santos, Francisco

    2015-01-01

    Psoriasis improves when IL-17 is blocked. Anti-TNF drugs reduce the IL-17 signaling pathway, and anti-IL-17 drugs are being developed to treat moderate-to-severe psoriasis. We analyzed three SNPs in IL-17A (rs2275913 and rs10484879) and IL-17F (rs763780) to look for an association with psoriasis and/or with response to anti-TNF drugs or ustekinumab. We included 197 healthy controls and 194 patients with moderate-to-severe psoriasis. The results of the univariate analysis showed an association between rs10484879 and psoriasis, although this relationship disappeared after adjustment for HLA-C (rs12191877). We also found an association between rs763780 (IL-17F) and response to ustekinumab (n = 70) and infliximab (n = 37) at 3 and 6 months and an association between rs763780 and the response to adalimumab at 6 months (n = 67).

  7. A putative gene sbe3-rs for resistant starch mutated from SBE3 for starch branching enzyme in rice (Oryza sativa L.).

    PubMed

    Yang, Ruifang; Sun, Chunlong; Bai, Jianjiang; Luo, Zhixiang; Shi, Biao; Zhang, Jianming; Yan, Wengui; Piao, Zhongze

    2012-01-01

    Foods high in resistant starch (RS) are beneficial to prevent various diseases including diabetes, colon cancers, diarrhea and chronic renal or hepatic diseases. Elevated RS in rice is important for public health since rice is a staple food for half of the world population. A japonica mutant 'Jiangtangdao 1' (RS = 11.67%) was crossed with an indica cultivar 'Miyang 23' (RS = 0.41%). The mutant sbe3-rs that explained 60.4% of RS variation was mapped between RM6611 and RM13366 on chromosome 2 (LOD = 36) using 178 F(2) plants genotyped with 106 genome-wide polymorphic SSR markers. Using 656 plants from four F(3:4) families, sbe3-rs was fine mapped to a 573.3 Kb region between InDel 2 and InDel 6 using one STS, five SSRs and seven InDel markers. SBE3 which codes for starch branching enzyme was identified as a candidate gene within the putative region. Nine pairs of primers covering 22 exons were designed to sequence genomic DNA of the wild type for SBE3 and the mutant for sbe3-rs comparatively. Sequence analysis identified a missense mutation site where Leu-599 of the wild was changed to Pro-599 of the mutant in the SBE3 coding region. Because the point mutation resulted in the loss of a restriction enzyme site, sbe3-rs was not digested by a CAPS marker for SpeI site while SBE3 was. Co-segregation of the digestion pattern with RS content among 178 F(2) plants further supported sbe3-rs responsible for RS in rice. As a result, the CAPS marker could be used in marker-assisted breeding to develop rice cultivars with elevated RS which is otherwise difficult to accurately assess in crops. Transgenic technology should be employed for a definitive conclusion of the sbe3-rs.

  8. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency

    PubMed Central

    Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y. Eugene; Zhang, Jifeng

    2016-01-01

    Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells. PMID:26817820

  9. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency.

    PubMed

    Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y Eugene; Zhang, Jifeng

    2016-01-28

    Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.

  10. Electrostatic solitary waves observed at Saturn by Cassini inside 10 Rs and near Enceladus

    NASA Astrophysics Data System (ADS)

    Pickett, J. S.; Kurth, W. S.; Gurnett, D. A.; Huff, R. L.; Faden, J. B.; Averkamp, T. F.; Píša, D.; Jones, G. H.

