Sample records for a1298c mtr a2756g

  1. Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in Northeast Brazil.

    PubMed

    de Cássia Carvalho Barbosa, Rita; da Costa, Débora Menezes; Cordeiro, Denise Ellen Francelino; Vieira, Ana Patricia Freitas; Rabenhorst, Silvia Helena Barem

    2012-11-01

    Polymorphisms in genes encoding enzymes of folate metabolism are a focus of breast cancer risk studies due of the role of these enzymes in DNA methylation, synthesis, and repair. MTHFR, encoding for 5,10-methylenetetrahydrofolate reductase, is one of the most studied genes in this regard, but findings are controversial, and the majority of studies have analyzed polymorphisms individually. In this case control study, we examined the combination of the polymorphisms MTHFR C677T and A1298C with MTR A2756G, where MTR, methionine synthase, is an important enzyme of the folate cycle in the methylation pathway. One hundred and forty-two patients with breast cancer and controls were included and the genotypes were determined using PCR-RFLP. In the population studied, individuals carrying the polymorphic allele in the heterozygous state for both enzymes, MTHFR C677T and MTR A2756G, had an increased risk [odds ratio, OR=2.77 (95% confidence interval, CI=1.19-6.52)] for disease, compared to those with the wild genotype. In addition, individuals carrying the MTR 2756 genotype AG had an increased risk when this was combined with the MTHFR 1298 genotype CC [OR=5.13 (95% CI=0.87-38.82)]. No significant results were found from the analyses associating the MTHFR C677T and A1298C genotypes. However, when stratifying the patients by age (50 years old as the cut-off), patients over 50 years old had greater risk, with the presence of both MTHFR polymorphisms in the heterozygous state [OR=5.33 (95% CI=1.42-21.03)]. This study points out the importance of the interactions between the MTHFR C677T, MTHFR A1298C and MTR A2756G polymorphisms, and also highlights the relevance of the MTR A2756G polymorphism and age in breast cancer risk. PMID:23155246

  2. Methionine synthase A2756G and methylenetetrahydrofolate reductase A1298C polymorphisms are not risk factors for idiopathic venous thromboembolism

    Microsoft Academic Search

    Ophira Salomon; Nurit Rosenberg; Ariella Zivelin; David M Steinberg; Nurit Kornbrot; Rima Dardik; Aida Inbal; Uri Seligsohn

    2001-01-01

    Hyperhomocysteinemia is a defined risk factor for venous thromboembolism (VTE). Several polymorphisms of genes encoding for enzymes acting in the remethylation pathway of homocysteine metabolism, ie, methionine synthase (MS) A2756G, methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C, can cause increased homocysteine levels particularly in patients with deficiencies of folic acid, vitamin B6, or B12 and hence be potential risk factors

  3. Association between MTR A2756G polymorphism and childhood acute lymphoblastic leukemia: a meta-analysis.

    PubMed

    Xia, Jia; Wang, Yadan; Zhang, Hang; Hu, Yu

    2014-06-01

    Abstract To date, many studies on the association between methionine synthase (MTR) A2756G and childhood acute lymphoblastic leukemia (ALL) have provided either controversial or inconclusive results. To clarify the effect of MTR A2756G on the risk of childhood acute lymphoblastic leukemia, a meta-analysis of all relevant studies was performed. The fixed effects model showed that the 2756A allele was associated with a decreased risk of childhood ALL compared with the G allele (ORA vs. G = 0.872; 95% CI 0.782-0.974; p = 0.015, I(2) = 46.9%). Additionally, when comparing subjects with ALL and controls with AA vs. AG or AA vs. AG + GG (dominant model), significant differences were found in the fixed effects model (ORAA vs. AG = 0.869; 95% CI 0.760-0.994; p = 0.040, I(2) = 26.4%; ORAA vs. AG+ GG = 0.858; 95% CI 0.754-0.976; p = 0.020, I(2) = 39.6%). In a subgroup analysis in a population with the same background, individuals with the AA genotype had a reduced risk of developing ALL compared to individuals with the AG genotype. In conclusion, our study provides evidence suggesting that MTR A2756G is associated with a reduced risk of developing childhood ALL. PMID:23906019

  4. Association between MTHFR C677T, MTHFR A1298C and MS A2756G polymorphisms and risk of cervical intraepithelial neoplasia II/III and cervical cancer: a meta-analysis.

    PubMed

    Zhu, Jie; Wu, Lei; Kohlmeier, Martin; Ye, Fangli; Cai, Wei

    2013-09-01

    Numerous case-control studies on the association between polymorphisms of key genes involved in methionine remethylation [methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS)] and the susceptibility of cervical intraepithelial neoplasia (CIN) and cervical cancer have provided inconclusive results. The aim of the present meta-analysis was to determine the effects of two MTHFR (C677T and A1298C) and one MS gene polymorphism (A2756G) on the risk of CIN II/III or cervical cancer. Relevant data were retrieved following a systematic search in PubMed, Web of Science, MEDLINE and Wanfang Data up to November 2012. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated from eligible studies by meta-analysis with subgroup analyses stratified by ethnicity. A total of 13 studies with 1,936 cases and 2,858 controls were included in the present meta?analysis. An increased risk of cervical cancer was found in Asian women with the MTHFR 677T allele (TT vs. CC: OR=1.41, 95% CI=1.07?1.86, P=0.01; TT vs. CC+CT: OR=1.38, 95% CI=1.08-1.75, P=0.008), while a decreased risk was observed in Caucasian women (TT vs. CC: OR=0.65, 95% CI=0.45-0.93, P=0.02; TT+CT vs. CC: OR=0.7, 95% CI=0.58-0.86, P=0.0005). No effects of MTHFR C677T polymorphism on CIN II/III risk and MTHFR A1298C or MS A2756G polymorphisms on cervical cancer risk were detected. The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. The MTHFR 677T allele may enhance the risk of cervical cancer in the Asian female population and play a protective role in Caucasian females. However, limited association is suggested between MTHFR A1298C and MS A2756G polymorphisms with cervical tumorigenesis. PMID:23864153

  5. Methionine synthase A2756G polymorphism and cancer risk: a meta-analysis

    Microsoft Academic Search

    Ke Yu; Jing Zhang; Jiyuan Zhang; Chao Dou; Shaohua Gu; Yi Xie; Yumin Mao; Chaoneng Ji; C ji

    2010-01-01

    Polymorphisms in methionine synthase (MTR) gene may be involved in carcinogenesis by affecting DNA methylation. However, association studies on MTR A2756G polymorphism in cancers have reported conflicting results. Therefore we performed a meta-analysis to better assess the associations. A total of 24 896 cancer patients and 33 862 controls from 52 articles for MTR A2756G were investigated. Overall, individuals carrying

  6. Polymorphisms of methylenetetrahydrofolate reductase ( MTHFR), methionine synthase ( MTR), methionine synthase reductase ( MTRR), and thymidylate synthase ( TYMS) in multiple myeloma risk

    Microsoft Academic Search

    Carmen S. P. Lima; Manoela M. Ortega; Margareth C. Ozelo; Renato C. Araujo; Cármino A. De Souza; Irene Lorand-Metze; Joyce M. Annichino-Bizzacchi; Fernando F. Costa

    2008-01-01

    We tested whether the polymorphisms of the methylenetetrahydrofolate reductase gene, MTHFR C677T and A1298C, the methionine synthase gene, MTR A2756G, the methionine synthase reductase gene, MTRR A66G, and the thymidylate synthase gene, TYMS 2R?3R, involved in folate and methionine metabolism, altered the risk for multiple myeloma (MM). Genomic DNA from 123MM patients and 188 controls was analysed by polymerase chain

  7. Methionine synthase A2756G polymorphism and breast cancer risk: an up-to-date meta-analysis.

    PubMed

    Zhong, Shanliang; Xu, Jinjin; Li, Wenjing; Chen, Zhiyuan; Ma, Tengfei; Zhao, Jianhua

    2013-09-25

    The methionine synthase (MTR) gene polymorphism A2756G has been linked to the risk of developing breast cancer, but the available results were inconsistent and underpowered. To derive a more precise estimation of the association between A2756G and breast cancer risk, an updated meta-analysis of 16 available studies with 9866 cases and 11,702 controls estimating the association between MTR A2756G and breast cancer risk was conducted. The quality of these studies was generally good except 2 studies with a lowest score 4 according to the Newcastle-Ottawa Scale (NOS). The results suggested that there is no significant association between A2756G and breast cancer risk in overall results. In the stratified analysis by ethnicity, source of controls (population or hospital-based), Hardy-Weinberg equilibrium (HWE) in controls, sample size (?1000 and <1000 subjects), and menopausal status, the 2756G allele was associated with a decreased risk in Caucasians, PB (population-based) subgroup, and large studies. But the associations disappeared after removing the studies not in HWE. On the contrary, an increased risk was found in small studies. In conclusion, the findings suggest that MTR A2756G polymorphism is not associated with altered susceptibility to breast cancer, while the observed decreased risk in Caucasians, PB subgroup, and large studies and increased risk in small studies may be due to selection bias or other unknown factors. PMID:23845785

  8. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women

    Microsoft Academic Search

    P R Barbosa; S P Stabler; A L K Machado; R C Braga; R D C Hirata; M H Hirata; L F Sampaio-Neto; R H Allen; E M Guerra-Shinohara; EM Guerra-Shinohara

    2008-01-01

    Objectives:To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine\\/S-adenosylhomocysteine (SAM\\/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status.Subjects\\/Methods:Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy,

  9. Association between the methionine synthase A2756G polymorphism and neural tube defect risk: a meta-analysis.

    PubMed

    Yang, Mei; Yang, Liping; Qi, Ling; Guo, Yiyang; Lin, Xiaofang; Zhang, Yu; Du, Yukai

    2013-05-10

    Many studies have accessed the association between methionine synthase (MTR) A2756G polymorphism and neural tube defect (NTD). However, the conclusions are inconsistent. Our study aimed to clarify the nature of the genetic risks contributed by this polymorphism for NTD using meta-analysis. We searched electronic literature from the PubMed, EMBASE, and Medline databases, from which 10 articles were selected according to the inclusion criteria. The meta-analysis was conducted in 3 groups, namely, NTD patients, mothers with NTD offspring and fathers with NTD offspring. Pooled odds ratios (ORs) and 95% confidence intervals were used to evaluate the strength of the association and the result was corrected by multiple testing. To sum up, no associations between the MTR A2756G polymorphism and NTD risk were found among the 3 groups in all genetic models. However, as their sample size is not large enough, this result needs further research. PMID:23438943

  10. Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G polymorphisms influence on leukocyte genomic DNA methylation level.

    PubMed

    Weiner, Alexandra S; Boyarskikh, Uljana A; Voronina, Elena N; Mishukova, Olga V; Filipenko, Maxim L

    2014-01-01

    Methionine synthase (MTR) and methylenetetrahydrofolate reductase (MTHFR) enzymes are involved in the metabolism of methyl groups, and thus have an important role in the maintenance of proper DNA methylation level. In our study we aimed to evaluate the effect of the polymorphism A2756G (rs1805087) in the MTR gene on the level of human leukocyte genomic DNA methylation. Since the well-studied polymorphism C677T (rs1801133) in the MTHFR gene has already been shown to affect DNA methylation, we aimed to analyze the effect of MTR A2756G independently of the MTHFR C677T polymorphism. For this purpose, we collected the groups of 80 subjects with the MTR 2756AA genotype and 80 subjects with the MTR 2756GG genotype, having equal numbers of individuals with the MTHFR 677CC and the MTHFR 677TT genotypes, and determined the level of DNA methylation in each group. Individuals homozygous for the mutant MTR 2756G allele showed higher DNA methylation level than those harboring the MTR 2756AA genotype (5.061 ± 1.761% vs. 4.501 ± 1.621%, P=0.0391). Individuals with wild-type MTHFR 677?C genotype displayed higher DNA methylation level than the subjects with mutant MTHFR 677TT genotype (5.103 ± 1.767% vs. 4.323 ± 1.525%, P=0.0034). Our data provide evidence that the MTR A2756G polymorphism increases the level of DNA methylation and confirm the previous reports that the MTHFR C677T polymorphism is associated with DNA hypomethylation. PMID:24103477

  11. Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects

    Microsoft Academic Search

    Meiping LuFeng; Feng Wang; Jinrong Qiu

    2010-01-01

    The A2756G polymorphism in the methionine synthase (MTR) gene has been implicated in breast cancer risk. However, the published\\u000a findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Eleven published case–control\\u000a studies, including 8,438 breast cancer cases and 10,515 controls were identified. Odds ratios (ORs) and 95% confidence intervals\\u000a (CIs) were used to assess the strength of

  12. Methionine synthase A2756G polymorphism and risk of colorectal adenoma and cancer: evidence based on 27 studies.

    PubMed

    Ding, Weixing; Zhou, Dong-Lei; Jiang, Xun; Lu, Lie-Sheng

    2013-01-01

    Methionine synthase (MTR), which plays a central role in maintaining adequate intracellular folate, methionine and normal homocysteine concentrations, was thought to be involved in the development of colorectal cancer (CRC) and colorectal adenoma (CRA) by affecting DNA methylation. However, studies on the association between MTR A2756G polymorphism and CRC/CRA remain conflicting. We conducted a meta-analysis of 27 studies, including 13465 cases and 20430 controls for CRC, and 4844 cases and 11743 controls for CRA. Potential sources of heterogeneity and publication bias were also systematically explored. Overall, the summary odds ratio of G variant for CRC was 1.03 (95% CI: 0.96-1.09) and 1.05 (95% CI: 0.99-1.12) for CRA. No significant results were observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the stratified analyses according to ethnicity, source of controls, sample size, sex, and tumor site, no evidence of any gene-disease association was obtained. Results from the meta-analysis of four studies on MTR stratified according to smoking and alcohol drinking status showed an increased CRC risk in heavy smokers (OR?=?2.06, 95% CI: 1.32-3.20) and heavy drinkers (OR?=?2.00, 95% CI: 1.28-3.09) for G allele carriers. This meta-analysis suggests that the MTR A2756G polymorphism is not associated with CRC/CRA susceptibility and that gene-environment interaction may exist. PMID:23593229

  13. Research on the relationship between the polymorphisms of Methionine synthase (MS A2756G ) gene and ischemic cerebrovascular disease

    Microsoft Academic Search

    Li Aifan; Zheng Hong; Xu Yuming; Zhang Xiaoman; Song Bo

    Objective: To explore the relationship between the polymorphisms of Methionine synthase (MS A2756G ) gene and ischemic cerebrovascular disease. Methods: The genotypes of MS A2756G were determined by PCR-RFLP, in 512 patients with ischemic cerebrovascular disease and 500 healthy controls in Henan Han population. Result: The distribution of genotype and allele in MS A2756G had no significant difference between the

  14. 5,10-Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) gene polymorphisms and adult meningioma risk.

    PubMed

    Zhang, Jun; Zhou, Yan-Wen; Shi, Hua-Ping; Wang, Yan-Zhong; Li, Gui-Ling; Yu, Hai-Tao; Xie, Xin-You

    2013-11-01

    The causes of meningiomas are not well understood. Folate metabolism gene polymorphisms have been shown to be associated with various human cancers. It is still controversial and ambiguous between the functional polymorphisms of folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) and risk of adult meningioma. A population-based case–control study involving 600 meningioma patients (World Health Organization [WHO] Grade I, 391 cases; WHO Grade II, 167 cases; WHO Grade III, 42 cases) and 600 controls was done for the MTHFR C677T and A1298C, MTRR A66G, and MTR A2756G variants in Chinese Han population. The folate metabolism gene polymorphisms were determined by using a polymerase chain reaction–restriction fragment length polymorphism assay. Meningioma cases had a significantly lower frequency of MTHFR 677 TT genotype [odds ratio (OR) = 0.49, 95 % confidence interval (CI) 0.33–0.74; P = 0.001] and T allele (OR = 0.80, 95 % CI 0.67–0.95; P = 0.01) than controls. A significant association between risk of meningioma and MTRR 66 GG (OR = 1.41, 95 % CI 1.02–1.96; P = 0.04) was also observed. When stratifying by the WHO grade of meningioma, no association was found. Our study suggested that MTHFR C677T and MTRR A66G variants may affect the risk of adult meningioma in Chinese Han population. PMID:23959833

  15. Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response. We screened 224 subjects (52% female, mean age 39 +/- 11 years) with SCID-diagnosed major...

  16. Association of the MTHFR A1298C Variant with Unexplained Severe Male Infertility

    Microsoft Academic Search

    Abdelmajid Eloualid; Omar Abidi; Majida Charif; Brahim El houate; Houda Benrahma; Noureddine Louanjli; Elbakkay Chadli; Maria Ajjemami; Abdelhamid Barakat; Anu Bashamboo; Ken McElreavey; Houria Rhaissi; Hassan Rouba

    2012-01-01

    The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group

  17. Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population.

    PubMed

    Kumar, Jitender; Das, Swapan K; Sharma, Priyanka; Karthikeyan, Ganesan; Ramakrishnan, Lakshmy; Sengupta, Shantanu

    2005-01-01

    An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)--a critical nutritional factor, deficiency of which results in hyperhomocysteinemia. Hence, polymorphisms in the genes responsible for homocysteine metabolism can be perceived to have a greater impact in relation to hyperhomocysteinemia in Indian population. For this reason, the effects of diet and/or methylenetetrahydrofolate reductase (MTHFR) polymorphism were assessed in 200 individuals having varying homocysteine levels. Homocysteine levels were significantly elevated in individuals adhering to a vegetarian diet (P = 0.019) or having MTHFR A1298C polymorphism (P = 0.006). The minor allele frequency (MAF) of MTHFR C677T and A1298C was 0.15 and 0.44 respectively in this cohort. Since the MAF of these polymorphisms differed considerably from Caucasian and other Asian populations, frequencies of these polymorphisms were also determined in more than 400 individuals from different ethnic populations, selected from the entire country based on their geographical location and linguistic lineage, and was found to be similar to that of our cohort. The fact that MTHFR A1298C polymorphism is significantly associated with homocysteine levels, and that the CC genotype is present at a higher frequency in the Indian population, makes it extremely relevant in terms of its potential impact on hyperhomocysteinemia. PMID:16244782

  18. Is methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphism related with varicocele risk?

    PubMed

    Ucar, V B; Nami, B; Acar, H; Kilinç, M

    2015-02-01

    Varicocele is one of the main reasons for male infertility the exact aetiology of which remains unclear. Methylenetetrahydrofolate reductase (MTHFR) is important for DNA synthesis and methylation, which has a key role during spermatogenesis. Numerous literature suggests that the MTHFR polymorphism may be genetic risk factors for male infertility. In this study, we evaluated C677T and A1298C MTHFR gene polymorphism frequency in patients with varicocele and normal men. A total of 107 varicocele patients and 109 fertile healthy individuals were included. Genotyping of the MTHFR gene in C677T and A1298C base pairs carried out by using real-time PCR technique and afterwards, the statistical analysis accomplished. There is a statistical difference for the frequency of 1298AA genotype in patients with varicocele compared with normal controls (P = 0.0051, OR = 2.2750). Instead, subsequently, 1298/A allel frequency in patient group was significantly higher in comparison with control group (P = 0.0174). According to our results, 1298AA genotype in MTHFR gene raises the risk of varicocele approximately 2.3 times more compared with men carrying other genotypes. The results show that genetic factors have an important role in the molecular basis of varicocele. PMID:24456105

  19. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility

    PubMed Central

    Xia, Lei-Zhou; Liu, Yi; Xu, Xiao-Zhou; Jiang, Peng-Cheng; Ma, Gui; Bu, Xue-Feng; Zhang, Yong-Jun; Yu, Feng; Xu, Ke-Sen; Li, Hua

    2014-01-01

    AIM: To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility. METHODS: Systematic searches were performed on the electronic databases PubMed, ISI, Web of knowledge, CNKI and Wanfang, as well as manual searching of the references of the identified articles. A total of 26 papers were included in this meta-analysis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95%CI were used to evaluate the associations between MTHFR polymorphisms and GC risk. The I2 statistics were used to evaluate between-study heterogeneity. Sensitivity analysis was also performed. RESULTS: Increased risk was found for the MTHFR C677T polymorphism under four genetic models (TT + CT vs CC: OR = 1.23, P = 0.002; T vs C: OR = 1.15, P = 0.001; TT vs CC: OR = 1.37, P = 0.0005; TT vs CT + CC: OR = 1.17, P = 0.0008). Subgroup analysis by ethnicity suggested that C677T polymorphism conferred a risk of GC in eastern but not in western populations. Stratification by tumor site showed an association between the C677T polymorphism and gastric cardia cancer and non-cardia GC in the worldwide population and in eastern populations. Regardless of comparisons with controls or diffuse-type GC, a positive association was found for the C677T polymorphism and an increased risk of intestinal-type GC in the whole population and in western populations. With regard to the A1298C polymorphism, we found that genotype CC was significantly decreased and conferred protection against GC in eastern populations (CC vs AA: OR = 0.44, P = 0.03; CC vs AC + AA: OR = 0.46, P = 0.04). CONCLUSION: MTHFR C677T polymorphism is a risk factor for GC, and the A1298C polymorphism may be a protective factor against GC in eastern populations. PMID:25170232

  20. Methionine synthase A2756G polymorphism may predict ulcerative colitis and methylenetetrahydrofolate reductase C677T pancolitis, in Central China

    Microsoft Academic Search

    Min Chen; Laurent Peyrin-Biroulet; Bing Xia; Rosa-Maria Guéant-Rodriguez; Jean-Pierre Bronowicki; Marc-André Bigard; Jean-Louis Guéant

    2008-01-01

    BACKGROUND: The association of genetic polymorphisms related to metabolism of homocysteine with inflammatory bowel disease has been evidenced in Crohn disease and remains an open question in ulcerative colitis. We evaluated the association of the polymorphisms of MTHFR, MTR, MTRR and TCN2 genes with ulcerative colitis in Central China. METHODS: 168 patients were genotyped for these polymorphisms and compared to

  1. Methylenetetrahydrofolate Reductase A1298C Polymorphism and Breast Cancer Risk: A Meta-analysis of 33 Studies

    PubMed Central

    Rai, V

    2014-01-01

    Methylenetetrahydrofolate reductase (MTHFR) enzyme is essential for DNA synthesis and DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and different types of cancers. Several studies have investigated the association between the MTHFR A1298C polymorphism and breast cancer (BC) risk, but the results were inconclusive. To assess the risk associated with MTHFR A1298C polymorphism, a comprehensive meta-analysis was performed. PubMed, Google Scholar, Elsevier and Springer Link databases were searched for case-control studies relating the association between MTHFR A1298C polymorphism and BC risk and estimated summary odds ratios (ORs) with confidence intervals (CIs) for assessment. Up to January 2014, 33 case-control studies involving 15,919 BC patients and 19,700 controls were included in the present meta-analysis. The results showed that the A1298C polymorphism was not associated with BC risk in all the five genetic models (C vs. A allele (allele contrast): OR = 0.99, 95% confidence interval (CI): 0.93–1.05; AC versus AA (heterozygote/codominant): OR = 0.97, 95% CI: 0.89–1.04; CC versus AA (homozygote): OR = 0.99, 95% CI: 0.91–1.06; CC + AC versus AA (dominant model): OR = 0.97, 95% CI: 0.90–1.05; and CC versus AC + AA (recessive model): OR = 0.99, 95% CI: 0.91–1.07). The present meta-analysis did not support any association between the MTHFR A1298C polymorphism and BC risk. PMID:25506474

  2. Prevalence of myocardial infarction is related to hyperhomocysteinemia but not influenced by C677T methylenetetrahydrofolate reductase and A2756G methionine synthase polymorphisms in diabetic and non-diabetic subjects

    Microsoft Academic Search

    Tatiana Helfenstein; Francisco A. H. Fonseca; Waldir G. M. Relvas; Andreza O. Santos; Maria L. Dabela; Simone C. P. Matheus; Vânia D'Almeida; Sérgio Tufik; Fernanda G. Souza; Paula R. Rodrigues; Rosely Taglieri; Éder F. Sousa; Maria C. O. Izar

    2005-01-01

    BackgroundHyperhomocysteinemia has emerged as a novel risk factor for myocardial infarction (MI). Some mechanisms proposed to explain its relationship with coronary events are also shared by major coronary risk factors. We examined whether C677T methylenetetrahydrofolate reductase and A2756G methionine synthase polymorphisms could affect the relative risk for MI.

  3. MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt

    PubMed Central

    Aly, Rabab M; Taalab, Mona M; Ghazy, Hayam F

    2014-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. We aimed to evaluate the association between MTHFR A1298C and C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Eighty-five patients with CML and a control group containing 100 healthy, age and sex matched individuals were examined for MTHFR C677T and A1298C polymorphisms using polymerase chain reaction-restriction fragment-length (PCR-RFLP) method. The frequency of 677TT genotype in patients with CML was significantly higher compared to controls (OR = 2.513, 95% CI: 0.722-4.086, P = 0.025). No such association was shown for heterozygous 677CT (OR = 1.010, 95% CI: 0.460-2.218, P = 0.981). Moreover, for A1298C genotype, a statistically significant higher frequency of 1298CC was also detected in CML patients compared to control group (OR = 1.1816, 95% CI: 0.952-3.573, P = 0.036), 0.036). No such statistical significance was demonstrable for heterozygote 1298AC (OR = 1.046, 95% CI: 0.740-1.759, P = 0.092). In addition, patients with joint 677CT/1298AC or 677TT/1298CC genotypes showed an association with increased risk of CML (OR = 1.849, 95% CI: 0.935-2.540, P = 0.024; OR = 1.915, 95% CI: 1.202-3.845, P = 0.020 respectively). .A statistically significant increased risk of resistant to therapy was observed with 677CT and 1298AC genotypes (P = 0.001, P = 0.002 respectively). We conclude that both MTHFR 677TT and 1298CC polymorphisms have been associated with risk of CML and both 677CT and 1298AC genotypes are associated with higher risk of resistant to therapy. PMID:24966971

  4. Polymorphisms in methionine synthase (A2756G) and cystathionine ?-synthase (844ins68) and susceptibility to carcinomas of the upper gastrointestinal tract

    Microsoft Academic Search

    N. Ott; H. Geddert; M. Sarbia

    2008-01-01

    Purpose  Folate deficiency is considered to increase the risk for the development of malignant tumors such as prostate and colorectal\\u000a cancer. Methionine synthase (MTR) and cystathionine ß-synthase (CBS) are enzymes that play a central role in folate metabolism,\\u000a thereby affecting DNA methylation and synthesis. A single A?G substitution at nucleotide 2756 of the MTR and a 68 bp CBS insertion polymorphism in

  5. Genetic Variant in MTRR, but Not MTR, Is Associated with Risk of Congenital Heart Disease: An Integrated Meta-Analysis

    PubMed Central

    Zhong, Rong; Zou, Li; Zhu, Beibei; Chen, Wei; Shen, Na; Ke, Juntao; Lou, Jiao; Wang, Zhenling; Sun, Yu; Liu, Lifeng; Song, Ranran

    2014-01-01

    Background Congenital heart disease (CHD) is one of the most common birth defects and the leading cause of deaths among individuals with congenital structural abnormalities worldwide. Both Methionine synthase reductase (MTRR) and Methionine synthase (MTR) are key enzymes involved in the metabolic pathway of homocysteine, which are significant in the earlier period embryogenesis, particularly in the cardiac development. Evidence is mounting for the association between MTRR A66G (rs1801394)/MTR A2756G (rs1805087) and the CHD risk, but results are controversial. Therefore, we conducted a meta-analysis integrating case-control and transmitted disequilibrium test (TDT) studies to obtain more precise estimate of the associations of these two variants with the CHD risk. Methods To combine case-control and TDT studies, we used the Catmap package of R software to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 9 reports were included in the final meta-analysis. Eight of them comprised of 914 cases, 964 controls, and 441 families that were germane to MTRR A66G polymorphism; and 4 reports comprised of 250 cases, 205 controls, and 53 families that were relevant to MTR A2756G polymorphism. The pooled OR for the MTRR 66 G allele versus A allele was 1.35 (95% CI?=?1.14–1.59, P<0.001, Pheterogeneity?=?0.073). For MTR A2756G, the G allele conferred a pooled OR of 1.10 (95% CI?=?0.78–1.57, P?=?0.597, Pheterogeneity?=?0.173) compared with the A allele. Sensitivity analyses were carried out to asses the effects of each individual study on the pooled OR, indicating the stability of the outcome. Moreover, positive results were also obtained in all subgroups stratified by study type and ethnicity except the subgroup of TDT studies in MTRR A66G variant. Conclusions This meta-analysis demonstrated a suggestive result that the A66G variant in MTRR, but not the A2756G in MTR, may be associated with the increase of CHD risks. PMID:24595101

  6. Association between MTHFR C677T and A1298C, and MTRR A66G polymorphisms and susceptibility to schizophrenia in a Syrian study cohort.

    PubMed

    Lajin, Bassam; Alhaj Sakur, Amir; Michati, Roula; Alachkar, Amal

    2012-06-01

    The folate-homocystiene metabolic pathway has been shown to be involved in the susceptibility for developing schizophrenia by several studies. In the present study we investigated the role of three common polymorphisms of the folate-homocysteine metabolic pathway in an Arab population from Syria consisting of 85 schizophrenic patients and 126 healthy controls. The studied polymorphisms included the MTHFR C677T and A1298C, and MTRR A66G, all of which result into amino acid changes, and were previously shown to yield decreased enzymatic activity and alter plasma homocysteine concentration. While MTHFR C677T and A1298C polymorphisms were not previously studied in an Arab population with respect to the susceptibility for developing schizophrenia, the MTRR A66G was not previously investigated in any population around the world. Our results indicated a strong association between MTHFR A1298C and schizophrenia. The variant C allele frequency was significantly higher in the patients group (40% vs 29.4%, OR=1.6, 95% CI (1.06-2.41), p=0.023). A statistically significant association was found for MTHFR 677TT genotype under the recessive model in the male patients subgroup (OR=2.6, 95% CI (1.04-6.5), p=0.036), and MTHFR 677CT genotype under the overdominant model in the total patients group (OR=0.52 95% CI (0.29-0.92), p=0.024). No statistically significant association was found for MTRR A66G polymorphism on an individual basis. However, a borderline association was found for the CC/GG (C677T/A66G) compound genotype (OR=2.24, 95% CI (0.97-5.15), p=0.053). Our results support the hypothesis of association between schizophrenia and folate-homocystiene metabolic pathway genes. PMID:22813657

  7. Genetic interactions between MTHFR (C677T), methionine synthase (A2756G, C2758G) variants with vitamin B12 and folic acid determine susceptibility to premature coronary artery disease in Indian population

    PubMed Central

    Kanth, V. V. Ravi; Golla, Jaya Prakash; Sastry, B. K. S; Naik, Sudhir; Kabra, Nitin; Sujatha, Madireddi

    2011-01-01

    Background: Researchers have determined that Indians face a higher risk of heart disease, despite the fact that nearly half of them are vegetarians and lack many of the other traditional risk factors. In the below-30 age group, coronary artery disease mortality among Indians is three-fold higher than in the whites in United Kingdom and ten-fold higher than the Chinese in Singapore. High levels of homocysteine have been widely linked to the early onset of heart diseases in other populations, although a definite proof among Indians is lacking, which needs to be investigated by way of screening for factors responsible for high homocysteine levels. Objective: To screen for genetic factors responsible for hyperhomocysteinemia and the risk for premature coronary artery disease. Materials and Methods: A total of 100 individuals with proven premature coronary artery disease and 200 age-and-sex matched controls were screened for polymorphisms in Methylenetetrahydrofolate reductase (MTHFR) (C677T) Methionine synthase (MS) genes (A2756G, C2758G), and the B12 and Folate levels were estimated. Results: Results from the mutational analysis revealed that in the study group, seven individuals had a polymorphism for the C677T allele in the MTHFR gene (one homozygous and six heterozygous) (Fischer's Exact test P > 0.046) (OR: 0.2711 95% CI 0.0774 to 0.9491). Six were heterozygous for the A2756G polymorphism in the MS gene (Fischer's Exact test P > 0.0012). None showed a polymorphism at the C2758G allele in the MS gene. Four controls showed heterozygosity for the C677T polymorphism and none for the MS gene. The B12 and Folate levels were significantly lower in the study group as compared to the controls. Conclusions: It is important to know which factors determine the total homocysteine concentrations. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the total homocysteine concentrations, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors. PMID:22022143

  8. Effects of Maternal 5,10-Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Tobacco Smoking on Infant Birth Weight in a Japanese Population

    PubMed Central

    Yila, Thamar Ayo; Sasaki, Seiko; Miyashita, Chihiro; Braimoh, Titilola Serifat; Kashino, Ikuko; Kobayashi, Sumitaka; Okada, Emiko; Baba, Toshiaki; Yoshioka, Eiji; Minakami, Hisanori; Endo, Toshiaki; Sengoku, Kazuo; Kishi, Reiko

    2012-01-01

    Background Intracellular folate hemostasis depends on the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Because 5,10-MTHFR 677TT homozygosity and tobacco smoking are associated with low folate status, we tested the hypothesis that smoking in mothers with 5,10-MTHFR C677T or A1298C polymorphisms would be independently associated with lower birth weight among their offspring. Methods We assessed 1784 native Japanese mother-child pairs drawn from the ongoing birth cohort of The Hokkaido Study on Environment and Children’s Health. Data (demographic information, hospital birth records, and biological specimens) were extracted from recruitments that took place during the period from February 2003 to March 2006. Maternal serum folate were assayed by chemiluminescent immunoassay, and genotyping of 5,10-MTHFR C677T/A1298C polymorphisms was done using a TaqMan allelic discrimination assay. Results The prevalence of folate deficiency (<6.8 nmol/L) was 0.3%. The 5,10-MTHFR 677CT genotype was independently associated with an increase of 36.40 g (95% CI: 2.60 to 70.30, P = 0.035) in mean infant birth weight and an increase of 90.70 g (95% CI: 6.00 to 175.50, P = 0.036) among male infants of nonsmokers. Female infants of 677TT homozygous passive smokers were 99.00 g (95% CI: ?190.26 to ?7.56, P = 0.034) lighter. The birth weight of the offspring of smokers with 5,10-MTHFR 1298AA homozygosity was lower by 107.00 g (95% CI: ?180.00 to ?33.90, P = 0.004). Conclusions The results suggest that, in this population, maternal 5,10-MTHFR C677T polymorphism, but not the 5,10-MTHFR A1298C variant, is independently associated with improvement in infant birth weight, especially among nonsmokers. However, 5,10-MTHFR 1298AA might be associated with folate impairment and could interact with tobacco smoke to further decrease birth weight. PMID:22277790

  9. Polymorphisms in the folate-metabolizing genes MTR, MTRR, and CBS and breast cancer risk.

    PubMed

    Weiner, Alexandra S; Boyarskikh, Uljana A; Voronina, Elena N; Selezneva, Inna A; Sinkina, Tatiana V; Lazarev, Alexandr F; Petrova, Valentina D; Filipenko, Maxim L

    2012-04-01

    Alterations in the nucleotide sequences of folate-metabolizing genes can increase the risk of malignant transformation. The aim of our study was to investigate the association of three single-nucleotide polymorphisms (SNPs) in the folate-metabolizing genes - A2756G MTR, A66G MTRR, and 844ins68 CBS - which have putative functional significance in breast cancer risk. The allele and genotype frequencies of the SNPs were determined in a case group (840 women with sporadic breast cancer) and a control group (770 women). No statistically significant association of studied SNPs with breast cancer was revealed. A meta-analysis, which included data obtained from the literature and the present research, did not reveal any statistically significant associations of these SNPs with breast cancer. The results obtained provide evidence that these SNPs are not involved in the development of breast cancer. PMID:22236648

  10. Geographical Distribution of MTHFR C677T, A1298C and MTRR A66G Gene Polymorphisms in China: Findings from 15357 Adults of Han Nationality

    PubMed Central

    Yang, Boyi; Liu, Yuyan; Li, Yongfang; Fan, Shujun; Zhi, Xueyuan; Lu, Xiangxiang; Wang, Da; Zheng, Quanmei; Wang, Yinuo; Wang, Yanxun; Sun, Guifan

    2013-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms are important genetic determinants for homocysteine (Hcy) levels, and are associated with several disorders. These polymorphisms are heterogeneously distributed worldwide. Our objective was to explore the geographical distributions of these polymorphisms in China. Methodologies 15357 healthy adults were recruited from 10 regions. Buccal samples were collected and genomic DNA was isolated. Genotyping was performed using the fluorogenic 5?-nuclease assay. Principal Findings The prevalence of the three polymorphisms among different populations from China varied significantly and showed apparent geographical gradients. For MTHFR C677T, the frequencies of the 677T allele and the 677TT genotype were significantly higher among northern populations and ranged from the lowest values (24.0% and 6.4%, respectively) in Hainan (southern) to the highest values (63.1% and 40.8%, respectively) in Shandong (northern). For MTHFR A1298C, the 1298C allele and the 1298CC genotype frequencies were significantly higher among southern populations and increased from low values (13.1% and 1.4%, respectively) in Shandong to high values (25.7% and 6.7%, respectively) in Hainan. For A66G, the 66G allele and the 66GG genotype frequencies increased from lower values (23.7% and 5.4%, respectively) in Shandong to higher values (29.2% and 8.6%, respectively) in Hainan. The overall frequency of the 677T allele, 677TT genotype, 1298C allele, 1298CC genotype, 66G allele and 66GG genotype in the Chinese Han population was 45.2%, 23.2%, 18.6%, 3.9%, 25.7%, and 6.6%, respectively. No gender differences were found in the prevalence of both the MTHFR C677T and MTRR A66G polymorphisms. Conclusions This study indicates that there are marked geographical variations in the prevalence of the three polymorphisms among Chinese Han populations. Our baseline data may be useful for future researches in related fields. PMID:23472119

  11. A retrospective comparative exploratory study on two Methylentetrahydrofolate Reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients

    PubMed Central

    2014-01-01

    Background Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. Methods 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). Results Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p?=?0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p?=?0.001) and 7th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p?=?0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact. Conclusions The MTHFR A1298C polymorphisms was an independent prognostic factor in patients with neoadjuvantly treated gastric adenocarcinomas (according to both UICC 6th or 7th definitions for gastric cancer) but not in AEG I nor in primarily resected patients, which confirms the impact of this enzyme on chemotherapy associated outcome. PMID:24490800

  12. Maternal Supplementary Folate Intake, Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms and the Risk of Orofacial Cleft in Iranian Children

    PubMed Central

    Ebadifar, Asghar; KhorramKhorshid, Hamid Reza; Kamali, Koorosh; Salehi Zeinabadi, Mehdi; Khoshbakht, Tayyebeh; Ameli, Nazila

    2015-01-01

    Background: The purpose of this study was to describe the association of MTHFR gene single nucleotide polymorphisms (C677T and A1298C) and maternal supplementary folate intake with orofacial clefts in the Iranian population. Methods: In this case-control study, peripheral venous blood was taken from 65 patients with orofacial clefts and 215 unaffected controls for DNA extraction and kept in EDTA for further analysis. The genotyping was carried out using Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) and gel electrophoresis. Data were analyzed using Chi square test and logistic regression tests. Results: Genotype frequencies of 677TT were reported to be 13.5 and 36.1% in controls and CL/P patients, respectively, which showed a significant difference compared to CC as reference (OR=4.118; 95% CI=1.997–8.492; p=0.001). Conversely, 1298CC with frequencies of 10.8 and 12.7% in controls and patients, respectively, showed no significant difference compared to AA (OR=2.359; 95% CI=0.792–7.023; p=0.123). Comparing patients whose mothers did not report the folate supplement intake during pregnancy, to controls, it was observed that lack of folate intake was a predisposing factor for having a child with oral clefts (OR=5/718, p=0.000). Conclusion: Children carrying the 677TT variant of the MTHFR gene may have an increased risk of CL/P. In addition, the finding that the risk associated with this allele was obviously higher when the mothers didn’t use folic acid, supports the hypothesis that folic acid may play a role in the etiology of CL/P. PMID:26140186

  13. MTR MAIN FLOOR. MTR TRACTOR IS IN CENTER OF VIEW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR MAIN FLOOR. MTR TRACTOR IS IN CENTER OF VIEW AMIDST AN ACCUMULATION OF CLUTTER ON THE FLOOR. TRACTOR HAD ATTACHMENTS IN FRONT TO FACILITATE MOVING OF COFFINS. INL NEGATIVE NO. 56-3027. Jack L. Anderson, Photographer, 9/17/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  14. Evaluation of Factor V G1691A, prothrombin G20210A, Factor XIII V34L, MTHFR A1298C, MTHFR C677T and PAI-1 4G/5G genotype frequencies of patients subjected to cardiovascular disease (CVD) panel in south-east region of Turkey.

    PubMed

    Oztuzcu, Serdar; Ergun, Sercan; Ula?l?, Mustafa; Nacarkahya, Gülper; I?ci, Yusuf Ziya; I?ci, Mehri; Bayraktar, Recep; Tamer, Ali; Çakmak, Ecir Ali; Arslan, Ahmet

    2014-06-01

    Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 -675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66%, respectively. No mutation was detected in 92 (1.95%) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in south-east region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population. PMID:24532105

  15. Maternal gene polymorphisms involved in folate metabolism and the risk of having a Down syndrome offspring: a meta-analysis.

    PubMed

    Yang, Mei; Gong, Tian; Lin, Xiaofang; Qi, Ling; Guo, Yiyang; Cao, Zhongqiang; Shen, Min; Du, Yukai

    2013-11-01

    Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Our study aimed to arrive at a more accurate estimation. Therefore, we carried out a meta-analysis of 26, 17, 9, 15, 9 and 6 case-control studies on the relationship between maternal methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G, reduced folate carrier 1 A80G and cystathionine ?-synthase 844ins68 polymorphisms and the risk of having a DS offspring. The allele contrast and model-free approach were used. Results showed marginal significant associations for MTHFR C677T, overall [odds ratio (OR) = 1.28 (1.22, 1.46) and generalised odds ratio (ORG) = 1.35 (1.16, 1.57)] and in Caucasian [OR = 1.15 (1.03, 1.29) and ORG = 1.20 (1.04, 1.38)], Asian [OR = 1.68 (1.08, 2.63) and ORG = 1.74 (1.08, 2.80)] and Brazilian [OR = 1.22 (1.04, 1.43) and ORG = 1.28 (1.06, 1.55)] populations; for MTRR A66G, overall [OR = 1.22 (1.02, 1.46) and ORG = 1.31 (1.06, 1.62)]; and for RFC1 A80G, overall [OR = 1.16 (1.02, 1.31) and ORG = 1.18 (1.01, 1.37)]. MTHFR A1298C, MTR 12756G and CBS 844ins68 polymorphisms produced non-significant results. Since potential confounders could not be ruled out completely in this meta-analysis, further studies are needed to confirm these results. PMID:24068460

  16. MTR BASEMENT. WORKERS (DON ALVORD AND CYRIL VAN ORDEN OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BASEMENT. WORKERS (DON ALVORD AND CYRIL VAN ORDEN OF PHILLIPS PETROLEUM CO.) POSE FOR GAMMA IRRADIATION EXPERIMENT IN MTR CANAL. CANS OF FOOD WILL BE LOWERED TO CANAL BOTTOM, WHERE SPENT MTR FUEL ELEMENTS EMIT GAMMA RADIATION. INL NEGATIVE NO. 11746. Unknown Photographer, 8/20/1954 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  17. MTR, SOUTH FACE OF REACTOR. SPECIAL SUPPLEMENTAL SHIELDING WAS REQUIRED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, SOUTH FACE OF REACTOR. SPECIAL SUPPLEMENTAL SHIELDING WAS REQUIRED OUTSIDE OF MTR FOR EXPERIMENTS. THE AIRCRAFT NUCLEAR PROPULSION PROJECT DOMINATED THE USE OF THIS PART OF THE MTR. INL NEGATIVE NO. 7225. Unknown Photographer, 11/28/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  18. DUGWAY FOOD IRRADIATOR USES 8 MTR ELEMENTS

    Microsoft Academic Search

    C. J. Christensen; A. Jacobsen; Q. Klinger; G. Abel

    1957-01-01

    Eight spent MTR fuel elements are the radintion source in the Dugway ; high-level gamma irradiation facility, designed especially for canned-food ; processing. The system will accept any can up to the No. 10 size and deliver a ; specified uniform radiation dose between 25,000 and 10⁷ r. Variation in ; total dose is limited to a few per cent.

  19. [Development of the high-throughput fluorescence assay detecting SNPs in hemostasis and folate metabolism genes for clinical use].

    PubMed

    Prasolova, M A; Shchepotina, E G; Dymshits, G M

    2013-01-01

    Genetic predisposition of an individual patient should be taken in account to choose the proper treatment. Implementation to clinical practice requires the development of rapid, high-throughput, and easy assays intended to detect single nucleotide polymorphisms. A detection kit intended to identify the hemostasis and folate cycle gene mutations G20210A FII, G1691A FV, G10976A FVII, G103T FXIII, C807T ITGA2, T1565C ITGB3, 5G(-675)4G PAI, G(-455)A FGB, C677T and A1298C MTHFR, A2756G MTR, A66G MTRR was suggested in this work. The method is based on the polymerase chain reaction and subsequent melt curve analysis of the complexes of amplicons with specific probe. Three single nucleotide polymorphisms can be identified in one tube using our detection kit that increases the productivity of the analysis in the clinical use. Different types of biological samples (buccal epithelium, saliva, plasma, serum, and urogenital swabs) can be used as the initial material for DNA isolation and further analysis by the method developed in this work. PMID:23785789

  20. 33 CFR 154.1041 - Specific response information to be maintained on mobile MTR facilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...Specific response information to be maintained on mobile MTR facilities. 154.1041 Section 154...Specific response information to be maintained on mobile MTR facilities. (a) Each mobile MTR facility must carry the following...

  1. Methylenetetrahydrofolate reductase and methionine synthase polymorphisms and risk of bladder cancer in a Tunisian population

    Microsoft Academic Search

    Slah Ouerhani; Elisabete Oliveira; Raja Marrakchi; Mohamed R. Ben Slama; Mohamed Sfaxi; Mohsen Ayed; Mohamed Chebil; António Amorim; Amel Benammar El Gaaied; Maria João Prata

    2007-01-01

    Folate insufficiency can induce carcinogenesis by decreasing DNA methylation. It is well known that DNA hypomethylation is a common feature in a number of cancers. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are enzymes that play central roles in the folate metabolic pathway. Two common polymorphisms in the MTHFR gene (C677T and A1298C) and one in the MS gene (A2756G)

  2. Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis

    Microsoft Academic Search

    Meilin Wang; Haixia Zhu; Guangbo Fu; Miaomiao Wang; Zhizhong Zhang; Qiang Lu; Shizhi Wang; Zhengdong Zhang

    2009-01-01

    Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis\\u000a by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case–control study of 239 bladder cancer cases and\\u000a 250 cancer-free controls, we found that the MTHFR 677TT

  3. MTR AND ETR COMPLEXES. CAMERA FACING EASTERLY TOWARD CHEMICAL PROCESSING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR AND ETR COMPLEXES. CAMERA FACING EASTERLY TOWARD CHEMICAL PROCESSING PLANT. MTR AND ITS ATTACHMENTS IN FOREGROUND. ETR BEYOND TO RIGHT. INL NEGATIVE NO. 56-4100. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  4. REACTIVITY MEASUREMENT FACILITY, UNDER CONSTRUCTION OVER MTR CANAL IN BASEMENT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    REACTIVITY MEASUREMENT FACILITY, UNDER CONSTRUCTION OVER MTR CANAL IN BASEMENT OF MTR BUILDING, TRA-603. WOOD PLANKS REST ON CANAL WALL OBSERVABLE IN FOREGROUND. INL NEGATIVE NO. 11745. Unknown Photographer, 8/20/1954 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  5. MTR BUILDING AND BALCONY FLOORS. CAMERA FACING EASTERLY. PHOTOGRAPHER DID ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BUILDING AND BALCONY FLOORS. CAMERA FACING EASTERLY. PHOTOGRAPHER DID NOT EXPLAIN DARK CLOUD. MTR WING WILL ATTACH TO GROUND FLOOR. INL NEGATIVE NO. 1567. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  6. MTR CANAL IS FILLED WITH WATER. MAN STANDS ON MOVABLE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR CANAL IS FILLED WITH WATER. MAN STANDS ON MOVABLE BRIDGE. NOTE CHAINS AND HOOK AT LEFT. THIS SECTION OF CANAL PROJECTED EAST BEYOND THE SITE OF THE MTR BUILDING. INL NEGATIVE NO. 6003. Unknown Photographer, 6/16/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  7. CONTEXTUAL AERIAL VIEW OF "EXCLUSION" MTR AREA WITH IDAHO CHEMICAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CONTEXTUAL AERIAL VIEW OF "EXCLUSION" MTR AREA WITH IDAHO CHEMICAL PROCESSING PLANT IN BACKGROUND AT CENTER TOP OF VIEW. CAMERA FACING EAST. EXCLUSION GATE HOUSE AT LEFT OF VIEW. BEYOND MTR BUILDING AND ITS WING, THE PROCESS WATER BUILDING AND WORKING RESERVOIR ARE LEFT-MOST. FAN HOUSE AND STACK ARE TO ITS RIGHT. PLUG STORAGE BUILDING IS RIGHT-MOST STRUCTURE. NOTE FAN LOFT ABOVE MTR BUILDING'S ONE-STORY WING. THIS WAS LATER CONVERTED FOR OFFICES. INL NEGATIVE NO. 3610. Unknown Photographer, 10/30/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. Genetic polymorphisms of the enzymes involved in DNA methylation and synthesis in elite athletes.

    PubMed

    Terruzzi, Ileana; Senesi, Pamela; Montesano, Anna; La Torre, Antonio; Alberti, Giampietro; Benedini, Stefano; Caumo, Andrea; Fermo, Isabella; Luzi, Livio

    2011-08-24

    Physical exercise induces adaptive changes leading to a muscle phenotype with enhanced performance. We first investigated whether genetic polymorphisms altering enzymes involved in DNA methylation, probably responsible of DNA methylation deficiency, are present in athletes' DNA. We determined the polymorphic variants C667T/A1298C of 5,10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR), G742A of betaine:homocysteine methyltransferase (BHMT), and 68-bp ins of cystathionine ?-synthase (CBS) genes in 77 athletes and 54 control subjects. The frequency of MTHFR (AC), MTR (AG), and MTRR (AG) heterozygous genotypes was found statistically different in the athletes compared with the control group (P=0.0001, P=0.018, and P=0.0001), suggesting a reduced DNA methylating capacity. We therefore assessed whether DNA hypomethylation might increase the expression of myogenic proteins expressed during early (Myf-5 and MyoD), intermediate (Myf-6), and late-phase (MHC) of myogenesis in a cellular model of hypomethylated or unhypomethylated C2C12 myoblasts. Myogenic proteins are largely induced in hypomethylated cells [fold change (FC)=Myf-5: 1.21, 1.35; MyoD: 0.9, 1.47; Myf-6: 1.39, 1.66; MHC: 1.35, 3.10 in GMA, DMA, respectively] compared with the control groups (FC=Myf-5: 1.0, 1.38; MyoD: 1.0, 1.14; Myf-6: 1.0, 1.44; MHC: 1.0, 2.20 in GM, DM, respectively). Diameters and length of hypomethylated myotubes were greater then their respective controls. Our findings suggest that DNA hypomethylation due to lesser efficiency of polymorphic MTHFR, MS, and MSR enzymes induces the activation of factors determining proliferation and differentiation of myoblasts promoting muscle growth and increase of muscle mass. PMID:21673074

  9. MTR BASEMENT. GENERAL ELECTRIC CONTROL CONSOLE FOR AIRCRAFT NUCLEAR PROPULSION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BASEMENT. GENERAL ELECTRIC CONTROL CONSOLE FOR AIRCRAFT NUCLEAR PROPULSION EXPERIMENT NO. 1. INL NEGATIVE NO. 6510. Unknown Photographer, 9/29/1959 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  10. The MATROSHKA experiment: results and comparison from extravehicular activity (MTR-1) and intravehicular activity (MTR-2A/2B) exposure.

    PubMed

    Berger, Thomas; Bilski, Pawe?; Hajek, Michael; Puchalska, Monika; Reitz, Günther

    2013-12-01

    Astronauts working and living in space are exposed to considerably higher doses and different qualities of ionizing radiation than people on Earth. The multilateral MATROSHKA (MTR) experiment, coordinated by the German Aerospace Center, represents the most comprehensive effort to date in radiation protection dosimetry in space using an anthropomorphic upper-torso phantom used for radiotherapy treatment planning. The anthropomorphic upper-torso phantom maps the radiation distribution as a simulated human body installed outside (MTR-1) and inside different compartments (MTR-2A: Pirs; MTR-2B: Zvezda) of the Russian Segment of the International Space Station. Thermoluminescence dosimeters arranged in a 2.54 cm orthogonal grid, at the site of vital organs and on the surface of the phantom allow for visualization of the absorbed dose distribution with superior spatial resolution. These results should help improve the estimation of radiation risks for long-term human space exploration and support benchmarking of radiation transport codes. PMID:24252101

  11. Inducible, but Not Constitutive, Resistance of Gonococci to Hydrophobic Agents Due to the MtrC-MtrD-MtrE Efflux Pump Requires TonB-ExbB-ExbD Proteins

    Microsoft Academic Search

    Corinne Rouquette-Loughlin; Igor Stojiljkovic; Tara Hrobowski; Jacqueline T. Balthazar; William M. Shafer

    2002-01-01

    The MtrC-MtrD-MtrE efflux pump possessed by Neisseria gonorrhoeae is very similar to the MexA-MexB- OprM efflux pump of Pseudomonas aeruginosa. Because the antimicrobial resistance property afforded by the MexA-MexB-OprM efflux pump also requires the TonB protein, we asked whether a similar requirement exists for the gonococcal efflux pump. Unlike earlier studies with P. aeruginosa, we found that constitutive levels of

  12. CONTROL ROOM ON MARCH 31, 1952, AS THE MTR GOES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CONTROL ROOM ON MARCH 31, 1952, AS THE MTR GOES CRITICAL FOR THE FIRST TIME. COMPARE CEILING FIXTURES IN THIS PHOTO AND PHOTO ID-33-G-212 FOR COMMON PERSPECTIVE. INL NEGATIVE NO. 4517. Unknown Photographer, 3/31/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  13. MTR CONTROL ROOM WITH CONTROL CONSOLE AND STATUS READOUTS ALONG ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR CONTROL ROOM WITH CONTROL CONSOLE AND STATUS READOUTS ALONG WALL. WORKERS MAKE ELECTRICAL AND OTHER CONNECTIONS. INL NEGATIVE NO. 4289. Unknown Photographer, 2/26/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  14. MTR COOLING TOWER. BASIN IS ADJACENT TO PUMP HOUSE. CAMERA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR COOLING TOWER. BASIN IS ADJACENT TO PUMP HOUSE. CAMERA FACES SOUTHEAST TOWARD NORTH SIDE OF PUMP HOUSE. INL NEGATIVE NO. 2690. Unknown Photographer, 6/1951. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  15. REACTIVITY MEASUREMENT FACILITY. CAMERA LOOKS DOWN INTO MTR CANAL. REACTOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    REACTIVITY MEASUREMENT FACILITY. CAMERA LOOKS DOWN INTO MTR CANAL. REACTOR IS FUELED AS AN ETR MOCK-UP. LIGHTS DANGLE BELOW WATER LEVEL. CONTROL RODS AND OTHER APPARATUS DESCEND FROM ABOVE WATER LEVEL. INL NEGATIVE NO. 56-900. Jack L. Anderson, Photographer, 3/26/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  16. CAMERA IS ON CATWALK ABOVE MTR. CRANE HOOK LOWERS TOP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CAMERA IS ON CATWALK ABOVE MTR. CRANE HOOK LOWERS TOP PLUG ONTO REACTOR. NOTE PLANK-LIKE BRIDGE (WALKWAY) TO BALCONY AT UPPER RIGHT. INL NEGATIVE NO. 4502. Unknown Photographer, probable date 3/31/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  17. ELECTRICAL LINES ARRIVE FROM CENTRAL FACILITIES AREA, SOUTH OF MTR. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ELECTRICAL LINES ARRIVE FROM CENTRAL FACILITIES AREA, SOUTH OF MTR. EXCAVATION RUBBLE IN FOREGROUND. CONTRACTOR CRAFT SHOPS, CRANES, AND OTHER MATERIALS ON SITE. CAMERA FACES EAST, WITH LITTLE BUTTE AND MIDDLE BUTTE IN DISTANCE. INL NEGATIVE NO. 335. Unknown Photographer, 7/1/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  18. Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity?

    PubMed

    Terruzzi, I; Senesi, P; Fermo, I; Lattuada, G; Luzi, L

    2007-10-01

    Obesity, due to the combination of inherited genes and environmental factors, is continually increasing. We evaluated the relationship between polymorphisms of methylene-tetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), betaine:homocysteine methyltransferase (BHMT G742A) and cystathionine beta-synthase (CBS 68-bp ins) genes and the risk of obesity. We studied these polymorphic variants in 54 normal and 82 obese subjects [body mass index (BMI)=22.4+/-1.8, 34.1+/-7.1; ages 35.2+/-10.7, 43.3+/-10.6 respectively]. Levels of total plasma homocysteine (t-Hcy), folates, and vitamins B6 and B12 were not significantly different, while leptin concentration was significantly higher (p=0.005) in the obese patients compared to the lean controls. The frequency of only (a) MTHFR (AC), (b) MTR (AG), and (c) MTRR (AG) heterozygous genotypes was statistically different in the obese compared to the control group (p=0.03, p=0.007, and p=0.01). Single (a), (b), and (c) heterozygous genotypes had a significant risk of developing obesity [p=0.02, 0.01, and 0.03; odds ratio (OR)=2.5, 3.0, and 2.4; 95% confidence interval (CI)=1.2-5.3, 1.3-7.1, and 1.2-5.1 respectively] and the risk remarkably increased for combined genotypes a+b, a+c, b+c, and a+b+c (p=0.002, 0.002, 0.016, 0.006; OR=7.7, 5.4, 5.8, 15.4; 95% CI=1.9-30.4, 1.7-16.8, 1.4-23.2, 1.6- 152.3). These findings suggest that in obese subjects, Hcy cycle efficiency is impaired by MTHFR, MTR, and MTRR inability to supply methyl-group donors, providing evidence that MTHFR, MTR, and MTRR gene polymorphisms are genetic risk factors for obesity. PMID:17993766

  19. Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population

    Microsoft Academic Search

    Jitender Kumar; Swapan K. Das; Priyanka Sharma; Ganesan Karthikeyan; Lakshmy Ramakrishnan; Shantanu Sengupta

    2005-01-01

    An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and\\/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)—a critical nutritional factor, deficiency of which results in hyperhomocysteinemia. Hence, polymorphisms in

  20. MTR BASEMENT. DOORWAY TO SOURCE STORAGE VAULT IS AT CENTER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BASEMENT. DOORWAY TO SOURCE STORAGE VAULT IS AT CENTER OF VIEW; TO DECONTAMINATION ROOM, AT RIGHT. PART OF MAZE ENTRY IS VISIBLE INSIDE VAULT DOORWAY. INL NEGATIVE NO. 7763. Unknown Photographer, photo was dated as 3/30/1953, but this was probably an error. The more likely date is 3/30/1952. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  1. MTR CAISSONS WERE DRILLED INTO BEDROCK. IN CENTER OF VIEW, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR CAISSONS WERE DRILLED INTO BEDROCK. IN CENTER OF VIEW, CONCRETE FLOWS FROM TRUCK INTO DRUM, WHICH IS LOWERED INTO CAISSON AND RELEASED AT BOTTOM OF HOLE. BEYOND, TRUCK-MOUNTED DRILLING RIG DRILLS HOLE FOR ANOTHER CAISSON NEAR EDGE OF EXCAVATION. MATERIAL REMOVED FROM HOLE IS CARRIED BY CONVEYOR TO WAITING TRUCK. INL NEGATIVE NO. 307. Unknown Photographer, 6/1950. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  2. MTR BUILDING INTERIOR, TRA603. BASEMENT. CAMERA IN WEST CORRIDOR FACING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BUILDING INTERIOR, TRA-603. BASEMENT. CAMERA IN WEST CORRIDOR FACING SOUTH. FREIGHT ELEVATOR IS AT RIGHT OF VIEW. AT CENTER VIEW IS MTR VAULT NO. 1, USED TO STORE SPECIAL OR FISSIONABLE MATERIALS. INL NEGATIVE NO. HD46-6-3. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  3. Review of enigmatic MTrPs as a common cause of enigmatic musculoskeletal pain and dysfunction

    Microsoft Academic Search

    David G Simons

    2004-01-01

    This article explores how myofascial trigger points (MTrPs) may relate to musculoskeletal dysfunction (MSD) in the workplace and what might be done about it. The cause of much MSD and pain is often enigmatic to modern medicine and very costly, just as the cause of MTrPs has been elusive for the past century, despite an extensive literature that is confusing

  4. Thermal–hydraulic modeling of the onset of flow instability in MTR reactors

    Microsoft Academic Search

    Hany A. Khater; Salah El-Din El-Morshedy; Mohamed M. A. Ibrahim

    2007-01-01

    Prediction of the onset of the flow instability (OFI) in steady and transient sub-cooled flow boiling is an important consideration in the design and operation of nuclear reactors, in particular for materials testing reactors (MTR). In this study, a predictive model for OFI in the MTR has been developed. The model is based on both the heat balance during the

  5. WORKERS FABRICATE ROOF SLABS FOR MTR BUILDING AT THE CONSTRUCTION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    WORKERS FABRICATE ROOF SLABS FOR MTR BUILDING AT THE CONSTRUCTION SITE. FORMS WERE MADE OF STEEL. AFTER AN INCH OF CONCRETE HAD BEEN POURED IN THE FORM, A MAT OF REINFORCING STEEL WAS PLACED ON IT. THE REMAINDER OF THE FORM WAS FILLED, AND THE CONCRETE WAS VIBRATED, STRUCK, AND TROWELED. GROOVES AT CORNER WILL HAVE 1/4 INCH RODS WELDED INTO THE EYE OF THE STEEL MAT FOR GROUNDING. INL NEGATIVE NO. 578. Unknown Photographer, 9/1/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  6. TEST REACTOR AREA PLOT PLAN CA. 1968. MTR AND ETR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    TEST REACTOR AREA PLOT PLAN CA. 1968. MTR AND ETR AREAS SOUTH OF PERCH AVENUE. "COLD" SERVICES NORTH OF PERCH. ADVANCED TEST REACTOR IN NEW SECTION WEST OF COLD SERVICES SECTION. NEW PERIMETER FENCE ENCLOSES BETA RAY SPECTROMETER, TRA-669, AN ATR SUPPORT FACILITY, AND ATR STACK. UTM LOCATORS HAVE BEEN DELETED. IDAHO NUCLEAR CORPORATION, FROM A BLAW-KNOX DRAWING, 3/1968. INL INDEX NO. 530-0100-00-400-011646, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  7. CONCRETE POURS HAVE PRODUCED A REINFORCED SUPPORT BASE FOR MTR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CONCRETE POURS HAVE PRODUCED A REINFORCED SUPPORT BASE FOR MTR REACTOR. PIPE TUNNEL IS UNDER CONSTRUCTION AT CENTER OF VIEW. PIPES WILL CARRY RADIOACTIVE WATER FROM REACTOR TO WATER PROCESS BUILDING. CAMERA LOOKS SOUTH INTO TUNNEL ALONG WEST SIDE OF REACTOR BASE. TWO CAISSONS ARE AT LEFT SIDE OF VIEW. NOTE "WINDOW" IN SOUTH FACE OF REACTOR BASE AND ALSO GROUP OF PENETRATIONS TO ITS LEFT. INL NEGATIVE NO. 733. Unknown Photographer, 10/6/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.

    PubMed

    Collin, Simon M; Metcalfe, Chris; Zuccolo, Luisa; Lewis, Sarah J; Chen, Lina; Cox, Angela; Davis, Michael; Lane, J Athene; Donovan, Jenny; Smith, George Davey; Neal, David E; Hamdy, Freddie C; Gudmundsson, Julius; Sulem, Patrick; Rafnar, Thorunn; Benediktsdottir, Kristrun R; Eeles, Rosalind A; Guy, Michelle; Kote-Jarai, Zsofia; Morrison, Jonathan; Al Olama, Ali Amin; Stefansson, Kari; Easton, Douglas F; Martin, Richard M

    2009-09-01

    Folate-pathway gene polymorphisms have been implicated in several cancers and investigated inconclusively in relation to prostate cancer. We conducted a systematic review, which identified nine case-control studies (eight included, one excluded). We also included data from four genome-wide association studies and from a case-control study nested within the UK population-based Prostate Testing for Cancer and Treatment study. We investigated by meta-analysis the effects of eight polymorphisms: MTHFR C677T (rs1801133; 12 studies; 10,745 cases; 40,158 controls), MTHFR A1298C (rs1801131; 5 studies; 3,176 cases; 4,829 controls), MTR A2756G (rs1805087; 8 studies; 7,810 cases; 37,543 controls), MTRR A66G (rs1801394; 4 studies; 3,032 cases; 4,515 controls), MTHFD1 G1958A (rs2236225; 6 studies; 7,493 cases; 36,941 controls), SLC19A1/RFC1 G80A (rs1051266; 4 studies; 6,222 cases; 35,821 controls), SHMT1 C1420T (rs1979277; 2 studies; 2,689 cases; 4,110 controls), and FOLH1 T1561C (rs202676; 5 studies; 6,314 cases; 35,190 controls). The majority (10 of 13) of eligible studies had 100% Caucasian subjects; only one study had <90% Caucasian subjects. We found weak evidence of dominant effects of two alleles: MTR 2756A>G [random effects pooled odds ratio, 1.06 (1.00-1.12); P = 0.06 (P = 0.59 for heterogeneity across studies)] and SHMT1 1420C>T [random effects pooled odds ratio, 1.11 (1.00-1.22); P = 0.05 (P = 0.38 for heterogeneity across studies)]. We found no effect of MTHFR 677C>T or any of the other alleles in dominant, recessive or additive models, or in comparing a/a versus A/A homozygous. Neither did we find any difference in effects on advanced or localized cancers. Our meta-analysis suggests that known common folate-pathway single nucleotide polymorphisms do not have significant effects on susceptibility to prostate cancer. PMID:19706844

  9. Regulation of expression of the Escherichia coli K-12 mtr gene by TyrR protein and Trp repressor.

    PubMed Central

    Sarsero, J P; Wookey, P J; Pittard, A J

    1991-01-01

    The Escherichia coli K-12 mtr gene, which encodes a tryptophan-specific permease, was cloned, and its nucleotide sequence was determined. The precise location of the mtr gene at 69 min on the E. coli chromosome was determined. The mtr gene product was identified as a 414-amino-acid residue protein with a calculated molecular weight of 44,332. The protein is very hydrophobic, consistent with its presumed location spanning the cytoplasmic membrane. The initiation sites of transcription and translation were identified. Construction of an mtr-lacZ transcriptional fusion facilitated investigation of the molecular basis of mtr regulation. The TyrR protein in association with phenylalanine or tyrosine is responsible for the activation of mtr expression, whereas the Trp repressor in conjunction with tryptophan serves to repress expression of this gene. Site-directed mutagenesis confirmed that sequences in the mtr regulatory region homologous to TyrR protein and to Trp repressor-binding sites were involved in the activation and repression of mtr expression, respectively. Sequences homologous to sigma 70- and sigma 54-dependent promoters were identified upstream of the transcription start point of mtr. It was determined that transcription of mtr occurs only via a sigma 70-dependent promoter. Images PMID:2061290

  10. Methionine synthase and thymidylate synthase gene polymorphisms and colorectal adenoma risk: the self defense forces study.

    PubMed

    Yoshimitsu, Shinichiro; Morita, Makiko; Hamachi, Tadamichi; Tabata, Shinji; Abe, Hiroshi; Tajima, Osamu; Uezono, Kousaku; Ohnaka, Keizo; Kono, Suminori

    2012-10-01

    Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3' untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (?30 mL/d), but not in those with low alcohol consumption (interaction P = 0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas. PMID:22407825

  11. Association between methionine synthase reductase A66G polymorphism and primary infertility in Chinese males.

    PubMed

    Li, X Y; Ye, J Z; Ding, X P; Zhang, X H; Ma, T J; Zhong, R; Ren, H Y

    2015-01-01

    We examined the association between the methionine synthase reductase (MTRR A66G), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), and methionine synthase (MS A2756G) genotypes and non-obstructive male infertility in a Chinese population. This case-control study included 162 infertile Chinese patients with azoospermia (N = 100) or oligoasthenozoospermia (N = 62) and 120 fertile men as controls. The polymorphisms MTRR A66G, MTHFR C677T, A1298C, and MS A2756G were identified by direct DNA sequencing and the results were statistically analyzed. We found no association between the incidence of any of these variants in azoospermia patients and control populations. The frequency of the MTRR66 polymorphic genotypes (AG, AG+GG) was significantly higher in the oligoasthenozoospermia group compared to the controls (P = 0.013, 0.012). Our findings revealed an association between the single-nucleotide polymorphism A66G in the MTRR gene and male infertility, particularly in oligoasthenozoospermia males, suggesting that this polymorphism is a genetic risk factor for male infertility in Chinese men. PMID:25966116

  12. PUMP HOUSE FOR MTR WELL NO. 1, TRA601. FLOOR PLAN, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    PUMP HOUSE FOR MTR WELL NO. 1, TRA-601. FLOOR PLAN, ELEVATIONS, SECTION SHOWING WELL CASING, ROOF FRAMING PLAN. AS BUILT. WELL HOUSE FOR WELL NO. 2, TRA-602, WAS IDENTICAL IN ALL PARTICULARS EXCEPT FLOOR DIMENSIONS AND ARRANGEMENT OF PUMP AND ELECTRICAL EQUIPMENT INSIDE. IDAHO OPERATIONS OFFICE MTR-601-IDO-1, 12/1954. INL INDEX NO. 531-0601-00-396-110463, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  13. The Transcriptional Repressor, MtrR, of the mtrCDE Efflux Pump Operon of Neisseria gonorrhoeae Can Also Serve as an Activator of “off Target” Gene (glnE) Expression

    PubMed Central

    Johnson, Paul J. T.; Shafer, William M.

    2015-01-01

    MtrR is a well-characterized repressor of the Neisseria gonorrhoeae mtrCDE efflux pump operon. However, results from a previous transcriptional profiling study suggested that MtrR also represses or activates expression of at least sixty genes outside of the mtr locus. Evidence that MtrR can directly repress so-called “off target” genes has previously been reported; in particular, MtrR was shown to directly repress glnA, which encodes glutamine synthetase. In contrast, evidence for the ability of MtrR to directly activate expression of gonococcal genes has been lacking; herein, we provide such evidence. We now report that MtrR has the ability to directly activate expression of glnE, which encodes the dual functional adenyltransferase/deadenylase enzyme GlnE that modifies GlnA resulting in regulation of its role in glutamine biosynthesis. With its capacity to repress expression of glnA, the results presented herein emphasize the diverse and often opposing regulatory properties of MtrR that likely contributes to the overall physiology and metabolism of N. gonorrhoeae. PMID:26078871

  14. The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma

    Microsoft Academic Search

    M Sarbia; M Stahl; C von Weyhern; G Weirich; F Pühringer-Oppermann

    2006-01-01

    The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy±surgical resection), and the presence of genetic polymorphisms in genes involved in folate metabolism. In total, 68 patients who took part in a prospective multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy, optionally followed by surgery. DNA

  15. Correlation of Homocysteine Metabolic Enzymes Gene Polymorphism and Mild Cognitive Impairment in the Xinjiang Uygur Population

    PubMed Central

    Luo, Mei; Ji, Huihui; Zhou, Xiaohui; Liang, Jie; Zou, Ting

    2015-01-01

    Background The aim of this study was to investigate the genetic polymorphisms in the homocysteine (HCY) metabolic enzymes in the Xinjiang Uygur population who have mild cognitive impairment (MCI). Material/Methods Based on the epidemiological investigation, 129 cases of diagnosed Uygur MCI patients and a matched control group with 131 cases were enrolled for analyzing the association between the polymorphisms in the HCY metabolism related genes (C677T, A1298C, and G1968A polymorphisms in MTHFR, as well as the A2756G polymorphism in MS) and MCI by using the SNaPshot method. We then determined the homocysteine level in patients. Results In Xinjiang Uygur subjects, the A1298C polymorphisms in MTHFR and the A2756G polymorphisms in the MS gene in the MCI group were different from those in the control group. However, the C677T and G1968A polymorphisms in the MTHFR gene in MCI patients were not different from those in the control group. Multivariate logistic regression showed that, in addition to the well-known risk factors, such as low education level, high cholesterol level, high level of low-density lipoprotein, and high homocysteine levels, the A>G mutation in the MS gene at the rs1805087 locus was another independent risk factor for MCI in the Uyghur MCI population. The risk of MCI in G allele carriers was 2.265 times higher than that in matched control individuals (95% CI: 1.205~4.256, P<0.05). Conclusions The genetic polymorphism of HCY metabolizing enzymes is correlated to the occurrence of MCI in the Xinjiang Uygur population. The A2756G polymorphism in the MS gene could be an independent risk factor for MCI in the Xinjiang Uygur population. PMID:25625218

  16. Mtr Extracellular Electron Transfer Pathways in Fe(III)-reducing or Fe(II)-oxidizing Bacteria: A Genomic Perspective

    SciTech Connect

    Shi, Liang; Rosso, Kevin M.; Zachara, John M.; Fredrickson, Jim K.

    2012-12-01

    Originally discovered in the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), the Mtr (i.e., metal-reducing) pathway exists in all characterized strains of metal-reducing Shewanella. The protein components identified to date for the Mtr pathway of MR-1 include four multi-heme c-type cytochromes (c-Cyts), CymA, MtrA, MtrC and OmcA, and a porin-like, outer membrane protein MtrB. They are strategically positioned along the width of the MR-1 cell envelope to mediate electron transfer from the quinone/quinol pool in the inner-membrane to the Fe(III)-containing minerals external to the bacterial cells. A survey of microbial genomes revealed homologues of the Mtr pathway in other dissimilatory Fe(III)-reducing bacteria, including Aeromonas hydrophila, Ferrimonas balearica and Rhodoferax ferrireducens, and in the Fe(II)-oxidizing bacteria Dechloromonas aromatica RCB, Gallionella capsiferriformans ES-2 and Sideroxydans lithotrophicus ES-1. The widespread distribution of Mtr pathways in Fe(III)-reducing or Fe(II)-oxidizing bacteria emphasizes the importance of this type of extracellular electron transfer pathway in microbial redox transformation of Fe. Their distribution in these two different functional groups of bacteria also emphasizes the bi-directional nature of electron transfer reactions carried out by the Mtr pathways. The characteristics of the Mtr pathways may be shared by other pathways used by microorganisms for exchanging electrons with their extracellular environments.

  17. Unique properties of the Mtr4p-poly(A) complex suggest a role in substrate targeting†

    PubMed Central

    Bernstein, Jade; Ballin, Jeff D.; Patterson, Dimeka N.; Wilson, Gerald M.; Toth, Eric A.

    2010-01-01

    Mtr4p is a DEVH-box helicase required for 3?-end processing and degradation of various nuclear RNA substrates. In particular, Mtr4p is essential for the creation of 5.8S rRNA, U4 snRNA, and some snoRNAs, and for the degradation of cryptic unstable transcripts (CUTs), aberrant mRNAs and aberrant tRNAs. Many instances of 3?-end processing require limited polyadenylation to proceed. While polyadenylation can signal degradation in species from bacteria to humans, the mechanism whereby polyadenylated substrates are delivered to the degradation machinery is unknown. Our previous work has shown that Mtr4p preferentially binds poly(A) RNA. We suspect that this preference aids in targeting polyadenylated RNAs to the exosome. In these studies, we have investigated the mechanism underlying the preference of Mtr4p for poly(A) substrates as a means to understand how Mtr4p might facilitate targeting. Our analysis has revealed that recognition of poly(A) substrates involves sequence-specific changes in the architecture of Mtr4p-RNA complexes. Furthermore, these differences significantly affect downstream activities. In particular, homopolymeric stretches like poly(A) ineffectively stimulate the ATPase activity of Mtr4p and suppress the rate of Mtr4p-RNA complex dissociation. These findings indicate that the Mtr4p-poly(A) complex is unique and ideally suited for targeting key substrates to the exosome. PMID:21058657

  18. The energy conserving methyltetrahydromethanopterin:coenzyme M methyltransferase complex from methanogenic archaea: function of the subunit MtrH.

    PubMed

    Hippler, B; Thauer, R K

    1999-04-23

    In methanogenic archaea the transfer of the methyl group of N5-methyltetrahydromethanopterin to coenzyme M is coupled with energy conservation. The reaction is catalyzed by a membrane associated multienzyme complex composed of eight different subunits MtrA-H. The 23 kDa subunit MtrA harbors a corrinoid prosthetic group which is methylated and demethylated in the catalytic cycle. We report here that the 34 kDa subunit MtrH catalyzes the methylation reaction. MtrH was purified and shown to exhibit methyltetrahydromethanopterin:cob(I)alamin methyltransferase activity. Sequence comparison revealed similarity of MtrH with MetH from Escherichia coli and AcsE from Clostridium thermoaceticum: both enzymes exhibit methyltetrahydrofolate:cob(I)alamin methyltransferase activity. PMID:10338124

  19. MTR WING, TRA604, INTERIOR. BASEMENT. INTERIOR VIEW FROM SAME LOCATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR WING, TRA-604, INTERIOR. BASEMENT. INTERIOR VIEW FROM SAME LOCATION IN WEST CORRIDOR AS PHOTO ID-33-G-42 BUT CAMERA FACES SOUTH. SIGN ON DOOR FOR "PIPE TUNNEL" WARNS OF RADIOLOGICAL AND ASBESTOS HAZARDS. DOOR HAS METAL HASPS. SIGN ON OVERHEAD WASTE HEAT RECOVERY PIPES SAYS THEY CONTAIN "ASBESTOS FREE INSULATION." FIRE DOOR AT LEFT LEADS TO STAIRWAY TO FIRST FLOOR. DOOR AT RIGHT LEADS TO ROOM WHICH ONCE CONTAINED MTR LIBRARY. INL NEGATIVE NO. HD46-13-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  20. MTR,TRA603. EXPERIMENTERS' SPACE ALLOCATIONS IN BASEMENT AS OF 1963. SHIELDED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR,TRA-603. EXPERIMENTERS' SPACE ALLOCATIONS IN BASEMENT AS OF 1963. SHIELDED CUBICLES WERE IDENTIFIED BY SPONSORING LABORATORY AND ITS TEST HOLE NUMBER IN THE REACTOR, IE, "KAPL HB-1" SIGNIFIED KNOLLS ATOMIC POWER LABORATORY, HORIZONTAL BEAM NO. 1. "WAPD" WAS WESTINGHOUSE ATOMIC POWER DIVISION. CATCH TANKS AND SAMPLE STATIONS FOR TEST LOOPS WERE ASSOCIATED WITH THESE CUBICLES. NOTE DESKS, STORAGE CABINETS, SWITCH GEAR, INSTRUMENT PANELS. PHILLIPS PETROLEUM COMPANY MTR-E-5205, 4/1963. INL INDEX NO. 531-0603-00-706-009757, REV. 5. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  1. Polymorphisms in genes involved in folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia.

    PubMed

    Tomita, Luciana Y; D'Almeida, Vania; Villa, Luisa L; Franco, Eduardo L; Cardoso, Marly A

    2013-12-01

    High folate intake has been suggested as an important factor in cancer prevention; however, previous studies on the relation among folate intake, serum folate, and plasma homocysteine (hcy) are controversial. We conducted a hospital-based, case-control study in Brazil investigating associations between dietary and circulating vitamins B-6 and B-12 and folate, hcy, genotypes of folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), methionine synthase reductase (MTRR A66G), and reduced folate carrier (RFC1 G80A) and risk of cervical intraepithelial neoplasia (CIN) grades 1 (CIN1), 2 (CIN2), and 3 (CIN3). The study was composed by 453 controls, 140 CIN1, 126 CIN2, and 231 CIN3. We investigated the joint effects of genetic variants of folate-related genes using genetic risk scores (GRSs) by summing the number of risk alleles for CIN1 and CIN2+ (CIN2 and CIN3 cases). The OR (95% CI) for CIN1 and CIN2+ per each risk allele were 1.29 (1.01, 1.65) and 1.22 (1.01, 1.46), respectively. An association between folate intake and CIN2+ was observed only after stratification according to GRS: crude OR (95% CI) for lower folate intake and GRS ? 4 was 1.67 (0.92, 3.04) (P-trend < 0.001) compared with higher folate intake (above the median) and GRS ? 3. The CIN2+ risk of lower serum vitamin B-6 and GRS ? 4 was 2.14 (0.92, 5.02) (P-trend = 0.05) and lower serum folate (below the median) and GRS ? 4 was 0.49 (0.20, 1.17) (P-trend = 0.05) after adjustment for confounding variables and human papillomavirus infection. Our data suggest that polymorphisms in genes related to folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia. PMID:24089416

  2. MTR, TRA603. SUBBASEMENT FLOOR PLAN. INLET/OUTLET TUNNELS FOR COOLANT WATER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. SUB-BASEMENT FLOOR PLAN. INLET/OUTLET TUNNELS FOR COOLANT WATER (NORTH SIDE) AND AIR (SOUTH SIDE). RABBIT CANAL AND BULKHEADS. SUMPS AND DRAINS. BLAW-KNOX 3150-3-7, 3/1950. INL INDEX NO. 531-0603-00-098-100006, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  3. MTR, TRA603. NORTH ELEVATION. PLUG STORAGE AREA WITH ROLLING STEEL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. NORTH ELEVATION. PLUG STORAGE AREA WITH ROLLING STEEL DOOR. PIPE TUNNEL IN SUB-BASEMENT. FIXED SASH WINDOWS IN BALCONY SECTION. DOOR DETAILS. BLAW-KNOX 3150-803-7, 7/1950. INL INDEX NO. 531-0603-00-098-100566, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  4. MTR, TRA603. SUBPILE ROOM PLAN AND SECTIONS. CONCRETE FILL AT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. SUB-PILE ROOM PLAN AND SECTIONS. CONCRETE FILL AT TWO ELEVATIONS. EXIT AIR DUCT. EXIT AND INLET WATER. PEBBLE CUBICLE AND BIN. BLAW-KNOX 3150-803-45, 9/1950. INL INDEX NO. 531-0603-62-098-100601, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  5. MTR, TRA603. FOUNDATION PLAN, SECTION B ALONG EAST/WEST AXIS SHOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. FOUNDATION PLAN, SECTION B ALONG EAST/WEST AXIS SHOWS TUNNELS, SUB-PILE ROOM SHIELDING AND OPENINGS, CANAL AND RELATED SECTIONS. BLAW-KNOX 3150-803-34, 5/1950. INL INDEX NO. 531-0603-62-098-100590, REV. 7. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  6. MTR WING, TRA604. SECTIONS SHOW COUNTING ROOM SHIELDING AND MAZE. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR WING, TRA-604. SECTIONS SHOW COUNTING ROOM SHIELDING AND MAZE. RECORD ROOM BELOW. STAIRWAYS TO BASEMENT AND FAN LOFT. BLAW-KNOX 3150-804-7, 11/1950. INL INDEX NO. 531-0604-00-098-100632, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  7. MTR WING A, TRA604, INTERIOR. MAIN FLOOR. DETAIL VIEW INSIDE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR WING A, TRA-604, INTERIOR. MAIN FLOOR. DETAIL VIEW INSIDE LABORATORY 114. CAMERA FACING NORTH. DISPOSAL OF RADIOACTIVE MATERIALS IS UNDERWAY. INL NEGATIVE NO. HD46-12-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. SOUTH WING, MTR661. INTERIOR DETAIL INSIDE LAB ROOM 127. CAMERA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    SOUTH WING, MTR-661. INTERIOR DETAIL INSIDE LAB ROOM 127. CAMERA FACES WEST, LOOKING DIRECTLY AT A PAIR OF HOT CELLS, THEIR WINDOWS, AND MASTER/SLAVE MANIPULATORS. CABINET AT LEFT IS ABOVE GLOVE BOX. INL NEGATIVE NO. HD46-8-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  9. SOUTH WING, MTR661. INTERIOR DETAIL INSIDE LAB ROOM 131. CAMERA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    SOUTH WING, MTR-661. INTERIOR DETAIL INSIDE LAB ROOM 131. CAMERA FACING NORTHEAST. NOTE CONCRETE BLOCK WALLS. SAFETY SHOWER AND EYE WASHER AT REAR WALL. INL NEGATIVE NO. HD46-7-2. Mike Crane, Photographer, 2/2005. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  10. MTR-ETR TECHNICAL BRANCHES QUARTERLY REPORT FOR PERIOD ENDING SEPTEMBER 31, 1958

    Microsoft Academic Search

    McCollom; K. A. ed

    1958-01-01

    6 4 6 8 7 8 6 7 9 6 2 6 G 8 1 6 : 9 ; 5 6 8 4 8 5 MTR while fueled with plutonium. Slight modifications ; to the reactor control system allowed safe operation despite the lower delayed ; neutron fraction from plutonium. ETR Technical Assistance. Three major loop ; experiments scheduled for

  11. 28 MTR October 2009 Ocean gliders are autonomous underwater vehicles that

    E-print Network

    Fratantoni, David

    28 MTR October 2009 Ocean gliders are autonomous underwater vehicles that profile the water column and accent. Initially used by academic institu- tions primarily for research interests, gliders are now becoming more ubiquitous in military, commercial, and operational oceanographic applications. Gliders can

  12. Structure and Function of Neisseria gonorrhoeae MtrF Illuminates a Class of Antimetabolite Efflux Pumps

    DOE PAGESBeta

    Su, Chih-Chia; Bolla, Jani Reddy; Kumar, Nitin; Radhakrishnan, Abhijith; Long, Feng; Delmar, Jared A.; Chou, Tsung-Han; Rajashankar, Kanagalaghatta R.; Shafer, William M.; Yu, Edward W.