    2015-08-01

    We have analyzed the Cassini Radio and Plasma Wave Science Wideband Receiver (WBR) data specifically looking for the presence of bipolar electrostatic solitary waves (ESWs). Typical examples of these ESWs are provided to show that when they are present, several of them may be detected over a few to several millisecond time span. We carried out an event study of an Enceladus encounter which took place on 9 October 2008. Approximately 30 min prior to and during the crossing of the Enceladus dust plume, several ESWs are observed with amplitudes of about 100 μV/m up to about 140 mV/m, and time durations of several tens of microseconds up to 250 µs. The highest amplitudes (over 10 mV/m) were observed only during the closest approach to Enceladus. We also carried out an ESW survey using the WBR for all years from 2004 to 2008 for distances less than 10 Rs. The survey clearly shows that most of the ESWs are found on the nightside, with a high percentage of them in the range of 4-6 Rs. This location is consistent with the densest part of Saturn's E ring and Enceladus' orbit. These are the first extended survey results of ESWs near Saturn and the first reported ESWs in connection with Enceladus. We discuss possibilities for the generation of these nonlinear ESWs, which involve current, beam, and acoustic, including dust, instabilities.

  11. Electrochemical evaluation of the interaction between ascorbic acid and the cardiotonic drug RS-82856.

    PubMed

    Visor, G C; Lin, L H; Kenley, R A; Venuti, M C; Alvarez, R

    1987-12-01

    The solution phase interaction between ascorbic acid and the cardiotonic drug N-cyclohexyl-N-methyl-4(7-oxy 1,2,3,5-tetrahydroimidazol[2,1-b] quinazolin-2-one butyramide (RS-82856) was evaluated using a differential pulse voltammetric technique. Shifts in the peak potential of ascorbic acid to higher energy as well as decreases in peak current values were monitored as a function of RS-82856 concentration. The electrochemical data were obtained under conditions where both the drug and the ascorbic acid concentrations exhibited linear relationships with peak current values. The methodology was extended to the study of two other structurally related phosphodiesterase inhibitors cilostamide and anagrelide. The complexation of these drugs with ascorbic acid were also characterized by decreases in the diffusion currents of ascorbic acid as well as by anodic shifts in the peak potential. The significance of these observations may be related to the inhibition of cyclic nucleotide phosphodiesterase activity by both the drugs tested and the ascorbic acid.

  12. Strategy of Making Hand Washing a Routine Habit: Principles of 5Es and 3Rs.

    PubMed

    Kandel, N; Lamichane, J

    2016-01-01

    Regular hand washing habit has potential to reduce morbidity and mortality due to diseases and improves child development and reduces absenteeism of children, teachers and workforce. Improving hand washing behavior is more cost effective than improving clean water and sanitation infrastructure. There are numbers of initiatives and interventions in place, which have gained momentum with key messages of a call to action with increasing investment in schools, engaging policy makers and demonstration them with evidence. However, change in behavior as a routine habit has not reached to an optimum level and requires institutionalizing hand washing practices in schools, from schools and by schools and develop it as a curriculum. Therefore, we are purposing principles of 5Es and 3Rs - a strategy to make hand washing a routine habit. These 5E principles are: i) Embedding in a system, ii) Enabling Environment, iii) Eliminating Friction, iv) Encouraging all, and v) Establishing intervention and 3Rs are practicing them Religiously, Routinely and Repeatedly. Numbers of interventions have well demonstrated that hand hygiene educational interventions can help maintaining good practices. Finally, if schools and community start doing today, we can observe behavioral change practices for hand washing as a routine habit by at least 10 years after.

  13. RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.

    PubMed

    Chandna, Andrew R; Nair, Manoj; Chang, Christine; Pennington, Paul R; Yamamoto, Yasuhiko; Mousseau, Darrell D; Campanucci, Verónica A

    2015-02-01

    Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation-mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co-treatment with either antioxidants or an anti-RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock-out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes.