    2015-04-01

    Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm tomore »halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump mediating bacterial resistance to sulfonamide antimetabolite drugs.« less

  13. MTR, TRA603. CONTROL ROOM DETAILS. ACOUSTIC PLASTER CEILING, USHAPED CONSOLE, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. CONTROL ROOM DETAILS. ACOUSTIC PLASTER CEILING, U-SHAPED CONSOLE, INSTRUMENT PANELS, GLASS DOOR, ASPHALT TILE FLOOR AND COLORS. BLAW-KNOX 3150-803-11, 10/1950. INL INDEX NO. 531-0603-00-098-100570, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  14. MTR STACK, TRA710, CONTEXTUAL VIEW, CAMERA FACING SOUTH. PERIMETER SECURITY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR STACK, TRA-710, CONTEXTUAL VIEW, CAMERA FACING SOUTH. PERIMETER SECURITY FENCE AND SECURITY LIGHTING IN VIEW AT LEFT. INL NEGATIVE NO. HD52-1-1. Mike Crane, Photographer, 5/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  15. MTR BUILDING INTERIOR, TRA603. BASEMENT. CAMERA IS IN SOUTHWEST QUADRANT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BUILDING INTERIOR, TRA-603. BASEMENT. CAMERA IS IN SOUTHWEST QUADRANT OF BASEMENT AND FACING NORTHEAST. PANEL DISPLAYS DATA READOUTS. INL NEGATIVE NO. HD46-6-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  16. Shewanella putrefaciens mtrB Encodes an Outer Membrane Protein Required for Fe(III) and Mn(IV) Reduction

    PubMed Central

    Beliaev, Alexander S.; Saffarini, Daad A.

    1998-01-01

    Iron and manganese oxides or oxyhydroxides are abundant transition metals, and in aquatic environments they serve as terminal electron acceptors for a large number of bacterial species. The molecular mechanisms of anaerobic metal reduction, however, are not understood. Shewanella putrefaciens is a facultative anaerobe that uses Fe(III) and Mn(IV) as terminal electron acceptors during anaerobic respiration. Transposon mutagenesis was used to generate mutants of S. putrefaciens, and one such mutant, SR-21, was analyzed in detail. Growth and enzyme assays indicated that the mutation in SR-21 resulted in loss of Fe(III) and Mn(IV) reduction but did not affect its ability to reduce other electron acceptors used by the wild type. This deficiency was due to Tn5 inactivation of an open reading frame (ORF) designated mtrB. mtrB encodes a protein of 679 amino acids and contains a signal sequence characteristic of secreted proteins. Analysis of membrane fractions of the mutant, SR-21, and wild-type cells indicated that MtrB is located on the outer membrane of S. putrefaciens. A 5.2-kb DNA fragment that contains mtrB was isolated and completely sequenced. A second ORF, designated mtrA, was found directly upstream of mtrB. The two ORFs appear to be arranged in an operon. mtrA encodes a putative 10-heme c-type cytochrome of 333 amino acids. The N-terminal sequence of MtrA contains a potential signal sequence for secretion across the cell membrane. The amino acid sequence of MtrA exhibited 34% identity to NrfB from Escherichia coli, which is involved in formate-dependent nitrite reduction. To our knowledge, this is the first report of genes encoding proteins involved in metal reduction. PMID:9829939

  17. Increased prevalence of combined MTR and MTHFR genotypes among individuals with severely elevated total homocysteine plasma levels

    Microsoft Academic Search

    Alexandra Feix; Robert Fritsche-Polanz; Josef Kletzmayr; Andreas Vychytil; Walter H. Hörl; Gere Sunder-Plassmann; Manuela Födinger

    2001-01-01

    The prevalence of the methionine synthase (MTR) 2756A?G polymorphism among individuals with severely elevated total homocysteine (tHcy) plasma levels is unknown. Therefore, 1,716 subjects, including 415 hemodialysis patients, 179 peritoneal dialysis patients, 733 kidney graft recipients, and 389 healthy subjects, were investigated. The distribution of MTR 2756A?G, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C?T\\/1298A?C, genotypes among study participants with extremely

  18. An Assessment of the MTR Aquatic Plant Bioindication System for Determining the Trophic Status of Polish Rivers

    Microsoft Academic Search

    K. Szoszkiewicz; K. Karolewicz; A. ?awniczak; F. H. Dawson

    2002-01-01

    Mean Trophic Rank (MTR), a new British biological macrophyte-based method for assessing trophic status of rivers was applied in Poland in 2000-2001. The occurrence and abundance of 86 aquatic plant species was recorded at 48 sites on 19 rivers in the lowland part of Poland. Forty-six of these species are MTR scoring taxa used in the British system, but another

  19. Association of Aberrations in One Carbon Metabolism with Intimal Medial Thickening in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Dhananjayan, R; Malati, T; Rupasree, Y; Kutala, Vijay Kumar

    2015-07-01

    The present work was aimed to study the association of one carbon genetic variants, hyperhomocysteinemia and oxidative stress markers, i.e., serum nitrite, plasma malondialdehyde (MDA) and glutathione (GSH) on intimal medial thickening (IMT) in patients with type 2 diabetes mellitus (T2D). A total number of 76 subjects from ACS Medical College and Hospital, Chennai, India were included in the study, i.e., Group I (n = 42) of T2D and Group II (n = 34) of age- and sex matched healthy controls. The glycated haemoglobin was measured by ion-exchange resin method; plasma homocysteine by Enzyme Linked Immunosorbant Assay method; serum nitrite (nitric oxide, NO), plasma MDA and GSH by spectrophotometric methods; the IMT by high frequency ultrasound. The polymorphisms of one carbon genetic variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism and amplified fragment length polymorphism methods. Results indicate that methyltetrahydrofolate homocysteine methyl transferase (MTR) A2756G allele was found to be protective in T2D and the other variants were not significantly associated with T2D. Glutamate carboxypeptidase II (GCP II) C1561T (r = 0.34; p = 0.05) and methylene tetrahydrofolate reductase (MTHFR) C677T (r = 0.35; 0.04) showed positive correlation with plasma homocysteine in T2D cases. In this study, MTR A2756G allele was found to be protective in T2D; GCP II C1561T and MTHFR C677T showed positive association with plasma homocysteine in T2D cases. Among all the genetic variants, MTR A2756G was found influence IMT. RFC 1 G80A and TYMS 5'-UTR 2R3R showed synergistically interact with MTR A2756G in influencing increase in IMT. PMID:26089610

  20. MTR, TRA603. TRANSVERSE SECTION LOOKS DOWN EAST/WEST AXIS TO SHOW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. TRANSVERSE SECTION LOOKS DOWN EAST/WEST AXIS TO SHOW PATH OF PROCESS WATER LINES IN PIPE TUNNEL FROM SUMP PUMP, AIR DUCTS, ELEVATORS, CANAL IN BASEMENT LEVEL, CANAL CRANE DOWN CENTER LINE OF CANAL, AND REACTOR ROOM CRANE ON TRAVELING RAIL. BLAW-KNOX BKC-3150, 3/1950. INL INDEX NO. 531-0603-00-098-100005, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  1. MTR BUILDING, TRA603. EAST SIDE. CAMERA FACING WEST. CORRUGATED IRON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BUILDING, TRA-603. EAST SIDE. CAMERA FACING WEST. CORRUGATED IRON BUILDING MARKED WITH "X" IS TRA-651. TRA-626, TO ITS RIGHT, HOUSED COMPRESSOR EQUIPMENT FOR THE AIRCRAFT NUCLEAR PROPULSION PROGRAM. LATER, IT WAS USED FOR STORAGE. INL NEGATIVE NO. HD46-42-4. Mike Crane, Photographer, April 2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  2. MTR BUILDING, TRA603. SOUTHEAST CORNER, EAST SIDE FACING TOWARD RIGHT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR BUILDING, TRA-603. SOUTHEAST CORNER, EAST SIDE FACING TOWARD RIGHT OF VIEW. CAMERA FACING NORTHWEST. LIGHT-COLORED PROJECTION AT LEFT IS ENGINEERING SERVICES BUILDING, TRA-635. SMALL CONCRETE BLOCK BUILDING AT CENTER OF VIEW IS FAST CHOPPER DETECTOR HOUSE, TRA-665. INL NEGATIVE NO. HD46-43-3. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  3. Thermodynamics of Electron Flow in the Bacterial Deca-heme Cytochrome MtrF

    SciTech Connect

    Breuer, Marian; Zarzycki, Piotr P.; Blumberger, Jochen; Rosso, Kevin M.

    2012-07-01

    Electron transporting multiheme cytochromes are essential to the metabolism of microbes that inhabit soils and carry out important biogeochemical processes. Recently the first crystal structure of a prototype bacterial deca-heme cytochrome (MtrF) has been resolved and its electrochemistry characterized. However, the molecular details of electron conductance along heme chains in the cytochrome are difficult to access via experiment due to the nearly identical chemical nature of the heme cofactors. Here we employ large-scale molecular dynamics simulations to compute the reduction potentials of the ten hemes of MtrF in aqueous solution. We find that as a whole they fall within a range of about 0.3 V in agreement with experiment. Individual reduction potentials give rise to a free energy profile for electron conduction that is approximately symmetric with respect to the center of the protein. Our calculations indicate that there is no significant potential bias along the orthogonal octa- and tetra-heme chains suggesting that under aqueous conditions MtrF is a nearly reversible two-dimensional conductor.

  4. Radionuclide Compositions and Total Activity of Spent MTR-HEU Fuel Elements of the IAN-R1 Research Reactor

    NASA Astrophysics Data System (ADS)

    Sarta, Josè A.; Castiblanco, Luis A.

    2005-05-01

    With cooperation of the International Atomic Energy Agency (IAEA) and the Department of Energy (DOE) of the United States, several calculations and tasks related to the waste disposal of spent MTR fuel enriched nominally to 93% were carried out for the conversion of the IAN-R1 Research Reactor from MTR-HEU fuel to TRIGA-LEU fuel. In order to remove the spent MTR-HEU fuel of the core and store it safely a program was established at the Instituto de Ciencias Nucleares y Energìas Alternativas (INEA). This program included training, acquisition of hardware and software, design and construction of a decay pool, transfer of the spent HEU fuel elements into the decay pool and his final transport to Savannah River in United States. In this paper are presented data of activities calculated for each relevant radionuclide present in spent MTR-HEU fuel elements of the IAN-R1 Research Reactor and the total activity. The total activity calculated takes in consideration contributions of fission, activation and actinides products. The data obtained were the base for shielding calculations for the decay pool concerning the storage of spent MTR-HEU fuel elements and the respective dosimetric evaluations in the transferring operations of fuel elements into the decay pool.

  5. Dose Rate Calculations of Spent MTR-HEU Fuel Elements of the IAN-R1 Research Reactor

    NASA Astrophysics Data System (ADS)

    Sarta Fuentes, Jose Antonio

    2005-04-01

    With cooperation of the International Atomic Energy Agency (IAEA) and the Department of Energy (DOE) of the United States, several tasks related to the waste disposal of spent MTR fuel enriched nominally to 93% were carried out for the conversion of the IAN-R1 Research Reactor from MTR-HEU fuel to TRIGA-LEU fuel. In order to remove the spent MTR-HEU fuel of the core and store it safetly, a program was established at the Instituto de Ciencias Nucleares y Energìas Alternativas (INEA). This program included training, acquisition of hardware and sofware, design and construction of a decay pool, transfer of the spent HEU fuel elements into the decay pool and his final transport to Savanah River in United States. In this paper are presented external dose rates which were calculated for a standard spent MTR-HEU fuel element of the IAN-R1 Research Reactor. The calculations take in consideration the activity due to contributions of fission, activation and actinides products for each relevant radionuclide present in a standard spent MTR-HEU fuel. The datas obtained were the base for the respective dosimetric evaluations in the transfering operations of fuel elements into the decay pool and for shielding calculations in designing of the decay pool.

  6. The use of experimental data in an MTR-type nuclear reactor safety analysis

    NASA Astrophysics Data System (ADS)

    Day, Simon E.

    Reactivity initiated accidents (RIAs) are a category of events required for research reactor safety analysis. A subset of this is unprotected RIAs in which mechanical systems or human intervention are not credited in the response of the system. Light-water cooled and moderated MTR-type ( i.e., aluminum-clad uranium plate fuel) reactors are self-limiting up to some reactivity insertion limit beyond which fuel damage occurs. This characteristic was studied in the Borax and Spert reactor tests of the 1950s and 1960s in the USA. This thesis considers the use of this experimental data in generic MTR-type reactor safety analysis. The approach presented herein is based on fundamental phenomenological understanding and uses correlations in the reactor test data with suitable account taken for differences in important system parameters. Specifically, a semi-empirical approach is used to quantify the relationship between the power, energy and temperature rise response of the system as well as parametric dependencies on void coefficient and the degree of subcooling. Secondary effects including the dependence on coolant flow are also examined. A rigorous curve fitting approach and error assessment is used to quantify the trends in the experimental data. In addition to the initial power burst stage of an unprotected transient, the longer term stability of the system is considered with a stylized treatment of characteristic power/temperature oscillations (chugging). A bridge from the HEU-based experimental data to the LEU fuel cycle is assessed and outlined based on existing simulation results presented in the literature. A cell-model based parametric study is included. The results are used to construct a practical safety analysis methodology for determining reactivity insertion safety limits for a light-water moderated and cooled MTR-type core.

  7. MTR, TRA603. FIRST FLOOR PLAN. REACTOR AT CENTER. TWENTYMETER CHOPPER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR, TRA-603. FIRST FLOOR PLAN. REACTOR AT CENTER. TWENTY-METER CHOPPER HOUSE. COFFIN TURNING ROLLS. REMOVABLE PANEL OVER CANAL ON EAST SIDE. NEW PLUG STORAGE ACCESS. DOOR SCHEDULE INDICATES STEEL (FOR VAULT), WIRE MESH, AND HOLLOW METAL TYPES. STORAGE AND ISSUE ROOM. SAFETY SHOWERS. DOORWAY TO WING, TRA-604. BLAW-KNOX 3150-803-2, 7/1950. INL INDEX NO. 531-0603-00-098-100561, REV. 10. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. WATER PROCESS SYSTEM FLOW DIAGRAM FOR MTR, TRA603. SUMMARY OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    WATER PROCESS SYSTEM FLOW DIAGRAM FOR MTR, TRA-603. SUMMARY OF COOLANT FLOW FROM WORKING RESERVOIR TO INTERIOR OF REACTOR'S THERMAL SHIELD. NAMES TANK SECTIONS. PIPE AND DRAIN-LINE SIZES. SHOWS DIRECTION OF AIR FLOW THROUGH PEBBLE AND GRAPHITE BLOCK ZONE. NEUTRON CURTAIN AND THERMAL COLUMN DOOR. BLAW-KNOX 3150-92-7, 3/1950. INL INDEX NO. 531-0603-51-098-100036, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  9. Isolation of a High-Affinity Functional Protein Complex between OmcA and MtrC: Two Outer Membrane Decaheme c-type Cytochromes of Shewanella oneidensis MR-1

    SciTech Connect

    Shi, Liang; Chen, Baowei; Wang, Zheming; Elias, Dwayne A.; Mayer, M. Uljana; Gorby, Yuri A.; Ni, Shuisong; Lower, Brian H.; Kennedy, David W.; Wunschel, David S.; Mottaz, Heather M.; Marshall, Matthew J.; Hill, Eric A.; Beliaev, Alex S.; Zachara, John M.; Fredrickson, Jim K.; Squier, Thomas C.

    2006-07-01

    SUMMARY Shewanella oneidensis MR-1 is a facultatively anaerobic bacterium that is capable of using insoluble oxidized metals, such as manganese [Mn(III, IV)] and iron [Fe(III)] oxides and oxyhydroxides, as terminal electron acceptors during anaerobic respiration. The ability of S. oneidensis MR-1 to reduce oxidized Mn and/or Fe has previously been linked to OmcA and MtrC: two decaheme c-type cytochromes that are localized to the outer membrane. To investigate how the electron transport proteins OmcA and MtrC are organized, we expressed and purified recombinant OmcA and MtrC from wild type S. oneidensis MR-1 as well as a mutant that lacked OmcA and MtrC (?omcA/mtrC). After purification to the nearly electrophoretic homogeneity from the ?omcA/mtrC mutant, the recombinant OmcA and MtrC exhibited the characteristics of c-type cytochromes, and each of their polypeptides was confirmed to contain 10 hemes. When purified from wild type cells, endogenous MtrC or OmcA was always co-purified with recombinant OmcA or MtrC, respectively. Fluorescence polarization experiment showed that recombinant OmcA bound to the FlAsH-labeled MtrC with a dissociation constant of 7 ×10-7 M. The purified recombinant OmcA or MtrC alone displayed intrinsic ferric reductase activity with NADH used as an electron donor. Ferric reductase specific activity increased by 35 to 41% when nearly equimolar concentrations of OmcA and MtrC were assayed relative to the two proteins assayed independently. These results demonstrate that OmcA and MtrC directly interact with each other to form a stable complex with high ferric reductase activity.

  10. Direct Involvement of Type II Secretion System in Extracellular Translocation of Shewanella Oneidensis Outer Membrane Cytochromes MtrC and OmcA

    SciTech Connect

    Shi, Liang; Deng, Shuang; Marshall, Matthew J.; Wang, Zheming; Kennedy, David W.; Dohnalkova, Alice; Mottaz, Heather M.; Hill, Eric A.; Gorby, Yuri A.; Beliaev, Alex S.; Richardson, David J.; Zachara, John M.; Fredrickson, Jim K.

    2008-08-01

    Outer membrane decaheme c-type cytochromes MtrC and OmcA of Shewanella oneidensis MR-1 are extracellular lipoproteins important for dissimilatory reduction of solid metal (hydr)oxides during anaerobic respiration. To investigate the roles of type II secretion system (T2S) in translocation of MtrC and OmcA across outer membrane, we measured the effects of deleting two T2S genes, gspD and gspG, on the secretion of MtrC and OmcA when cells were grown under anaerobic conditions. Deletion of gspD or gspG resulted in slightly yellowish supernatants, different from the pink supernatant of wild type (wt). Comparative proteomic analyses revealed that, although MtrC, OmcA and NrfA, a periplasmic nitrite reductase, were present the supernatants of wt and ?gspD mutant, their peptides counts were much lower in ?gspD than in wt. Subsequent analyses with heme-staining and Western blot not only confirmed that deletion of gspD or gspG reduced the abundances of MtrC and OmcA in the supernatants, but also revealed that the deletions consequently increased their abundances inside the cells. Complementation of ?gspG mutant with functional GspG could reverse the effects of deleting gspG on the colors of the supernatants and the abundances of MtrC and OmcA. In contrast, Western results showed that the abundance of NrfA was reduced in the supernatant and the cells of ?gspD mutant, suggesting that reduced NrfA in the periplasm, where MtrC and OmcA were accumulated, contributed to its reduction in the supernatant. Thus, our results demonstrate at the first time that T2S facilitates translocation of MtrC and OmcA across outer membrane.

  11. Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors

    SciTech Connect

    Hartshorne, Robert S.; Jepson, Brian N.; Clarke, Thomas A.; Field, Sarah J.; Fredrickson, Jim K.; Zachara, John M.; Shi, Liang; Butt, Julea N.; Richardson, David

    2007-09-04

    Abstract MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately *500 mV (vs. the standard hydrogen electrode). Across this potential window the UV– vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled lowspin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate.

  12. Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine ?-synthase and A 2756G of methionine synthase, with lowered plasma homocysteine levels

    Microsoft Academic Search

    Michael Y Tsai; Michelle Bignell; Feng Yang; Barry G Welge; Kevin J Graham; Naomi Q Hanson

    2000-01-01

    A moderately elevated plasma total homocysteine (tHcy), whether measured during fasting or post-methionine load (PML), is increasingly being recognized as a risk factor for coronary artery diseases (CAD). However, etiologies for moderately elevated plasma tHcy, particularly with regard to the role of genetic influence on plasma tHcy levels, are still not well understood. In the current investigation, we studied 1025

  13. Utilization of high-density fuel and beryllium elements for the neutron flux enhancement in typical MTR type research reactors

    Microsoft Academic Search

    Rizwan Ahmed; Aslam; Nasir Ahmad; Mohammad Javed Khan; Mujahid Tanvir

    2007-01-01

    Pakistan Research Reactor-1 (PARR-1) is a typical MTR type swimming pool reactor utilizing low enriched uranium (LEU), i.e. 19.99% enriched in 235U, silicide dispersion fuel of density 3.28gU\\/cm3. This simulation study was conducted by employing the standard reactor physics simulation codes WIMS-D\\/4, CITATION, and a burnup analysis code FCAP along with a reactor thermal hydraulic simulation code PARET. The present

  14. A study of reduction in fuel requirement and enhancement of neutron flux in typical MTR type research reactors

    Microsoft Academic Search

    Rizwan Ahmed; Aslam; Nasir Ahmad; Mohammad Javed Khan; Abdul Manan

    2007-01-01

    Pakistan Research Reactor-1 (PARR-1) is a typical swimming pool type MTR utilizing low enriched uranium (19.99% in 235U) silicide dispersion fuel of density 3.28gU\\/cm3. The benefits of loading available and upcoming higher density fuels in the existing PARR-1 core have been explored in this study with constraints of no change in the existing moderator\\/coolant channel width and existing reactor systems.

  15. Electrochemical interaction of Shewanella oneidensis MR-1 and its outer membrane cytochromes OmcA and MtrC with hematite electrodes

    SciTech Connect

    Meitl, Leisa A.; Eggleston, Carrick M.; Colberg, Patricia J.; Khare, Nidhi; Reardon, Catherine L.; Shi, Liang

    2009-09-15

    Bacterial metal reduction is an important biogeochemical process in anaerobic environments. An understanding of electron transfer pathways from dissimilatory metal reducing bacteria (DMRB) to solid phase metal (hydr)oxides is important for understanding metal redox cycling in soils and sediments, for utilizing DMRB in bioremedation, and for developing technologies such as microbial fuel cells. Here we hypothesize that the outer membrane cytochromes OmcA and MtrC from Shewanella oneidensis MR-1 are the only terminal reductases capable of direct electron transfer to a hematite working electrode. Cyclic voltammetry (CV) was used to study electron transfer between hematite electrodes and protein films, S. oneidensis MR-1 wild-type cell suspensions, and cytochrome deletion mutants. After controlling for hematite electrode dissolution at negative potential, the midpoint potentials of adsorbed OmcA and MtrC were measured (-201 mV and -163 mV vs. Ag/AgCl, respectively). Cell suspensions of wild-type MR-1, deletion mutants deficient in OmcA (?omcA), MtrC (?mtrC), and both OmcA and MtrC (?mtrC-?omcA) were also studied; voltammograms for ?mtrC-?omcA were indistinguishable from the control. When the control was subtracted from the single deletion mutant voltammograms, redox peaks were consistent with the present cytochrome (i.e., ?omcA consistent with MtrC and ?mtrC consistent with OmcA). The results indicate that OmcA and MtrC are capable of direct electron exchange with hematite electrodes, consistent with a role as terminal reductases in the S. oneidensis MR-1 anaerobic respiratory pathway involving ferric minerals. There was no evidence for other terminal reductases operating under the conditions investigated. A Marcus-based approach to electron transfer kinetics indicated that the rate constant for electron transfer ket varies from 0.025 s-1 in the absence of a barrier to 63.5 s-1 with a 0.2 eV barrier.

  16. Exploring the Effects of Methylenetetrahydrofolate Reductase Gene Variants C677T and A1298C on the Risk of Orofacial Clefts in 261 Norwegian Case-Parent Triads

    Microsoft Academic Search

    Astanand Jugessur; Allen J. Wilcox; Rolv T. Lie; Jeffrey C. Murray; Jack A. Taylor

    2003-01-01

    Folic acid and the methylenetetrahydrofolate reductase (MTHFR) gene have both been implicated in the etiology of orofacial clefts. The authors selected 261 case-parent triads (173 cases with cleft lip with or without cleft palate (CL\\/P) and 88 cases with cleft palate only (CPO)) from a Norwegian population-based study of orofacial clefts (May 1996-1998). A case-parent triad design was used to

  17. The RNA Helicases AtMTR4 and HEN2 Target Specific Subsets of Nuclear Transcripts for Degradation by the Nuclear Exosome in Arabidopsis thaliana

    PubMed Central

    Lange, Heike; Zuber, Hélène; Sement, François M.; Chicher, Johana; Kuhn, Lauriane; Hammann, Philippe; Brunaud, Véronique; Bérard, Caroline; Bouteiller, Nathalie; Balzergue, Sandrine; Aubourg, Sébastien; Martin-Magniette, Marie-Laure; Vaucheret, Hervé; Gagliardi, Dominique

    2014-01-01

    The RNA exosome is the major 3?-5? RNA degradation machine of eukaryotic cells and participates in processing, surveillance and turnover of both nuclear and cytoplasmic RNA. In both yeast and human, all nuclear functions of the exosome require the RNA helicase MTR4. We show that the Arabidopsis core exosome can associate with two related RNA helicases, AtMTR4 and HEN2. Reciprocal co-immunoprecipitation shows that each of the RNA helicases co-purifies with the exosome core complex and with distinct sets of specific proteins. While AtMTR4 is a predominantly nucleolar protein, HEN2 is located in the nucleoplasm and appears to be excluded from nucleoli. We have previously shown that the major role of AtMTR4 is the degradation of rRNA precursors and rRNA maturation by-products. Here, we demonstrate that HEN2 is involved in the degradation of a large number of polyadenylated nuclear exosome substrates such as snoRNA and miRNA precursors, incompletely spliced mRNAs, and spurious transcripts produced from pseudogenes and intergenic regions. Only a weak accumulation of these exosome substrate targets is observed in mtr4 mutants, suggesting that MTR4 can contribute, but plays rather a minor role for the degradation of non-ribosomal RNAs and cryptic transcripts in Arabidopsis. Consistently, transgene post-transcriptional gene silencing (PTGS) is marginally affected in mtr4 mutants, but increased in hen2 mutants, suggesting that it is mostly the nucleoplasmic exosome that degrades aberrant transgene RNAs to limit their entry in the PTGS pathway. Interestingly, HEN2 is conserved throughout green algae, mosses and land plants but absent from metazoans and other eukaryotic lineages. Our data indicate that, in contrast to human and yeast, plants have two functionally specialized RNA helicases that assist the exosome in the degradation of specific nucleolar and nucleoplasmic RNA populations, respectively. PMID:25144737

  18. Spectropolarimetric Comparison Between SDO/HMI and Hinode-SOT/SP Through THEMIS/MTR

    NASA Astrophysics Data System (ADS)

    Sainz Dalda, A.; Lopez Ariste, A.; Gelly, B.; Tarbell, T. D.; Centeno, R.; DeRosa, M. L.; Hoeksema, J. T.

    2011-12-01

    In the golden age of solar spacecraft observatories, the use of similar instruments observing same targets offers us the possibility to get more accurate information of the physical processes taking place on them. We present a comparison between the vector magnetic field and thermodynamic quantities obtained by three different spectropolarimetric instruments. We have used the simultaneous multi-wavelength capabilities of THEMIS/MTR as bridge between the observations at Fe I 6173 Å provided by SDO/HMI and at Fe I 6301 & 6302 Å by Hinode-SOT/SP observations. The official inversion codes for these instruments (PCA based-on, VFISV and MERLIN respectively) have been used with the data properly arranged for them. Therefore, we compare the final products usually offered to the community, i.e. after the inversion, using different codes and these different wavelengths. The cross-calibration of these products shall allow us to go forward from one instrument result to other one in an easy, convenient way.

  19. Missense mutations that alter the DNA-binding domain of the MtrR protein occur frequently in rectal isolates of Neisseria gonorrhoeae that are resistant to faecal lipids.

    PubMed

    Shafer, W M; Balthazar, J T; Hagman, K E; Morse, S A

    1995-04-01

    Resistance of Neisseria gonorrhoeae to structurally diverse hydrophobic agents (HAs) has been associated with missense or deletion mutations in the mtrR (multiple transferable resistance Regulator) gene of laboratory-derived strains but their prevalence in clinical isolates was heretofore unknown. Since faecal lipids provide strong selective pressure for the emergence of variants resistant to HAs (HAR), the nucleotide sequence of the mtrR gene from rectal isolates of N. gonorrhoeae, which displayed different levels of HAR, was determined. Compared to the mtrR gene possessed by the HA-sensitive strain FA19, each clinical isolate contained mutations in the coding and/or promoter regions of their mtrR gene. A missense mutation in codon 45 (Gly-45 to Asp) was the most common mutation found in the strains studied and impacted the structure of the helix-turn-helix domain of the MtrR protein thought to be important in DNA-binding activity. Two clinical isolates bearing a missense mutation in codon 45 also contained a single basepair deletion in a 13 bp inverted sequence positioned within the mtrR promoter region. Introduction of mtrR sequences amplified from the clinical isolates into strain FA19 revealed that acquisition of the single basepair deletion was correlated with high level HAR while mutations in the mtrR-coding region provided for an intermediate level of HAR. PMID:7773394

  20. MTR-Fill: A Simulated Annealing-Based X-Filling Technique to Reduce Test Power Dissipation for scan-Based Designs

    NASA Astrophysics Data System (ADS)

    Song, Dong-Sup; Ahn, Jin-Ho; Kim, Tae-Jin; Kang, Sungho

    This paper proposes the minimum transition random X-filling (MTR-fill) technique, which is a new X-filling method, to reduce the amount of power dissipation during scan-based testing. In order to model the amount of power dissipated during scan load/unload cycles, the total weighted transition metric (TWTM) is introduced, which is calculated by the sum of the weighted transitions in a scan-load of a test pattern and a scan-unload of a test response. The proposed MTR-fill is implemented by simulated annealing method. During the annealing process, the TWTM of a pair of test patterns and test responses are minimized. Simultaneously, the MTR-fill attempts to increase the randomness of test patterns in order to reduce the number of test patterns needed to achieve adequate fault coverage. The effectiveness of the proposed technique is shown through experiments for ISCAS' 89 benchmark circuits.

  1. Specific Bonds between an Iron Oxide Surface and Outer Membrane Cytochromes MtrC and OmcA from Shewanella oneidensis MR-1

    SciTech Connect

    Lower, Brian H.; Shi, Liang; Yongsunthon, Ruchirej; Droubay, Timothy C.; Mccready, David E.; Lower, Steven

    2007-07-31

    Shewanella oneidensis MR-1 is purported to express outer membrane cytochromes (e.g., MtrC and OmcA) that transfer electrons directly to Fe(III) in a mineral during anaerobic respiration.  A prerequisite for this type of reaction would be the formation of a stable bond between a cytochrome and an iron oxide surface.  Atomic force microscopy (AFM) was used to detect whether a specific bond forms between a hematite (Fe2O3) thin film, created with oxygen plasma assisted molecular beam epitaxy (MBE), and recombinant MtrC or OmcA molecules coupled to gold substrates.  Force spectra displayed a unique force signature indicative of a specific bond between each cytochrome and the hematite surface.  The strength of the OmcA-hematite bond was approximately twice as strong as the MtrC-hematite bond, but direct binding to hematite was twice as favorable for MtrC.  Reversible folding/unfolding reactions were observed for mechanically denatured MtrC molecules bound to hematite.  The force measurements for the hematite-cytochrome pairs were compared to spectra collected between an iron oxide and S. oneidensis under anaerobic conditions.  There is a strong correlation between the whole cell and pure protein force spectra suggesting that the unique binding attributes of each cytochrome complement one another and allow both MtrC and OmcA to play a prominent role in the transfer of electrons to Fe(III) in minerals.  Finally, by comparing the magnitude of binding force for the whole cell vs. pure protein data, we were able to estimate that a single bacterium of S. oneidensis (2 x 0.5 ?m) expresses ~104 cytochromes on its outer surface. 

  2. Structural characterization of the principal mRNA-export factor Mex67-Mtr2 from Chaetomium thermophilum.

    PubMed

    Aibara, Shintaro; Valkov, Eugene; Lamers, Meindert H; Dimitrova, Lyudmila; Hurt, Ed; Stewart, Murray

    2015-07-01

    Members of the Mex67-Mtr2/NXF-NXT1 family are the principal mediators of the nuclear export of mRNA. Mex67/NXF1 has a modular structure based on four domains (RRM, LRR, NTF2-like and UBA) that are thought to be present across species, although the level of sequence conservation between organisms, especially in lower eukaryotes, is low. Here, the crystal structures of these domains from the thermophilic fungus Chaetomium thermophilum are presented together with small-angle X-ray scattering (SAXS) and in vitro RNA-binding data that indicate that, not withstanding the limited sequence conservation between different NXF family members, the molecules retain similar structural and RNA-binding properties. Moreover, the resolution of crystal structures obtained with the C. thermophilum domains was often higher than that obtained previously and, when combined with solution and biochemical studies, provided insight into the structural organization, self-association and RNA-binding properties of Mex67-Mtr2 that facilitate mRNA nuclear export. PMID:26144233

  3. In Vivo Identification of the Outer Membrane Protein OmcA-MtrC Interaction Network in Shewanella oneidensis MR-1 Cells Using Novel Hydrophobic Chemical Cross-Linkers

    SciTech Connect

    Zhang, Haizhen; Tang, Xiaoting; Munske, Gerhard R.; Zakharova, Natalia L.; Yang, Li; Zheng, Chunxiang; Wolff, Meagan A.; Tolic, Nikola; Anderson, Gordon A.; Shi, Liang; Marshall, Matthew J.; Fredrickson, Jim K.; Bruce, James E.

    2008-04-01

    Outer membrane (OM) cytochromes OmcA (SO1779) and MtrC (SO1778) are the integral components of electron transfer used by Shewanella oneidensis for anaerobic respiration of metal (hydr)oxides. Here the OmcA-MtrC interaction was identified in vivo using a novel hydrophobic chemical cross-linker (MRN) combined with immunoprecipitation techniques. In addition, identification of other OM proteins from the cross-linked complexes allows first visualization of the OmcA-MtrC interaction network. Further experiments on omcA and mtrC mutant cells showed OmcA plays a central role in the network interaction. For comparison, two commercial cross-linkers were also used in parallel and both resulted in fewer OM protein identifications, indicating the superior properties of MRN for identification of membrane protein interactions. Finally, comparison experiments of in vivo cross-linking and cell lysate cross-linking resulted in significantly different protein interaction data, demonstrating the importance of in vivo cross-linking for study of protein-protein interactions in cells.

  4. Certain Adenylated Non-Coding RNAs, Including 5? Leader Sequences of Primary MicroRNA Transcripts, Accumulate in Mouse Cells following Depletion of the RNA Helicase MTR4

    PubMed Central

    Dorweiler, Jane E.; Ni, Ting; Zhu, Jun; Munroe, Stephen H.; Anderson, James T.

    2014-01-01

    RNA surveillance plays an important role in posttranscriptional regulation. Seminal work in this field has largely focused on yeast as a model system, whereas exploration of RNA surveillance in mammals is only recently begun. The increased transcriptional complexity of mammalian systems provides a wider array of targets for RNA surveillance, and, while many questions remain unanswered, emerging data suggest the nuclear RNA surveillance machinery exhibits increased complexity as well. We have used a small interfering RNA in mouse N2A cells to target the homolog of a yeast protein that functions in RNA surveillance (Mtr4p). We used high-throughput sequencing of polyadenylated RNAs (PA-seq) to quantify the effects of the mMtr4 knockdown (KD) on RNA surveillance. We demonstrate that overall abundance of polyadenylated protein coding mRNAs is not affected, but several targets of RNA surveillance predicted from work in yeast accumulate as adenylated RNAs in the mMtr4KD. microRNAs are an added layer of transcriptional complexity not found in yeast. After Drosha cleavage separates the pre-miRNA from the microRNA's primary transcript, the byproducts of that transcript are generally thought to be degraded. We have identified the 5? leading segments of pri-miRNAs as novel targets of mMtr4 dependent RNA surveillance. PMID:24926684

  5. In Vivo Identification of the Outer Membrane Protein OmcA–MtrC Interaction Network in Shewanella oneidensis MR-1 Cells Using Novel Hydrophobic Chemical Cross-Linkers

    PubMed Central

    Zhang, Haizhen; Tang, Xiaoting; Munske, Gerhard R.; Zakharova, Natalia; Yang, Li; Zheng, Chunxiang; Wolff, Megan A.; Tolic, Nikola; Anderson, Gordon A.; Shi, Liang; Marshall, Matthew J.; Fredrickson, James K.; Bruce, James E.

    2008-01-01

    Outer membrane (OM) cytochromes OmcA (SO1779) and MtrC (SO1778) are the integral components of electron transfer used by Shewanella oneidensis for anaerobic respiration of metal (hydr)oxides. Here the OmcA–MtrC interaction was identified in vivo using a novel hydrophobic chemical cross-linker (MRN) combined with immunoprecipitation techniques. In addition, identification of other OM proteins from the cross-linked complexes allows first visualization of the OmcA–MtrC interaction network. Further experiments on omcA and mtrC mutant cells showed OmcA plays a central role in the network interaction. For comparison, two commercial cross-linkers were also used in parallel, and both resulted in fewer OM protein identifications, indicating the superior properties of MRN for identification of membrane protein interactions. Finally, comparison experiments of in vivo cross-linking and cell lysate cross-linking resulted in significantly different protein interaction data, demonstrating the importance of in vivo cross-linking for study of protein–protein interactions in cells. PMID:18303833

  6. Plasma homocysteine concentrations and the single nucleotide polymorphisms in the methionine synthase gene (MTR 2756A > G): Associations with the polycystic ovary syndrome

    Microsoft Academic Search

    M. Palep-Singh; H. M. Picton; Z. R. Yates; J. H. Barth; A. H. Balen

    2008-01-01

    BackgroundElevated plasma homocysteine (Hcy) is a recognized risk factor for cardiovascular disease (CVD) and other defects. Biochemical and genetic studies have characterized molecular determinants contributing to alter Hcy metabolism. The vitamin B12 dependent enzyme methionine synthase (MTR) regulates de novo production of methionine from homocysteine. Defects in the activity of this enzyme may possibly predispose to higher plasma Hcy concentrations.

  7. Molecular Structure and Free Energy Landscape for Electron Transport in the Deca-Heme Cytochrome MtrF

    SciTech Connect

    Breuer, Marian; Zarzycki, Piotr P.; Shi, Liang; Clarke, Thomas; Edwards, Marcus; Butt, Julea N.; Richardson, David J.; Fredrickson, Jim K.; Zachara, John M.; Blumberger, Jochen; Rosso, Kevin M.

    2012-12-01

    The free energy profile for electron flow through the bacterial deca-heme cytochrome MtrF has been computed using thermodynamic integration and classical molecular dynamics. The extensive calculations on two versions of the structure help validate the method and results, because differences in the profiles can be related to differences in the charged amino acids local to specific heme groups. First estimates of reorganization free energies ? yield a range consistent with expectations for partially solvent exposed cofactors, and reveal an activation energy range surmountable for electron flow. Future work will aim at increasing the accuracy of ? with polarizable force field dynamics and quantum chemical energy gap calculations, as well as quantum chemical computation of electronic coupling matrix elements.

  8. The characterization of conserved binding motifs and potential target genes for M. tuberculosis MtrAB reveals a link between the two-component system and the drug resistance of M. smegmatis

    Microsoft Academic Search

    Yuqing Li; Jumei Zeng; Hua Zhang; Zheng-Guo He

    2010-01-01

    BACKGROUND: The two-component systems of Mycobacterium tuberculosis are apparently required for its growth and resistance in hostile host environments. In such environments, MtrAB has been reported to regulate the expression of the M. tuberculosis replication initiator gene, dnaA. However, the dnaA promoter binding sites and many potential target genes for MtrA have yet to be precisely characterized. RESULTS: In this

  9. Kinetics of Reduction of Fe(III) Complexes by Outer Membrane Cytochromes MtrC and OmcA of Shewanella oneidensis MR1

    Microsoft Academic Search

    Zheming Wang; Chongxuan Liu; Xuelin Wang; Matthew J. Marshall; John M. Zachara; Kevin M. Rosso; Michel Dupuis; James K. Fredrickson; Steve M. Heald; Liang Shi

    2008-01-01

    Shewanella Oneidensis MR-1 possesses up to 42 c-type cytochromes with heme content varying between 1 to as many as 37. Among them, the outer-membrane cytochromes, particularly MtrC and OmcA, are suspected to function as terminal reductases and are responsible for its enzymatic catalysis capability. So far, the mechanisms of metal reduction by these outer-membrane cytochromes are unknown. In this work,

  10. Turbo-EEPRML: An EEPR4 channel with an error-correcting post-processor designed for 16\\/17 rate quasi-MTR code

    Microsoft Academic Search

    Takushi Nishiya; Kyoko Tsukano; T. Hirai; Takashi Nara; Seiichi Mita

    1998-01-01

    An EEPRML channel with a post processor has been developed for compensating for the degradation in performance due to noise correlation. This Turbo-EEPRML is designed for 16\\/17 rate quasi-MTR (QMTR) code. The proposed method has high performance and simple circuitry. Simulation showed that Turbo-EEPRML has a 2.0-2.5 dB coding gain over a conventional EPRML channel for 16\\/17 GCR code

  11. Structural Characterization of the Chaetomium thermophilum TREX-2 Complex and its Interaction with the mRNA Nuclear Export Factor Mex67:Mtr2.

    PubMed

    Dimitrova, Lyudmila; Valkov, Eugene; Aibara, Shintaro; Flemming, Dirk; McLaughlin, Stephen H; Hurt, Ed; Stewart, Murray

    2015-07-01

    The TREX-2 complex integrates mRNA nuclear export into the gene expression pathway and is based on a Sac3 scaffold to which Thp1, Sem1, Sus1, and Cdc31 bind. TREX-2 also binds the mRNA nuclear export factor, Mex67:Mtr2, through the Sac3 N-terminal region (Sac3N). Here, we characterize Chaetomium thermophilum TREX-2, show that the in vitro reconstituted complex has an annular structure, and define the structural basis for interactions between Sac3, Sus1, Cdc31, and Mex67:Mtr2. Crystal structures show that the binding of C. thermophilum Sac3N to the Mex67 NTF2-like domain (Mex67(NTF2L)) is mediated primarily through phenylalanine residues present in a series of repeating sequence motifs that resemble those seen in many nucleoporins, and Mlp1 also binds Mex67:Mtr2 using a similar motif. Deletion of Sac3N generated growth and mRNA export defects in Saccharomyces cerevisiae, and we propose TREX-2 and Mlp1 function to facilitate export by concentrating mature messenger ribonucleoparticles at the nuclear pore entrance. PMID:26051714

  12. Gene-environment and gene-gene interactions of specific MTHFR, MTR and CBS gene variants in relation to homocysteine in black South Africans.

    PubMed

    Nienaber-Rousseau, Cornelie; Ellis, Suria M; Moss, Sarah J; Melse-Boonstra, Alida; Towers, G Wayne

    2013-11-01

    The methylenetetrahydrofolate reductase (MTHFR), cystathione-?-synthase (CBS) and methionine synthase (MTR) genes interact with each other and the environment. These interactions could influence homocysteine (Hcy) and diseases contingent thereon. We determined single nucleotide polymorphisms (SNPs) within these genes, their relationships and interactions with total Hcy concentrations within black South Africans to address the increased prevalence of diseases associated with Hcy. The MTHFR 677 TT and MTR 2756 AA genotypes were associated with higher Hcy concentrations (16.6 and 10.1 ?mol/L; p<0.05) compared to subjects harboring the MTHFR 677 CT/CC and the MTR 2756 AG genotypes (10.5, 9.7 and 9.5 ?mol/L, respectively). The investigated CBS genotypes did not influence Hcy. We demonstrated interactions between the area of residence and the CBS T833C/844ins68 genotypes (p=0.005) so that when harboring the wildtype allele, rural subjects had significantly higher Hcy than their urban counterparts, but when hosting the variant allele the environment made no difference to Hcy. Between the CBS T833C/844ins68 or G9276A and MTHFR C677T genotypes, there were two-way interactions (p=0.003 and=0.004, respectively), with regard to Hcy. Subjects harboring the MTHFR 677 TT genotype in combination with the CBS 833 TT/homozygous 844 non-insert or the MTHFR 677 TT genotype in combination with the CBS 9276 GA/GG displayed higher Hcy concentrations. Therefore, some of the investigated genotypes affected Hcy; residential area changed the way in which the CBS T833C/844ins68 SNPs influenced Hcy concentrations highlighting the importance of environmental factors; and gene-gene interactions allude to epistatic effects. PMID:23954866

  13. Acute methotrexate-induced encephalopathy--causal relation to homozygous allelic state for MTR c.2756A>G (D919G)?

    PubMed

    Linnebank, M; Malessa, S; Moskau, S; Semmler, A; Pels, H; Klockgether, T; Schlegel, U

    2007-08-01

    Methotrexate (MTX) is widely used in the treatment of hematological diseases. The typical side-effects of high-dose MTX chemotherapy on the CNS range from asymptomatic white matter changes to severe CNS demyelination. MTX neuro - toxicity has been described to be associated with homocysteine and folate levels as well as genetic variants affecting methionine metabolism. Here we describe a case of severe, acute MTX-induced encephalopathy in a patient who was found to be homozygous for the rare missense variant methionine synthase (MTR) c.2756A>G (D919G), which may have modified the effect of MTX on homocysteine metabolism. This finding encourages further studies to determine to what extent the individual conditions of folate and methionine metabolism influence the effects or side-effects of MTX treatment. PMID:17855192

  14. Diagnostic Exome Sequencing and Tailored Bioinformatics of the Parents of a Deceased Child with Cobalamin Deficiency Suggests Digenic Inheritance of the MTR and LMBRD1 Genes.

    PubMed

    Farwell Gonzalez, Kelly D; Li, Xiang; Lu, Hsiao-Mei; Lu, Hong; Pellegrino, Joan E; Miller, Ryan T; Zeng, Wenqi; Chao, Elizabeth C

    2015-01-01

    Disorders of cobalamin deficiency are a heterogeneous group of disorders with at least 19 autosomal recessive-associated genes. Familial samples of an infant who died due to presumed cobalamin deficiency were referred for clinical exome sequencing. The patient died before obtaining a blood sample or skin biopsy, autopsy was declined, and DNA yielded from the newborn screening blood spot was insufficient for diagnostic testing. Whole-exome sequencing of the mother, father, and unaffected sister and tailored bioinformatics analysis was applied to search for mutations in underlying disorders with recessive inheritance. This approach identified alterations within two genes, each of which was carried by one parent. The mother carried a missense alteration in the MTR gene (c.3518C>T; p.P1173L) which was absent in the father and the sister. The father carried a translational frameshift alteration in the LMBRD1 gene (c.1056delG; p.L352Lfs*18) which was absent in the mother and present in the heterozygous state in the sister. These mutations in the MTR (MIM# 156570) and LMBRD1 (MIM# 612625) genes have been described in patients with disorders of cobalamin metabolism complementation groups cblG and cblF, respectively. The child's clinical presentation and biochemical results demonstrated overlap with both cblG and cblF. Sanger sequencing using DNA from the infant's blood spot confirmed the inheritance of the two alterations in compound heterozygous form. We present the first example of exome sequencing leading to a diagnosis in the absence of the affected patient. Furthermore, the data support the possibility for potential digenic inheritance associated with cobalamin deficiency. PMID:24664876

  15. A putative methyltransferase, mtrA, contributes to development, spore viability, protein secretion and virulence in the entomopathogenic fungus Beauveria bassiana.

    PubMed

    Qin, Yuqi; Ortiz-Urquiza, Almudena; Keyhani, Nemat O

    2014-11-01

    The filamentous fungus, Beauveria bassiana, is a ubiquitously distributed insect pathogen, currently used as an alternative to chemical pesticides for pest control. Conidiospores are the means by which the fungus disseminates in the environment, and these cells also represent the infectious agent most commonly used in field applications. Little, however, is known concerning the molecular basis for maintenance of spore viability, a critical feature for survival and persistence. Here, we report on the role of a putative methyltransferase, BbmtrA, in conidial viability, normal fungal growth and development, and virulence, via characterization of a targeted gene knockout strain. Loss of BbmtrA resulted in pleiotropic effects including reduced germination, growth and conidiation, with growing mycelia displaying greater branching than the WT parent. Conidial viability dramatically decreased over time, with <5?% of the cells remaining viable after 30 days as compared with >80?% of the WT. Reduced production of extracellular proteins was also observed for the ?BbmtrA mutant, including protease/peptidases, glycoside hydrolases and the hyd1 hydrophobin. The latter was further confirmed by hyd1 gene expression analysis. Insect bioassays using the greater wax moth, Galleria mellonella, further revealed that the ?BbmtrA strain was attenuated in virulence and failed to sporulate on host cadavers. These data support a global role for mtrA in fungal physiological processes. PMID:25194143

  16. Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B6, and vitamin B 12 intakes.

    PubMed

    Jiang-Hua, Qiao; De-Chuang, Jiao; Zhen-Duo, Lu; Shu-de, Cui; Zhenzhen, Liu

    2014-12-01

    We assessed the association between dietary intake of folate and the MTHFR genotype with breast cancer in a Chinese population, with additional analysis of the interactions of gene polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12. A case-control study was performed, and 535 patients with newly diagnosed breast cancer and 673 controls were enrolled into this study. The MTHFR 667TT genotype (odds ratio (OR)?=?1.82, 95 % confidence interval (CI)?=?1.24-2.97) and T allele (OR 0=?1.48, 95 % CI?=?1.15-1.78) were correlated with a moderately significant increased risk of breast cancer when compared with the CC genotype. Individuals carrying the MTR 2756GG genotype (OR?=?1.66, 95 % CI?=?1.16-2.56) and G allele (OR?=?1.42, 95 % CI?=?1.26-1.81) had a higher risk of breast cancer when compared with subjects with the AA genotype. The MTHFR 667 T allele and MTR 2756 G allele were associated with a higher risk of breast cancer in individuals with low folate intake, vitamin B6, and vitamin B12, but the association disappeared among subjects with moderate and high intake of folate, vitamin B6, and vitamin B12. This case-control study found that the MTHFR C677T and MTR A2756G polymorphisms are associated with risk of breast cancer, and folate, vitamin B6, and vitamin B12 intakes influence these associations. PMID:25217320

  17. Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism.

    PubMed

    Ho, Vikki; Massey, Thomas E; King, Will D

    2013-11-01

    Genetic and nutritional factors play a role in determining the functionality of the one-carbon (1C) metabolism cycle, a network of biochemical reactions critical to intracellular processes. Genes encoding enzymes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) may determine biomarkers of the cycle including homocysteine (HCY), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). MTHFR C677T is an established genetic determinant of HCY but less is known of its effect on SAM and SAH. Conversely, the relationship between MTR A2756G and HCY remains inconclusive, and its effect on SAM and SAH has only been previously investigated in a female-specific population. Folate and vitamin B12 are essential substrate and cofactor of 1C metabolism; thus, consideration of gene-nutrient interactions may clarify the role of genetic determinants of HCY, SAM and SAH. This cross-sectional study included 570 healthy volunteers from Kingston, Ontario, Ottawa, Ontario and Halifax, Nova Scotia, Canada. Least squares regression was used to examine the effects of MTR and MTHFR polymorphisms on plasma HCY, SAM and SAH concentrations; gene-gene and gene-nutrient interactions were considered with the inclusion of cross-products in the model. Main effects of MTR and MTHFR polymorphisms on HCY concentrations were observed; however, no gene-gene or gene-nutrient interactions were found. No association was observed for SAM. For SAH, interactions between MTR and MTHFR polymorphisms, and MTHFR polymorphism and serum folate were found. The findings of this research provide evidence that HCY and SAH, biomarkers of 1C metabolism, are influenced by genetic and nutritional factors and their interactions. PMID:24101362

  18. Thymidylate synthase and methionine synthase polymorphisms are not associated with susceptibility to childhood acute lymphoblastic leukemia in Kurdish population from Western Iran

    Microsoft Academic Search

    Zohreh Rahimi; Zainab Ahmadian; Reza Akramipour; Asad Vaisi-Raygani; Ziba Rahimi; Abbas Parsian

    In order to determine the influence of polymorphism in thymidylate synthase (TS 28-bp repeat) and methionine synthase (MS\\u000a A2756G) genes on the susceptibility to acute lymphoblastic leukemia (ALL), 73 children with ALL and 128 age and sex matched\\u000a unrelated healthy individuals from the Kermanshah Province of Iran were screened. The genotyping of TS 28-bp repeat and MS\\u000a A2756G polymorphisms were

  19. Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome.

    PubMed

    Biselli, J M; Zampieri, B L; Goloni-Bertollo, E M; Haddad, R; Fonseca, M F R; Eberlin, M N; Vannucchi, H; Carvalho, V M; Pavarino, E C

    2012-10-01

    Individuals with Down syndrome (DS) carry three copies of the Cystathionine ?-synthase (C?S) gene. The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Furthermore, previous studies in individuals with DS have shown that genetic variants in genes involved in the folate pathway influence the concentrations of this metabolism's products. The purpose of this study is to investigate whether polymorphisms in genes involved in folate metabolism affect the plasma concentrations of Hcy and methylmalonic acid (MMA) along with the concentration of serum folate in individuals with DS. Twelve genetic polymorphisms were investigated in 90 individuals with DS (median age 1.29 years, range 0.07-30.35 years; 49 male and 41 female). Genotyping for the polymorphisms was performed either by polymerase chain reaction (PCR) based techniques or by direct sequencing. Plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry as previously described, and serum folate was quantified using a competitive immunoassay. Our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21. PMID:22903356

  20. Modulatory effect of plasma folate and polymorphisms in one-carbon metabolism on catecholamine methyltransferase (COMT) H108L associated oxidative DNA damage and breast cancer risk.

    PubMed

    Naushad, Shaik Mohammad; Pavani, Addepalli; Rupasree, Yedluri; Sripurna, Deepti; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadha Rao; Kutala, Vijay Kumar

    2011-08-01

    The present study was aimed to investigate the modulatory role of plasma folate and eight putatively functional polymorphisms of one-carbon metabolism on catecholamine methyltransferase (COMT)-mediated oxidative DNA damage and breast cancer risk. Plasma folate and 8-oxo-2'-deoxyguanosine (8-oxodG) were estimated by commercially available kits, while polymorphisms were screened by PCR-RFLP and PCR-AFLP methods. COMT H108L polymorphism showed independent association with breast cancer (OR: 1.73, 95% CI: 1.31-2.30). No significant interaction was observed between folate status and COMT genotype. Multifactor dimensionality reduction (MDR) analysis gave evidence for the significant epistatic (gene-gene) interactions (p<0.0001) of COMT H108L with reduced folate carrier 1 (RFC1) G80A, thymidylate synthase (TYMS) 5'-UTR 3R2R, TYMS 3'-UTR ins6/de16. Increased plasma 8-oxodG were observed in cases compared to controls (mean +/- SE: 5.59 +/- 0.60 vs. 3.50 +/- 0.40 ng/ml, p<0.004). Plasma folate deficiency alone was not a significant predictor of 8-oxodG elevation. The genotype combinations namely, RFC1 G80A/methionine synthase reductase (MTRR) A66G, RFC1 G80A/SHMT C1420T/TYMS 3R2R and serine hydroxymethyltransferase (SHMT) C1420T/TYMS 3R2R/methionine synthase (MTR) A2756G/COMT H108L were strong predictors of 8-oxodG elevation in the order of risk. To conclude, the current study provides substantial evidence for a cross talk between one-carbon metabolism and COMT catalysis that might influence oxidative DNA damage and breast cancer risk. PMID:22053698

  1. Epistatic interactions between loci of one-carbon metabolism modulate susceptibility to breast cancer.

    PubMed

    Naushad, Shaik Mohammad; Pavani, Addepalli; Digumarti, Raghunadha Rao; Gottumukkala, Suryanarayana Raju; Kutala, Vijay Kumar

    2011-11-01

    In view of growing body of evidence substantiating the role of aberrations in one-carbon metabolism in the pathophysiology of breast cancer and lack of studies on gene-gene interactions, we investigated the role of dietary micronutrients and eight functional polymorphisms of one-carbon metabolism in modulating the breast cancer risk in 244 case-control pairs of Indian women and explored possible gene-gene interactions using Multifactor dimensionality reduction analysis (MDR). Dietary micronutrient status was assessed using the validated Food Frequency Questionnaire. Genotyping was done for glutamate carboxypeptidase II (GCPII) C1561T, reduced folate carrier (RFC)1 G80A, cytosolic serine hydroxymethyltransferase (cSHMT) C1420T, thymidylate synthase (TYMS) 5'-UTR tandem repeat, TYMS 3'-UTR ins6/del6, methylenetetrahydrofolate reductase (MTHFR) C677T, methyltetrahydrofolate-homocysteine methyltransferase (MTR) A2756G, methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) A66G polymorphisms by using the PCR-RFLP/AFLP methods. Low dietary folate intake (P < 0.001), RFC1 G80A (OR: 1.38, 95% CI 1.06-1.81) and MTHFR C677T (OR: 1.74 (1.11-2.73) were independently associated with the breast cancer risk whereas cSHMT C1420T conferred protection (OR: 0.72, 95% CI 0.55-0.94). MDR analysis demonstrated a significant tri-variate interaction among RFC1 80, MTHFR 677 and TYMS 5'-UTR loci (P (trend) < 0.02) with high-risk genotype combination showing inflated risk for breast cancer (OR 4.65, 95% CI 1.77-12.24). To conclude, dietary as well as genetic factors were found to influence susceptibility to breast cancer. Further, the current study highlighted the importance of multi-loci analyses over the single-locus analysis towards establishing the epistatic interactions between loci of one-carbon metabolism modulate susceptibility to the breast cancer. PMID:21161404

  2. Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia

    E-print Network

    California at Berkeley, University of

    (MTHFR) gene at positions C677T and A1298C were associated with lower risk of adult acute lymphocytic,10- methylenetetrahydrofolate reductase (MTHFR), and a decreased risk of adult acute lymphocytic leukemia (ALL).1 Similar

  3. Association of aberrations in one-carbon metabolism with molecular phenotype and grade of breast cancer.

    PubMed

    Naushad, Shaik Mohammad; Pavani, Addepalli; Rupasree, Yedluri; Divyya, Shree; Deepti, Sripurna; Digumarti, Raghunadha Rao; Gottumukkala, Suryanarayana Raju; Prayaga, Aruna; Kutala, Vijay Kumar

    2012-10-01

    We have earlier demonstrated the role of aberrant one-carbon metabolism in the etiology of breast cancer. In the current study, we examine the clinical utility of these factors in predicting the subtype of breast cancer and as indicators of disease progression. Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR-amplified fragment length polymorphism (AFLP) approaches were used for genetic analysis. Plasma folate and homocysteine were measured using Axsym folate kit and reverse phase HPLC, respectively. Multiple linear regression models were used to test the predictability of disease progression. Luminal A subtype was associated with late age of onset, higher body mass index and lack of family history of breast cancer. Thymidylate synthase (TYMS) 5'-UTR 28 bp tandem repeat (OR: 2.09, 95% CI: 1.05-4.16) and methylene tetrahydrofolate reductase (MTHFR) C677T (OR: 4.10, 95% CI: 1.40-11.95) were strongly associated with Luminal B. Reduced folate carrier (RFC1) G80A (OR: 2.92, 95% CI: 1.22-6.97) and methionine synthase (MTR) A2756G (OR: 4.71, 95% CI: 1.66-13.31) polymorphisms were associated with LuminA-HH subtype while MTHFR C677T showed association with HER-enriched (OR: 30.41, 95% CI: 6.47-142.91). Cytosolic serine hydroxymethyltransferase (cSHMT) conferred protection against basal-like breast cancer (OR: 0.47, 95% CI: 0.22-0.98). HER-enriched and basal-like subtypes showed positive association with familial breast cancer and inverse association with plasma folate. Hyperhomocysteinemia was observed in Luminal B and basal-like subtypes. Multiple linear regression models of aberrant one-carbon metabolism were found to be moderate predictors of breast cancer grade (area under the receiver operating characteristic curve, C = 0.72, 95% CI: 0.58-0.87, P = 0.008). To conclude, aberrations in one-carbon metabolism predict the subtype of breast cancer and disease progression. PMID:22086855

  4. High transition velocities for solid armatures in the 10-mm MTR railgun

    NASA Astrophysics Data System (ADS)

    Colon, N.; Tran, L.; Luu, K.; Paul, L.; Chang, D. I.; Sink, D. A.

    1993-01-01

    The study examines the transitioning of a solid armature on the Materials Test Railgun at the Armament Research, Development and Engineering Center and analyzes data on high-velocity transition. Solid aluminum, 7075-series alloy armatures were accelerated to 1.75 km/s and were observed to transition at approximately 1.3 km/s. The data show the development of the measured voltage as a continuous process involving the various phases for the contacts, and the model reflects this behavior. For transitioning times of about 500 microsec there is an initial period with low voltages (not more than 20 V) followed by a sharp rise to about 60 V. After that point there is a smooth rise to about 200 V and a quickly increasing voltage to 800 V after 600 microsec. An analysis based on a model for the contacts elucidates the contact physics during the transitioning process up to 200 V.

  5. Health and safety plan for characterization sampling of ETR and MTR facilities

    SciTech Connect

    Baxter, D.E.

    1994-10-01

    This health and safety plan establishes the procedures and requirements that will be used to minimize health and safety risks to persons performing Engineering Test Reactor and Materials Test Reactor characterization sampling activities, as required by the Occupational Safety and Health Administration standard, 29 CFR 1910.120. It contains information about the hazards involved in performing the tasks, and the specific actions and equipment that will be used to protect persons working at the site.

  6. Plasma folate, methylenetetrahydrofolate reductase (MTHFR), and colorectal cancer risk in three large nested case-control studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Few prospective studies have examined the associations between blood levels of folate, in conjunction with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and colorectal cancer. We evaluated the associations between plasma folate, MTHFR C677T, and A1298C, and colorectal cancer in three la...

  7. Polymorphisms in methylenetetrahydrofolate reductase gene and risk of non-Hodgkin lymphoma in a multi-ethnic population.

    PubMed

    Suthandiram, Sujatha; Gan, Gin Gin; Zain, Shamsul Mohd; Haerian, Batoul Sadat; Bee, Ping Chong; Lian, Lay Hoong; Chang, Kian Meng; Ong, Tee Chuan; Mohamed, Zahurin

    2014-05-01

    An imbalance in folate metabolism can adversely affect DNA synthesis and methylation systems which can lead to susceptibility to non-Hodgkin lymphoma (NHL). Whether single nucleotide polymorphisms (SNPs) and their haplotypes in the methylenetetrahydrofolate reductase (MTHFR) are associated with NHL, remain inconclusive. We investigated the association between MTHFR C677T and A1298C SNPs and NHL risk in a population which is made up of Malay, Chinese and Indian ethnic subgroups. A total of 372 NHL patients and 722 controls were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects failed to demonstrate significant association between the MTHFR C677T and A1298C SNPs with NHL and its subtypes. The results were in agreement with the previous meta-analyses. In the Indian ethnic subgroup however, single locus analysis of MTHFR A1298C appears to confer risk to NHL (Odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.22-3.00, P=0.006). The risk is almost doubled in homozygous carrier of MTHFR 1298CC (OR 4.03, 95% CI 1.56-10.43, P=0.004). Haplotype analysis revealed higher frequency of CC in the Indian NHL patients compared with controls (OR 1.86, 95% CI 1.18-2.93, P=0.007). There is lack of evidence to suggest an association between MTHFR C677T and A1298C with the risk of NHL in the Malays and Chinese. In the Indians however, the MTHFR A1298C confers risk to NHL. This study suggests ethnicity modifies the relationship between polymorphisms in the folate-metabolizing gene and NHL. PMID:24646728

  8. Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with ischemic stroke in the Eastern Chinese Han population.

    PubMed

    Lv, Q-Q; Lu, J; Sun, H; Zhang, J-S

    2015-01-01

    The association between the MTHFR genetic polymorphism and ischemic stroke has been reported by a number of investigators. However, the results have been controversial and conflicting. The aim of this study was to explore the association between the MTHFR variants C677T and A1298C and the risk of ischemic stroke in an Eastern Chinese Han population. A total of 199 patients with ischemic stroke and 241 controls were recruited. Genotyping of the MTHFR C677T and A1298C polymorphisms was carried out using the Taqman 7900HT Sequence Detection System. The overall estimates (odds ratio: OR) for the allele (C) and genotype (AC+CC) of the A1298C polymorphism were 1.57 [95% confidence interval (CI) = 1.16-2.10], and 2.36 (95%CI = 1.39-4.00), respectively, establishing significant association of the MTHFR A1298C polymorphism with ischemic stroke. In contrast, there were no statistically significant differences compared to controls between MTHFR C677T polymorphic variants in the association ischemic stroke risk. Furthermore, haplotype-based analysis demonstrated that compared with the C-677-A-1298 haplotype, the C-677-C-1298 and T-677-C-1298 haplotypes showed significant increased risk of ischemic stroke (OR = 1.56; 95%CI = 1.07- 2.2; P = 0.02; OR = 1.76; 95%CI = 1.17-2.65; P < 0.01, respectively). We concluded that the A1298C polymorphism and the haplotypes C-677-C-1298 and T-677-C-1298 in MTHFR might modulate the risk of ischemic stroke in the Eastern Chinese Han population. PMID:25966188

  9. Psychology 456: Social Psychology Summer 2011, 102 Peterson Hall, M-TR 12:00 1:50

    E-print Network

    Lockery, Shawn

    to produce informed hypotheses to questions such as "Why did fedora hats get so popular?" & "Why do women-line and tag sale while west-coaters say in line and garage sale?" & "Do opposites really attract?" Be prepared

  10. Psychology 456: Social Psychology Summer 2013, 116 Esslinger, M-TR 2:00 3:50

    E-print Network

    Lockery, Shawn

    to questions such as "Why did fedora hats get so popular?" & "Why do women tend to underperform in comparison to men in math and science?" & "Why do east-coasters say on-line and tag sale while west-coaters say in line and garage sale?" & "Do opposites really attract?" Be prepared to think, and be prepared

  11. Shewanella putrefaciens mtrB Encodes an Outer Membrane Protein Required for Fe(III) and Mn(IV) Reduction

    Microsoft Academic Search

    ALEXANDER S. BELIAEV; DAAD A. SAFFARINI

    1998-01-01

    Iron and manganese oxides or oxyhydroxides are abundant transition metals, and in aquatic environments they serve as terminal electron acceptors for a large number of bacterial species. The molecular mechanisms of anaerobic metal reduction, however, are not understood. Shewanella putrefaciens is a facultative anaerobe that uses Fe(III) and Mn(IV) as terminal electron acceptors during anaerobic respiration. Transposon mutagenesis was used

  12. Mind the gap: diversity and reactivity relationships among multihaem cytochromes of the MtrA/DmsE family

    E-print Network

    Bewley, Kathryn D.

    Shewanella oneidensis MR-1 has the ability to use many external terminal electron acceptors during anaerobic respiration, such as DMSO. The pathway that facilitates this electron transfer includes the decahaem cytochrome ...

  13. Potential Inherited Causes of Recurrent Prosthetic Mitral Valve Thrombosis in a Pregnant Patient Suffering from Recurrent Miscarriage

    PubMed Central

    Gursoy, M. Ozan; Karakoyun, Suleyman; Yesin, Mahmut; Astarcioglu, Mehmet Ali; Ozkan, Mehmet

    2014-01-01

    An effective anticoagulation is critical in pregnant patients with prosthetic heart valves. Inherited disorders may interfere with the coagulation cascade and may be associated with obstetrical complications as well as with prosthetic valve-derived complications. The patient in the present case had a history of recurrent prosthetic heart valve thrombosis (PHVT) despite an effective anticoagulation. She underwent a thrombolysis with low-dose prolonged infusion of tissue-type plasminogen activator for the management of her recurrrent prosthetic valve thrombosis. The genetic testing showed homozygous mutations of methylenetetrahydrofolate reductase (MTHFR) A 1298 C and heterozygous mutations of ?-fibrinogen 455 G-A. Inherited disorders such as MTHFR A 1298 C and fibrinogen 455G/A polymorphisms may be involved in the pathogenesis of recurrent PHVT and/or pregnancy loss. PMID:25089140

  14. Identification of six methylenetetrahydrofolate reductase ( MTHFR) genotypes resulting from common polymorphisms: impact on plasma homocysteine levels and development of coronary artery disease

    Microsoft Academic Search

    Christian Meisel; Ingolf Cascorbi; Thomas Gerloff; Verena Stangl; Michael Laule; Joachim M. Muller; Klaus D. Wernecke; Gert Baumann; Ivar Roots; Karl Stangl

    2001-01-01

    Although three common MTHFR polymorphisms (C677T, A1298C, T1317C) have been reported, only polymorphism C677T has been investigated intensively as a risk factor for coronary artery disease (CAD). We investigated polymorphism frequencies, allelic associations and the effect of the resulting MTHFR genotypes on total plasma homocysteine (tHcy) levels and on coronary risk in a case-control study with 1000 angiographically confirmed Middle-European

  15. Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis

    Microsoft Academic Search

    Elias Zintzaras

    2006-01-01

    To clarify the influence of MTHFR C677T and A1298C polymorphisms on gastric cancer (GC), a meta-analysis of eight case-control studies (1,584\\/2,785 cases\\/controls) was carried out. Overall, there was moderate heterogeneity among studies, and the C677T allele T was associated with a 27% increased risk of GC compared with C allele: the random effects (RE) OR (95% confidence interval in parenthesis)

  16. Metabolic and Genetic Risk Factors for Migraine in Children

    Microsoft Academic Search

    F Bottini; ME Celle; MG Calevo; S Amato; G Minniti; L Montaldi; D Di Pasquale; R Cerone; E Veneselli; AC Molinari

    2006-01-01

    Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C

  17. Study of MTHFR and MS polymorphisms as risk factors for NTD in the Italian population

    Microsoft Academic Search

    Patrizia De Marco; Maria Grazia Calevo; Anna Moroni; Lorenza Arata; Elisa Merello; Richard H. Finnell; Huiping Zhu; Luciano Andreussi; Armando Cama; Valeria Capra

    2002-01-01

    Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is a risk factor for neural tube defects (NTDs) in many populations, including Italians. Another common mutation on\\u000a the MTHFR gene, A1298C, has also been described as a risk mutation. Furthermore, several studies have suggested that a defective methionine\\u000a synthase (MS) enzyme could be a critical defect in folate-related

  18. Association between polymorphisms in genes encoding methylenetetrahydrofolate reductase and the risk of Ménière's disease.

    PubMed

    Huang, Yang; Teranishi, Masaaki; Uchida, Yasue; Nishio, Naoki; Kato, Ken; Otake, Hironao; Yoshida, Tadao; Sone, Michihiko; Sugiura, Saiko; Ando, Fujiko; Shimokata, Hiroshi; Nakashima, Tsutomu

    2013-06-01

    Folate metabolism is essential for cellular functioning. Despite extensive research on the roles of folate-metabolism-related gene polymorphisms in the pathophysiology of many diseases, such as cardiovascular disease, cancers, and sudden sensorineural hearing loss, little is known about their association with Ménière's disease (MD). The aim of this study was to investigate the effect of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) on the risk of MD in a Japanese population. We examined the C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the MTHFR gene and compared them between 1946 adults (986 men and 960 women) participating in the National Institute for Longevity Sciences Longitudinal Study of Aging and 86 cases of MD. A multiple logistic regression was performed to obtain odds ratios (ORs) for the risk of MD regarding the MTHFR polymorphisms before (model 1) and after (model 2) adjustment for age and sex factors. The OR of MTHFR C677T for the risk of MD was 0.669 (95% confidence interval [CI], 0.479-0.934) in model 1 and 0.680 (95% CI, 0.484-0.954) in model 2. In contrast, the OR of MTHFR A1298C for the risk of MD was 1.503 (95% CI, 1.064-2.123) in model 1 and 1.505 (95% CI, 1.045-2.167) in model 2. Our results imply that the MTHFR C677T and A1298C polymorphisms are associated with the risk of MD. PMID:23484733

  19. Association of Methylene Tetrahydrofolate Reductase Polymorphism with BMD and Homocysteine in Premenopausal North Indian Women

    PubMed Central

    Pandey, Sanjeev Kumar; Singh, Ankur; Polipalli, Sunil Kumar; Gupta, Sangeeta; Kapoor, Seema

    2013-01-01

    Background and Aim: Osteoporosis (OP) is a common nutrigenomic disease associated with various genetic components. Observational studies have indicated that mildly elevated homocysteine was a strong risk factor for osteoporotic fractures. Yet there is no clear biologic mechanism for an effect of homocysteine on bone.The aim of this study was to investigate the association of MTHFR C677T and A1298C polymorphisms, and to verify the association of these polymorphisms with bone mineral density and homocysteine in premenopausal women of northern India. Material and Methods: We included 402 north Indian patients with altered BMD, both Osteopenic (OPN) and Osteoporosis, and normal controls. Genotype identification for MTHFR C677T and A1298C polymorphisms were analyzed by PCR-RFLP method, correlated with Bone Mineral Density (BMD), Homocysteine (Hcy), Folate and Vitamin B12. Results: The study groups did not differ in terms of age, weight and body mass indices. Prevalence of Genotype frequencies (GFs) for MTHFRC677T OP were (n: 402): CC 361 (89.8%), CT 25 (6.22%), TT 16 (3.98%) and that for MTHFR A1298C were (n: 402) AA 353(87.81%), AC 29(7.21%), CC 20(4.98%). Folate was significantly lower in the OP group than those in both the other groups, while there was no significant difference in Hcy in the OP group relative to OPN, as compared to controls. Conclusion: The GFs for MTHFR C677T and A1298C polymorphisms were not different between both groups. In conclusion, polymorphism of the MTHFR 677T is associated with small differences in BMD with folate levels. Further, more investigations should be done in larger studies for other epigenetic pathways, that may increase the risk of Osteoporosis. PMID:24551672

  20. Polymorphisms and haplotypes in methylenetetrahydrofolate reductase gene and head and neck squamous cell carcinoma risk

    Microsoft Academic Search

    Ana Lívia Silva Galbiatti; Mariangela Torreglosa Ruiz; Juliana Olsen Rodrigues; Luiz Sérgio Raposo; José Victor Maníglia; Érika Cristina Pavarino; Eny Maria Goloni-Bertollo

    Functional polymorphisms in genes encoding enzymes involved in folate metabolism might modulate head and neck carcinoma risk\\u000a because folate participates in DNA methylation and synthesis. We therefore conducted a case–control study of 853 individuals\\u000a (322 head and neck cancer cases and 531 non-cancer controls) to investigate associations among MTHFR C677T and MTHFR A1298C polymorphisms and head and neck squamous cell

  1. Association between 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and congenital heart disease: A meta-analysis?

    PubMed Central

    Wang, Wenju; Hou, Zongliu; Wang, Chunhui; Wei, Chuanyu; Li, Yaxiong; Jiang, Lihong

    2013-01-01

    Background Inconsistent results were reported in recent literature regarding the association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility of congenital heart disease (CHD). In this study, we performed a meta-analysis to investigate the associations by employing multiple analytical methods. Methods Literature search was performed and published articles were obtained from PubMed, Embase and CNKI databases based on the exclusion and inclusion criteria. Data were extracted from eligible studies and the crude odds ratios and their corresponding 95% confidence intervals (CIs) were calculated using random or fix effects model to evaluate the associations between the MTHFR C677T/A1298C polymorphisms and CHD development. Subgroup based analysis was performed by Hardy–Weinberg equilibrium, ethnicity, types of CHD, source of control and sample size. Results Twenty-four eligible studies were included in this meta-analysis. Significant association was found between fetal MTHFR C677T polymorphism and CHD development in all genetic models. The pooled ORs and 95% CIs in all genetic models indicated that MTHFR C677T polymorphism was significantly associated with CHD in Asian, but not Caucasian in subgroup analysis. The maternal MTHFR C677T polymorphism was not associated with CHD except for recessive model. Moreover, neither maternal nor fetal MTHFR A1298C polymorphism was associated with CHD. Conclusion The fetal MTHFR C677T polymorphism may increase the susceptibility to CHD. Fetal MTHFR C677T polymorphism was more likely to affect Asian fetus than Caucasian. The MTHFR A1298C polymorphism may not be a risk of congenital heart disease. PMID:25606381

  2. Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups

    Microsoft Academic Search

    Setareh Torabian Esfahani; Edward A Cogger; Marie A Caudill

    2003-01-01

    Objective To determine the prevalence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in women of different ethnic groups and to relate these common mutations to plasma homocysteine, red cell folate, and serum folate. Design A one-time fasting blood sample was obtained for MTHFR genotype (C677T and A1298C) determinations (n=433). Serum folate, red cell folate, and homocysteine analyses were performed in nonfolic

  3. Mutations and Polymorphisms in Genes Affecting Hemostasis Proteins and Homocysteine Metabolism in Children with Arterial Ischemic Stroke

    Microsoft Academic Search

    A. Komitopoulou; H. Platokouki; Z. Kapsimali; H. Pergantou; E. Adamtziki; S. Aronis

    2006-01-01

    Background: The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and environmental factors. Aim: To compare the distributions of mutations\\/polymorphisms in genes affecting hemostasis (factor V Leiden – FVL, FV H1298R-FVR2, FII 20210A, b-Fib 455G>A, FXIII V34L, PAI-1 4G, HPA-1b) or homocysteine metabolism (MTHFR C677T, MTHFR A1298C) among 90 children with arterial ischemic stroke (AIS) and 103

  4. Urinary Tract Anomalies Associated with MTHFR Gene Polymorphism C677T in Girls

    Microsoft Academic Search

    Jana Behunova; Lucia Klimcakova; Ludmila Podracka

    2011-01-01

    Background\\/Aims: Periconceptional folate has a preventive effect not only on neural tube defects, but possibly also on other birth defects such as urinary tract anomalies (UTA), orofacial clefts and conotruncal heart defects. Folate metabolism gene variants are therefore being investigated as potential susceptibility factors. Methods: We assessed the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C genotypes in 132 UTA patients

  5. 5,10-Methylenetetrahydrofolate Reductase Gene Variants and Congenital Anomalies: A HuGE Review

    Microsoft Academic Search

    Lorenzo D. Botto; Quanhe Yang

    2000-01-01

    The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism. The MTHFR gene is located on chromosome 1 (1p36.3), and two common alleles, the C677T (thermolabile) allele and the A1298C allele, have been described. The population frequency of C677T homozygosity ranges from 1% or less among Blacks from Africa and the United States to 20% or more among Italians and

  6. The Association between MTHFR Gene Polymorphisms and Hepatocellular Carcinoma Risk: A Meta-Analysis

    PubMed Central

    Deng, Yan; Huang, Shan; Xu, Juanjuan; Li, Haiwei; Li, Shan; Zhao, Jinmin

    2013-01-01

    Background The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) risk was inconsistent and underpowered. To clarify the effects of MTHFR gene polymorphisms on the risk of HCC, a meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of HCC was conducted. Methods The authors searched PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature database (CBM) for the period up to July 2012. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results Finally, 12 studies with 2,351 cases and 4,091 controls were included for C677T polymorphism and 6 studies with 1,333 cases and 1,878 controls were included for A1298C polymorphism. With respect to A1298C polymorphism, significantly decreased HCC risk was found in the overall population (CC vs. AA: OR?=?0.660, 95%CI 0.460–0.946, P?=?0.024; recessive model: OR?=?0.667, 95%CI?=?0.470–0.948, P?=?0.024). In subgroup analyses, significantly decreased HCC risk was found in Asian population (CC vs. AA: OR?=?0.647, 95%CI?=?0.435–0.963; P?=?0.032) and population-based studies (CC vs. AA: OR?=?0.519, 95%CI?=?0.327–0.823; P?=?0.005). With respect to C677T polymorphism, no significant association with HCC risk was demonstrated in overall and stratified analyses. Conclusions We concluded that MTHFR A1298C polymorphism may play a protective role in the carcinogenesis of HCC. Further large and well-designed studies are needed to confirm this association. PMID:23457501

  7. Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation

    Microsoft Academic Search

    Inho Kim; Kyung-Hun Lee; Jin Hee Kim; Eun Kyung Ra; Sung-Soo Yoon; Yun-Chul Hong; Sung Sup Park; Chul Soo Kim; Byoung Kook Kim

    2007-01-01

    To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a

  8. Common Mutations of the Methylenetetrahydrofolate Reductase (MTHFR) Gene in Non-Syndromic Cleft Lips and Palates Children in North-West of Iran

    PubMed Central

    Abdollahi-Fakhim, Shahin; Asghari Estiar, Mehrdad; Varghaei, Parizad; Alizadeh Sharafi, Mahdi; Sakhinia, Masoud; Sakhinia, Ebrahim

    2015-01-01

    Introduction: Cleft lips and cleft palates are common congenital abnormalities in children. Various chromosomal loci have been suggested to be responsible the development of these abnormalities. The present study was carried out to investigate the association between the suspected genes (methylenetetrahydrofolate reductase [MTHFR] A1298C and C677T) that might contribute into the etiology of these disorders through application of molecular methods. Materials and Methods: This cross-sectional and explanatory study was carried out on a study population of 65 affected children, 130 respective parents and 50 healthy individuals between 2009 and 2012 at Tabriz University of Medical Sciences, IR Iran. After DNA extraction, amplification refractory mutation system–polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphism (RFLP)-PCR were used respectively to investigate the C677T and A1298C mutations for the MTHFR gene. Results: There was a significant difference in the rates of the C677T mutation when affected patients and their fathers were compared with the control group (odds ratio [OR]=0.44) (OR=0.64). However, there was no significant difference observed in the rate of this mutation between the patients’ mothers and the control group (OR=1.35). In addition, the abnormality rate was higher in patients with the A1298C mutation and their parents, when compared with the control group. This abnormality rate was higher for the affected children and their fathers in comparison with their mothers (Fathers, OR=0.26; Mothers, OR=0.65; Children, OR=0.55). No significant difference was seen in the rate of the polymorphism C677T in its CC, when the affected children and their parents were compared with the control group. However, there was a significant difference in the A1298C mutation. Conclusion: An association was seen between the A1298C mutation and cleft lip and cleft palate abnormalities in Iran. However, there seems to be a stronger relationship between the C67TT mutation and these abnormalities in other countries, which could be explained by racial differences. Moreover, this association was more notable between the affected children and their fathers than their mothers. The findings in this study may be helpful in future studies and screening programs. PMID:25745606

  9. Myelinated Afferents Are Involved in Pathology of the Spontaneous Electrical Activity and Mechanical Hyperalgesia of Myofascial Trigger Spots in Rats

    PubMed Central

    2015-01-01

    Myofascial trigger points (MTrPs) are common causes for chronic pain. Myelinated afferents were considered to be related with muscular pain, and our clinical researches indicated they might participate in the pathology of MTrPs. Here, we applied myofascial trigger spots (MTrSs, equal to MTrPs in human) of rats to further investigate role of myelinated afferents. Modified pyridine-silver staining revealed more nerve endings at MTrSs than non-MTrSs (P < 0.01), and immunohistochemistry with Neurofilament 200 indicated more myelinated afferents existed in MTrSs (P < 0.01). Spontaneous electrical activity (SEA) recordings at MTrSs showed that specific block of myelinated afferents in sciatic nerve with tetrodotoxin (TTX) led to significantly decreased SEA (P < 0.05). Behavioral assessment showed that mechanical pain thresholds (MPTs) of MTrSs were lower than those of non-MTrSs (P < 0.01). Block of myelinated afferents by intramuscular TTX injection increased MPTs of MTrSs significantly (P < 0.01), while MPTs of non-MTrSs first decreased (P < 0.05) and then increased (P > 0.05). 30?min after the injection, MPTs at MTrSs were significantly lower than those of non-MTrSs (P < 0.01). Therefore, we concluded that proliferated myelinated afferents existed at MTrSs, which were closely related to pathology of SEA and mechanical hyperalgesia of MTrSs.

  10. New Trends in Myofascial Pain Syn drome

    Microsoft Academic Search

    Chang-Zern Hong

    This re view ar ti cle sum ma rizes re cent stud ies on myofascial trig ger point (MTrP) to fur ther clar ify the mech a nism of MTrP. MTrP is the ma jor cause of mus cle pain (myofascial pain) in clin i cal prac tice. There are mul ti ple MTrP loci in an MTrP re gion.