  14. Resilience in the General Population: Standardization of the Resilience Scale (RS-11)

    PubMed Central

    Kocalevent, Rüya-Daniela; Zenger, Markus; Heinen, Ines; Dwinger, Sarah; Decker, Oliver; Brähler, Elmar

    2015-01-01

    Background The objectives of the study were to generate normative data for the RS-11 for different age groups for men and women and to further investigate the construct validity and factor structure in the general population. Methods Nationally representative face-to face household surveys were conducted in Germany in 2006 (n = 5,036). Results Normative data for the RS-11 were generated for men and women (53.7% female) and different age levels (mean age (SD) of 48.4 (18.0) years). Men had significantly higher mean scores compared with women (60.0 [SD = 10.2] vs. 59.3 [SD = 11.0]). Results of CFA supported a one-factor model of resilience. Self-esteem (standardized β = .50) and life satisfaction (standardized β =.20) were associated with resilience. Conclusions The normative data provide a framework for the interpretation and comparisons of resilience with other populations. Results demonstrate a special importance of self-esteem in the understanding of resilience. PMID:26523927

  15. Interleukin-28B rs12979860 C/T Polymorphism and Acute Cellular Rejection after Liver Transplantation

    PubMed Central

    Fereidooni, H.; Azarpira, N.; Yaghobi, R.; Vahdati, A.; Malek-Hoseini, S. A.

    2017-01-01

    Background: Interleukin-28 (IL-28B) rs12979860 C/T polymorphism is a known predictor of sustained virological response after antiviral treatment in hepatitis C. IL-28B affects the innate immune system as well as intrahepatic expression level of interferon-stimulated genes. Objective: To investigate the effect of recipient IL-28B polymorphism on occurrence of acute rejection after liver transplantation. Methods: 140 liver allograft recipients were selected. Acute rejection episodes were recorded in 39 patients (AR group); the remaining had normal graft function (non-AR group). 70 normal subjects were also studied as the control group. The IL-28B rs12979860 was genotyped through PCR-RFLP method. Results: No significant difference was found between AR and non-AR groups in terms of genotype and allele frequency. However, the CC genotype was significantly (p<0.001) more frequent in patients than in the control group; the C allele variants increased the risk of end-stage liver disease (OR: 2.60). Conclusion: Liver damage in association with the carriage of IL-28B C allele is associated with a higher likelihood of developing cirrhosis. PMID:28299025

  16. Detection of an X-ray flare in the RS CVn binary Sigma Coronae Borealis

    NASA Technical Reports Server (NTRS)

    Agrawal, P. C.; Rao, A. R.; Riegler, G. R.

    1986-01-01

    The detection of an X-ray flare in the RS CVn binary Sigma Coronae Borealis with the Monitor Proportional Counter on the Einstein Observatory is described. During the 513 min of observation, an X-ray flare of 208 min duration was detected at a significance level of 26 sigma in the 1.19-10.16 keV band. The rise time of the flare is between 25 and 70 min and the decay time is greater than or equal to 34 min. The X-ray luminosity at the flare maximum is found to be 6 x 10 to the 30th erg/s and the total energy radiated in X-rays during the flare is 2 x 10 to the 34th erg. The energy spectrum in the flaring state is found to be harder (temperature T about 2.5 x 10 to the 7th K) compared to the one observed in the quiescent state (T about 6 x 10 to the 6th K). Applying the coronal loop model, the loop parameters are calculated and compared for the X-ray flares observed in the various RS CVn binaries and the sun. The significance of the differences in the observed and derived parameters of the X-ray flares is briefly discussed.

  17. A novel TaqMAMA assay for allelic discrimination of TLR9 rs352140 polymorphism.

    PubMed

    Bergallo, Massimiliano; Montanari, Paola; Mareschi, Katia; Rassu, Marco; Galliano, Ilaria; Ravanini, Paolo

    2017-05-01

    TaqMAMA is an allele-specific PCR-based (ASPCR) method that may be suitable for broad and cost-effective genotyping applications in all types of laboratories. There is evidence that interactions between some toll like receptors (TLRs) with viruses influence both the immune response and outcome of HCMV infection. We developed a TaqMAMA genotyping assay for the detection of rs352140 TLR9 polymorphism in transplant recipients with and without HCMV infections. Performance parameters to ensure a solid pre-validation protocol have been here argued. We analysed a population of 74 kidney transplants recipients subdivided in 58 HCMV PCR positive and 16 HCMV PCR negative in the post-transplant routine control. All 74 samples were tested with 31/74 (41.9%) homozygotes (11 CC and 20 TT) and 43/74 (58.1%) heterozygotes (CT). Our preliminary data suggest that there is no correlation between TLR9 rs352140 polymorphism and frequency of HCMV infection.

  18. Assessment of Tachykinin Receptor 3′ Gene Polymorphism rs3733631 in Rosacea

    PubMed Central

    Karpouzis, Anthony; Avgeridis, Paschalis; Tripsianis, Gregory; Kourmouli, Niki

    2015-01-01

    Background. Rosacea is a chronic skin disease, possibly following the neurogenic skin inflammation model. Neurokinin B, involved in the pathogenesis of Parkinson's disease, frequently coexisting with subsequent onset of rosacea, is an endogenous ligand of the tachykinin receptor 3 (TACR3). Methods. 128 rosacea patients and 121 matched controls were genotyped for rs3733631 by PCR-RFLP and analyzed by chi-square test. Results. We observed statistically significant predominance of the C/G or G/G genotype (p = 0.006) and of the G allele (p = 0.004) in the papulopustular (PP) form of rosacea and statistically marginal significance of the C/G or G/G genotype in erythematotelangiectatic (ET) rosacea (p = 0.052). Significantly higher frequency of the C/G or G/G genotype and G allele in PP rosacea (p = 0.021 and p = 0.008, resp.) was ascertained within male patients. Conclusion. TACR3 rs3733631 G allele possibly predisposes the evolution of the initial phase of rosacea to the PP and not the ET form in male patients. PMID:27347521

  19. Crystallization of lysozyme with (R)-, (S)- and (RS)-2-methyl-2, 4-pentanediol

    SciTech Connect

    Stauber, Mark; Jakoncic, Jean; Berger, Jacob; Karp, Jerome M.; Axelbaum, Ariel; Sastow, Dahniel; Buldyrev, Sergey V.; Hrnjez, Bruce J.; Asherie, Neer

    2015-03-01

    Crystallization of lysozyme with (R)-2-methyl-2, 4-pentanediol produces more ordered crystals and a higher resolution protein structure than crystallization with (S)-2-methyl-2, 4-pentanediol. The results suggest that chiral interactions with chiral additives are important in protein crystal formation. Chiral control of crystallization has ample precedent in the small-molecule world, but relatively little is known about the role of chirality in protein crystallization. In this study, lysozyme was crystallized in the presence of the chiral additive 2-methyl-2, 4-pentanediol (MPD) separately using the R and S enantiomers as well as with a racemic RS mixture. Crystals grown with (R)-MPD had the most order and produced the highest resolution protein structures. This result is consistent with the observation that in the crystals grown with (R)-MPD and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there is preferential interaction between lysozyme and this enantiomer. These findings suggest that chiral interactions are important in protein crystallization.

  20. Methadone's effect on nAChRs--a link between methadone use and smoking?

    PubMed

    Talka, Reeta; Tuominen, Raimo K; Salminen, Outi

    2015-10-15

    Methadone is a long-acting opioid agonist that is frequently prescribed as a treatment for opioid addiction. Almost all methadone maintenance patients are smokers, and there is a correlation between smoking habit and use of methadone. Methadone administration increases tobacco smoking, and heavy smokers use higher doses of methadone. Nevertheless, methadone maintenance patients are willing to quit smoking although their quit rates are low. Studies on nicotine-methadone interactions provide an example of the bedside-to-bench approach, i.e., observations in clinical settings have been studied experimentally in vivo and in vitro. In vivo studies have revealed the interplay between nicotine and the endogenous opioid system. At the receptor level, methadone has been shown to be an agonist of human α7 nAChRs and a non-competitive antagonist of human α4β2 and α3* nAChRs. These drugs do not have significant interactions at the level of drug metabolism, and thus the interaction is most likely pharmacodynamic. The net effect of the interaction may depend on individual characteristics because pharmacogenetic factors influence the disposition of both methadone and nicotine.