  11. HWMA/RCRA Closure Plan for the TRA/MTR Warm Waste System Voluntary Consent Order SITE-TANK-005 Tank System TRA-007

    SciTech Connect

    K. Winterholler

    2007-01-30

    This Hazardous Waste Management Act/Resource Conservation and Recovery Act Closure Plan was developed for portions of the Test Reactor Area/Materials Test Reactor Warm Waste System located in the Materials Test Reactor Building (TRA-603) at the Reactor Technology Complex, Idaho National Laboratory Site, to meet a further milestone established under Voluntary Consent Order Action Plan SITE-TANK-005 for the Tank System TRA-007. The reactor drain tank and canal sump to be closed are included in the Test Reactor Area/Materials Test Reactor Warm Waste System. The reactor drain tank and the canal sump will be closed in accordance with the interim status requirements of the Hazardous Waste Management Act/Resource Conservation and Recovery Act as implemented by the Idaho Administrative Procedures Act 58.01.05.009 and Code of Federal Regulations 265. This closure plan presents the closure performance standards and methods for achieving those standards.

  12. Phylogeny of Japanese Stag Beetles (Coleoptera: Lucanidae) Inferred from 16S mtrRNA Gene Sequences, with Reference to the Evolution of Sexual Dimorphism of Mandibles

    Microsoft Academic Search

    Tadatsugu Hosoya; Kunio Araya

    2005-01-01

    As a first step in reconstructing the phylogeny of world stag beetles (Coleoptera: Lucanidae), phylogenetic relationships among the major members of Japanese stag beetles were explored by analyzing a sequence of 1030 nucleotides from the mitochondrial 16S ribosomal RNA (16S rRNA) gene. A total of 20 species and three additional subspecies representing 13 genera were examined to pro- vide basic

  13. Plasma homocysteine levels and genetic polymorphisms in folate metablism are associated with breast cancer risk in chinese women

    PubMed Central

    2014-01-01

    Background Folate plays a pivotal role in DNA synthesis, repair, methylation and homocysteine (Hcy) metabolism. Therefore, alterations in the folate-mediated one-carbon metabolism may lead to abnormal methylation proliferation, increases of tumor/neoplasia and vein thrombosis/cardiovascular risk. The serine hydroxymethyhransferase (SHMT), methionine synthase (MS), methionine synthase reductase (MTRR) and cystathionine beta synthase (CBS) regulate key reactions in the folate and Hcy metabolism. Therefore, we investigated whether the genetic variants of the SHMT, MS, MTRR and CBS gene can affect plasma Hcy levels and are associated with breast cancer risk. Methods Genotyping was performed by PCR-RFLP method. Plasma Hcy levels were measured by the fluorescence polarization immunoassay on samples of 96 cases and 85 controls. Results (a) The SHMT 1420 T, MS 2756G, MTRR 66G allele frequency distribution showed significant difference between case and controls (p?A2756G (OR?=?2.32, 95% CI?=?0.29?~?0.82), MTRR A66G (OR?=?1.84, 95% CI?=?0.25?~?1.66) polymorphism is significantly associated with breast cancer risk. And elevated plasma Hcy levels were significantly linked to increased risk of breast cancer (adjusted OR?=?4.45, 95% CI?=?1.89-6.24 for the highest tertile as compared with the lowest tertile). Conclusions The current study results seem to suggest a possibility that SHMT C1420T mutation may be negatively correlated with breast cancer susceptibility; while MS A2756G and MTRR A66G mutation may be positively associated with breast cancer risk. SHMT C1420T, MS A2756G, MTRR A66G, CBS C1080T, CBS C699T locus mutation may be factors affecting plasma levels of Hcy. The plasma Hcy levels could be metabolic risk factor for breast cancer risk to a certain extent. PMID:24559276

  14. MTHFR Polymorphisms, Folate Intake, and Carcinogen DNA Adducts in the Lung

    PubMed Central

    Lee, Mi-Sun; Asomaning, Kofi; Su, Li; Wain, John C.; Mark, Eugene J.; Christiani, David C.

    2011-01-01

    The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin, was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by 32P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced - 111.3% (95% CI, ?3.0 to 360.5%) among 1298AC+CC patients who consumed the lowest level of folate intake as compared with 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations. PMID:22052259

  15. Association of polymorphisms in one-carbon metabolizing genes with breast cancer risk in Syrian women.

    PubMed

    Lajin, Bassam; Alhaj Sakur, Amir; Ghabreau, Lina; Alachkar, Amal

    2012-08-01

    Dietary folate status as well as polymorphisms in one-carbon metabolism genes may affect the risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and DNA repair. A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results. Association between multiple polymorphisms in one-carbon metabolism genes and breast cancer was not studied before in an Arab population. The purpose of the present study is to test the hypothesis that polymorphisms in one-carbon metabolism genes are associated with breast cancer susceptibility in Syrian breast cancer women patients. A total of 245 subjects (119 breast cancer women patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and MTRR A66G polymorphisms. Association was tested for under numerous genetic models. A statistically significant association was found for MTHFR A1298C polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68, 95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no significant association was found for MTHFR C677T or MTRR A66G under any of the genetic models tested. The effects of the compound genotypes were also examined. The 66GG genotype was found to be protective against breast cancer when combined with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR = 0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk for breast cancer, particularly the A1298C polymorphism of the MTHFR gene. PMID:22373582

  16. A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae

    PubMed Central

    Ohneck, Elizabeth A.; Zalucki, Yaramah M.; Johnson, Paul J. T.; Dhulipala, Vijaya; Golparian, Daniel; Unemo, Magnus; Jerse, Ann E.; Shafer, William M.

    2011-01-01

    ABSTRACT The MtrC-MtrD-MtrE multidrug efflux pump of Neisseria gonorrhoeae confers resistance to a diverse array of antimicrobial agents by transporting these toxic compounds out of the gonococcus. Frequently in gonococcal strains, the expression of the mtrCDE operon is differentially regulated by both a repressor, MtrR, and an activator, MtrA. The mtrR gene lies 250 bp upstream of and is transcribed divergently from the mtrCDE operon. Previous research has shown that mutations in the mtrR coding region and in the mtrR-mtrCDE intergenic region increase levels of gonococcal antibiotic resistance and in vivo fitness. Recently, a C-to-T transition mutation 120 bp upstream of the mtrC start codon, termed mtr120, was identified in strain MS11 and shown to be sufficient to confer high levels of antimicrobial resistance when introduced into strain FA19. Here we report that this mutation results in a consensus ?10 element and that its presence generates a novel promoter for mtrCDE transcription. This newly generated promoter was found to be stronger than the wild-type promoter and does not appear to be subject to MtrR repression or MtrA activation. Although rare, the mtr120 mutation was identified in an additional clinical isolate during sequence analysis of antibiotic-resistant strains cultured from patients with gonococcal infections. We propose that cis-acting mutations can develop in gonococci that significantly alter the regulation of the mtrCDE operon and result in increased resistance to antimicrobials. PMID:21933917

  17. Chromosomal aberration leads to recurrent pregnancy loss and partial trisomy of 5p12-15.3 in the offspring: report of a Syrian couple and review of the literature .

    PubMed

    Al-Achkar, Walid; Moassass, Faten; Al-Ablog, Ayman; Liehr, Thomas; Fan, Xiaobo; Wafa, Abdulsamad

    2015-03-01

    Here we describe a Syrian couple having recurrent pregnancy loss in the first trimester, fetal malformations, and/or neonatal death. The father had a balanced chromosomal translocation t(5;15), an sY125 microdeletion of locus b in the azoospermia factor (AZF) gene, and an MTHFR C677T homozygous polymorphism with normal phenotype. Interestingly, his healthy wife had another MTHFR A1298C homozygous polymorphism. The couple experienced two pregnancy losses and had two stillborn children with severe malformations due to partial trisomy of the short arm of chromosome 5. The couple does not have any living offspring after 10 years of marriage. PMID:25898552

  18. TPMT and MTHFR genotype is not associated with altered risk of thioguanine-related sinusoidal obstruction syndrome in pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group.

    PubMed

    Wray, Lisa; Vujkovic, Marijana; McWilliams, Thomas; Cannon, Shannon; Devidas, Meenakshi; Stork, Linda; Aplenc, Richard

    2014-11-01

    Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL and may be modified by thiopurine methyltransferase activity as well as by MTHFR genotype. We assessed TPMT *3A, *3B, *3C, and MTHFR C677T and A1298C germline genetic polymorphisms among 351 patients enrolled in the thioguanine treatment arm of CCG-1952 clinical trial. TPMT and MTHFR C677T genotypes were not associated with SOS risk. The combination of MTHFR and TPMT variant genotypes was not associated with SOS risk. These suggest that germline genetic variation in TPMT and MTHFR do not significantly alter SOS risk in patients exposed to thioguanine. PMID:24737678

  19. (RE67757), and dCsl4 (RE64677). They were amplified by PCR using the following primers: dRrp6 1F and dRrp6 579R; dMtr3 1F and dMtr3 326R; Rrp4 1F

    E-print Network

    Cai, Long

    were separated on a 12% denaturing polyacrylamide gel and analysed by phosphoimaging. ChIP with transcription. Cell 108, 501­512 (2002). 4. Kaplan, C. D., Morris, J. R., Wu, C. & Winston, F. Spt5 and spt6

  20. Myofascial trigger points: pathophysiology and correlation with acupuncture points

    Microsoft Academic Search

    Chang-Zern Hong

    2000-01-01

    SummaryA review is made of recent studies on myofascial trigger points (MTrP) and their mechanism is discussed. Clinical and basic science studies have shown that there are multiple MTrP loci in a MTrP region. A MTrP locus contains a sensory component (sensitive locus) and a motor component (active locus). A sensitive locus is a point from which tenderness or pain,

  1. Association of dietary intake of folate and MTHFR genotype with breast cancer risk.

    PubMed

    Wang, Z G; Cui, W; Yang, L F; Zhu, Y Q; Wei, W H

    2014-01-01

    We conducted a hospital-based case-control study to investigate the associations of dietary intake of folate and MTHFR C677T and A1298C polymorphisms with breast cancer in a Chinese population. A 1:1-matched case-control study was conducted. Two hundred and thirty patients who were newly diagnosed and histologically confirmed breast cancer and 230 controls were enrolled from Xinxiang Central Hospital. Folate intake was calculated by standard portion size and relative size for each food item in the questionnaire. Genotyping of MTHFR C677T and A1298C was performed by PCR-RFLP. MTHFR 677TT (OR = 2.26, 95%CI = 1.09-4.87, P = 0.02) and T allele (OR = 1.40, 95%CI = 1.03-1.90, P = 0.03) had an increased risk of laryngeal cancer when compared with the CC genotype. We found any interaction between MTHFR C677T and folate intake (P for interaction = 0.02). In conclusion, our study demonstrated that MTHFR C677T polymorphism and folate are associated with risk of breast cancer. PMID:25078601

  2. Associations of variants in MTHFR and MTRR genes with male infertility in the Jordanian population.

    PubMed

    Mfady, Doaa S; Sadiq, May F; Khabour, Omar F; Fararjeh, Abdulfattah S; Abu-Awad, Aymen; Khader, Yousef

    2014-02-15

    Folate pathway is expected to play an important role in spermatogenesis since it is involved in DNA synthesis, repair and methylation. The purpose of this study was to examine the association between male infertility and the MTHFR (C677T and A1298C) and MTRR (A66G) polymorphisms. A group of 300 males was recruited in this study from different Jordanian infertility clinics. Of these, 150 cases of infertile men that included oligozoospermia cases (n=45), severe oligozoospermia (n=71) and azoospermia (n=34) were studied. The other 150 males were age matched fertile controls. Genotyping of MTHFR and MTRR polymorphisms was performed using PCR-RFLP technique. The results showed an association between MTHFR 677TT genotype and male infertility (P<0.05). However, the distribution of MTHFR A1298C and MTRR A66G genotypes were not different between the fertile and infertile groups (P>0.05). In addition, none of the examined polymorphisms was related to any of the semen parameters in the infertile group. In conclusion, this study showed that MTHFR C677T polymorphism is associated with male infertility in Jordanians. PMID:24334125

  3. The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes.

    PubMed

    Cao, Yunlei; Zhang, Zhaofeng; Zheng, Yanmin; Yuan, Wei; Wang, Jian; Liang, Hong; Chen, Jianping; Du, Jing; Shen, Yueping

    2014-05-01

    The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P < 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P > 0.05 (P = 0.093 and P = 0.084, respectively). PMID:24728915

  4. Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: an experimental, computational and meta-analysis.

    PubMed

    Bellampalli, Ravishankara; Phani, Nagaraja M; Bhat, Kamalakshi G; Prasad, Krishna; Bhaskaranand, Nalini; Guruprasad, Kanive P; Rai, Padmalatha S; Satyamoorthy, Kapaettu

    2015-05-01

    Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an effect of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case-control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignificant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3' untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3'UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the significant role of MTHFR in ALL development. PMID:25115513

  5. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review.

    PubMed

    Botto, L D; Yang, Q

    2000-05-01

    The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism. The MTHFR gene is located on chromosome 1 (1p36.3), and two common alleles, the C677T (thermolabile) allele and the A1298C allele, have been described. The population frequency of C677T homozygosity ranges from 1% or less among Blacks from Africa and the United States to 20% or more among Italians and US Hispanics. C677T homozygosity in infants is associated with a moderately increased risk for spina bifida (pooled odds ratio = 1.8; 95% confidence interval: 1.4, 2.2). Maternal C677T homozygosity also appears to be a moderate risk factor (pooled odds ratio = 2.0; 95% confidence interval: 1.5, 2.8). The A 1298C allele combined with the C677T allele also could be associated with an increased risk for spina bifida. Some data suggest that the risk for spina bifida associated with C677T homozygosity may depend on nutritional status (e.g., blood folate levels, intake of vitamins) or on the genotype of other folate-related genes (e.g., cystathionine-beta-synthase and methionine synthase reductase). Studies of the C677T allele in relation to oral clefts, Down syndrome, and fetal anticonvulsant syndrome either have yielded conflicting results or have not been yet replicated. PMID:10791559

  6. 5,10-Methylenetetrahydrofolate reductase single nucleotide polymorphisms and gene-environment interaction analysis in non-syndromic cleft lip/palate.

    PubMed

    Estandia-Ortega, Bernardette; Velázquez-Aragón, José A; Alcántara-Ortigoza, Miguel A; Reyna-Fabian, Miriam E; Villagómez-Martínez, Sandra; González-Del Angel, Ariadna

    2014-04-01

    Non-syndromic cleft lip/palate (NSCL/P) is a common congenital defect in Mexico. Periconceptional intake of folic acid (FA) may reduce the risk of this malformation. Although the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme participates in folate metabolism, several studies failed to find any association between NSCL/P and the MTHFR C677T and A1298C polymorphisms. However, interactions among NSCL/P, MTHFR gene polymorphisms, and FA intake have not been explored in Mexican populations. This case-control study included 132 patients with NSCL/P and 370 controls from Mexico City. Maternal FA consumption during pregnancy was examined, as were the MTHFR C677T and A1298C polymorphisms and gene-FA interactions. Maternal FA intake during the periconceptional period was lower in cases (1.5%) than in controls (13%), with the risk of delivering a child with NSCL/P lower in mothers who consumed FA (OR = 0.29, 95% CI: 0.19-0.44). In addition, the risk of NSCL/P was lower in children with the TT than the CC genotype of MTHFR C677T (OR = 0.39, 95% CI: 0.23-0.68), after Bonferroni correction and exclusion of stratification. No evidence of gene-FA interaction was found. These results indicate that maternal FA intake and the TT genotype of the MTHFR C677T polymorphism in children independently reduced the risk of NSCL/P in our population. PMID:24460828

  7. Serial Magnetization Transfer Imaging in Acute Optic Neuritis

    ERIC Educational Resources Information Center

    Hickman, S. J.; Toosy, A. T.; Jones, S. J.; Altmann, D. R.; Miszkiel, K. A.; MacManus, D. G.; Barker, G. J.; Plant, G. T.; Thompson, A. J.; Miller, D.H.

    2004-01-01

    In serial studies of multiple sclerosis lesions, reductions in magnetization transfer ratio (MTR) are thought to be due to demyelination and axonal loss, with later rises due to remyelination. This study followed serial changes in MTR in acute optic neuritis in combination with clinical and electrophysiological measurements to determine if the MTR…

  8. Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association

    Microsoft Academic Search

    Valerie B. O’Leary; James L. Mills; Faith Pangilinan; Peadar N. Kirke; Christopher Cox; Mary Conley; Andrea Weiler; Kun Peng; Barry Shane; John M. Scott; Anne Parle-McDermott; Anne M. Molloy; Lawrence C. Brody

    2005-01-01

    Methionine synthase reductase (MTRR) regenerates methylated cobalamin levels from the oxidised cob(II)alamin form and in so doing plays a crucial role in maintaining the active state of methionine synthase (MTR). MTR is an essential enzyme catalyzing the conversion of homocysteine to methionine. Single nucleotide polymorphisms (SNPs) within the MTRR gene may potentially compromise MTR activity leading to elevated homocysteine levels,

  9. Depth dose distributions measured with thermoluminescence detectors inside the anthropomorphic torso of the MATROSHKA experiment inside and outside the ISS

    Microsoft Academic Search

    Thomas Berger; Guenther Reitz; Michael Hajek; Robert Bergmann; Pawel Bilski; Msc. Monika Puchalska

    2008-01-01

    The ESA MATROSHKA (MTR) facility was realized through the German Aerospace Center, DLR, Cologne, as main contractor, aiming for the determination of skin and organ doses within a simulated human upper torso. MTR simulates, by applying an anthropomorphic upper torso, as exact as possible an astronaut performing either an extravehicular activity (EVA) (MTR Phase 1) or an astronaut working inside

  10. Myofascial trigger points and innervation zone locations in upper trapezius muscles

    PubMed Central

    2013-01-01

    Background Myofascial trigger points (MTrPs) are hyperirritable spots located in taut bands of muscle fibres. Electrophysiological studies indicate that abnormal electrical activity is detectable near MTrPs. This phenomenon has been described as endplate noise and it has been purported to be associated MTrP pathophysiology. Thus, it is suggested that MTrPs will be overlap the innervation zone (IZ). The purpose of this work was to describe the location of MTrPs and the IZ in the right upper trapezius. Methods We screened 71 individuals and eventually enrolled 24 subjects with neck pain and active MTrPs and 24 neck pain-free subjects with latent MTrPs. Surface electromyography (sEMG) signals were detected using an electrode matrix during isometric contraction of the upper trapezius. A physiotherapist subsequently examined the subject’s trapezius to confirm the presence of MTrPs and establish their location. IZ locations were identified by visual analysis of sEMG signals. IZ and MTrPs locations were described using an anatomical coordinate system (ACS), with the skin area covered by the matrix divided into four quadrants. Results No significant difference was observed between active and latent MTrPs locations (P = 0.6). Forty-five MTrPs were in the third quadrant of the ACS, and 3 were included in second quadrant. IZs were located approximately midway between the seventh cervical vertebrae and the acromial angle in a limited area in the second and third quadrants. The mean distance between MTrP and IZ was 10.4 ± 5.8 mm. Conclusions According to the acquired results, we conclude that IZ and MTrPs are located in well-defined areas in upper trapezius muscle. Moreover, MTrPs in upper trapezius are proximally located to the IZ but not overlapped. PMID:23758854

  11. Structure of Arabidopsis thaliana 5-methylthioribose Kinase Reveals a More Occluded Active Site Than its Bacterial Homolog

    SciTech Connect

    Ku,S.; Cornell, K.; Howell, P.

    2007-01-01

    Metabolic variations exist between the methionine salvage pathway of humans and a number of plants and microbial pathogens. 5-Methylthioribose (MTR) kinase is a key enzyme required for methionine salvage in plants and many bacteria. The absence of a mammalian homolog suggests that MTR kinase is a good target for the design of specific herbicides or antibiotics. The structure of Arabidopsis thaliana MTR kinase co-crystallized with ATP?S and MTR has been determined at 1.9 Angstroms resolution. The structure is similar to B. subtilis MTR kinase and has the same protein kinase fold observed in other evolutionarily related protein kinase-like phosphotransferases. The active site is comparable between the two enzymes with the DXE-motif coordinating the nucleotide-Mg, the D238 of the HGD catalytic loop polarizing the MTR O1 oxygen, and the RR-motif interacting with the substrate MTR. Unlike its bacterial homolog, however, the Gly-rich loop (G-loop) of A. thaliana MTR kinase has an extended conformation, which shields most of the active site from solvent, a feature that resembles eukaryotic protein kinases more than the bacterial enzyme. The G- and W-loops of A. thaliana and B. subtilis MTR kinase adopt different conformations despite high sequence similarity. The ATP?S analog was hydrolyzed during the co-crystallization procedure, resulting in ADP in the active site. This suggests that the A. thaliana enzyme, like its bacterial homolog, may have significant ATPase activity in the absence of MTR. The structure of A. thaliana MTR kinase provides a template for structure-based design of agrochemicals, particularly herbicides whose effectiveness could be regulated by nutrient levels. Features of the MTR binding site offer an opportunity for a simple organic salt of an MTR analog to specifically inhibit MTR kinase.

  12. TRA Closure Plan REV 0-9-20-06 HWMA/RCRA Closure Plan for the TRA/MTR Warm Waste System Voluntary Consent Order SITE-TANK-005 Tank System TRA-007

    SciTech Connect

    Winterholler, K.

    2007-01-31

    This Hazardous Waste Management Act/Resource Conservation and Recovery Act closure plan was developed for portions of the Test Reactor Area/Materials Test Reactor Warm Waste System located in the Materials Test Reactor Building (TRA-603) at the Reactor Technology Complex, Idaho National Laboratory Site, to meet a further milestone established under Voluntary Consent Order Action Plan SITE-TANK-005 for Tank System TRA-007. The reactor drain tank and canal sump to be closed are included in the Test Reactor Area/Materials Test Reactor Warm Waste System. The reactor drain tank and the canal sump were characterized as having managed hazardous waste. The reactor drain tank and canal sump will be closed in accordance with the interim status requirements of the Hazardous Waste Management Act/Resource Conservation and Recovery Act as implemented by the Idaho Administrative Procedures Act 58.01.05.009 and 40 Code of Federal Regulations 265. This closure plan presents the closure performance standards and methods for achieving those standards.

  13. Association between Maternal MTHFR Polymorphisms and Nonsyndromic Cleft Lip with or without Cleft Palate in Offspring, A Meta-Analysis Based on 15 Case-Control Studies

    PubMed Central

    Pan, Xinjuan; Wang, Ping; Yin, Xinjuan; Liu, Xiaozhuan; Li, Di; Li, Xing; Wang, Yongchao; Li, Hongle; Yu, Zengli

    2015-01-01

    Background The methylenetetrahydrofolate reductase (MTHFR) is thought to be involved in the development of nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, conflicting results have been obtained when evaluating the association between maternal MTHFR C677T and A1298C polymorphisms and the risk of NSCL/P. In light of this gap, a meta-analysis of all eligible case-control studies was conducted in the present study. Materials and Methods A total of 15 case-control studies were ultimately identified after a comprehensive literature search and Hardy-Weinberg equilibrium (HWE) examination. Cochrane’s Q test and index of heterogeneity (I2) indicated no obvious heterogeneity among studies. Results Fixed or random-effects models were used to calculate the pooled odds ratios (ORs). The results showed that the TT genotype in mothers increased the likelihood of having NSCL/P offspring 1.25 times (95% CI: 1.047-1.494) more than the CC homozygotes. Meanwhile, maternal TT genotype increased the risk of producing NSCL/P offspring in recessive model (OR=1.325, 95% CI: 1.124-1.562). However, the CT heterozygote and the CT+TT dominant models had no association with NSCL/P offspring compared with the CC wild-type homozygote model. Subgroup analyses based on ethnicity indicated that maternal TT genotype increased the likelihood of having NSCL/P offspring in Whites (OR=1.308, 95% CI: 1.059-1.617) and Asians (OR=1.726, 95% CI: 1.090-2.733) in recessive model. Also, subgroup analyses based on source of control showed that mothers with the 677TT genotype had a significantly increased susceptibility of having NSCL/P children in hospital based population (HB) when compared with CC homozygotes (OR=1.248, 95% CI: 1.024-1.520) and un- der the recessive model (OR=1.324, 95% CI: 1.104-1.588). Furthermore, maternal A1298C polymorphism had no significant association with producing NSCL/P offspring (dominant model OR=0.952, 95% CI: 0.816-1.111, recessive model OR=0.766, 95% CI: 0.567-1.036). Conclusion MTHFR C677T polymorphism is associated with the risk of generating NSCL/P offspring, and being a 677TT homozygote is a risk factor. MTHFR A1298C polymorphism was not associated with generating NSCL/P offspring. However, further work should be performed to confirm these findings. PMID:25780529

  14. MTHFR genetic polymorphisms may contribute to the risk of chronic myelogenous leukemia in adults: a meta-analysis of 12 genetic association studies.

    PubMed

    Li, Bin; Zhang, Jian; Wang, Lei; Li, Yan; Jin, Juping; Ai, Limei; Li, Chong; Li, Zhe; Mao, Shudan

    2014-05-01

    Chronic myelogenous leukemia (CML) is a complex disease with a genetic basis. The genetic association studies (GASs) that have investigated the association between adult CML and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have produced contradictory and inconclusive results. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the association of these polymorphisms with adult CML risk. A literature search for eligible GAS published before September 15, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. All analyses were performed using the Stata software, version 12.0. Twelve case-control studies were included in this meta-analysis with a total of 932 CML patients and 3,465 healthy controls. For MTHFR C677T (dbSNP: rs1801133, C>T), though the pooled ORs were not significant in the overall population, all the ORs greater than 1 suggested an increased risk of CML for carriers of the risk allele. However, stratified analysis based on genotyping method revealed a significant association in the PCR-restriction fragment length polymorphism (RFLP) subgroup, possibly as a result of heterogeneity. For MTHFR A1298C (dbSNP: rs1801131, A>C), the combined results showed that carriers of the C allele may be associated with a decreased risk of adult CML. Stratified analysis showed that the magnitude of this effect was especially significant among Asians, indicating ethnicity differences in adult CML susceptibility. This meta-analysis shows that the C allele of MTHFR A1298C may be associated with a decreased risk in adult CML, especially among Asians, while MTHFR C677T may not be associated with adult CML risk. However, the development of adult CML may be the result of gene-gene and gene-environment interactions, which should be considered in future individual GAS and subsequent meta-analyses. PMID:24379141

  15. Characterization of an electron conduit between bacteria and the extracellular environment

    SciTech Connect

    Hartshorne, Robert S.; Reardon, Catherine L.; Ross, Daniel E.; Nuester, Jochen; Clarke, Thomas A.; Gates, Andrew J.; Mills, Paul C.; Fredrickson, Jim K.; Zachara, John M.; Shi, Liang; Beliaev, Alex S.; Marshall, Matthew J.; Tien, Ming; Brantley, Susan L.; Butt, Julea N.; Richardson, David

    2009-12-29

    A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella deca-heme electron transfer proteins lie at the extracellular face of the outer membrane where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here we present a spectro-potentiometric characterization of a trans-outer membrane icosa-heme protein complex, MtrCAB. Incorporation into proteoliposomes demonstrates its functional capacity to move electrons across a lipid bilayer. We also show that a stable MtrAB sub-complex can assemble in the absence of MtrC, that an MtrBC sub-complex was not assembled in the absence of MtrA and that MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-outer membrane spanning ?-barrel protein that serves as a sheath to house the deca-heme MtrA allowing it to span the membrane to form a trans-membrane electron delivery module that services MtrC. We have identified the MtrAB module in a range of bacterial phyla suggesting that it is widely used in electron exchange with the extracellular environment

  16. Effect of MTHFR, TGF?1, and TNFB polymorphisms on osteoporosis in rheumatoid arthritis patients.

    PubMed

    Saad, Mohamed N; Mabrouk, Mai S; Eldeib, Ayman M; Shaker, Olfat G

    2015-09-01

    Diseases of the immune and the skeletal systems should be studied together for the deep interaction between them. Many studies consider osteoporosis (OP) as a risk factor for the prediction of disease progression in rheumatoid arthritis (RA). The aim of this research is to study the effect of four single nucleotide polymorphisms (SNPs) on RA patients with and without OP. The examined SNPs (MTHFR (C677T, and A1298C), TGF?1 (T869C), and TNFB (A252G)) were tested by genotyping 17 RA patients with OP and 72 RA patients without OP. Associations were tested using four models (multiplicative, dominant, recessive, and co-dominant). The studied SNPs were not significantly associated with the risk of OP in RA. MTHFR, TGF?1, and TNFB polymorphisms don't appear to be clinically useful genetic markers for predicting RA severity in Egyptian women population. PMID:25981594

  17. Congenital IL-12R1? receptor deficiency and thrombophilia in a girl homozygous for an IL12RB1 mutation and compound heterozygous for MTFHR mutations: A case report and literature review

    PubMed Central

    Kose, M.; Ceylan, O.; Patiroglu, T.; Bustamante, J.; Casanova, J. L.; Akyildiz, B. N.; Doganay, S.

    2014-01-01

    Interleukin-12 (IL-12) plays an important role in the production of interferon gamma from T cells and natural killer cells and is essential for protection against intra-macrophagic pathogens such as Mycobacterium and Salmonella. Here, we describe a 16-year-old girl with homozygous mutation in exon 12 of the IL12RB1 gene, which causes complete IL-12R?1 deficiency in association with heterozygous mutation (C677T and A1298C) in the methylenetetrahydrofolate reductase gene. She presented with disseminated Mycobacterium tuberculosis complex infection, retroperitoneal fungal abscess and also thrombosis in the superior mesenteric–portal vein junction. This is the first case report of a primary immunodeficiency associated with a genetically determined venous thrombosis. PMID:24678409

  18. Meta-analysis of the association of MTHFR polymorphisms with multiple myeloma risk.

    PubMed

    Ma, Li-Min; Ruan, Lin-Hai; Yang, Hai-Ping

    2015-01-01

    The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR?=?0.99, 95%CI?=?0.82-1.20; CC vs. AA, OR?=?1.14, 95%CI?=?0.77-1.68; recessive model, OR?=?1.10, 95%CI?=?0.76-1.59; dominant model, OR?=?1.01, 95%CI?=?0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR?=?1.04, 95%CI?=?0.93-1.17; TT vs. CC, OR?=?1.16, 95%CI?=?0.98-1.37; recessive model, OR?=?1.13, 95%CI?=?0.98-1.32; dominant model, OR?=?1.07, 95%CI?=?0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk. PMID:26022785

  19. No Association of Functional Polymorphisms in Methlylenetetrahydrofolate Reductase and the Risk and Minor Physical Anomalies of Schizophrenia in Korean Population

    PubMed Central

    Kim, Su-Gyeong; Song, Joo Yun; Joo, Eun-Jeong; Jeong, Seong Hoon; Kim, Se Hyun; Lee, Kyu Young; Lee, Nam Young; Ahn, Yong Min; Kim, Yong Sik

    2011-01-01

    Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia. PMID:22022190

  20. Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis

    PubMed Central

    Mabrouk, Mai S.; Eldeib, Ayman M.

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease which has a significant socio-economic impact. The aim of the current study was to investigate eight candidate RA susceptibility loci to identify the associated variants in Egyptian population. Eight single nucleotide polymorphisms (SNPs) (MTHFR—C677T and A1298C, TGF?1 T869C, TNFB A252G, and VDR—ApaI, BsmI, FokI, and TaqI) were tested by genotyping patients with RA (n = 105) and unrelated controls (n = 80). Associations were tested using multiplicative, dominant, recessive, and co-dominant models. Also, the linkage disequilibrium (LD) between the VDR SNPs was measured to detect any indirect association. By comparing RA patients with controls (TNFB, BsmI, and TaqI), SNPs were associated with RA using all models. MTHFR C677T was associated with RA using all models except the recessive model. TGF?1 and MTHFR A1298C were associated with RA using the dominant and the co-dominant models. The recessive model represented the association for ApaI variant. There were no significant differences for FokI and the presence of RA disease by the used models examination. For LD results, There was a high D? value between BsmI and FokI (D? = 0.91), but the r2 value between them was poor. All the studied SNPs may contribute to the susceptibility of RA disease in Egyptian population except for FokI SNP. PMID:26147289

  1. Meta-analysis of the association of MTHFR polymorphisms with multiple myeloma risk

    PubMed Central

    Ma, Li-Min; Ruan, Lin-Hai; Yang, Hai-Ping

    2015-01-01

    The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR?=?0.99, 95%CI?=?0.82-1.20; CC vs. AA, OR?=?1.14, 95%CI?=?0.77-1.68; recessive model, OR?=?1.10, 95%CI?=?0.76-1.59; dominant model, OR?=?1.01, 95%CI?=?0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR?=?1.04, 95%CI?=?0.93-1.17; TT vs. CC, OR?=?1.16, 95%CI?=?0.98-1.37; recessive model, OR?=?1.13, 95%CI?=?0.98-1.32; dominant model, OR?=?1.07, 95%CI?=?0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk. PMID:26022785

  2. Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced weight gain and metabolic disturbances.

    PubMed

    Kao, A C C; Rojnic Kuzman, M; Tiwari, A K; Zivkovic, M V; Chowdhury, N I; Medved, V; Kekin, I; Zai, C C; Lieberman, J A; Meltzer, H Y; Bozina, T; Bozina, N; Kennedy, J L; Sertic, J; Müller, D J

    2014-07-01

    Weight gain and metabolic disturbances represent serious side-effects in antipsychotic (AP) treatment, particularly with clozapine and olanzapine. The methylenetetrahydrofolate reductase (MTHFR) gene is a key determinant in the folate metabolism and previous studies reported a significant effect on AP-induced weight gain and related metabolic abnormalities. Thus, we investigated MTHFR gene variants and changes in several important metabolic parameters in AP-treated patients. In this study, two functional MTHFR polymorphisms, rs1801133 (C677T) and rs1801131 (A1298C), were investigated for changes in weight and metabolic parameters. Genotypic associations were evaluated in a large population (n = 347 including 66 first episode psychosis, FEP patients) treated mostly with clozapine and olanzapine. We did not detect any genotypic association with weight changes (p > 0.05) in our total sample and in the sample refined for ancestry and medication. In our allelic analyses, we observed a trend for the 677-C allele to be associated with weight gain in the total sample (p = 0.03). This effect appeared to be driven by the FEP patients where those carrying the C-allele gained, on average, twice as much weight. Exploratory analyses revealed a significant association between the C677T and the A1298C polymorphism with HDL cholesterol serum levels in patients (p = 0.031). Overall we did not detect a major effect of two functional MTHFR gene variants and AP-induced weight gain. However, our findings suggest an effect of the C677T polymorphism in FEP patients and changes in weight and cholesterol levels. Further investigations in a larger sample are required. PMID:24725652

  3. Genetics University of Toronto Thrombophilia Study in Women (GUTTSI): genetic and other risk factors for venous thromboembolism in women

    PubMed Central

    Ray, Joel G; Langman, Loralie J; Vermeulen, Marian J; Evrovski, Jovan; Yeo, Erik L; Cole, David EC

    2001-01-01

    Background Women may be at increased risk for venous thromboembolism (VTE) as compared with men. We studied the effects of genetic and biochemical markers of thrombophilia in women, in conjunction with other established risk factors for VTE. Method The present retrospective case-control study was conducted in a thrombosis treatment programme at a large Toronto hospital. The cases were 129 women aged 16-79 years with objectively confirmed VTE. Age-matched control individuals were women who were free of venous thrombosis. Neither cases nor control individuals had known cardiovascular disease. Participants were interviewed regarding personal risk factors for VTE, including smoking, history of malignancy, pregnancy, and oestrogen or oral contraceptive use. Blood specimens were analyzed for common single nucleotide polymorphisms of prothrombin, factor V and methylenetetrahydrofolate reductase (MTHFR; C677T, A1298C and T1317C), and the A66G polymorphism for methionine synthase reductase (MTRR).Fasting plasma homocysteine was also analyzed. Results Women with VTE were significantly more likely than female control individuals to carry the prothrombin polymorphism and the factor V polymorphism, or to have fasting hyperhomocysteinaemia. Homozygosity for the C677T MTHFR gene was not a significant risk factor for VTE, or were the A1298C or T1317C MTHFR homozygous variants. Also, the A66G MTRR homozygous state did not confer an increased risk for VTE. Conclusion Prothrombin and factor V polymorphisms increased the risk for VTE in women, independent from other established risk factors. Although hyperhomocysteinaemia also heightens this risk, common polymorphisms in two genes that are responsible for homocysteine remethylation do not. These findings are consistent with previous studies that included both men and women. PMID:11806787

  4. "Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis".

    PubMed

    Yadav, Upendra; Kumar, Pradeep; Yadav, Sushil Kumar; Mishra, Om Prakash; Rai, Vandana

    2015-02-01

    Epidemiological studies have evaluated the association between maternal methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms and risk of neural tube defects (NTDs) in offspring. However, the results from the published studies on the association between these three polymorphisms and NTD risk are conflicting. To derive a clearer picture of association between these three maternal polymorphisms and risk of NTD, we performed meta-analysis. A comprehensive search was conducted to identify all case-control studies of maternal MTHFR and MTRR polymorphisms and NTD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that maternal MTHFR C677T polymorphism (OR(TvsC) =1.20; 95% CI = 1.13-1.28) and MTRR A66G polymorphism (OR(GvsA) = 1.21; 95% CI = 0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (OR(CvsA) = 0.91; 95% CI = 0.78-1.07) was not associated with NTD risk. However, in stratified analysis by geographical regions, we found that the maternal C677T polymorphism was significantly associated with the risk of NTD in Asian (OR(TvsC)?= 1.43; 95% CI: 1.05-1.94), European (OR(TvsC)?= 1.13; 95% CI: 1.04-1.24) and American (OR(TvsC)?= 1.26; 95% CI: 1.13-1.41) populations. In conclusion, present meta-analysis supports that the maternal MTHFR C677T and MTRR A66G are polymorphisms contributory to risk for NTD. PMID:25005003

  5. The Association of Methylenetetrahydrofolate Reductase Genotypes with the Risk of Childhood Leukemia in Taiwan

    PubMed Central

    Chang, Wen-Shin; Ji, Hong-Xue; Hsiao, Chieh-Lun; Miao, Chia-En; Hsu, Yuan-Nian; Bau, Da-Tian

    2015-01-01

    Background Acute lymphoblastic leukemia (ALL) is the most prevalent type of pediatric cancer, the causes of which are likely to involve an interaction between genetic and environmental factors. To evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) on childhood ALL risk in Taiwan, two well-known polymorphic genotypes of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed to examine the extent of their associations with childhood ALL susceptibility and to discuss the MTHFR genotypic contribution to childhood ALL risk among different populations. Methodology/Principal Findings In total, 266 patients with childhood ALL and an equal number of non-cancer controls recruited were genotyped utilizing PCR-RFLP methodology. The MTHFR C677T genotype, but not the A1298C, was differently distributed between childhood ALL and control groups. The CT and TT of MTHFR C677T genotypes were significantly more frequently found in controls than in childhood ALL patients (odds ratios=0.60 and 0.48, 95% confidence intervals=0.42–0.87 and 0.24–0.97, respectively). As for gender, the boys carrying the MTHFR C677T CT or TT genotype conferred a lower odds ratio of 0.51 (95% confidence interval=0.32–0.81, P=0.0113) for childhood ALL. As for age, those equal to or greater than 3.5 years of age at onset of disease carrying the MTHFR C677T CT or TT genotype were of lower risk (odds ratio= 0.43 and 95% confidence interval=0.26–0.71, P=0.0016). Conclusions Our results indicated that the MTHFR C677T T allele was a protective biomarker for childhood ALL in Taiwan, and the association was more significant in male patients and in patients 3.5 years of age or older at onset of disease. PMID:25793509

  6. Structure of Arabidopsis thaliana 5-methylthioribose kinase reveals a more occluded active site than its bacterial homolog

    Microsoft Academic Search

    Shao-Yang Ku; Kenneth A Cornell; P Lynne Howell

    2007-01-01

    BACKGROUND: Metabolic variations exist between the methionine salvage pathway of humans and a number of plants and microbial pathogens. 5-Methylthioribose (MTR) kinase is a key enzyme required for methionine salvage in plants and many bacteria. The absence of a mammalian homolog suggests that MTR kinase is a good target for the design of specific herbicides or antibiotics. RESULTS: The structure

  7. Computation of the residual stresses in magnetic-tape rolls with allowance for operational factors

    Microsoft Academic Search

    E. S. Umanskii; N. S. Shidlovskii; D. G. Kofto; L. L. Stezhko

    1987-01-01

    .to malfunctioning of the roll and to downtime of the apparatus. Experimental investigation of residual stresses in MTR is associated with rather cumbersome and time-consuming experiments [3]. It is therefore important to develop a reliable method for the analytical evaluation of the stress--strain state of MTR, which takes into account such factors as the winding conditions of the rolls and

  8. Programming the quorum sensing-based AND gate in Shewanella oneidensis for logic gated-microbial fuel cells.

    PubMed

    Hu, Yidan; Yang, Yun; Katz, Evgeny; Song, Hao

    2015-03-11

    An AND logic gate based on a synthetic quorum-sensing (QS) module was constructed in a Shewanella oneidensis MR-1 mtrA knockout mutant. The presence of two input signals activated the expression of a periplasmic decaheme cytochrome MtrA to regenerate the extracellular electron transfer conduit, enabling the construction of AND-gated microbial fuel cells. PMID:25673159

  9. Master of Science Translational Research

    E-print Network

    Bushman, Frederic

    Master of Science Translational Research Emma A. Meagher, MD Program Director emma@upenn.edu #12 · J Craniofac Surg. MD-MTR Graduates - Outcomes #12;12 MTR Contact Information Emma A. Meagher, MD emma@upenn.edu Megan Maxwell Program Coordinator 215-349-8627 ITMATEd@mail.med.upenn.edu Visit website

  10. Comparison of Neisseria gonorrhoeae isolates from homosexual and heterosexual men

    Microsoft Academic Search

    D Fagan

    1985-01-01

    The gene locus known as mtr confers resistance to hydrophobic dyes, detergents, and antibiotics. It has been suggested previously that the host environment is important in the selection of gonococcal strains with this outer membrane phenotype, and thus that strains with mtr gene loci should predominate in environments high in hydrophobic molecules. Furthermore, resistance to hydrophobic molecules has been related

  11. 33 CFR 154.1015 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...be expected to cause at least substantial harm to the environment by discharging oil...reasonably be expected to cause substantial harm to the environment by discharging oil...shorelines and are classified as substantial harm MTR facilities: (1) Fixed MTR...