  1. Whole genome sequence of Desulfovibrio magneticus strain RS-1 revealed common gene clusters in magnetotactic bacteria

    PubMed Central

    Nakazawa, Hidekazu; Arakaki, Atsushi; Narita-Yamada, Sachiko; Yashiro, Isao; Jinno, Koji; Aoki, Natsuko; Tsuruyama, Ai; Okamura, Yoshiko; Tanikawa, Satoshi; Fujita, Nobuyuki; Takeyama, Haruko; Matsunaga, Tadashi

    2009-01-01

    Magnetotactic bacteria are ubiquitous microorganisms that synthesize intracellular magnetite particles (magnetosomes) by accumulating Fe ions from aquatic environments. Recent molecular studies, including comprehensive proteomic, transcriptomic, and genomic analyses, have considerably improved our hypotheses of the magnetosome-formation mechanism. However, most of these studies have been conducted using pure-cultured bacterial strains of α-proteobacteria. Here, we report the whole-genome sequence of Desulfovibrio magneticus strain RS-1, the only isolate of magnetotactic microorganisms classified under δ-proteobacteria. Comparative genomics of the RS-1 and four α-proteobacterial strains revealed the presence of three separate gene regions (nuo and mamAB-like gene clusters, and gene region of a cryptic plasmid) conserved in all magnetotactic bacteria. The nuo gene cluster, encoding NADH dehydrogenase (complex I), was also common to the genomes of three iron-reducing bacteria exhibiting uncontrolled extracellular and/or intracellular magnetite synthesis. A cryptic plasmid, pDMC1, encodes three homologous genes that exhibit high similarities with those of other magnetotactic bacterial strains. In addition, the mamAB-like gene cluster, encoding the key components for magnetosome formation such as iron transport and magnetosome alignment, was conserved only in the genomes of magnetotactic bacteria as a similar genomic island-like structure. Our findings suggest the presence of core genetic components for magnetosome biosynthesis; these genes may have been acquired into the magnetotactic bacterial genomes by multiple gene-transfer events during proteobacterial evolution. PMID:19675025

  2. V474 Car: A RARE HALO RS CVn BINARY IN RETROGRADE GALACTIC ORBIT

    SciTech Connect

    Bubar, Eric J.; Mamajek, Eric E.; Jensen, Eric L. N.; Walter, Frederick M.

    2011-04-15

    We report the discovery that the star V474 Car is an extremely active, high velocity halo RS CVn system. The star was originally identified as a possible pre-main-sequence star in Carina, given its enhanced stellar activity, rapid rotation (10.3 days), enhanced Li, and absolute magnitude which places it above the main sequence (MS). However, its extreme radial velocity (264 km s{sup -1}) suggested that this system was unlike any previously known pre-MS system. Our detailed spectroscopic analysis of echelle spectra taken with the CTIO 4 m finds that V474 Car is both a spectroscopic binary with an orbital period similar to the photometric rotation period and metal-poor ([Fe/H] {approx_equal}-0.99). The star's Galactic orbit is extremely eccentric (e {approx_equal} 0.93) with a perigalacticon of only {approx}0.3 kpc of the Galactic center-and the eccentricity and smallness of its perigalacticon are surpassed by only {approx}0.05% of local F/G-type field stars. The observed characteristics are consistent with V474 Car being a high-velocity, metal-poor, tidally locked, chromospherically active binary, i.e., a halo RS CVn binary, and one of only a few such specimens known.

  3. RS slope detection algorithm for extraction of heart rate from noisy, multimodal recordings.

    PubMed

    Gierałtowski, Jan; Ciuchciński, Kamil; Grzegorczyk, Iga; Kośna, Katarzyna; Soliński, Mateusz; Podziemski, Piotr

    2015-08-01

    Current gold-standard algorithms for heart beat detection do not work properly in the case of high noise levels and do not make use of multichannel data collected by modern patient monitors. The main idea behind the method presented in this paper is to detect the most prominent part of the QRS complex, i.e. the RS slope. We localize the RS slope based on the consistency of its characteristics, i.e. adequate, automatically determined amplitude and duration. It is a very simple and non-standard, yet very effective, solution. Minor data pre-processing and parameter adaptations make our algorithm fast and noise-resistant. As one of a few algorithms in the PhysioNet/Computing in Cardiology Challenge 2014, our algorithm uses more than two channels (i.e. ECG, BP, EEG, EOG and EMG). Simple fundamental working rules make the algorithm universal: it is able to work on all of these channels with no or only little changes. The final result of our algorithm in phase III of the Challenge was 86.38 (88.07 for a 200 record test set), which gave us fourth place. Our algorithm shows that current standards for heart beat detection could be improved significantly by taking a multichannel approach. This is an open-source algorithm available through the PhysioNet library.

  4. Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

    PubMed Central

    Liang, Xudong; Yu, Chuanxin; Sun, Junsong; Liu, Hong; Landwehr, Christina; Holmes, David; Ji, Yinduo

    2006-01-01

    Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-component signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding α-, β-, and γ-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells. PMID:16861653

  5. Somatic Mutation of the SNP rs11614913 and Its Association with Increased MIR 196A2 Expression in Breast Cancer.

    PubMed

    Zhao, Huanhuan; Xu, Jingman; Zhao, Dan; Geng, Meijuan; Ge, Haize; Fu, Li; Zhu, Zhengmao

    2016-02-01

    Common genetic variants (single-nucleotide polymorphisms [SNPs]) in microRNA genes may alter their maturation or expression, resulting in varied functional consequences. Several studies have evaluated the association between the SNP rs11614913 and cancer risk in diverse populations and in a range of cancers, with contradictory outcomes. In this study, we examined 114 paired samples (tumor and normal tissues) from breast cancer patients to study the genotype distribution and somatic mutation of the SNP in MIR 196A2 (rs11614913 C-T). In addition, we evaluated their influence on the mature MIR 196A2 expression. We found that 14% (16/114) of tumors underwent somatic mutation of the SNP rs11614913. Moreover, the CT heterozygous and the CC homozygous states of SNP rs11614913 were more prone to mutation, while the TT homozygous state appeared to be resistant. We further detected a significant increase (p = 0.002) in mature MIR 196A2 expression in breast cancer. In particular, we found a significant association between the occurrence of SNP rs11614913 mutation and high expression (p = 0.0002). In addition, the mature MIR 196A2 expression level was significantly associated with the higher tumor grade (p = 0.004). Taken together, our results seem to demonstrate that somatic mutation of SNP rs11614913 in MIR 196A2 can have an influence on its expression. In addition, it indicated that an unknown mechanism is responsible for both the mutation of SNP rs11614913 and the dysregulation of mature MIR 196A2 expression.

  6. Modification of heparanase gene expression in response to conditioning and LPS treatment: strong correlation to rs4693608 SNP.

    PubMed

    Ostrovsky, Olga; Shimoni, Avichai; Baryakh, Polina; Morgulis, Yan; Mayorov, Margarita; Beider, Katia; Shteingauz, Anna; Ilan, Neta; Vlodavsky, Israel; Nagler, Arnon

    2014-04-01

    Heparanase is an endo-β-glucuronidase that specifically cleaves the saccharide chains of HSPGs, important structural and functional components of the ECM. Cleavage of HS leads to loss of the structural integrity of the ECM and release of HS-bound cytokines, chemokines, and bioactive angiogenic- and growth-promoting factors. Our previous study revealed a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing GVHD. We now demonstrate that HPSE is up-regulated in response to pretransplantation conditioning, followed by a gradual decrease thereafter. Expression of heparanase correlated with the rs4693608 HPSE SNP before and after conditioning. Moreover, a positive correlation was found between recipient and donor rs4693608 SNP discrepancy and the time of neutrophil and platelet recovery. Similarly, the discrepancy in rs4693608 HPSE SNP between recipients and donors was found to be a more significant factor for the risk of aGVHD than patient genotype. The rs4693608 SNP also affected HPSE gene expression in LPS-treated MNCs from PB and CB. Possessors of the AA genotype exhibited up-regulation of heparanase with a high ratio in the LPS-treated MNCs, whereas individuals with genotype GG showed down-regulation or no effect on HPSE gene expression. HPSE up-regulation was mediated by TLR4. The study emphasizes the importance of rs4693608 SNP for HPSE gene expression in activated MNCs, indicating a role in allogeneic stem cell transplantation, including postconditioning, engraftment, and GVHD.