  12. Utilization of Egyptian Research Reactor and Modes of Collaboration

    Microsoft Academic Search

    M. K. Shaat; M. A. Gaheen

    The new Egyptian Research Reactor (ETRR-2) is a Material Testing Reactor (MTR) and it was commissioned in 1997. It is open pool Research Reactor (RR) using low enriched MTR fuel elements (less than 20% enrichment), cooled and moderated with light water and reflected by beryllium. The reactor power is 22 MW with high neutron flux irradiation positions (flux > 10

  13. Whole Brain Imaging of HIV-Infected Patients: Quantitative Analysis of Magnetization Transfer Ratio Histogram and Fractional Brain Volume

    Microsoft Academic Search

    Yulin Ge; Dennis L. Kolson; James S. Babb; Lois J. Mannon; Robert I. Grossman

    2003-01-01

    BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) histogram analysis and volumetric MR imaging are sensitive tools with which to quantify the tissue destructive effects in patients with white matter or neurodegenerative disease. Our purpose was to deter- mine whether whole brain MTR and fractional brain parenchyma volume measurements are altered in HIV-1-infected patients who are neurologically symptomatic and in those

  14. SOUTH WING, TRA661. WEST SIDE. CAMERA FACING EAST. COVERED STAIRWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    SOUTH WING, TRA-661. WEST SIDE. CAMERA FACING EAST. COVERED STAIRWAY AND BUILDING END AT LEFT OF VIEW IS TRA-652, ANOTHER MTR OFFICE WING. WEST SIDE OF MTR HIGH BAY BEYOND. INL NEGATIVE NO. HD46-45-2. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  15. Wide-color gamut multi-twist retarders

    NASA Astrophysics Data System (ADS)

    Hornburg, Kathryn J.; Brickson, Leandra L.; Escuti, Michael J.

    2015-03-01

    We show how highly chromatic Multi-Twist Retarder (MTR) films can be used to create a single-film color filter wherein the color may be selected only by the MTR orientation angle. By this approach, we can create multi- color images with just an MTR between polarizers. We study the design method and limits of the available color gamut possibilities in this approach, and experimentally demonstrate several designs of continuous and discrete patterns. This technique may be useful in art, displays, microscopy, and remote sensing.

  16. The Methionine Synthase Polymorphism c.2756A>G Alters Susceptibility to Glioblastoma Multiforme

    Microsoft Academic Search

    Alexander Semmler; Matthias Simon; Susanna Moskau; Michael Linnebank

    Genetic polymorphisms of methionine metabolism, in particular methionine synthase (MTR) c.2756A>G (D919G) and methylenetetrahydrofolate reductase (MTHFR) c.677C>T (A222V), have been associated with various human cancers. We investigated MTR c.2756A>G, MTHFR c.677C>T, and a third polymorphism, transcobalamin 2 c.776C>G (P259R), for a potential association with the formation of glioblastoma multiforme. The MTR c.2756G allele was significantly underrepresented among 328 glioblastoma multiforme

  17. Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression

    Microsoft Academic Search

    Dirk Prawitt; Thorsten Enklaar; Gabi Klemm; Barbara Gärtner; Christian Spangenberg; Andreas Winterpacht; Michael Higgins; Jerry Pelletier; Bernhard Zabel

    2000-01-01

    Alterations within human chromosomal region 11p15.5 are associated with the Beckwith-Wiedemann syndrome (BWS) and predisposition to a variety of neoplasias, including Wilms' tumors (WTs), rhabdoid tumors and rhabdomyosarcomas. To identify candidate genes for 11p15.5-related diseases we compared human genomic sequence with expressed sequence tag and protein databases from different organisms to discover evolutionarily conserved sequences. Herein we describe the identification

  18. Molecular Underpinnings of Fe(III) Oxide Reduction by Shewanella oneidensis MR-1

    SciTech Connect

    Shi, Liang; Rosso, Kevin M.; Clarke, Thomas A.; Richardson, David J.; Zachara, John M.; Fredrickson, Jim K.

    2012-02-15

    In the absence of O2 and other electron acceptors, the Gram-negative bacterium Shewanella oneidensis MR-1 can use ferric [Fe(III)] (oxy)(hydr)oxide minerals as the terminal electron acceptors for anaerobic respiration. At circumneutral pH and in the absence of strong complexing ligands, Fe(III) oxides are relatively insoluble and thus are external to the bacterial cells. S. oneidensis MR-1 and related strains of metal-reducing Shewanella have evolved the machinery (i.e., metal-reducing or Mtr pathway) for transferring electrons from the inner-membrane, through the periplasm and across the outer-membrane to the surface of extracellular Fe(III) oxides. The protein components identified to date for the Mtr pathway include CymA, MtrA, MtrB, MtrC and OmcA. CymA is an inner-membrane tetraheme c-type cytochrome (c-Cyt) that belongs to the NapC/NrfH family of quinol dehydrogenases. It is proposed that CymA oxidizes the quinol in the inner-membrane and transfers the released electrons to redox proteins in the periplasm. Although the periplasmic proteins receiving electrons from CymA during Fe(III) oxidation have not been identified, they are believed to relay the electrons in the periplasm to MtrA. A decaheme c-Cyt, MtrA is thought to be embedded in the trans outer-membrane and porin-like protein MtrB. Together, MtrAB deliver the electrons through the outer-membrane to the MtrC and OmcA on the outmost bacterial surface. MtrC and OmcA are the outer-membrane decaheme c-Cyts that are translocated across the outer-membrane by the bacterial type II secretion system. Functioning as terminal reductases, MtrC and OmcA can bind the surface of Fe(III) oxides and transfer electrons directly to these minerals via their solvent-exposed hemes. To increase their reaction rates, MtrC and OmcA can use the flavins secreted by S. oneidensis MR-1 cells as diffusible co-factors for reduction of Fe(III) oxides. Because of their extracellular location and broad redox potentials, MtrC and OmcA can also serve as the terminal reductases for soluble forms of Fe(III). Although our understanding of the Mtr pathway is still far from complete, it is the best characterized microbial pathway used for extracellular electron exchange. Characterizations of the Mtr pathway have made significant contributions to the molecular understanding of microbial reduction of Fe(III) oxides.

  19. 75 FR 74768 - Madison Terminal Railway, LLC-Lease and Operation Exemption-Line of Railroad in Dane County, WI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ...TRANSPORTATION Surface Transportation Board [Docket No. FD 35433] Madison Terminal Railway, LLC--Lease and Operation Exemption-- Line of Railroad in Dane County, WI Madison Terminal Railway, LLC (MTR), a noncarrier, has filed a verified...

  20. GTamSTATISTICA, NEW DELHI : Phone:91-ll-41493980

    E-print Network

    Bandyopadhyay, Antar

    .300 mtr length in two side c) depth 60 cm wadth 30 cm length 30 cm 5 Providing and laying cement concrete, pillars, posts, struts, buttresses, string or lacing courses, parapets, coping, bed blocks, anchor blocks

  1. February 2009 TIMOTHY K. STANTON

    E-print Network

    Stanton, Tim

    and transceiver testing of Advanced Lightweight Torpedo (MK50) prototype sonar at various Naval facilities (mostly Torpedo proposal and MK50 contract. Acoustic compatibility design in Mobile Tracking Range (MTR) proposal

  2. September 2010 TIMOTHY K. STANTON

    E-print Network

    Stanton, Tim

    and transceiver testing of Advanced Lightweight Torpedo (MK50) prototype sonar at various Naval facilities (mostly Torpedo proposal and MK50 contract. Acoustic compatibility design in Mobile Tracking Range (MTR) proposal

  3. The role of multihaem cytochromes in the respiration of nitrite in Escherichia coli and Fe(III) in Shewanella oneidensis

    SciTech Connect

    Clarke, Thomas A.; Holley, Tracey; Hartshorne, Robert S.; Fredrickson, Jim K.; Zachara, John M.; Shi, Liang; Richardson, David

    2008-10-01

    The periplasmic nitrite reductase system from Escherichia coli and the extracellular Fe(III) reductase system from Shewanella oneidensis contain multihaem c-type cytochromes as electron carriers and terminal reductases. The position and orientation of the haem cofactors in multihaem cytochromes from different bacteria often show significant conservation despite different arrangements of the polypeptide chain. We propose that the decahaem cytochromes of the iron reductase system MtrA, MtrC and OmcA comprise pentahaem ‘modules’ similar to the electron donor protein, NrfB, from E. coli. To demonstrate this, we have isolated and characterized the N-terminal pentahaem module of MtrA by preparing a truncated form containing five covalently attached haems. UV–visible spectroscopy indicated that all five haems were low-spin, consistent with the presence of bis-His ligand co-ordination as found in full-length MtrA.

  4. Mechanism and Consequences of Anaerobic Respiration of Cobalt by Shewanella oneidensis Strain MR1

    Microsoft Academic Search

    Heidi H. Hau; Alan Gilbert; Dan Coursolle; Jeffrey A. Gralnick

    2008-01-01

    formation of a toxic by-product. We found that (Co(II)-EDTA)2, the product of (Co(III)-EDTA) respiration, inhibited the growth of S. oneidensis strain MR-1 and that this toxicity was partially abolished by the addition of MgSO4. We demonstrate that (Co(III)-EDTA) reduction by S. oneidensis requires the Mtr extracellular respiratory pathway and associated pathways required to develop functional Mtr enzymes (the c-type cyto-

  5. Structures of 5-Methylthioribose Kinase Reveal Substrate Specificity and Unusual Mode of Nucleotide Binding

    SciTech Connect

    Ku,S.; Yip, P.; Cornell, K.; Riscoe, M.; Behr, J.; Guillerm, G.; Howell, P.

    2007-01-01

    The methionine salvage pathway is ubiquitous in all organisms, but metabolic variations exist between bacteria and mammals. 5-Methylthioribose (MTR) kinase is a key enzyme in methionine salvage in bacteria and the absence of a mammalian homolog suggests that it is a good target for the design of novel antibiotics. The structures of the apo-form of Bacillus subtilis MTR kinase, as well as its ADP, ADP-PO4, AMPPCP, and AMPPCP-MTR complexes have been determined. MTR kinase has a bilobal eukaryotic protein kinase fold but exhibits a number of unique features. The protein lacks the DFG motif typically found at the beginning of the activation loop and instead coordinates magnesium via a DXE motif (Asp{sup 250}-Glu{sup 252}). In addition, the glycine-rich loop of the protein, analogous to the 'Gly triad' in protein kinases, does not interact extensively with the nucleotide. The MTR substrate-binding site consists of Asp{sup 233} of the catalytic HGD motif, a novel twin arginine motif (Arg{sup 340}/Arg{sup 341}), and a semi-conserved W-loop, which appears to regulate MTR binding specificity. No lobe closure is observed for MTR kinase upon substrate binding. This is probably because the enzyme lacks the lobe closure/inducing interactions between the C-lobe of the protein and the ribosyl moiety of the nucleotide that are typically responsible for lobe closure in protein kinases. The current structures suggest that MTR kinase has a dissociative mechanism.

  6. Methionine Metabolism in Apple Tissue

    PubMed Central

    Adams, Douglas O.; Yang, Shang Fa

    1977-01-01

    If S-adenosylmethionine (SAM) is the direct precursor of ethylene as previously proposed, it is expected that 5?-S-methyl-5?-thioadenosine (MTA) would be the fragment nucleoside. When [Me-14C] or [35S]methionine was fed to climacteric apple (Malus sylvestris Mill) tissue, radioactive 5-S-methyl-5-thioribose (MTR) was identified as the predominant product and MTA as a minor one. When the conversion of methionine into ethylene was inhibited by l-2-amino-4-(2?-aminoethoxy)-trans-3-butenoic acid, the conversion of [35S] or [Me14C]methionine into MTR was similarly inhibited. Furthermore, the formation of MTA and MTR from [35S]methionine was observed only in climacteric tissue which produced ethylene and actively converted methionine to ethylene but not in preclimacteric tissue which did not produce ethylene or convert methionine to ethylene. These observations suggest that the conversion of methionine into MTA and MTR is closely related to ethylene biosynthesis and provide indirect evidence that SAM may be an intermediate in the conversion of methionine to ethylene. When [35S]MTA was fed to climacteric or preclimacteric apple tissue, radioactivity was efficiently incorporated into MTR and methionine. However, when [35S]MTR was administered, radioactivity was efficiently incorporated into methionine but not MTA. This suggests that the sulfur of MTA is incorporated into methionine via MTR. A dual label experiment with [35S, Me-3H]MTA indicates that the CH3S group of MTA was transferred as a unit to form methionine. A scheme is presented for the production of ethylene from methionine, the first step being the activation of methionine by ATP to give SAM. SAM is fragmented to give ethylene, MTA, and other products. MTA is then hydrolyzed to MTR which donates its methylthio group to a four-carbon acceptor to reform methionine. PMID:16660208

  7. Methionine synthase reductase A66G polymorphism contributes to tumor susceptibility: evidence from 35 case–control studies

    Microsoft Academic Search

    Dong Han; Chao Shen; Xiangning Meng; Jing Bai; Feng Chen; Yang Yu; Yan Jin; Songbin Fu

    Methionine synthase reductase (MTRR) gene is involved in tumorigenesis by regulating DNA methylation through activation of methionine synthase (MTR). MTRR is polymorphic at nucleotide 66 (A-to-G) and the resulting variant enzyme has a lower affinity for MTR. The reported associations of MTRR A66G polymorphism with cancer risk are contradictory. Therefore, we performed a meta-analysis to better assess the associations,\\u000a including

  8. The 2756A>G variant in the gene encoding methionine synthase: its relation with plasma homocysteine levels and risk of coronary heart disease in a Dutch case-control study

    Microsoft Academic Search

    Mariska Klerk; Karin J. A Lievers; Leo A. J Kluijtmans; Henk J Blom; Martin den Heijer; Evert G Schouten; Frans J Kok; Petra Verhoef

    2003-01-01

    Introduction: Elevated plasma homocysteine levels have been associated with increased risk of cardiovascular disease. A 2756A>G polymorphism has been found in the gene (MTR) coding for methionine synthase, an enzyme catalyzing remethylation of homocysteine to methionine. Materials and methods: In a Dutch case-control study comprising 123 cases with coronary heart disease (CHD) and 540 controls, we evaluated whether the MTR

  9. Relation between plasma homocysteine, gene polymorphisms of homocysteine metabolism-related enzymes, and angiographically proven coronary artery disease

    Microsoft Academic Search

    Abdelilah Laraqui; Abdellatif Allami; Alain Carrié; Alain Raisonnier; Anne-Sofie Coiffard; Fatima Benkouka; Abdenabi Bendriss; Abdelaziz Benjouad; N. Bennouar; Nizar El Kadiri; Anwar Benomar; Seddik Fellat; Mohamed Benomar

    2007-01-01

    BackgroundHyperhomocyteinemia (HHcy) is a risk factor for coronary artery disease (CAD), and methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) polymorphisms may contribute to plasma total homocysteine (tHcy) variation. We investigated the association of polymorphisms 1298A?C in the MTHFR gene, 2756A?G in the MTR gene, and 66A?G in the MTRR gene with tHcy levels and with CAD

  10. Methylenetetrahydrofolate Reductase 677C.T and Methionine Synthase 2756A.G Mutations: No Impact on Survival, Cognitive Functioning, or Cognitive Decline in Nonagenarians

    Microsoft Academic Search

    Lise Bathum; Jacob von Bornemann Hjelmborg; Lene Christiansen; Matt McGue; Bernard Jeune; Kaare Christensen

    Background. Several reports have shown an association between homocysteine, cognitive functioning, and survival among the oldest-old. Two common polymorphisms in the genes coding for methylenetetrahydrofolate reductase (MTHFR 677C.T) and methionine synthase (MTR 2756A.G) have an impact on plasma homocysteine level. Methods. We examined the effect of the MTHFR 677C.T and MTR 2756A.G genotypes on baseline cognitive functioning, cognitive decline over

  11. Transformation of Helicobacter pylori by chromosomal metronidazole resistance and by a plasmid with a selectable chloramphenicol resistance marker

    Microsoft Academic Search

    YNG WANG; K. P. Roos; DIANE E. TAYLOR

    1993-01-01

    per viable cell using a plate transformation procedure. Transformation of a metronidazole resistance marker (MtrR) was demonstrated when either a laboratory-derived mutant or a MtrR clinical isolate were used as the source of donor DNA. MtF was transformed at a frequency of 3 x per viable cell. All H. pylori strains tested produce large amounts of DNAase, which may reduce

  12. Deep Gray Matter Demyelination Detected by Magnetization Transfer Ratio in the Cuprizone Model

    PubMed Central

    Fjær, Sveinung; Bø, Lars; Lundervold, Arvid; Myhr, Kjell-Morten; Pavlin, Tina; Torkildsen, Øivind; Wergeland, Stig

    2013-01-01

    In multiple sclerosis (MS), the correlation between lesion load on conventional magnetic resonance imaging (MRI) and clinical disability is weak. This clinico-radiological paradox might partly be due to the low sensitivity of conventional MRI to detect gray matter demyelination. Magnetization transfer ratio (MTR) has previously been shown to detect white matter demyelination in mice. In this study, we investigated whether MTR can detect gray matter demyelination in cuprizone exposed mice. A total of 54 female C57BL/6 mice were split into one control group () and eight cuprizone exposed groups (). The mice were exposed to (w/w) cuprizone for up to six weeks. MTR images were obtained at a 7 Tesla Bruker MR-scanner before cuprizone exposure, weekly for six weeks during cuprizone exposure, and once two weeks after termination of cuprizone exposure. Immunohistochemistry staining for myelin (anti-Proteolopid Protein) and oligodendrocytes (anti-Neurite Outgrowth Inhibitor Protein A) was obtained after each weekly scanning. Rates of MTR change and correlations between MTR values and histological findings were calculated in five brain regions. In the corpus callosum and the deep gray matter a significant rate of MTR value decrease was found, per week () and per week () respectively. The MTR values correlated to myelin loss as evaluated by immunohistochemistry (Corpus callosum: . Deep gray matter: ), but did not correlate to oligodendrocyte density. Significant results were not found in the cerebellum, the olfactory bulb or the cerebral cortex. This study shows that MTR can be used to detect demyelination in the deep gray matter, which is of particular interest for imaging of patients with MS, as deep gray matter demyelination is common in MS, and is not easily detected on conventional clinical MRI. PMID:24386344

  13. MTHFR polymorphisms in Puerto Rican children with isolated congenital heart disease and their mothers

    PubMed Central

    García-Fragoso, Lourdes; García-García, Inés; Leavitt, Gloria; Renta, Jessicca; Ayala, Miguel A.; Cadilla, Carmen L.

    2010-01-01

    Congenital heart defects (CHD) are among the most common birth defects. There is evidence suggesting that polymorphisms in folate metabolism could alter susceptibility to CHD. The MTHFR 677TT genotype has been associated with the development of structural congenital heart malformations. The objective of this study was to identify common polymorphisms in the MTHFR gene in children with isolated CHD and their mothers. The DNA analysis for the C677T and A1298C mutations was performed. The study group included 27 mothers, 27 children with CHD, and 220 controls. The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes. The higher prevalence of C677T polymorphisms in mothers of children with CHD and of compound heterozygosity for both polymorphisms suggests the possible role of folic acid in the prevention of CHD. Due to the relation of this enzyme to folate metabolism, current folate recommendations for women in childbearing age in Puerto Rico to reduce neural tube defects may need to be extended to the prevention of CHD. PMID:20657745

  14. Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper deficiency after gastric bypass surgery.

    PubMed

    Yarandi, Shadi S; Griffith, Daniel P; Sharma, Rahul; Mohan, Arun; Zhao, Vivian M; Ziegler, Thomas R

    2014-01-01

    Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations. Here we present a case of an undiagnosed copper deficiency several years after bariatric gastric bypass surgery, in a patient who concomitantly used zinc-containing denture cream for several years, associated with anemia, neutropenia, myelopathy, respiratory failure, and bilateral optic neuropathy, which caused major vision loss. This patient was also a heterozygote carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism, which may affect copper metabolism. Intravenous copper repletion resulted in rapid correction of hematologic indices. However, neurological manifestations, including vision loss responded only modestly to copper supplementation, despite achieving normal blood copper concentrations. Clinicians should consider copper deficiency in patients at risk, as in this case, as a delayed diagnosis can lead to irreversible disability due to neurological manifestations. PMID:24583748

  15. Mutational spectrum of F8 gene and prothrombotic gene variants in haemophilia A patients from Southern Italy.

    PubMed

    Sanna, V; Zarrilli, F; Nardiello, P; D'Argenio, V; Rocino, A; Coppola, A; DI Minno, G; Castaldo, G

    2008-07-01

    Haemophilia A (HA) is an X-linked recessive haemorrhagic disorder caused by a deficiency of coagulation factor VIII. Disease causative mutations are heterogeneous and spread all over the F8 gene sequence, with the exception of intron 22 inversion occurring in about 50% of severe patients. To define the specific mutational repertoire and mutation detection rate, we analysed F8 gene, by polymerase chain reaction and direct sequencing, in 128 unrelated patients from Southern Italy with severe (n = 108), moderate (n = 9) or mild (n = 11) HA. We identified 120 mutations, including 64 cases of intron 22 inversion (53.3%), three of intron 1 inversion (2.5%), one large deletion (0,8%) and 52 point mutations (43.3%). In particular, 19/120 were novel and 7/52 point mutations (13.5%) occurred at CpG sites. We also investigated eight prothrombotic genetic variants in a subgroup of 74 severe HA patients to evaluate their possible protective effect on the severity of clinical expression. Methylenetetrahydrofolate reductase A1298C and plasminogen activator inhibitor-1 4G variants recurred more frequently in HA patients with a less-severe phenotype. Clinical impact of these findings needs large-scale studies to further define the role of these prothrombotic variants as possible modifier factors of HA phenotype. PMID:18459951

  16. Elevated Homocysteine Level and Folate Deficiency Associated with Increased Overall Risk of Carcinogenesis: Meta-Analysis of 83 Case-Control Studies Involving 35,758 Individuals

    PubMed Central

    Wu, Wei; Guo, Ye; Cui, Wei

    2015-01-01

    Background Results of the association of folate metabolism and carcinogenesis are conflicting. We performed a meta-analysis to examine the effect of the interaction of serum concentration of homocysteine (Hcy), folate, and vitamin B12 and 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism on risk of cancer overall. Method Two reviewers independently searched for all published studies of Hcy and cancer in PubMed, EMBASE-MEDLINE and Chinese databases. Pooled results were reported as odds ratios (ORs) and mean differences and presented with 95% confidence intervals (95% CIs) and 2-sided probability values. Results We identified 83 eligible studies of 15,046 cases and 20,712 controls. High level of Hcy but low level of folate was associated with risk of cancer overall, with little effect by type of cancer or ethnicity. Vitamin B12 level was inversely associated with only urinary-system and gastrointestinal carcinomas and for Asian and Middle Eastern patients. As well, MTHFR C677T, A1298C and G1793A polymorphisms were related to elevated serum level of Hcy, and folate and vitamin B12 deficiency. However, only MTHFR C677T homogeneity/wild-type (TT/CC) polymorphism was positively associated with overall risk of cancer. Conclusion Elevated serum Hcy level and folate deficiency are associated with increased overall risk of cancer. PMID:25985325

  17. Folate Intake, MTHFR Polymorphisms, and the Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Kennedy, Deborah A.; Stern, Seth J.; Matok, Ilan; Moretti, Myla E.; Sarkar, Moumita; Adams-Webber, Thomasin; Koren, Gideon

    2012-01-01

    Background. The objective was to determine whether relationships exist between the methylene-tetrahydrofolate reductase (MTHFR) polymorphisms and risk of colorectal cancer (CRC) and examine whether the risk is modified by level of folate intake. Methods. MEDLINE, Embase, and SCOPUS were searched to May 2012 using the terms “folic acid,” “folate,” “colorectal cancer,” “methylenetetrahydrofolate reductase,” “MTHFR.” Observational studies were included which (1) assessed the risk of CRC for each polymorphism and/or (2) had defined levels of folate intake for each polymorphism and assessed the risk of CRC. Results. From 910 references, 67 studies met our criteria; hand searching yielded 10 studies. The summary risk estimate comparing the 677CT versus CC genotype was 1.02 (95% CI 0.95–1.10) and for 677TT versus CC was 0.88 (95% CI 0.80–0.96) both with heterogeneity. The summary risk estimates for A1298C polymorphisms suggested no reduced risk. The summary risk estimate for high versus low total folate for the 677CC genotype was 0.70 (95% CI 0.56–0.89) and the 677TT genotype 0.63 (95% CI 0.41–0.97). Conclusion. These results suggest that the 677TT genotype is associated with a reduced risk of developing CRC, under conditions of high total folate intake, and this associated risk remains reduced for both MTHFR 677 CC and TT genotypes. PMID:23125859

  18. Rapid electron exchange between surface-exposed bacterial cytochromes and Fe(III) minerals

    SciTech Connect

    White, Gaye F.; Shi, Zhi; Shi, Liang; Wang, Zheming; Dohnalkova, Alice; Marshall, Matthew J.; Fredrickson, Jim K.; Zachara, John M.; Butt, Julea N.; Richardson, David; Clarke, Thomas A.

    2013-04-16

    The mineral respiring bacterium Shewanella oneidensis uses a protein complex, MtrCAB, composed of two decaheme cytochromes brought together inside a transmembrane porin to transport electrons across the outer membrane to a variety of mineral-based electron acceptors. A proteoliposome system that contains methyl viologen as an internalised electron carrier has been used to investigate how the topology of the MtrCAB complex relates to its ability to transport electrons across a lipid bilayer to externally-located Fe(III) oxides. With MtrA facing the interior and MtrC exposed on the outer surface of the phospholipid bilayer, direct electron transfer from the interior through MtrCAB to solid-phase Fe(III) oxides was demonstrated. The observed rates of conduction through the protein complex were 2 to 3 orders of magnitude higher than that observed in whole cells, demonstrating that direct electron exchange between MtrCAB and Fe(III) oxides is efficient enough to support in-vivo, anaerobic, solid phase iron respiration.

  19. Probable Mechanisms of Needling Therapies for Myofascial Pain Control

    PubMed Central

    Chou, Li-Wei; Kao, Mu-Jung; Lin, Jaung-Geng

    2012-01-01

    Myofascial pain syndrome (MPS) has been defined as a regional pain syndrome characterized by muscle pain caused by myofascial trigger points (MTrPs) clinically. MTrP is defined as the hyperirritable spot in a palpable taut band of skeletal muscle fibers. Appropriate treatment to MTrPs can effectively relieve the clinical pain of MPS. Needling therapies, such as MTrP injection, dry needling, or acupuncture (AcP) can effectively eliminate pain immediately. AcP is probably the first reported technique in treating MPS patients with dry needling based on the Traditional Chinese Medicine (TCM) theory. The possible mechanism of AcP analgesia were studied and published in recent decades. The analgesic effect of AcP is hypothesized to be related to immune, hormonal, and nervous systems. Compared to slow-acting hormonal system, nervous system acts in a faster manner. Given these complexities, AcP analgesia cannot be explained by any single mechanism. There are several principles for selection of acupoints based on the TCM principles: “Ah-Shi” point, proximal or remote acupoints on the meridian, and extra-meridian acupoints. Correlations between acupoints and MTrPs are discussed. Some clinical and animal studies of remote AcP for MTrPs and the possible mechanisms of remote effectiveness are reviewed and discussed. PMID:23346211

  20. Remote Subcutaneous Needling to Suppress the Irritability of Myofascial Trigger Spots: An Experimental Study in Rabbits

    PubMed Central

    Fu, Zhonghua; Hsieh, Yueh-Ling; Hong, Chang-Zern; Kao, Mu-Jung; Lin, Jaung-Geng; Chou, Li-Wei

    2012-01-01

    Objective. To obtain electrophysiological effects of Fu's subcutaneous needling (FSN) on needling distance by assessment of endplate noise (EPN) recorded from the myofascial trigger spots (MTrSs) in rabbit skeletal muscle. Method. Eighteen New Zealand rabbits weighing 2.5–3.0 kg were randomly divided into two groups as follows: proximal needling (PN) group and distal needling (DN) group. The needling procedure followed the instructions described by the inventor of FSN, including needling insertion and swaying movement. The amplitudes of EPN on the MTrS region of BF muscle were recorded as an index of MTrS irritability. Random sampling of EPN tracings were taken for further analyses before, during, and after FSN treatment. Results. In PN and DN groups, the trends of EPN amplitude alterations were similar at conditions before, during, and after FSN treatment. The degree of reduction in the EPN amplitude in PN group was significantly higher than that in DN group. There were no significant changes in EPN amplitudes in the MTrS of contralateral BF without FSN intervention either in DN or PN group. Conclusion. The irritability of proximal MTrSs could be modulated after ipsilateral FSNs. The placement of FSN may affect the effectiveness of suppression of irritability of MTrSs. PMID:23346200

  1. Magnetization transfer ratio recovery in new lesions decreases during adolescence in pediatric-onset multiple sclerosis patients

    PubMed Central

    Brown, Robert A.; Narayanan, Sridar; Banwell, Brenda; Arnold, Douglas L.

    2014-01-01

    Children and adolescents diagnosed with multiple sclerosis rarely accrue physical disability early in their disease. This could be explained by greater remyelination in children, a capacity that may be lost in adolescence or early adulthood. Magnetization transfer ratio (MTR) MRI can be used to quantify changes in myelin in MS. We used serial MTR imaging and longitudinal random effects analysis to quantify recovery of MTR in acute lesions and to evaluate MTR changes in normal-appearing tissue in 19 adolescent MS patients. Our objective was to determine whether younger adolescents have a greater capacity for remyelination and whether this decreases as patients approach adulthood. We detected a significant decrease in MTR recovery between ages 16 and 20 years (p = 0.023), with older subjects approaching typical recovery levels for adult-onset MS. MTR recovery in acute MS lesions decreases with age in adolescents, suggesting loss of remyelination capacity. This may be related to the conclusion of primary myelination or other developmental factors. PMID:25379436

  2. Two-dimensional ultrasound and ultrasound elastography imaging of trigger points in women with myofascial pain syndrome treated by acupuncture and electroacupuncture: a double-blinded randomized controlled pilot study.

    PubMed

    Müller, Cristina Emöke Erika; Aranha, Maria Fernanda Montans; Gavião, Maria Beatriz Duarte

    2015-04-01

    Chronic pain has been often associated with myofascial pain syndrome (MPS), which is determined by myofascial trigger points (MTrP). New features have been tested for MTrP diagnosis. The aim of this study was to evaluate two-dimensional ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC) treatment. 24 women participated, aged between 20 and 40 years (M ± SD = 27.33 ± 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 ± 3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz) and left trapezius (LTPz) and local or referred pain for up to six months. Subjects were randomized into EA and AC treatment groups and the control sham AC (SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p < 0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001). Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was lower than pre-treatment in both treatment groups. 2D US and UE effectively characterized MTrP and surrounding tissue, pointing to the possibility of objective confirmation of subjective EA and AC treatment effects. PMID:25116293

  3. Effect of Treatment with Interferon Beta-1a on Changes in Voxel-Wise Magnetization Transfer Ratio in Normal Appearing Brain Tissue and Lesions of Patients with Relapsing–Remitting Multiple Sclerosis: A 24-Week, Controlled Pilot Study

    PubMed Central

    Zivadinov, Robert; Dwyer, Michael G.; Markovic-Plese, Silva; Kennedy, Cheryl; Bergsland, Niels; Ramasamy, Deepa P.; Durfee, Jacqueline; Hojnacki, David; Hayward, Brooke; Dangond, Fernando; Weinstock-Guttman, Bianca

    2014-01-01

    Background This pilot study investigated changes in remyelinating and demyelinating activity in normal appearing brain tissue (NABT) and lesions, by using voxel-wise magnetization transfer ratio (VW-MTR), in patients with relapsing–remitting multiple sclerosis (RRMS) receiving interferon beta-1a 44 mcg subcutaneously (IFN ?-1a SC) three times weekly versus healthy controls (HCs) (NCT01085318). Methods Increasing (suggestive of remyelination) and decreasing (suggestive of demyelination) VW-MTR changes in NABT and in T2, T1 and gadolinium (Gd)-enhancing lesion volume were measured over 24 weeks in 23 patients treated with IFN ?-1a SC and in 15 HCs (where applicable). VW-MTR changes were tested using the Wilcoxon signed–rank or Wilcoxon rank–sum test. Results A trend for greater volume of NABT with increasing VW-MTR at 24 weeks was observed for patients versus HCs (median [range] 1206 [0–15278]; 342 [0–951] mm3; p?=?0.061). NABT volume with increasing VW-MTR at 12 weeks was significantly greater in patients than in HCs (852 [6–11577]; 360 [0–1755] mm3; p?=?0.028). Similar findings were detected for lesion volumes. Two patients with notably high numbers of Gd-enhancing lesions at baseline had a markedly greater volume of tissue with increasing VW-MTR compared with other patients. Volume of NABT tissue with decreasing VW-MTR was significantly greater in patients versus HCs at 24 weeks (942 [0–6141]; 297 [0–852] mm3; p<0.001). Conclusions The significant change in NABT volume with increasing VW-MTR at 12 weeks suggests that active remyelination in patients with RRMS may occur during treatment with IFN ?-1a SC. Findings from two patients with the highest number of Gd-enhancing lesions at baseline suggest that extensive remyelination in NABT may occur in patients with high disease activity. Tissue volume with decreasing VW-MTR was greater in patients than in HCs, despite treatment, validating the sensitivity of this technique for detecting MS disease activity. Trial Registration ClinicalTrials.gov NCT01085318. PMID:24625687

  4. Structure of MRDI Explains its Dual Function as a Metabolic Enzyme and a Mediator of Cell Invasion

    PubMed Central

    Templeton, Paul D.; Litman, Elizabeth S.; Metzner, Sandra I.; Ahn, Natalie G.; Sousa, Marcelo C.

    2013-01-01

    Metastatic melanoma is among the most intractable cancers to treat, where patients show resistance to therapy and limited survival time. A critical step in the development of metastatic melanoma is the acquisition of invasion and transition from thin to thick tumors on the skin, followed by invasion to lymph nodes. Prior studies have shown that metastatic melanoma is associated with dysregulation of RhoA and enhanced expression of a protein named “mediator of RhoA-dependent invasion (MRDI)”. Importantly, MRDI is a “moonlighting” enzyme, with two distinct functions in melanoma cells. First, MRDI acts as a methylthioribose-1-phosphate (MTR-1-P) isomerase, catalyzing a critical step in methionine salvage. Second, MRDI promotes and is necessary for melanoma cell invasion, independent of its catalytic activity. Here, we demonstrate that MtnA, a bacterial MTR-1-P isomerase, rescues the methionine salvage function of MRDI, but is unable to rescue its role in invasion. We then solve the crystal structure of MRDI to a resolution of 2.5 Å, in order to identify structural elements important for its invasion activity. We present this structure and its comparison with other MTR-1-P isomerases, and identify mutations within a region separate from the MTR-1-P binding site which interfere with invasion. Thus, structural elements in MRDI distal from the MTR-1-P catalytic site are responsible for the invasion phenotype. PMID:23859498

  5. Magnetization Transfer Imaging of Suicidal Patients with Major Depressive Disorder

    PubMed Central

    Chen, Ziqi; Zhang, Huawei; Jia, Zhiyun; Zhong, Jingjie; Huang, Xiaoqi; Du, Mingying; Chen, Lizhou; Kuang, Weihong; Sweeney, John A.; Gong, Qiyong

    2015-01-01

    Magnetization transfer imaging (MTI) provides a quantitative measure of the macromolecular structural integrity of brain tissue, as represented by magnetization transfer ratio (MTR). In this study, we utilized MTI to identify biophysical alterations in MDD patients with a history of suicide attempts relative to MDD patients without such history. The participants were 36 medication-free MDD patients, with (N = 17) and without (N = 19) a history of a suicide attempt, and 28 healthy controls matched for age and gender. Whole brain voxel-based analysis was used to compare MTR across three groups and to analyze correlations with symptom severity and illness duration. We identified decreased MTR in left inferior parietal lobule and right superior parietal lobule in suicide attempters relative to both non-attempters and controls. Non-attempters also showed significantly reduced MTR in left inferior parietal lobule relative to controls, as well as an MTR reduction in left cerebellum. These abnormalities were not correlated with symptom severity or illness duration. Depressed patients with a history of suicide attempt showed bilateral abnormalities in parietal cortex compared to nonsuicidal depressed patients and healthy controls. Parietal lobe abnormalities might cause attentional dysfunction and impaired decision making to increase risk for suicidal behavior in MDD. PMID:25853872

  6. Structure of mediator of RhoA-dependent invasion (MRDI) explains its dual function as a metabolic enzyme and a mediator of cell invasion.

    PubMed

    Templeton, Paul D; Litman, Elizabeth S; Metzner, Sandra I; Ahn, Natalie G; Sousa, Marcelo C

    2013-08-20

    Metastatic melanoma is among the most intractable cancers to treat; patients show resistance to therapy and limited survival time. A critical step in the development of metastatic melanoma is the acquisition of invasion and transition from thin to thick tumors on the skin, followed by invasion to lymph nodes. Prior studies have shown that metastatic melanoma is associated with dysregulation of RhoA and enhanced expression of a protein named "mediator of RhoA-dependent invasion (MRDI)". Importantly, MRDI is a "moonlighting" enzyme, with two distinct functions in melanoma cells. First, MRDI acts as a methylthioribose-1-phosphate (MTR-1-P) isomerase, catalyzing a critical step in methionine salvage. Second, MRDI promotes and is necessary for melanoma cell invasion, independent of its catalytic activity. This paper demonstrates that MtnA, a bacterial MTR-1-P isomerase, rescues the methionine salvage function of MRDI, but is unable to rescue its role in invasion. The crystal structure of MRDI was solved to a resolution of 2.5 Å to identify structural elements important for its invasion activity. This structure and its comparison with other MTR-1-P isomerases are presented, and mutations within a region separate from the MTR-1-P binding site, which interfere with invasion, are identified. Thus, structural elements in MRDI distal from the MTR-1-P catalytic site are responsible for the invasion phenotype. PMID:23859498

  7. 2?-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family

    PubMed Central

    Werner, Maria; Purta, El?bieta; Kaminska, Katarzyna H.; Cymerman, Iwona A.; Campbell, David A.; Mittra, Bidyottam; Zamudio, Jesse R.; Sturm, Nancy R.; Jaworski, Jacek; Bujnicki, Janusz M.

    2011-01-01

    The 5? cap of human messenger RNA consists of an inverted 7-methylguanosine linked to the first transcribed nucleotide by a unique 5?–5? triphosphate bond followed by 2?-O-ribose methylation of the first and often the second transcribed nucleotides, likely serving to modify efficiency of transcript processing, translation and stability. We report the validation of a human enzyme that methylates the ribose of the second transcribed nucleotide encoded by FTSJD1, henceforth renamed HMTR2 to reflect function. Purified recombinant hMTr2 protein transfers a methyl group from S-adenosylmethionine to the 2?-O-ribose of the second nucleotide of messenger RNA and small nuclear RNA. Neither N7 methylation of the guanosine cap nor 2?-O-ribose methylation of the first transcribed nucleotide are required for hMTr2, but the presence of cap1 methylation increases hMTr2 activity. The hMTr2 protein is distributed throughout the nucleus and cytosol, in contrast to the nuclear hMTr1. The details of how and why specific transcripts undergo modification with these ribose methylations remains to be elucidated. The 2?-O-ribose RNA cap methyltransferases are present in varying combinations in most eukaryotic and many viral genomes. With the capping enzymes in hand their biological purpose can be ascertained. PMID:21310715

  8. Synergistic activity of 5-trifluoromethylthioribose and inhibitors of methionine synthesis against Klebsiella pneumoniae.

    PubMed Central

    Tower, P A; Johnson, L L; Ferro, A J; Fitchen, J H; Riscoe, M K

    1991-01-01

    5-Methylthioribose (MTR) is an intermediate in the methionine recycling pathway of organisms containing the enzyme MTR kinase. Analogs of MTR have been proposed as a new class of antimicrobial agents because of their ability to perturb the growth of MTR kinase-containing pathogens through inhibition of methionine salvage or by conversion to toxic products. One such analog, 5-trifluoromethylthioribose (TFMTR), has demonstrated potent inhibitory effects on the growth of Klebsiella pneumoniae (A. G. Gianotti, P. A. Tower, J. H. Sheley, P. A. Conte, C. Spiro, J. H. Fitchen, and M. K. Riscoe, J. Biol. Chem. 265:831-837, 1990). Although the mode of action of TFMTR has yet to be determined, it is believed that the drug is converted to the toxic products trifluoromethionine or carbonothioic difluoride via MTR kinase and the methionine recycling pathway. On the basis of this assumption, we theorized that blocking de novo methionine synthesis would increase dependence on the methionine salvage pathway and lead to an increased rate of synthesis of toxic metabolites from TFMTR. In this report, we show that three separate inhibitors of de novo methionine synthesis (1,2,4-triazole, azaserine, and propargylglycine) act synergistically with TFMTR in inhibiting the growth of K. pneumoniae. PMID:1929327

  9. Imaging of repeated episodes of demyelination and remyelination in multiple sclerosis

    PubMed Central

    Brown, Robert A.; Narayanan, Sridar; Arnold, Douglas L.

    2014-01-01

    Multiple sclerosis (MS) is characterized by the formation of demyelinating lesions in the white matter (WM). However, the timecourse of the evolution of healthy white matter into fully demyelinated lesions in MS is not well understood. We use a recently proposed technique to examine magnetization transfer ratio (MTR) timecourses in lesions segmented from MTR images in patients with relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS). In both groups we found MTR lesions forming both in previously normal appearing WM (de novo lesions) as well as in previously lesional tissue that appears to be experiencing a second round of inflammatory demyelination (repeat lesions). Both de novo and repeat lesions exhibited significant, but incomplete MTR recovery, suggesting partial remyelination; post-lesion MTR values in de novo lesions were similar to pre-lesion values in repeat lesions. Both de novo and repeat lesions were found in subjects in relapsing–remitting and secondary progressive stages of MS, and repeat lesions appeared relatively more common in the secondary progressive phase. These observations support the hypothesis that entirely demyelinated lesions found on histopathology are the result of multiple episodes of demyelination and incomplete remyelination, and may have implications for MS treatment development efforts aimed at neuroprotection and enhancing remyelination. PMID:25610760

  10. Axonal damage in the making: Neurofilament phosphorylation, proton mobility and magnetisation transfer in multiple sclerosis normal appearing white matter?