  7. ABCG1 rs57137919G>A Polymorphism Is Functionally Associated with Varying Gene Expression and Apoptosis of Macrophages

    PubMed Central

    Liu, Fang; Wang, Wei; Xu, Yan; Wang, Yu; Chen, Lian-Feng; Fang, Quan; Yan, Xiao-Wei

    2014-01-01

    ATP-binding cassette transporter G1 (ABCG1) is a transmembrane cholesterol transporter involved in macrophage sterol homeostasis, reverse cholesterol transport (RCT), and atherosclerosis. The role of ABCG1 in atherosclerosis remains controversial, especially in animal models. Our previous study showed that single nucleotide polymorphism rs57137919 (-367G>A) in the ABCG1 promoter region was associated with reduced risk for atherosclerotic coronary artery disease (CAD). This study was designed to provide functional evidence for the role of rs57137919G>A in atherosclerosis in humans. We combined in vitro and ex vivo studies using cell lines and human monocyte-derived macrophages to investigate the functional consequences of the promoter polymorphism by observing the effects of the rs57137919A allele on promoter activity, transcription factor binding, gene expression, cholesterol efflux, and apoptosis levels. The results showed that the rs57137919A allele was significantly associated with decreased ABCG1 gene expression possibly due to the impaired ability of protein-DNA binding. ABCG1-mediated cholesterol efflux decreased by 23% with rs57137919 A/A versus the G/G genotype. Cholesterol-loaded macrophage apoptosis was induced 2-fold with the A/A genotype compared with the G/G genotype. Proapoptotic genes Bok and Bid mRNA levels were significantly increased in macrophages from the A/A genotype compared with those from the G/G genotype. These findings demonstrated that the ABCG1 promoter rs57137919G>A variant had an allele-specific effect on ABCG1 expression and was associated with an increased apoptosis in cholesterol-loaded macrophages, providing functional evidence to explain the reduced risk for atherosclerosis in subjects with the ABCG1 promoter rs57137919A allele as reported in our previous study. PMID:24972087

  8. Association of C-Reactive Protein (rs1205) Gene Polymorphism with Susceptibility to Psoriasis in South Indian Tamils

    PubMed Central

    Sudhesan, Anjana; Chandrashekar, Laxmisha; Ananthanarayanan, Palghat Hariharan; Thappa, Devinder Mohan; Satheesh, Santhosh; Chandrasekaran, Adithan; Devaraju, Panneer

    2016-01-01

    Introduction Psoriasis is a multi-factorial heritable T-helper Th-1/Th-17 mediated inflammatory disease, affecting the skin. It is associated with co-morbidities such as Cardiovascular Disease (CVD). C-Reactive Protein (CRP) is a good inflammatory marker. CRP rs1205 polymorphism is associated with circulating plasma CRP levels. Although there is association between the rs1205 Single Nucleotide Polymorphism (SNP) and CVD, there are no prior reports regarding the association of CRP rs1205 SNP with psoriasis susceptibility. Aim To study the association of the genetic variant rs1205 in the CRP gene with susceptibility to the disease and protein levels in South Indian Tamils with psoriasis. Materials and Methods In this case-control genetic study, 300 cases of psoriasis and 300 age and gender matched controls were genotyped for CRP SNP rs1205 using Taq Man 5’allele discrimination assay at Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India from February 2014 to January 2016. Plasma high sensitivity (hs)-CRP levels were estimated by ELISA. Disease severity was assessed by Psoriasis Area Severity Index (PASI). Results CRP genetic variation rs1205 was not associated with psoriasis risk in our South Indian Tamil population. However, the circulating levels of hs-CRP was significantly higher in patients with psoriasis, as compared with controls (p < 0.0001) and the protein levels were significantly associated with disease severity, as assessed by PASI scoring. No genotype was found significantly associated with PASI or CRP levels. Conclusion Our results suggest that plasma CRP levels are higher in patients with psoriasis and correlate with disease severity, whilst CRP rs1205 is not associated with susceptibility to psoriasis in South Indian Tamils. PMID:27891353