    PubMed Central

    Petzold, A.; Tozer, D.J.; Schmierer, K.

    2011-01-01

    Aims Multiple sclerosis (MS) leaves a signature on the phosphorylation and thus proton binding capacity of axonal neurofilament (Nf) proteins. The proton binding capacity in a tissue is the major determinant for exchange between bound and free protons and thus the magnetisation transfer ratio (MTR). This study investigated whether the MTR of non-lesional white matter (NLWM) was related to the brain tissue concentration of neurofilament phosphoforms. Methods Unfixed post-mortem brain slices of 12 MS patients were analysed using MTR, T1 at 1.5 T. Blocks containing NLWM were processed for embedding in paraffin and inspected microscopically. Adjacent tissue was microdissected, homogenised and specific protein levels were quantified by ELISA for the Nf heavy chain (NfH) phosphoforms, glial fibrillary acidic protein (GFAP), S100B and ferritin. Results Averaged hyperphosphorylated NfH (SMI34) but not phosphorylated NfH (SMI35) levels were different between individual patients NLWM. The concentration of hyperphosphorylated NfH-SMI34 correlated with T1 (R = 0.70, p = 0.0114) and — inversely — with MTR (R =?0.73, p = 0.0065). NfH-SMI35 was not correlated to any of the MR indices. Conclusions Post-translational modifications of axonal proteins such as phosphorylation of neurofilaments occur in NLWM and may precede demyelination. The resulting change of proton mobility influences MTR and T1. This permits the in vivo detection of these subtle tissue changes on a proteomic level in patients with MS. PMID:21958956

  11. Electron tunneling properties of outer-membrane decaheme cytochromes from Shewanella oneidensis

    SciTech Connect

    Wigginton, Nicholas S.; Rosso, Kevin M.; Lower, Brian H.; Shi, Liang; Hochella, Michael F.

    2007-02-01

    In this report, we describe the characterization of two outer-membrane decaheme cytochromes OmcA and MtrC purified from the metal-reducing bacterium Shewanella oneidensis using scanning tunneling microscopy (STM) and tunneling spectroscopy (TS). OmcA and MtrC were solubilized with a common detergent and irreversibly bound to Au (111) substrates as self-assembled cytochrome films. X-ray photoelectron spectroscopy (XPS) verified that OmcA and MtrC were covalently bound to the Au surface via thiol bonds to cysteine residues. Initial STM images show that a layer of detergent covers and protects the cytochrome films. Temporary application of high bias voltage causes the detergent film to reorganize around the tip, opening a window for direct STM imaging of the cytochrome layer underneath. The STM apparent sizes of both OmcA and MtrC are 5?8 nanometers in diameter consistent with expectations from their molecular masses. Current-voltage TS over individual cytochromes showed that OmcA and MtrC have different abilities to mediate the tunneling current, reflecting differences in their electronic structures. The data suggest that the two cytochromes could have different roles in the electron transport chain during metal reduction.

  12. Magnetization Transfer Ratio Relates to Cognitive Impairment in Normal Elderly

    PubMed Central

    Seiler, Stephan; Pirpamer, Lukas; Hofer, Edith; Duering, Marco; Jouvent, Eric; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2014-01-01

    Magnetization transfer imaging (MTI) can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR) in gray and white matter (WM) and cognitive functioning in 355 participants of the Austrian stroke prevention family study (ASPS-Fam) aged 38–86?years. MTR maps were generated for the neocortex, deep gray matter structures, WM hyperintensities, and normal appearing WM (NAWM). Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function, and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and NAWM correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions, and cortex volume. Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia. PMID:25309438

  13. Mutation of a Rice Gene Encoding a Phenylalanine Biosynthetic Enzyme Results in Accumulation of Phenylalanine and Tryptophan[W

    PubMed Central

    Yamada, Tetsuya; Matsuda, Fumio; Kasai, Koji; Fukuoka, Shuichi; Kitamura, Keisuke; Tozawa, Yuzuru; Miyagawa, Hisashi; Wakasa, Kyo

    2008-01-01

    Two distinct biosynthetic pathways for Phe in plants have been proposed: conversion of prephenate to Phe via phenylpyruvate or arogenate. The reactions catalyzed by prephenate dehydratase (PDT) and arogenate dehydratase (ADT) contribute to these respective pathways. The Mtr1 mutant of rice (Oryza sativa) manifests accumulation of Phe, Trp, and several phenylpropanoids, suggesting a link between the synthesis of Phe and Trp. Here, we show that the Mtr1 mutant gene (mtr1-D) encodes a form of rice PDT with a point mutation in the putative allosteric regulatory region of the protein. Transformed callus lines expressing mtr1-D exhibited all the characteristics of Mtr1 callus tissue. Biochemical analysis revealed that rice PDT possesses both PDT and ADT activities, with a preference for arogenate as substrate, suggesting that it functions primarily as an ADT. The wild-type enzyme is feedback regulated by Phe, whereas the mutant enzyme showed a reduced feedback sensitivity, resulting in Phe accumulation. In addition, these observations indicate that rice PDT is critical for regulating the size of the Phe pool in plant cells. Feeding external Phe to wild-type callus tissue and seedlings resulted in Trp accumulation, demonstrating a connection between Phe accumulation and Trp pool size. PMID:18487352

  14. Hereditary Thrombophilia and thrombotic events in pregnancy: single-center experience.

    PubMed

    Coriu, L; Ungureanu, R; Talmaci, R; Uscatescu, V; Cirstoiu, M; Coriu, D; Copaciu, E

    2014-01-01

    Pregnancy is a normal physiological state that predisposes to thrombosis, determined by hormonal changes in the body. These changes occur in the blood flow (venous stasis), changes in the vascular wall (hypotonia, endothelial lesion) and changes in the coagulation factors (increased levels of factor VII, factor VIII, factor X, von Willebrand factor) and decreased activity levels of natural anticoagulants (protein C, protein S). In this study, we tried to determine a possible association between thrombosis and inherited thrombophilia in pregnant women. This is a retrospective study of 151 pregnant women with a history of complicated pregnancy: maternal thrombosis and placental vascular pathology (intrauterine growth restriction, preeclampsia, recurrent pregnancy loss), who were admitted in our hospital during the period January 2010 to July 2014. We performed genetic analyses to detect the factor V Leiden mutation, the G20210A mutation in the prothrombin gene, the C677T mutation and the A1298C mutation in methylenetetrahydrofolate reductase (MTHFR) gene. The risk of thrombosis in patients with factor V Leiden is 2.66 times higher than the patients negative for this mutation (OR 2.66 95% CI 0.96-7.37 P=0.059). We did not find any statistical association with mutations in the MTHFR gene. Pregnant women with a family history of thrombosis present a 2.18-fold higher risk of thrombosis (OR 2.18 CI 0.9-5.26 P=0.085). Of 151 pregnant women, thrombotic events occurred in 24 patients: deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis and ischemic stroke. The occurrence of thrombotic events was identified in the last trimester of pregnancy, but especially postpartum. Thrombosis in pregnancy is a redoubtable complication requiring an excellent cooperation between the obstetrician and anesthesiologist. PMID:25713624

  15. Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China.

    PubMed

    Stolzenberg-Solomon, Rachael Z; Qiao, You-Lin; Abnet, Christian C; Ratnasinghe, D Luke; Dawsey, Sanford M; Dong, Zhi Wei; Taylor, Philip R; Mark, Steven D

    2003-11-01

    Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in the world. Its inhabitants have documented chronic nutritional inadequacies, including folate and vitamin B(12) deficiencies. Using a cohort we have been studying in Linxian since 1985, we examined the relationship between incident ESCC and GCA cancers and three polymorphisms in two genes that code for enzymes that require folate and B(12) as cofactors: methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. We conducted a case-cohort study among 4005 individuals in our cohort who were alive and cancer free in 1991 and had blood samples adequate for DNA extraction. Polymorphisms were measured on all 219 incident cancers (129 ESCCs and 90 GCAs) that developed through May 1996 and on 398 controls. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Individuals with the MTHFR 677TT genotype had significantly higher combined ESCC/GCA risks (RR, 1.45; 95% CI, 1.02-2.05) than those with CC or CT genotypes. The only subjects to have MTHFR 1298CC were three ESCC cases (P = 0.03). Compared with subjects with the MTRR 66AA genotype, subjects with the AG or GG genotypes had significantly higher risk of ESCC (RR, 1.59; 95% CI, 1.04-2.42). No association was observed for GCA. Our results suggest that the MTHFR C677T and MTRR A66G polymorphisms influence the risk of ESCC and GCA in this population. PMID:14652285

  16. MTHFR 677C/T and 1298A/C mutations and non-alcoholic fatty liver disease.

    PubMed

    Kasapoglu, Benan; Turkay, Cansel; Yalcin, Kadir Serkan; Kosar, Ali; Bozkurt, Alper

    2015-06-01

    Common genetic mutations encountered in folate metabolism may result in increased homocysteine (Hcy) levels. It has been reported that increased serum Hcy levels may affect the intracellular fat metabolism and may cause enhanced fatty infiltration in the liver resulting in non-alcoholic fatty liver disease (NAFLD). In total, 150 patients diagnosed with FLD by ultrasound examination and 136 healthy control patients that do not have any fatty infiltration in the liver were included in the study. Patients were grouped as mild (n = 88), moderate (n = 38) or severe (n = 24) according to the stage of fatty liver in ultrasound. Serum liver function tests, Hcy, folic acid and vitamin B12 levels of the patients were studied. The genetic MTHFR C677T and A1298C polymorphisms of the patients were also evaluated. Although there was no significant difference in vitamin B12 and folic acid levels, in the severe group, Hcy levels were significantly higher than that of control and mild groups (p<0.001). By contrast, there was no significant difference in heterozygote MTHFR 677C/T and 1298A/C mutations, both MTHFR 677C/T and MTHFR 1298A/C mutations were more common in NAFLD groups compared with the control patients (p<0.001). We have determined increased Hcy levels and increased prevalence of homozygote MTHFR 677C/T and MTHFR 1298A/C mutations in patients with NAFLD compared with healthy controls. Larger studies are warranted to clarify the etiological role of the MTHFR mutations and Hcy levels in FLD. PMID:26031974

  17. Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site.

    PubMed

    Chen, J; Yuan, L; Duan, Y Q; Jiang, J Q; Zhang, R; Huang, Z J; Xiao, X R

    2014-01-01

    Folic acid and methylenetetrahydrofolate reductase (MTHFR) may both affect the development of human cancer. We conducted a population-based case-control study in a Chinese population to investigate the potential role of folate intake and MTHFR gene polymorphisms in gastric cancer, and their interaction with infection by Helicobacter pylori and tumor location. A total of 767 patients with newly diagnosed gastric cancer and 775 controls were selected for this study. Genotyping of MTHFR C677T and A1298C was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System, and information on folate intake was collected by questionnaire. Compared with the CC genotype of MTHFR C677T, the TT genotype was significantly associated with a decreased risk of gastric cancer when the analysis was adjusted for other potential risk factors. We found a marginal significantly decreased risk of gastric cancer for individuals carrying the T allele [adjusted odds ratio (OR) = 0.83; 95% confidence interval (CI) = 0.65-1.01]. We detected an inverse relationship between folate intake and risk of gastric cancer, and the adjusted ORs (95%CI) for moderate and high folate intake were 0.97 (0.74-1.25) and 0.64 (0.49-0.87), respectively. Moreover, H. pylori infection, folate intake, and location of the tumor showed a significant interaction with the MTHFR C677T polymorphism. Our study suggests a protective role of MTHFR 677TT and high folate intake against gastric cancer, and the effect of the MTHFR C677T genotype may differ by H. pylori infection, folate consumption, and tumor site. PMID:24615072

  18. Folate Metabolism Genes, Dietary Folate and Response to Antidepressant Medications in Late-Life Depression

    PubMed Central

    Jamerson, Brenda D.; Payne, Martha E.; Garrett, Melanie E.; Ashley-Koch, Allison E.; Speer, Marcy C.; Steffens, David C.

    2013-01-01

    Objective The primary aims of this study were to 1) determine whether folate metabolism genetic polymorphisms predict age of onset and occurrence of late life depression and 2) determine whether folate metabolism genetic polymorphisms predict response to antidepressant medications in late-life depression. Methods This study used the Conte Center for the Neuroscience of Depression, and the Neurocognitive Outcomes of Depression in the Elderly Study database which includes individuals age ? 60. The folate nutrition assessment was determined by the Block Food Frequency Questionnaire. Genotype was evaluated for 15 single nucleotide polymorphisms (SNPs) from 10 folate metabolism genes. Logistic regression models were used to examine genetic polymorphisms and folate estimates with association with depression age of onset and remission status. Results There were 304 Caucasians in the database, 106 of these who were not depressed and 198 who had a diagnosis of depression. There were no significant differences between remitters and nonremitters in age, sex or estimated folate intakes. There were no folate estimates or folate metabolism gene SNPs that significantly predicted age of onset of depression or occurrence of depression. MTRR A66G (rs1801394) was significantly associated with remission status (p=0.0077) such that those with the AA genotype were 3.2 times as likely as those with the GG genotype to be in remission (p=0.0020). MTHFR A1298C (rs1801131) achieved a borderline significance for association with remission status (p=0.0313). Conclusion The major finding from this study is that the MTRR A66G genotype predicts response to SSRI antidepressants in late life depression. PMID:23280573

  19. Magnetization transfer ratio in the delayed-release dimethyl fumarate DEFINE study.

    PubMed

    Arnold, Douglas L; Gold, Ralf; Kappos, Ludwig; Bar-Or, Amit; Giovannoni, Gavin; Selmaj, Krzysztof; Yang, Minhua; Zhang, Ray; Stephan, Monica; Sheikh, Sarah I; Dawson, Katherine T

    2014-12-01

    We measured changes in brain magnetization transfer ratio (MTR) as a potential indicator of myelin density in brain tissue of patients with relapsing-remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) in the Phase 3 DEFINE study. DEFINE was a randomized, double-blind, placebo-controlled study in which patients with RRMS were randomized 1:1:1 to 2 years of treatment with delayed-release DMF 240 mg twice daily (BID) or three times daily (TID) or placebo. MTR was analyzed in whole brain and normal-appearing brain tissue (NABT) at baseline, week 24, 1 year, and 2 years in a subset of patients. MTR data from 392 patients were analyzed. Mean percentage reduction from baseline to 2 years in median whole brain MTR was -0.386% in the placebo group vs increases of 0.129% (p = 0.0027) and 0.096% (p = 0.0051) in the delayed-release DMF BID and TID groups, respectively. Similarly, mean percentage reduction from baseline in median NABT MTR was -0.392% with placebo vs increases of 0.190% (p = 0.0006) and 0.115% (p = 0.0029) with delayed-release DMF BID and TID, respectively. Post hoc analysis of data from patients with no new or enlarging T2 lesions (n = 147), or who experienced no relapses (n = 238), yielded similar results. In this analysis, increases in MTR in brain tissue most likely reflect increases in myelin density in response to delayed-release DMF. These data in patients with RRMS are consistent with preclinical studies that indicate a potential for cytoprotection and remyelination with delayed-release DMF treatment. PMID:25270680

  20. HOT CELL BUILDING, TRA632. CONTEXTUAL AERIAL VIEW OF HOT CELL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    HOT CELL BUILDING, TRA-632. CONTEXTUAL AERIAL VIEW OF HOT CELL BUILDING, IN VIEW AT LEFT, AS YET WITHOUT ROOF. PLUG STORAGE BUILDING LIES BETWEEN IT AND THE SOUTH SIDE OF THE MTR BUILDING AND ITS WING. NOTE CONCRETE DRIVE BETWEEN ROLL-UP DOOR IN MTR BUILDING AND CHARGING FACE OF PLUG STORAGE. REACTOR SERVICES BUILDING (TRA-635) WILL COVER THIS DRIVE AND BUTT UP TO CHARGING FACE. DOTTED LINE IS ON ORIGINAL NEGATIVE. TRA PARKING LOT IN LEFT CORNER OF THE VIEW. CAMERA FACING NORTHWESTERLY. INL NEGATIVE NO. 8274. Unknown Photographer, 7/2/1953 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  1. Effect of Sb 2 O 3 addition on the varistor characteristics of ZnO-Bi 2 O 3 -ZrO 2 -M tr O (M tr = Mn, Co)

    Microsoft Academic Search

    Han Ik Oh; Jin Ho Kim

    2006-01-01

    Effect of Sb2O3 addition on the varistor characteristics of pyrochlore-free ZnO-Bi2O3-ZrO2-MtrO (Mtr = Mn, Co) system previously proposed has been studied. With Sb2O3 up to 0.1 mol%, a gradual enhancement of densification and the grain growth inhibition were seen in the system sintered between\\u000a 900 and 1200?C. In X-ray diffraction patterns, small amount of pyrochlore appeared in the specimens doped

  2. The Multi-index Mittag-Leffler Functions and Their Applications for Solving Fractional Order Problems in Applied Analysis

    NASA Astrophysics Data System (ADS)

    Kiryakova, V. S.; Luchko, Yu. F.

    2010-11-01

    During the last few decades, differential equations and systems of fractional order (that is arbitrary one, not necessarily integer) begun to play an important role in modeling of various phenomena of physical, engineering, automatization, biological and biomedical, chemical, earth, economics, social relations, etc. nature. The so-called Special Functions of Fractional Calculus (SF of FC) provide an important tool of Fractional Calculus (FC) and Applied Analysis (AA). In particular, they are often used to represent the solutions of fractional differential equations in explicit form. Among the most popular representatives of the SF of FC are: the Mittag-Leffler (ML) function, the Wright generalized hypergeometric function p?q, the more general Fox H-function, and the Inayat-HussainH-function. The classical Special Functions (called also SF of Mathematical Physics), including the orthogonal polynomials, and the pFq-hypergeometric functions fall in this scheme as examples of the simpler Meijer G-function. In this survey talk, we overview the properties and some applications of an important class of SF of FC, introduced for the first time in our works. For integer m>1 and arbitrary real (or complex, under suitable restrictions) indices ?1,…,?m>0 and ?1,…,?m, we define the multi-index (vector-index) Mittag-Leffler functions by: E(1/?i),(?i)(z) = E)1/?i),(?i)(m)(z) = ? K=0?zk/?(?1+k?1)…?(?m+k/?m) = 1?m[mtr>(1,1)mtr>>(?1,1/?i)1m;zmtr>] = H1,m+11,1[-z?mtr>(0,1)mtr>>(0,1),(1-?i,1/?i)1mmtr>]. We propose also a list of examples of SF of FC that are E(1/?i),(?i)-functions and play important role in pure mathematics and in solving problems from natural, applied and social sciences, and state some open problems.

  3. MTRETR MAINTENANCE SHOP, TRA653. FLOOR PLAN FOR FIRST FLOOR: MACHINE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MTR-ETR MAINTENANCE SHOP, TRA-653. FLOOR PLAN FOR FIRST FLOOR: MACHINE SHOP, ELECTRICAL AND INSTRUMENT SHOP, TOOL CRIB, ELECTRONIC SHOP, LOCKER ROOM, SPECIAL TEMPERATURE CONTROLLED ROOM, AND OFFICES. "NEW" ON DRAWING REFERS TO REVISION OF 11/1956 DRAWING ON WHICH AREAS WERE DESIGNATED AS "FUTURE." HUMMEL HUMMEL & JONES 810-MTR-ETR-653-A-7, 5/1957. INL INDEX NO. 532-0653-00-381-101839, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  4. FAST CHOPPER DETECTOR HOUSE, TRA665. FIRST FLOOR, PLAN AND SECTION, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FAST CHOPPER DETECTOR HOUSE, TRA-665. FIRST FLOOR, PLAN AND SECTION, AS PROPOSED FOR MODIFICATION IN 1962. CONCRETE WALLS THREE FEET THICK. EXISTING WINDOWS IN MTR AND DETECTOR HOUSE WALLS WERE TO BE FILLED IN WITH HIGH-DENSITY BRICK. NOTE 20-METER MARK, WHERE THE FAST CHOPPER DETECTOR HAD BEEN LOCATED. F.C. TORKELSON 842-MTR-665-S-2, 4/1962. INL INDEX NO. 531-0665-60-851-150996, REV. 5. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  5. Catalog of experimental projects for a fissioning plasma reactor

    NASA Technical Reports Server (NTRS)

    Lanzo, C. D.

    1973-01-01

    Experimental and theoretical investigations were carried out to determine the feasibility of using a small scale fissioning uranium plasma as the power source in a driver reactor. The driver system is a light water cooled and moderated reactor of the MTR type. The eight experiments and proposed configurations for the reactor are outlined.

  6. The neurophysiological effects of dry needling in patients with upper trapezius myofascial trigger points: study protocol of a controlled clinical trial

    PubMed Central

    Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

    2013-01-01

    Introduction Dry needling (DN) is an effective method for the treatment of myofascial trigger points (MTrPs). There is no report on the neurophysiological effects of DN in patients with MTrPs. The aim of the present study will be to assess the immediate neurophysiological efficacy of deep DN in patients with upper trapezius MTrPs. Methods and analysis A prospective, controlled clinical trial was designed to include patients with upper trapezius MTrPs and volunteered healthy participants to receive one session of DN. The primary outcome measures are neuromuscular junction response and sympathetic skin response. The secondary outcomes are pain intensity and pressure pain threshold. Data will be collected at baseline and immediately after intervention. Ethics and dissemination This study protocol has been approved by the Research Council, School of Rehabilitation and the Ethics Committee of Tehran University of Medical Sciences. The results of the study will be disseminated in a peer-reviewed journal and presented at international congresses. PMID:23793673

  7. Dry Needling at Myofascial Trigger Spots of Rabbit Skeletal Muscles Modulates the Biochemicals Associated with Pain, Inflammation, and Hypoxia

    PubMed Central

    Hsieh, Yueh-Ling; Yang, Shun-An; Yang, Chen-Chia; Chou, Li-Wei

    2012-01-01

    Background and Purpose. Dry needling is an effective therapy for the treatment of pain associated with myofascial trigger point (MTrP). However, the biochemical effects of dry needling that are associated with pain, inflammation, and hypoxia are unclear. This study investigated the activities of ?-endorphin, substance P, TNF-?, COX-2, HIF-1?, iNOS, and VEGF after different dosages of dry needling at the myofascial trigger spots (MTrSs) of a skeletal muscle in rabbit. Materials and Methods. Dry needling was performed either with one dosage (1D) or five dosages (5D) into the biceps femoris with MTrSs in New Zealand rabbits. Biceps femoris, serum, and dorsal root ganglion (DRG) were sampled immediately and 5 d after dry needling for ?-endorphin, substance P, TNF-?, COX-2, HIF-1?, iNOS, and VEGF immunoassays. Results. The 1D treatment enhanced the ?-endorphin levels in the biceps femoris and serum and reduced substance P in the biceps femoris and DRG. The 5D treatment reversed these effects and was accompanied by increase of TNF-?, COX-2, HIF-1?, iNOS, and VEGF production in the biceps femoris. Moreover, the higher levels of these biochemicals were still maintained 5?d after treatment. Conclusion. Dry needling at the MTrSs modulates various biochemicals associated with pain, inflammation, and hypoxia in a dose-dependent manner. PMID:23346198

  8. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells

    PubMed Central

    2012-01-01

    Background Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. Methods After IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10–300 ?M) in the continued presence of IL-13. Cellular and secreted MUC5AC, mucociliary transport rates (MTR), mucus rheology at several time points, and the antioxidant capacity of the drugs were assessed. Results IL-13 increased MUC5AC content (~25%) and secretion (~2-fold) and decreased MTR, but only slightly affected the G’ (elastic) or G” (viscous) moduli of the secretions. GGE significantly inhibited MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 ?M, respectively). NAC or Amb were less effective. All drugs increased MTR and decreased G’ and G” relative to IL-13 alone. Cell viability was not affected and only NAC exhibited antioxidant capacity. Conclusions Thus, GGE effectively reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus rheology, and may therefore be useful in treating airway mucus hypersecretion and mucostasis in airway diseases. PMID:23113953

  9. Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis

    PubMed Central

    Deloire, M; Salort, E; Bonnet, M; Arimone, Y; Boudineau, M; Amieva, H; Barroso, B; Ouallet, J; Pachai, C; Galliaud, E; Petry, K; Dousset, V; Fabrigoule, C; Brochet, B

    2005-01-01

    Objectives: To establish the frequency of cognitive impairment in a population based sample of patients with recently diagnosed relapsing-remitting multiple sclerosis (RRMS), and to determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage revealed by magnetic resonance imaging (MRI) and magnetisation transfer (MT) imaging. Methods: 58 patients with RRMS consecutively diagnosed in the previous six months in Aquitaine and 70 healthy controls underwent a battery of neuropsychological tests. Lesion load and atrophy indices (brain parenchymal fraction and ventricular fraction) were measured on brain MRI. MT ratio (MTR) histograms were obtained from lesions, normal appearing white matter (NAWM), and normal appearing grey matter (NAGM). Gadolinium enhanced lesions were counted. Results: 44 RRMS patients could be individually matched with healthy controls for age, sex, and education. Patients performed worse in tests of verbal and spatial memory, attention, information processing speed, inhibition, and conceptualisation. Measures of attention and information processing speed were correlated with lesion load, mean NAWM MTR, and the peak location of the NAGM MTR histogram in the patients. Multivariate regression analysis showed that lesion load and mean NAWM MTR were among the MR indices that were most significantly associated with impairment of attention and information processing speed in these early RRMS cases. Conclusions: Cognitive impairment appears to be common in the early stages of RRMS, mainly affecting attention, information processing speed, memory, inhibition, and conceptualisation. The severity of these deficits reflects the extent of the lesions and the severity of tissue disorganisation outside lesions. PMID:15774439

  10. FAST CHOPPER BUILDING, TRA665. DETAIL SHOWS UPPER AND LOWER LEVEL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FAST CHOPPER BUILDING, TRA-665. DETAIL SHOWS UPPER AND LOWER LEVEL WALLS OF DIFFERING MATERIALS. NOTE DOORWAY TO MTR TO RIGHT OF CHOPPER BUILDING'S CLIPPED CORNER. CAMERA FACING WEST. INL NEGATIVE NO. HD42-1. Mike Crane, Photographer, 3/2004 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  11. REACTOR SERVICES BUILDING, TRA635, INTERIOR. ALSO KNOWN AS MATERIAL RECEIVING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    REACTOR SERVICES BUILDING, TRA-635, INTERIOR. ALSO KNOWN AS MATERIAL RECEIVING AREA AND LABORATORY. CAMERA ON FIRST FLOOR FACING NORTH TOWARD MTR BUILDING. MOCK-UP AREA WAS TO THE RIGHT OF VIEW. INL NEGATIVE NO. HD46-10-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  12. Investigating Multiple Candidate Genes and Nutrients in the Folate Metabolism Pathway to Detect Genetic and

    E-print Network

    Vannucci, Marina

    investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate.31; 95% CI: 1.66­6.59), and MTHFR (rs9651118; OR = 0.63; 95% CI: 0.43­0.95) and three SNP

  13. IEEE TRANSACTIONS ON MEDICAL IMAGING, ACCEPTED FOR PUBLICATION 1 Spatial resolution properties of motion-compensated

    E-print Network

    Fessler, Jeffrey A.

    methods: post-reconstruction motion correction (PMC) [3]­ [5], motion-compensated temporal regularization single gated reconstruction PMC post-reconstruction motion correction MTR motion-compensated temporal of motion-compensated tomographic image reconstruction methods Se Young Chun, Member, IEEE, and Jeffrey A

  14. Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of the TRAMP complex is mediated by short peptides and important for snoRNA processing

    PubMed Central

    Losh, Jillian S.; King, Alejandra Klauer; Bakelar, Jeremy; Taylor, Lacy; Loomis, John; Rosenzweig, Jason A.; Johnson, Sean J.; van Hoof, Ambro

    2015-01-01

    The RNA exosome is one of the main 3? to 5? exoribonucleases in eukaryotic cells. Although it is responsible for degradation or processing of a wide variety of substrate RNAs, it is very specific and distinguishes between substrate and non-substrate RNAs as well as between substrates that need to be 3? processed and those that need to be completely degraded. This specificity does not appear to be determined by the exosome itself but rather by about a dozen other proteins. Four of these exosome cofactors have enzymatic activity, namely, the nuclear RNA-dependent ATPase Mtr4, its cytoplasmic paralog Ski2 and the nuclear non-canonical poly(A) polymerases, Trf4 and Trf5. Mtr4 and either Trf4 or Trf5 assemble into a TRAMP complex. However, how these enzymes assemble into a TRAMP complex and the functional consequences of TRAMP complex assembly remain unknown. Here, we identify an important interaction site between Mtr4 and Trf5, and show that disrupting the Mtr4/Trf interaction disrupts specific TRAMP and exosome functions, including snoRNA processing. PMID:25589546

  15. Myelin paucity of the superior cerebellar peduncle in individuals with Friedreich ataxia: an MRI magnetization transfer imaging study.

    PubMed

    Corben, Louise A; Kashuk, Saman R; Akhlaghi, Hamed; Jamadar, Sharna; Delatycki, Martin B; Fielding, Joanne; Johnson, Beth; Georgiou-Karistianis, Nellie; Egan, Gary F

    2014-08-15

    The dentate nucleus (DN) is the major relay station for neural connection between the cerebellum and cerebrum via the thalamus, and is a significant component of the neuropathological profile of Friedreich ataxia (FRDA). We have previously shown that the size of the superior cerebellar peduncle (SCP), which links the DN to cortical and subcortical structures via the thalamus, is significantly reduced in individuals with FRDA compared to control participants. This study used magnetization transfer imaging (MTI) to examine and contrast the integrity of white matter (WM) in the SCP and the corpus callosum (CC) (control region) in ten individuals with FRDA and ten controls. Individuals with FRDA demonstrated a significant reduction in the magnetization transfer ratio (MTR) in the SCP compared to control participants. However, there was no significant difference between groups in MTR in the CC. When comparing regions within groups, there was a significant reduction in MTR in the SCP compared to CC in participants with FRDA only. We suggest that the reduction in MTR in the SCP may be indicative of lack of myelin secondary to axonal loss and oligodendroglial dysfunction in WM tracts in individuals with FRDA. PMID:24930398

  16. HOT CELL BUILDING, TRA632. INSTRUMENT FITTINGS, MASTER/SLAVE MANIPULATOR, "POT LID ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    HOT CELL BUILDING, TRA-632. INSTRUMENT FITTINGS, MASTER/SLAVE MANIPULATOR, "POT LID CRANE." IDAHO OPERATIONS OFFICE MTR-632-IDO-16, 11/1952. INL INDEX NO. 531-0632-40-396-110574, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  17. Burnup study for Pakistan Research Reactor1 utilizing high density low enriched uranium fuel

    Microsoft Academic Search

    Rizwan Ahmed; Aslam; Nasir Ahmad

    2005-01-01

    Burnup study for Pakistan Research Reactor-1 (PARR-1), which is a typical swimming pool type MTR utilizing high density low enriched uranium fuel, was performed by using Fuel Cycle Analysis Program (FCAP). Existing equilibrium core of PARR-1, which is relatively economical but provides less neutron fluxes per unit power than the first equilibrium core, was formed by adding five more fuel

  18. ETR, TRA642. WALL SECTION DETAILS. METAL SIDING JOINS TO ELECTRICAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR, TRA-642. WALL SECTION DETAILS. METAL SIDING JOINS TO ELECTRICAL BUILDING, OFFICE BUILDING, AND ROOF. KAISER ETR-5528-MTR-A-13, 11/1955. INL INDEX NO. 532-0642-00-486-100920, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  19. ETR ELECTRICAL BUILDING, TRA648. FLOOR PLANS FOR FIRST FLOOR AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR ELECTRICAL BUILDING, TRA-648. FLOOR PLANS FOR FIRST FLOOR AND BASEMENT. SECTIONS. KAISER ETR-5528-MTR-648-A-2, 12/1955. INL INDEX NO. 532-0648-00-486-101402, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  20. ETR ELECTRICAL BUILDING, TRA648. ELEVATIONS AND DETAILS. ROOF PLAN. DOOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR ELECTRICAL BUILDING, TRA-648. ELEVATIONS AND DETAILS. ROOF PLAN. DOOR SCHEDULE. KAISER ETR-5528-MTR-648-A-3, 1/1956. INL INDEX NO. 532-0648-00-486-101403, REV. 5. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  1. ETR, TRA642. ELEVATIONS. METAL SIDING. OFFICE BUILDING (TRA647) AND ELECTRICAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR, TRA-642. ELEVATIONS. METAL SIDING. OFFICE BUILDING (TRA-647) AND ELECTRICAL BUILDING (TRA-648) ATTACHED. KAISER ETR-5528-MTR-642-A-11, 11/1955. INL INDEX NO. 532-0642-00-486-100919, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  2. ETR COOLING TOWER PUMP HOUSE, TRA645. PUMP HOUSE TAKES SHAPE. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR COOLING TOWER PUMP HOUSE, TRA-645. PUMP HOUSE TAKES SHAPE. CAMERA FACES NORTH TOWARD ETR CONSTRUCTION AND MTR BEYOND. INL NEGATIVE NO. 56-2041. Jack L. Anderson, Photographer, 6/14/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  3. Fiber Optics for Metrology in Nuclear Research Reactors—Applications to Dimensional Measurements

    Microsoft Academic Search

    G. Cheymol; B. Brichard; J. F. Villard

    2011-01-01

    In-situ measurement is a key issue for advanced irradiation programs in nuclear research reactors, especially in Material Testing Reactors (MTR). In that prospect, Optical Fiber Sensors (OFS) can feature unique intrinsic properties that bring substantial advantages over conventional sensing approaches. One of the objectives of the Joint Instrumentation Laboratory (JIL), gathering SCK CEN (Belgium) and CEA (France) resources and know-how,

  4. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Exercises. 154.1055 Section 154.1055...Plans for Oil Facilities § 154.1055 Exercises. (a) A response plan submitted...operator of an MTR facility must include an exercise program containing both announced...

  5. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Exercises. 154.1055 Section 154.1055...Plans for Oil Facilities § 154.1055 Exercises. (a) A response plan submitted...operator of an MTR facility must include an exercise program containing both announced...

  6. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Exercises. 154.1055 Section 154.1055...Plans for Oil Facilities § 154.1055 Exercises. (a) A response plan submitted...operator of an MTR facility must include an exercise program containing both announced...

  7. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 false Exercises. 154.1055 Section 154.1055...Plans for Oil Facilities § 154.1055 Exercises. (a) A response plan submitted...operator of an MTR facility must include an exercise program containing both announced...

  8. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Exercises. 154.1055 Section 154.1055...Plans for Oil Facilities § 154.1055 Exercises. (a) A response plan submitted...operator of an MTR facility must include an exercise program containing both announced...

  9. Effects of high density dispersion fuel loading on the dynamics of a low enriched uranium fueled material test research reactor

    Microsoft Academic Search

    Farhan Muhammad; Asad Majid

    2009-01-01

    The effects of using high density low enriched uranium on the dynamics of a material test research reactor were studied. For this purpose, the low density LEU fuel of an MTR was replaced with high density LEU fuels currently being developed under the RERTR program. Since the alloying elements have different properties affecting the reactor in different ways, fuels U–Mo

  10. Effects of high density dispersion fuel loading on the kinetic parameters of a low enriched uranium fueled material test research reactor

    Microsoft Academic Search

    Farhan Muhammad; Asad Majid

    2008-01-01

    The effects of using high density low enriched uranium on the neutronic parameters of a material test research reactor were studied. For this purpose, the low density LEU fuel of an MTR was replaced with high density LEU fuels currently being developed under the RERTR program. Since the alloying elements have different cross-sections affecting the reactor in different ways, therefore

  11. Impacts of Mountaintop Removal and Valley Fill Coal Mining on C and N Processing in Terrestrial Soils and Headwater Streams.

    EPA Science Inventory

    We measured C and N cycling indicators in Appalachian watersheds impacted by mountaintop removal and valley fill (MTR/VF) coal mining, and in nearby forested watersheds. These watersheds include ephemeral, intermittent, and perennial stream reaches, and the length of time since d...

  12. HOT CELL BUILDING, TRA632. FIRST FLOOR FOUNDATION PLAN SHOWS SECTIONALIZED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    HOT CELL BUILDING, TRA-632. FIRST FLOOR FOUNDATION PLAN SHOWS SECTIONALIZED FLOOR LOADINGS AND CONCRETE SLAB THICKNESSES, A TYPICAL FEATURE OF NUCLEAR ARCHITECTURE. IDAHO OPERATIONS OFFICE MTR-632-IDO-2, 11/1952. INL INDEX NO. 531-0632-62-396-110561, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  13. Single-Cell Imaging and Spectroscopic Analyses of Cr(VI) Reduction on the Surface of Bacterial Cells

    SciTech Connect

    Wang, Yuanmin; Sevinc, Papatya C.; Belchik, Sara M.; Fredrickson, Jim K.; Shi, Liang; Lu, H. Peter

    2013-01-22

    We investigate single-cell reduction of toxic Cr(VI) by the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), an important bioremediation process, using Raman spectroscopy and scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX). Our experiments indicate that the toxic and highly soluble Cr(VI) can be efficiently reduced to the less toxic and non-soluble Cr2O3 nanoparticles by MR-1. Cr2O3 is observed to emerge as nanoparticles adsorbed on the cell surface and its chemical nature is identified by EDX imaging and Raman spectroscopy. Co-localization of Cr2O3 and cytochromes by EDX imaging and Raman spectroscopy suggests a terminal reductase role for MR-1 surface-exposed cytochromes MtrC and OmcA. Our experiments revealed that the cooperation of surface proteins OmcA and MtrC makes the reduction reaction most efficient, and the sequence of the reducing reactivity of the MR-1 is: wild type > single mutant @mtrC or mutant @omcA > double mutant (@omcA-@mtrC). Moreover, our results also suggest that the direct microbial Cr(VI) reduction and Fe(II) (hematite)-mediated Cr(VI) reduction mechanisms may co-exist in the reduction processes.