  9. Association of Adiponectin Gene (ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis

    PubMed Central

    Wu, Jingjing; Liu, Zheng; Meng, Kai; Zhang, Ling

    2014-01-01

    Background Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults. Method Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis. Results A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I2 = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I2 = 51%). The susceptibility of obesity was increased based on genotypes of TTrs2241766 GG genotype increased obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19–2.00) but not in the non-Chinese studies (OR = 1.02, 95% CI: 0.66–1.58). Similar results were observed in allelic, recessive, and dominant genetic models. There was no significant evidence of publication bias in the overall, Chinese, and non-Chinese studies (P

  10. Associations between orosensory perception of oleic acid, the common single nucleotide polymorphisms (rs1761667 and rs1527483) in the CD36 gene, and 6-n-propylthiouracil (PROP) tasting.

    PubMed

    Melis, Melania; Sollai, Giorgia; Muroni, Patrizia; Crnjar, Roberto; Barbarossa, Iole Tomassini

    2015-03-20

    Orosensory perception of dietary fat varies in individuals, thus influencing nutritional status. Several studies associated fat detection and preference with CD36 or 6-n-propylthiouracil (PROP) sensitivity. Other studies have not confirmed the latter association. We analyzed the relationship between orosensory perception of oleic acid, two CD36 variants, and PROP tasting. Thresholds of oleic acid perception were assessed in 64 subjects using a modification of the three-alternative forced-choice procedure. Subjects were classified for PROP taster status and genotyped for TAS2R38 and CD36 (SNPs: rs1761667 and rs1527483). Subjects homozygous for GG of the rs1761667 polymorphism showed higher sensitivity to oleic acid than AA subjects. The capability to detect oleic acid was directly associated with TAS2R38 or PROP responsiveness. PROP non-tasters had a lower papilla density than tasters, and those with genotype GG of the rs1761667 polymorphism had lower oleic acid thresholds than PROP non-tasters with genotype AA. In conclusion, results showed a direct association between orosensory perception of oleic acid and PROP tasting or rs1761667 polymorphism of CD36, which play a significant role in PROP non-tasters, given their low number of taste papillae. Characterization of individual capability to detect fatty acids may have important nutritional implications by explaining variations in human fat preferences.

  11. Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype.

    PubMed

    Isnard, A; Kouriba, B; Doumbo, O; Chevillard, C

    2011-01-01

    Urinary schistosomiasis is a parasitic disease caused by Schistosoma haematobium helminths. S. haematobium eggs may remain trapped within the bladder or the ureter walls, causing major pathological disorders in the urogenital system. The polymorphism rs1800925(C/T) of the IL13 gene promoter, which is functional, has previously been associated with susceptibility to S. haematobium infection. The aim of this study was to further our understanding and to determine whether, in the 5q31-q33 region, rs1800925 affects infection levels alone or in synergy with other polymorphisms. After sequencing the IL13 promoter and increasing the single-nucleotide polymorphism density, we performed a linkage disequilibrium analysis between rs1800925 and the other markers in a Malian population. Multivariate linear regression analysis and electrophoretic mobility shift assay (EMSA) were performed to characterized markers in linkage disequilibrium with rs1800925. An additional polymorphism, rs7719175, in the IL13 promoter was associated with controlling infection levels in multivariate analysis. The haplotype rs7719175T-rs1800925C was associated with high infection levels. EMSA indicated that rs7719175 affects the binding of transcriptional factors to the promoter region. Polymorphis