  14. r Human Brain Mapping 000:000000 (2013) r Structural Abnormalities in the Thalamus

    E-print Network

    Hadjikhani, Nouchine

    2013-01-01

    r Human Brain Mapping 000:000­000 (2013) r Structural Abnormalities in the Thalamus of Migraineurs-channel coil. We acquired whole-brain T1 relaxation maps and computed magnetization transfer ratio (MTR and to assess iron deposition. We also correlated the obtained parametric values with the average monthly

  15. Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis

    Microsoft Academic Search

    K. T. M. Fernando; D. J. Tozer; K. A. Miszkiel; R. M. Gordon; J. K. Swanton; C. M. Dalton; G. J. Barker; A. J. Thompson; D. H. Miller

    2005-01-01

    In established multiple sclerosis, magnetization transfer ratio (MTR) histograms reveal abnormalities of normal-appearing white matter (NAWM) and grey matter (NAGM). The aim of this study was to investigate for such abnormalities in a large cohort of patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Magnetization transfer imaging was performed on 100 patients (67 women, 33 men, median age

  16. Acoustic Sensor for In-Pile Fuel Rod Fission Gas Release Measurement

    Microsoft Academic Search

    D. Fourmentel; J. F. Villard; J. Y. Ferrandis; F. Augereau; E. Rosenkrantz; M. Dierckx

    2011-01-01

    Innovative in-pile instrumentation is crucial for ad- vanced experimental programs in research reactors. In this field, we developed a specific acoustic sensor to improve the knowledge of fission gas release in Pressurized Water Reactor (PWR) fuel rods when irradiated in Material Testing Reactors (MTR). In order to perform experimental programs related to the study of the fission gas release kinetics,

  17. CHEMICAL PROCESSING TECHNOLOGY QUARTERLY PROGRESS REPORT, OCTOBER-DECEMBER 1961

    Microsoft Academic Search

    J. R. ed

    1962-01-01

    The ICPP processed Al fuel, prtncipally of the MTR-ETR type, durtng this ; quarter. Newly designed and installed processing equipment exhibited excellent ; operating performance. This included direct-air-pulsed extraction, stripping and ; scrub columns, and a cascade-controlled continuous evaporator in first cycle ; product concentration service. Aqueous zirconium fuel processing studies ; continued with the objective of adapting the hydrofluoric

  18. PLUTONIUM FUELS DEVELOPMENT, PLUTONIUM METALLURGY OPERATION QUARTERLY REPORT-JANUARY, FEBRUARY, MARCH 1958

    Microsoft Academic Search

    Wick

    1958-01-01

    The last two of four Zircaloy-clad capsules containing aluminum-; plutonium and aluminum-- silicon--plutonium were discharged from the MTR and are ; undergoing examination. These capsules withstood a fractional bunnout of ; plutonium atoms of 55 to 60% as determined by flux monitoring wires attached to ; the capsule holder. Additional capsules of these fuel alloys containing a higher ; concentration

  19. D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients

    Microsoft Academic Search

    Yan Zhang; Minmin Zhang; Tianhua Niu; Xin Xu; Guoying Zhu; Yong Huo; Changzhong Chen; Xiaobin Wang; Houxun Xing; Shaojie Peng; Aiqun Huang; Xiumei Hong; Xiping Xu

    2004-01-01

    Individual variation in drug response is considered to have multiple origins arising from interactions among susceptible genes and environmental factors. A total of 726 hypertensive patients who took benazepril 10 mg once a day for 15 days and their families from Huoqiu county of Anhui Province, China, were used to study the association between D919G polymorphism of methionine synthase (MTR) gene

  20. Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate the risk of neural tube defects in humans

    Microsoft Academic Search

    R. M. Guéant-Rodriguez; C. Rendeli; B. Namour; L. Venuti; A. Romano; G. Anello; P. Bosco; R. Debard; P. Gérard; M. Viola; E. Salvaggio; J. L. Guéant

    2003-01-01

    The pathogenic mechanism of neural tube defects may involve genetic polymorphisms and nutritional factors related to homocysteine metabolism. We evaluated the association of polymorphisms of three genes affecting vitamin B12-dependent remethylation of homocysteine, transcobalamin (TC), methioninesynthase (MTR) and MTRreductase (MTRR), combined or not with methylenetetrahydrofolatereductase (MTHFR), with the risk of having neural tube defect in 40 children with spina bifida

  1. Colorectal Cancer and the Methylenetetrahydrofolate Reductase 677C ! T and Methionine Synthase 2756A ! G Polymorphisms: A Study of 2,168 Case-Control Pairs from the JANUS Cohort

    Microsoft Academic Search

    Arve Ulvik; Stein Emil Vollset; Svein Hansen; Randi Gislefoss; Egil Jellum

    Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of colorectal cancer. We evaluated the relation be- tween the polymorphisms 677C ! T of the methylene- tetrahydrofolate reductase (MTHFR) and 2756A ! G of the methionine synthase (MTR) genes and risk of colorectal cancer. From the Norwegian JANUS cohort of 309,000 subjects,

  2. Homocysteine remethylation enzyme polymorphisms and increased risks for neural tube defects

    Microsoft Academic Search

    Huiping Zhu; Ned J Wicker; Gary M Shaw; Edward J Lammer; Kate Hendricks; Lucina Suarez; Mark Canfield; Richard H Finnell

    2003-01-01

    Folic acid supplementation can effectively reduce the risk of neural tube defects (NTDs); however, the mechanism underlying this beneficial effect remains unclear. Recent evidence suggests that certain folate pathway genes, as well as those related to homocysteine metabolism might be contributing to this effect. The purpose of this study is to investigate whether gene polymorphisms of methionine synthase (MTR) and

  3. ETRMTR MECHANICAL SERVICES BUILDING, TRA653, INTERIOR. CAMERA IS INSIDE MEN'S ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR-MTR MECHANICAL SERVICES BUILDING, TRA-653, INTERIOR. CAMERA IS INSIDE MEN'S LAVATORY AND SHOWER FACING SOUTHEAST. SHOWER AND TOILET STALLS ARE IN PLACE. ROUND COMMUNAL SINK AT LEFT. INL NEGATIVE NO. 57-3652. K. Mansfield, Photographer, 7/22/1957 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  4. ETRMTR MECHANICAL SERVICES BUILDING, TRA653. CAMERA FACING NORTHWEST AS BUILDING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR-MTR MECHANICAL SERVICES BUILDING, TRA-653. CAMERA FACING NORTHWEST AS BUILDING WAS NEARLY COMPLETE. INL NEGATIVE NO. 57-3653. K. Mansfield, Photographer, 7/22/1957 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  5. Mon. Not. R. Astron. Soc. 000, 000--000 (0000) Printed 9 November1998 (MN L A T E X style file v1.4) Circumstellar Kinematics and the Measurement of Stellar Mass for

    E-print Network

    Chandler, Claire

    to a radius of 1000 AU. The velocity field in these envelopes is well described by Keplerian rotation acc , is given by L acc = GM #3; â?? M(t)=R #3; : (1) Assuming a typical stellar mass of Class 0/I

  6. Mass spectrometric analysis of mycothiol levels in wild-type and mycothiol disulfide reductase mutant Mycobacterium smegmatis

    Microsoft Academic Search

    Cynthia M. Holsclaw; Wilson B. Muse; Kate S. Carroll; Julie A. Leary

    2011-01-01

    Mycothiol (MSH), the primary low-molecular weight thiol produced in mycobacteria, acts to protect the cell from oxidative stress and to maintain redox homeostasis, notably in the pathogenic Mycobacterium tuberculosis in the course of human infection. The mycothiol disulfide reductase (Mtr) enzyme reduces the oxidized form of mycothiol, mycothione (MSSM), back to MSH, however its role in bacterial viability is not

  7. TRITIUM LAB, TRA666. SECTIONS THROUGH LENGTH AND WIDTH OF BUILDING. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    TRITIUM LAB, TRA-666. SECTIONS THROUGH LENGTH AND WIDTH OF BUILDING. STRUCTURAL STEEL CEILING BEAM. CRANE BRIDGE WITH ENDLESS CHAIN. F.C. TORKELSON 842-MTR-666-A2, 12/1962. INL INDEX NO. 531-0666-00-851-150948, REV. 5. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. TRITIUM LAB, TRA666. SOUTH AND WEST ELEVATIONS. ROLLUP DOOR DETAILS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    TRITIUM LAB, TRA-666. SOUTH AND WEST ELEVATIONS. ROLLUP DOOR DETAILS (SOUTH ELEVATION). PERSONNEL DOOR ON WEST SIDE. F.C. TORKELSON 842-MTR-666-A-1, 10/1952. INL INDEX NO. 531-0666-00-851-150945, REV. 8. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  9. Network reconfiguration algorithm for automated distribution systems based on artificial intelligence approach

    Microsoft Academic Search

    Kyung-Hee Jung; Hoyong Kim; Yunseok Ko

    1993-01-01

    This study develops an expert system to solve the problem of the main transformer (MTr) or feeder overload and the feeder constraint violation in automated distribution systems, where each feeder is subject to the thermal overload and voltage drop limits. Then, the objective is to perform the network reconfiguration by switching the tie and sectionalizing switches so that the system

  10. PLUG STORAGE BUILDING, TRA611. STRUCTURAL DETAILS. FACE PLATE. FOURTEEN OPENINGS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    PLUG STORAGE BUILDING, TRA-611. STRUCTURAL DETAILS. FACE PLATE. FOURTEEN OPENINGS LABELED FOR PLUGS FROM SPECIFIC SIZE GROUPS IN THE MTR. BLAW-KNOX 3150-811-2, 1/1951. INL INDEX NO. 531-0611-00-098-100694, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  11. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2005-12-15

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR is now working with the company's Randall Gas Technology Group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group first found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produced about 1 MMscfd of gas containing 24% nitrogen. The membrane unit was built to bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid was built by ABB. NTE ordered the required compressor and MTR made the membrane modules for a December 2004 delivery. However, the gas supply was not steady enough for field testing, and MTR/ABB have now located other sites for field testing and commercial development.

  12. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2005-12-22

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR will be working with the company's Randall Gas Technology Group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group first found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produced about 1 MMscfd of gas containing 24% nitrogen. The membrane unit was built to bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid was built by ABB. NTE ordered the required compressor and MTR made the membrane modules for a December 2004 delivery. However, the gas supply was not steady enough for field testing, and MTR/ABB have now located other sites for field testing and commercial development.

  13. T2 relaxation time analysis in patients with multiple sclerosis: correlation with magnetization transfer ratio.

    PubMed

    Papanikolaou, Nickolas; Papadaki, Eufrosini; Karampekios, Spyros; Spilioti, Martha; Maris, Thomas; Prassopoulos, Panos; Gourtsoyiannis, Nicholas

    2004-01-01

    The aim of the current study was to perform T2 relaxation time measurements in multiple sclerosis (MS) patients and correlate them with magnetization transfer ratio (MTR) measurements, in order to investigate in more detail the various histopathological changes that occur in lesions and normal-appearing white matter (NAWM). A total number of 291 measurements of MTR and T2 relaxation times were performed in 13 MS patients and 10 age-matched healthy volunteers. Measurements concerned MS plaques (105), NAWM (80), and "dirty" white matter (DWM; 30), evenly divided between the MS patients, and normal white matter (NWM; 76) in the healthy volunteers. Biexponential T2 relaxation-time analysis was performed, and also possible linearity between MTR and mean T2 relaxation times was evaluated using linear regression analysis in all subgroups. Biexponential relaxation was more pronounced in "black-hole" lesions (16.6%) and homogeneous enhancing plaques (10%), whereas DWM, NAWM, and mildly hypointense lesions presented biexponential behavior with a lower frequency(6.6, 5, and 3.1%, respectively). Non-enhancing isointense lesions and normal white matter did not reveal any biexponential behavior. Linear regression analysis between monoexponential T2 relaxation time and MTR measurements demonstrated excellent correlation for DWM( r=-0.78, p<0.0001), very good correlation for black-hole lesions( r=-0.71, p=0.002), good correlation for isointense lesions( r=-0.60, p=0.005), moderate correlation for mildly hypointense lesions( r=-0.34, p=0.007), and non-significant correlation for homogeneous enhancing plaques, NAWM, and NWM. Biexponential T2 relaxation-time behavior is seen in only very few lesions (mainly on plaques with high degree of demyelination and axonal loss). A strong correlation between MTR and monoexponential T2 values was found in regions where either inflammation or demyelination predominates; however, when both pathological conditions coexist, this linear relationship is lost. PMID:14600774

  14. A multimodal MRI approach to identify and characterize microstructural brain changes in neuropsychiatric systemic lupus erythematosus

    PubMed Central

    Ercan, Ece; Ingo, Carson; Tritanon, Oranan; Magro-Checa, Cesar; Smith, Alex; Smith, Seth; Huizinga, Tom; van Buchem, Mark A.; Ronen, Itamar

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and results in neurological and psychiatric (NP) symptoms in up to 40% of the patients. To date, the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) poses a challenge due to the lack of neuroradiological gold standards. In this study, we aimed to better localize and characterize normal appearing white matter (NAWM) changes in NPSLE by combining data from two quantitative MRI techniques, diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI). 9 active NPSLE patients (37 ± 13 years, all females), 9 SLE patients without NP symptoms (44 ± 11 years, all females), and 14 healthy controls (HC) (40 ± 9 years, all females) were included in the study. MTI, DTI and fluid attenuated inversion recovery (FLAIR) images were collected from all subjects on a 3 T MRI scanner. Magnetization transfer ratio (MTR), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) maps and white matter lesion maps based on the FLAIR images were created for each subject. MTR and DTI data were then co-analyzed using tract-based spatial statistics and a cumulative lesion map to exclude lesions. Significantly lower MTR and FA and significantly higher AD, RD and MD were found in NPSLE compared to HC in NAWM regions. The differences in DTI measures and in MTR, however, were only moderately co-localized. Additionally, significant differences in DTI measures, but not in MTR, were found between NPSLE and SLE patients, suggesting that the underlying microstructural changes detected by MD are linked to the onset of NPSLE. The co-analysis of the anatomical distribution of MTI and DTI measures can potentially improve the diagnosis of NPSLE and contribute to the understanding of the underlying microstructural damage.

  15. Methionine recycling pathways and antimalarial drug design.

    PubMed Central

    Sufrin, J R; Meshnick, S R; Spiess, A J; Garofalo-Hannan, J; Pan, X Q; Bacchi, C J

    1995-01-01

    5'-Deoxy-5'-(methylthio)adenosine (MTA) is an S-adenosylmethionine metabolite that is generated as a by-product of polyamine biosynthesis. In mammalian cells, MTA undergoes a phosphorolytic cleavage catalyzed by MTA phosphorylase to produce adenine and 5-deoxy-5-(methylthio)ribose-1-phosphate (MTRP). Adenine is utilized in purine salvage pathways, and MTRP is subsequently recycled to methionine. Whereas some microorganisms metabolize MTA to MTRP via MTA phosphorylase, others metabolize MTA to MTRP in two steps via initial cleavage by MTA nucleosidase to adenine and 5-deoxy-5-(methylthio)ribose (MTR) followed by conversion of MTR to MTRP by MTR kinase. In order to assess the extent to which these pathways may be operative in Plasmodium falciparum, we have examined a series of 5'-alkyl-substituted analogs of MTA and the related MTR analogs and compared their abilities to inhibit in vitro growth of this malarial parasite. The MTR analogs 5-deoxy-5-(ethylthio)ribose and 5-deoxy-5-(hydroxyethylthio)ribose were inactive at concentrations up to 1 mM, and 5-deoxy-5-(monofluoroethylthio)ribose was weakly active (50% inhibitory concentration = 700 microM). In comparison, the MTA analogs, 5'-deoxy-5'-(ethylthio)adenosine,5'-deoxy-5'-(hydroxyethylthio)ade nosine (HETA), and 5'-deoxy-5'-(monofluoroethylthio)adenosine, had 50% inhibitory concentrations of 80, 46, and 61 microM, respectively. Extracts of P. falciparum were found to have substantial MTA phosphorylase activity. Coadministration of MTA with HETA partially protected the parasites against the growth-inhibitory effects of HETA. Results of this study indicate that P. falciparum has an active MTA phosphorylase that can be targeted by analogs of MTA. PMID:8585735

  16. Characterization of the periplasmic redox network that sustains the versatile anaerobic metabolism of Shewanella oneidensis MR-1

    PubMed Central

    Alves, Mónica N.; Neto, Sónia E.; Alves, Alexandra S.; Fonseca, Bruno M.; Carrêlo, Afonso; Pacheco, Isabel; Paquete, Catarina M.; Soares, Cláudio M.; Louro, Ricardo O.

    2015-01-01

    The versatile anaerobic metabolism of the Gram-negative bacterium Shewanella oneidensis MR-1 (SOMR-1) relies on a multitude of redox proteins found in its periplasm. Most are multiheme cytochromes that carry electrons to terminal reductases of insoluble electron acceptors located at the cell surface, or bona fide terminal reductases of soluble electron acceptors. In this study, the interaction network of several multiheme cytochromes was explored by a combination of NMR spectroscopy, activity assays followed by UV-visible spectroscopy and comparison of surface electrostatic potentials. From these data the small tetraheme cytochrome (STC) emerges as the main periplasmic redox shuttle in SOMR-1. It accepts electrons from CymA and distributes them to a number of terminal oxidoreductases involved in the respiration of various compounds. STC is also involved in the electron transfer pathway to reduce nitrite by interaction with the octaheme tetrathionate reductase (OTR), but not with cytochrome c nitrite reductase (ccNiR). In the main pathway leading the metal respiration STC pairs with flavocytochrome c (FccA), the other major periplasmic cytochrome, which provides redundancy in this important pathway. The data reveals that the two proteins compete for the binding site at the surface of MtrA, the decaheme cytochrome inserted on the periplasmic side of the MtrCAB–OmcA outer-membrane complex. However, this is not observed for the MtrA homologues. Indeed, neither STC nor FccA interact with MtrD, the best replacement for MtrA, and only STC is able to interact with the decaheme cytochrome DmsE of the outer-membrane complex DmsEFABGH. Overall, these results shown that STC plays a central role in the anaerobic respiratory metabolism of SOMR-1. Nonetheless, the trans-periplasmic electron transfer chain is functionally resilient as a consequence of redundancies that arise from the presence of alternative pathways that bypass/compete with STC.

  17. High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

    PubMed Central

    Mouawad, Charbel; Haddad, Katia; Hamoui, Samar; Azar, Albert; Fajloun, Ziad; Makdissy, Nehman

    2015-01-01

    Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI-1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles “Del” and “4G”. The frequencies of the Del and 4G alleles were found to be 0.98 and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively. Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-? and TNF-? contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations (Del/4G) are at high risk for the onset of CVDs. PMID:25973747

  18. High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin.

    PubMed

    AlBacha, Jeanne d'Arc; Khoury, Mira; Mouawad, Charbel; Haddad, Katia; Hamoui, Samar; Azar, Albert; Fajloun, Ziad; Makdissy, Nehman

    2015-01-01

    Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI-1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles "Del" and "4G". The frequencies of the Del and 4G alleles were found to be 0.98 and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively. Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-? and TNF-? contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations (Del/4G) are at high risk for the onset of CVDs. PMID:25973747

  19. Comparing Hydrologic Response Times Between a Forested and Mountaintop Mined Catchment

    NASA Astrophysics Data System (ADS)

    Miller, A. J.; Zegre, N.

    2012-12-01

    Mountaintop removal mining (MTR) represents the largest land cover/landuse change in the Central Appalachian region. By 2012, the U.S. EPA estimates that MTR will have impacted approximately 6.8% of the predominately forested Appalachian Coalfield region of West Virginia, Kentucky, Tennessee, and Virginia with nearly 4,000 miles of headwater streams buried under valley fills. In spite of the scale and extent of MTR, its hydrologic impacts are poorly understood. While MTR has a well-established pattern of downstream water quality degradation, its effect on the quantity and timing of catchment runoff is less clear. Several devastating floods in the region have been attributed to MTR, but there is little evidence to either confirm or refute this belief. Existing research has focused on statistical analysis of catchment outlet responses, but results from these studies only offer evidence of differences in hydrologic behavior, not process understanding of how the system is changing. This study begins to address that research gap by exploring differences in hydrologic response times, a fundamental hydraulic parameter that controls the conversion of rainfall to runoff. A simple rainfall-runoff model was used to quantify differences in response times for storm events in a mined and predominantly forested catchment. Results showed that the mountaintop mined catchment responded more quickly to storm events than the forested catchment. The mined catchment also showed more variability in response time than the forested catchment. These patterns repeated using multiple model structures. The more rapid response of the mined catchment is likely attributed to increased impervious surface, preferential flow paths within valley fills that rapidly route water to the stream, or rapid displacement of water stored in valley fills upon the onset of rain. However, further research using tools such as isotope tracers is needed to offer insight about the processes responsible for streamflow generation. Future research on the hydrologic impacts of MTR should focus on the process level to elucidate changes within catchment hydrology that can be used to explain changes at larger scales.

  20. Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

    PubMed Central

    2014-01-01

    Introduction Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We examine if these findings generalize to another population. Methods Texture patterns were recorded in digitalized pre-diagnosis (3.7 years) film mammograms of a nested case–control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls. The patterns were recognized in the same study using cross-validation to form resemblance scores associated with breast cancer. Texture patterns from S1 were examined in an independent nested case–control study within the Mayo Mammography Health Study cohort (S2) of 226 cases and 442 matched controls: mammograms on average 8.5 years prior to diagnosis, risk factor information and percent mammographic density (PD) estimated using Cumulus were available. MTR scores estimated from S1, S2 and S1?+?S2 (the latter two as cross-validations) were evaluated in S2. MTR scores were analyzed as both quartiles and continuously for association with breast cancer using odds ratios (OR) and adjusting for known risk factors including age, body mass index (BMI), and hormone usage. Results The mean ages of S1 and S2 were 58.0?±?5.7 years and 55.2?±?10.5 years, respectively. The MTR scores on S1 showed significant capability to discriminate cancers from controls (area under the operator characteristics curve (AUC)?=?0.63?±?0.02, P <0.001), which persisted after adjustment for PD. S2 showed an AUC of 0.63, 0.61, and 0.60 based on PD, MTR scores trained on S2, and MTR scores trained on S1, respectively. When adjusted for PD, MTR scores of S2 trained on S1 showed an association with breast cancer for the highest quartile alone: OR in quartiles of controls as reference; 1.04 (0.59 to 1.81); 0.95 (0.52 to 1.74); 1.84 (1.10 to 3.07) respectively. The combined continuous model with both PD and MTR scores based on S1 had an AUC of 0.66?±?0.03. Conclusions The local texture patterns associated with breast cancer risk in S1 were also an independent risk factor in S2. Additional textures identified in S2 did not significantly improve risk segregation. Hence, the textural patterns that indicated elevated risk persisted under differences in X-ray technology, population demographics, follow-up time and geography. PMID:24713478

  1. Genome sequence of a novel endornavirus from the phytopathogenic fungus Alternaria brassicicola.

    PubMed

    Shang, Hong-Hong; Zhong, Jie; Zhang, Ru-Jia; Chen, Chuan-Yuan; Gao, Bi-Da; Zhu, Hong-Jian

    2015-07-01

    In an effort to discover new mycoviruses from phytopathogenic fungi, a dsRNA molecule of 10,290 nt, resembling those associated with the viruses belonging to the family Endornaviridae, was isolated from Alternaria brassicicola, one of the causal agents of rapeseed black spot disease. Genome analysis revealed the presence of a single open reading frame coding for a polyprotein of 3400 aa containing conserved viral methyltransferase (MTR), viral RNA helicase 1 (Hel-1), and RNA-dependent RNA polymerase (RdRp) domains. In addition, a cysteine-rich region (CRR) with conserved CXCC motifs, shared among several endornaviruses, was also identified between the MTR and Hel-1 domains. Phylogenetic analysis based on the RdRp sequence strongly suggested that the virus infecting A. brassicicola should be considered a representative of a novel endornavirus species, and this virus was designated as Alternaria brassicicola endornavirus 1 (AbEV1). PMID:25951967

  2. Predictive Models in Multimodal Imaging

    Microsoft Academic Search

    K. Mouridsen; L. Østergaard

    The disease mechanism of multiple sclerosis (MS) causes progressive subcellular and cellular changes that may ultimately be\\u000a detected by magnetic resonance imaging (MRI): for instance, in normal-appearing white matter (NAWM) the effects of the disease\\u000a gradually alter the macromolecular and cellular compartmentalization of water, causing subtle changes in magnetization transfer\\u000a ratio (MTR) and diffusion-weighted imaging (DWI). Similarly, MS lesions are

  3. ADVANCED HEAT TRANSFER TEST FACILITY, TRA666A. ELEVATIONS. ROOF FRAMING PLAN. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ADVANCED HEAT TRANSFER TEST FACILITY, TRA-666A. ELEVATIONS. ROOF FRAMING PLAN. CONCRETE BLOCK SIDING. SLOPED ROOF. ROLL-UP DOOR. AIR INTAKE ENCLOSURE ON NORTH SIDE. F.C. TORKELSON 842-MTR-666-A5, 8/1966. INL INDEX NO. 531-0666-00-851-152258, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  4. LOW-PRESSURE MEMBRANE CONTACTORS FOR CARBON DIOXIDE CAPTURE

    SciTech Connect

    Baker, Richard; Kniep, Jay; Hao, Pingjiao; Chan, Chi Cheng; Nguyen, Vincent; Huang, Ivy; Amo, Karl; Freeman, Brice; Fulton, Don; Ly, Jennifer; Lipscomb, Glenn; Lou, Yuecun; Gogar, Ravikumar

    2014-09-30

    This final technical progress report describes work conducted by Membrane Technology and Research, Inc. (MTR) for the Department of Energy (DOE NETL) on development of low-pressure membrane contactors for carbon dioxide (CO2) capture from power plant flue gas (award number DE-FE0007553). The work was conducted from October 1, 2011 through September 30, 2014. The overall goal of this three-year project was to build and operate a prototype 500 m2 low-pressure sweep membrane module specifically designed to separate CO2 from coal-fired power plant flue gas. MTR was assisted in this project by a research group at the University of Toledo, which contributed to the computational fluid dynamics (CFD) analysis of module design and process simulation. This report details the work conducted to develop a new type of membrane contactor specifically designed for the high-gas-flow, low-pressure, countercurrent sweep operation required for affordable membrane-based CO2 capture at coal power plants. Work for this project included module development and testing, design and assembly of a large membrane module test unit at MTR, CFD comparative analysis of cross-flow, countercurrent, and novel partial-countercurrent sweep membrane module designs, CFD analysis of membrane spacers, design and fabrication of a 500 m2 membrane module skid for field tests, a detailed performance and cost analysis of the MTR CO2 capture process with low-pressure sweep modules, and a process design analysis of a membrane-hybrid separation process for CO2 removal from coal-fired flue gas. Key results for each major task are discussed in the report.

  5. Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma

    E-print Network

    California at Berkeley, University of

    (MTHFR 677C>T and 1298A>C); serine hy- droxymethyltransferase (SHMT1 C1420T); reduced folate carrier (RFC.10-0.82). Further, the MTR 2756AG/GG and the MTHFR 677TT geno- types were associated with increased risk for NHL (OR the cases and controls. The associations of DLCL and FL with TYMS 1494del6 and MTHFR 677TT genotypes

  6. Design trade-off report and risk DocNo.: E-TRC-MET-503-0008

    E-print Network

    Siebenmorgen, Ralf

    Design trade-off report and risk assessment DocNo.: E-TRC-MET-503-0008 Issue: 2.0 Date: 17: Frank Molster 17-11-2009 #12;Design trade-off report and risk Doc: E-TRC-MET-503-0008 Issue: 2.0 Date.10.2009 First Issue for MTR 2.0 12.11.2009 all Second issue for FR #12;Design trade-off report and risk Doc: E-TRC

  7. ETR COOLING TOWER. PUMP HOUSE (TRA645) IN SHADOW OF TOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ETR COOLING TOWER. PUMP HOUSE (TRA-645) IN SHADOW OF TOWER ON LEFT. AT LEFT OF VIEW, HIGH-BAY BUILDING IS ETR. ONE STORY ATTACHMENT IS ETR ELECTRICAL BUILDING. STACK AT RIGHT IS ETR STACK; MTR STACK IS TOWARD LEFT. CAMERA FACING NORTHEAST. INL NEGATIVE NO. 56-3799. Jack L. Anderson, 11/26/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. Reference Database for Bone Speed of Sound Measurement by a Novel Quantitative Multi-site Ultrasound Device

    Microsoft Academic Search

    M. Weiss; A. B. Ben-Shlomo; P. Hagag; M. Rapoport

    2000-01-01

    :   The nonuniform skeletal involvement in osteoporosis argues for multi-site evaluation. The Sunlight Omnisense (Sunlight Ultrasound\\u000a Technologies, Israel) is a multi-site device that measures speed of sound (SOS) at the appendicular skeleton. We report the\\u000a reference database for SOS at the radius (RAD), tibia (TIB), metatarsus (MTR) and phalanx (PLX). The database was obtained\\u000a from 1521 healthy Israeli women (age

  9. Colorectal cancer and the methylenetetrahydrofolate reductase 677C -> T and methionine synthase 2756A -> G polymorphisms: a study of 2,168 case-control pairs from the JANUS cohort.

    PubMed

    Ulvik, Arve; Vollset, Stein Emil; Hansen, Svein; Gislefoss, Randi; Jellum, Egil; Ueland, Per Magne

    2004-12-01

    Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of colorectal cancer. We evaluated the relation between the polymorphisms 677C --> T of the methylenetetrahydrofolate reductase (MTHFR) and 2756A --> G of the methionine synthase (MTR) genes and risk of colorectal cancer. From the Norwegian JANUS cohort of 309,000 subjects, 2,179 cases were identified and a similar number of controls were selected. The controls were matched for age, gender, time, and place of serum donation. Genotypes were obtained from 2,168 case-control pairs by real-time PCR of serum samples. Risk of colorectal cancer was estimated with conditional and unconditional logistic regression. Median age at diagnosis was 60 years and mean follow-up 13 years. The odds ratio for MTHFR TT versus CC was 0.73 [95% confidence interval (95% CI), 0.58-0.92] and for MTR GG versus AA was 0.65 (95% CI, 0.47-0.90). No interaction between the polymorphisms was found. Relative risk estimates were similar for men and women, and for young and old age at diagnosis. For the MTR GG genotype, risk reduction was observed at the two most distal sites (sigmoideum and rectum) only (P = 0.003). The folate marker, serum total homocysteine (tHcy), was measured in 1,837 subjects. Odds ratio for the upper versus the lower tertile of tHcy was 1.32 (95% CI, 1.04-1.68). No significant effect modification by tHcy levels was detected for either polymorphism. In summary, we found significantly reduced risk of colorectal cancer in subjects with the MTHFR 677 TT and MTR 2756 GG genotypes. No interaction between the polymorphisms, or of either polymorphism with tHcy, was detected. PMID:15598777

  10. IMPLICATIONS OF THE U-232 DECAY CHAIN ACTIVITY FOR THE PROCESSING OF IRRADIATED THORIUM AND RECOVERED U-233

    Microsoft Academic Search

    Feber

    1955-01-01

    The problems introduced by the associated beta and gamma radiation from ; the U²³² decay chain in U²³³ processing are of sufficient magnitude ; to introduce new considerations with respect to handling the U²³³ product, ; processing and recycling the irradiated thorium, and setting decontamination ; specifications. The U²³² from an MTR slug had a U²³² content which ; would

  11. Magnetization transfer ratio in the brain of preterm subjects: age-related changes during the first 2 years of life

    Microsoft Academic Search

    Vassilios Xydis; Loukas Astrakas; Anastasia Zikou; Kostandina Pantou; Styliani Andronikou; Maria I. Argyropoulou

    2006-01-01

    To study the progress of myelination in preterm-born subjects by measuring the MT ratio (MTR) from birth, up to 24 months of corrected age.One hundred twenty-five preterm subjects (64 males and 61 females of gestational age 33±2.4 weeks with chronologic and corrected age of 9.3±5.1 and 7.7±5.1 months, respectively) with normal brain MR using classic sequences were further evaluated for

  12. Adoption of ASME Code Section XI for ISI to Research Reactors

    Microsoft Academic Search

    Y. E. Tawfik; I. A. El-sesy; H. I. Shaban; M. M Ibrahim

    2002-01-01

    ETRR-2 (Second Egyptian thermal research reactor) is a multi-purpose, pool- type reactor with an open water surface and variable core arrangement. The core power is 22 MWth, cooled and moderated by light water and with beryllium reflectors. It contains plate- type fuel elements (MTR type, 19.7% enriched uranium) with aluminum clad. The ETRR-2 reactor consist of 57 systems and around

  13. The EMBO Journal Vol.18 No.19 pp.53995410, 1999 Functions of the exosome in rRNA, snoRNA and

    E-print Network

    Chanfreau, Guillaume

    of Escherichia coli RNase PH (Rrp41p, Rrp42p, Rrp43p, Rrp45p, Rrp46p and Mtr3p), a homologue of E.coli RNase R and RNase II (Rrp44p/Dis3p), and a homologue of E.coli RNase D (Rrp6p). Two other components, Rrp4p and Rrp to the components of the exosome, the yeast genome contains at le

  14. A Science Survice Feature---I..-D r . Charles ??.Broo;G,

    E-print Network

    ., t e l l s : HO!V TH3 SUW'S W?.T IS-?~ATVR%I - I 4 - To measure accu.ratc>ly thc heat of the sui- r e t i c a l surface prpoiidicular t o thc: sun's rays and mtr4d.a of thc! ntnosphcre ,vith tal, i n an arid, cloudless resion, preferably nea.r thc. equstor - conditions not cdculatcd t o

  15. FAST CHOPPER BUILDING, TRA665, INTERIOR. LOWER (DETECTOR) LEVEL. NOTE BRICKEDIN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FAST CHOPPER BUILDING, TRA-665, INTERIOR. LOWER (DETECTOR) LEVEL. NOTE BRICKED-IN WINDOW ON MTR SIDE. USED FOR STORAGE OF LEAD BRICKS AFTER EXPERIMENTAL NEUTRON INSTRUMENTS WERE REMOVED. SIGN SAYS "IN-PROCESS LEAD SOURCE STORAGE." INL NEGATIVE NO. HD-42-2. Mike Crane, Photographer, 3/2004 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  16. REACTOR SERVICE BUILDING, TRA635, CONTEXTUAL VIEW DURING CONSTRUCTION. CAMERA IS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    REACTOR SERVICE BUILDING, TRA-635, CONTEXTUAL VIEW DURING CONSTRUCTION. CAMERA IS ATOP MTR BUILDING AND LOOKING SOUTHERLY. FOUNDATION AND DRAINS ARE UNDER CONSTRUCTION. THE BUILDING WILL BUTT AGAINST CHARGING FACE OF PLUG STORAGE BUILDING. HOT CELL BUILDING, TRA-632, IS UNDER CONSTRUCTION AT TOP CENTER OF VIEW. INL NEGATIVE NO. 8518. Unknown Photographer, 8/25/1953 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  17. Assessment of technology gaps of tourist hotels in productive and service processes using meta-frontier DEA

    Microsoft Academic Search

    Chen-Hsien Lin; Yung-Ho Chiu; Chin-Wei Huang

    2011-01-01

    This study evaluated technology gaps of productive and service processes of Taiwanese non-chain, franchised, and company-owned hotels by using a meta-frontier model to calculate the meta-technology ratio (MTR) that represents the technical difference between types. We further develop an approach, extending from the meta-frontier model, to analyze the influence of technology gaps on inefficiency. The empirical results show that the

  18. Reactivity feedback coefficients of a material test research reactor fueled with high-density U 3Si 2 dispersion fuels

    Microsoft Academic Search

    Farhan Muhammad; Asad Majid

    2008-01-01

    The reactivity feedback coefficients of a material test research reactor fueled with high-density U3Si2 dispersion fuels were calculated. For this purpose, the low-density LEU fuel of an MTR was replaced with high-density U3Si2 LEU fuels currently being developed under the RERTR program. Calculations were carried out to find the fuel temperature reactivity coefficient, moderator temperature reactivity coefficient and moderator density

  19. Kinetic parameters of a material test research reactor fueled with high density U 3Si 2 dispersion fuels

    Microsoft Academic Search

    Farhan Muhammad; Asad Majid

    2009-01-01

    The kinetic parameters of a material test research reactor fueled with high density U3Si2 dispersion fuels were calculated. For this purpose, the low density LEU fuel of an MTR was replaced with high density U3Si2 LEU fuels currently being developed under the RERTR program. Calculations were carried out to find the core excess reactivity, prompt neutron generation time and effective

  20. Osmosensing and osmosignaling in Corynebacterium glutamicum

    Microsoft Academic Search

    Reinhard Krämer

    2009-01-01

    The Gram-positive soil bacterium Corynebacterium glutamicum is used in microbial biotechnology for the large-scale production of amino acids, e.g., l-glutamate and l-lysine. We have studied the response of this organism to hyperosmotic challenge at the level of both transcription and protein\\u000a activity. Two systems responding to hyperosmotic stress in C. glutamicum are reviewed here, the two component system MtrAB and

  1. Association between polymorphisms of folate-metabolizing enzymes and risk of prostate cancer

    Microsoft Academic Search

    C. Marchal; M. Redondo; A. Reyes-Engel; E. Perea-Milla; M. J. Gaitan; J. Machuca; F. Diaz; J. Caballero; J. Carnero

    2008-01-01

    Polymorphisms of the genes 5?-10?-methylenetetrahydrofolate reductase (MTHFR, 677CT and 1298AC), methionine synthase (MTR, 2756AC) and methionine synthase reductase (MTRR, 66AC) provoke variations in enzyme activity, which can lead to alterations in the metabolism of folates and in the synthesis of S-adenosyl-methionine (SAM), the most active methyl donor in the body. This could play an important role in carcinogenesis through the

  2. The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida

    Microsoft Academic Search

    Ivon J. M. van der Linden; Martin den Heijer; Lydia A. Afman; Henkjan Gellekink; Sita H. H. M. Vermeulen; Leo A. J. Kluijtmans; Henk J. Blom

    2006-01-01

    The methionine synthase reductase (MTRR) enzyme restores methionine synthase (MTR) enzyme activity and therefore plays an essential role in homocysteine remethylation. In some studies, the 66A>G polymorphism in the MTRR gene was associated with increased neural tube defect (NTD) risk. Using a case-control design, we studied the association between the MTRR 66A>G polymorphism and spina bifida risk in 121 mothers,

  3. Electron flow in multiheme bacterial cytochromes is a balancing act between heme electronic interaction and redox potentials

    PubMed Central

    Breuer, Marian; Rosso, Kevin M.; Blumberger, Jochen

    2014-01-01

    The naturally widespread process of electron transfer from metal reducing bacteria to extracellular solid metal oxides entails unique biomolecular machinery optimized for long-range electron transport. To perform this function efficiently, microorganisms have adapted multiheme c-type cytochromes to arrange heme cofactors into wires that cooperatively span the cellular envelope, transmitting electrons along distances greater than 100 Å. Implications and opportunities for bionanotechnological device design are self-evident. However, at the molecular level, how these proteins shuttle electrons along their heme wires, navigating intraprotein intersections and interprotein interfaces efficiently, remains a mystery thus far inaccessible to experiment. To shed light on this critical topic, we carried out extensive quantum mechanics/molecular mechanics simulations to calculate stepwise heme-to-heme electron transfer rates in the recently crystallized outer membrane deca-heme cytochrome MtrF. By solving a master equation for electron hopping, we estimate an intrinsic, maximum possible electron flux through solvated MtrF of 104–105 s?1, consistent with recently measured rates for the related multiheme protein complex MtrCAB. Intriguingly, our calculations show that the rapid electron transport through MtrF is the result of a clear correlation between heme redox potential and the strength of electronic coupling along the wire: thermodynamically uphill steps occur only between electronically well-connected stacked heme pairs. This observation suggests that the protein evolved to harbor low-potential hemes without slowing down electron flow. These findings are particularly profound in light of the apparently well-conserved staggered cross-heme wire structural motif in functionally related outer membrane proteins. PMID:24385579

  4. Sulfur-Mediated Electron Shuttling Sustains Microbial Long-Distance Extracellular Electron Transfer with the Aid of Metallic Iron Sulfides.

    PubMed

    Kondo, Katsuhito; Okamoto, Akihiro; Hashimoto, Kazuhito; Nakamura, Ryuhei

    2015-07-01

    In addition to serving as an energy source for microbial growth, iron sulfides are proposed to act as naturally occurring electrical wires that mediate long-distance extracellular electron transfer (EET) and bridge spatially discrete redox environments. These hypothetical EET reactions stand on the abilities of microbes to use the interfacial electrochemistry of metallic/semiconductive iron sulfides to maintain metabolisms; however, the mechanisms of these phenomena remain unexplored. To obtain insight into EET to iron sulfides, we monitored EET at the interface between Shewanella oneidensis MR-1 cells and biomineralized iron sulfides in an electrochemical cell. Respiratory current steeply increased with the concomitant formation of poorly crystalline mackinawite (FeS) minerals, indicating that S. oneidensis has the ability to exploit extracellularly formed metallic FeS for long-distance EET. Deletion of major proteins of the metal-reduction (Mtr) pathway (OmcA, MtrC, CymA, and PilD) caused only subtle effects on the EET efficiency, a finding that sharply contrasts the majority of studies that report that the Mtr pathway is indispensable for the reduction of metal oxides and electrodes. The gene expression analyses of polysulfide and thiosulfate reductase suggest the existence of a sulfur-mediated electron-shuttling mechanism by which HS(-) ions and water-soluble polysulfides (HSn(-), where n ? 2) generated in the periplasmic space deliver electrons from cellular metabolic processes to cell surface-associated FeS. The finding of this Mtr-independent pathway indicates that polysulfide reductases complement the function of outer-membrane cytochromes in EET reactions and, thus, significantly expand the number of microbial species potentially capable of long-distance EET in sulfur-rich anoxic environments. PMID:26070345

  5. Global Role for Polyadenylation-Assisted Nuclear RNA Degradation in Posttranscriptional Gene Silencing

    Microsoft Academic Search

    Shao-Win Wang; Abigail L. Stevenson; Stephen E. Kearsey; Stephen Watt; Jurg Bahler

    2008-01-01

    Fission yeast Cid14, a component of the TRAMP (Cid14\\/Trf4-Air1-Mtr4 polyadenylation) complex, polya- denylates nuclear RNA and stimulates degradation by the exosome for RNA quality control. Here, we analyze patterns of global gene expression in cells lacking the Cid14 or the Dis3\\/Rpr44 subunit of the nuclear exosome. We found that transcripts from many genes induced during meiosis, including key regulators, accumulated

  6. Mycothiol disulfide reductase: A continuous assay for slow time-dependent inhibitors

    Microsoft Academic Search

    Chris J. Hamilton; Richard M. J. Finlay; Matthew J. G. Stewart; Alexandra Bonner

    2009-01-01

    Mycothiol (MSH) is the principal low-molecular-weight thiol, unique to mycobacteria and other actinomycetes, that performs a role analogous to glutathione found in other organisms. MSH plays a key role in oxidative stress management and is oxidized to the dimeric mycothiol disulfide (MSSM) in the process. NADPH-dependent mycothiol disulfide reductase (Mtr) helps to maintain an intracellular reducing environment by reducing MSSM

  7. Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer

    Microsoft Academic Search

    ?ukasz Kruszyna; Margarita Lianeri; Ma?gorzata Rydzanicz; Marzena Gaj?cka; Krzysztof Szyfter; Pawe? P. Jagodzi?ski

    2010-01-01

    Carcinogenesis may result from abnormal methylation of cancer-related genes regulatory sequence. Though, the polymorphic variants\\u000a of genes encoding enzymes of folate and methionine metabolism may have an effect on DNA methylation. Using PCR-RFLPs, we examined\\u000a the polymorphism distribution of genes encoding methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR) in patients with larynx

  8. Imaging outcomes for trials of remyelination in multiple sclerosis

    PubMed Central

    Mallik, Shahrukh; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Miller, David H

    2014-01-01

    Trials of potential neuroreparative agents are becoming more important in the spectrum of multiple sclerosis research. Appropriate imaging outcomes are required that are feasible from a time and practicality point of view, as well as being sensitive and specific to myelin, while also being reproducible and clinically meaningful. Conventional MRI sequences have limited specificity for myelination. We evaluate the imaging modalities which are potentially more specific to myelin content in vivo, such as magnetisation transfer ratio (MTR), restricted proton fraction f (from quantitative magnetisation transfer measurements), myelin water fraction and diffusion tensor imaging (DTI) metrics, in addition to positron emission tomography (PET) imaging. Although most imaging applications to date have focused on the brain, we also consider measures with the potential to detect remyelination in the spinal cord and in the optic nerve. At present, MTR and DTI measures probably offer the most realistic and feasible outcome measures for such trials, especially in the brain. However, no one measure currently demonstrates sufficiently high sensitivity or specificity to myelin, or correlation with clinical features, and it should be useful to employ more than one outcome to maximise understanding and interpretation of findings with these sequences. PET may be less feasible for current and near-future trials, but is a promising technique because of its specificity. In the optic nerve, visual evoked potentials can indicate demyelination and should be correlated with an imaging outcome (such as optic nerve MTR), as well as clinical measures. PMID:24769473

  9. The Kinesio Taping Method for Myofascial Pain Control.

    PubMed

    Wu, Wei-Ting; Hong, Chang-Zern; Chou, Li-Wei

    2015-01-01

    Many people continue suffering from myofascial pain syndrome (MPS) defined as a regional pain syndrome characterized by muscle pain caused by myofascial trigger points (MTrPs) clinically. Muscle spasm and block of blood circulation can be noticed in the taut bands. In the MTrP region, nociceptors can be sensitized by the peripheral inflammatory factors and contracture of fascia can also be induced. Traditional treatments of MPS include stretching therapy, thermal treatment, electrical stimulation, massage, manipulation, trigger points injection, acupuncture, and medicine. However, the pain syndrome may not be relieved even under multiple therapies. Recently, the Kinesio Taping (KT) method is popularly used in sports injuries, postoperative complications, and various pain problems, but little research is focused on MPS with KT method. In this paper, we review the research studies on the application to KT in treating MPS and other related issues. It appears that the KT application can elevate the subcutaneous space and then increase the blood circulation and lymph fluid drainage to reduce the chemical factors around the MTrP region. Therefore, it is suggested that KT method can be used as a regular treatment or added to the previous treatment for myofascial pain. PMID:26185522

  10. Detection and quantification of major toxigenic Microcystis genotypes in Moo-Tan reservoir and associated water treatment plant.

    PubMed

    Yen, Hung-Kai; Lin, Tsair-Fuh; Tseng, I-Cheng

    2012-02-01

    Two molecular methods, denaturing gradient gel electrophoresis (DGGE) and quantitative real-time polymerase chain reaction (qPCR) with the Universal ProbeLibrary (UPL) probe, were developed and used for the characterization and quantification of several microcystin producers in Moo-Tan Reservoir (MTR), Taiwan and its associated water treatment plant (Shih-Men Water Treatment Plant, SMWTP). Internal transcribed spacer (ITS) sequence, a highly diversified region between the 16S rRNA and 23S rRNA genes, was used to further identify the isolated strains from MTR and also used in DGGE for the detection of the specific DNA fragments and biomarkers for 11 strains observed in MTR. These ITS-DGGE biomarkers were successfully applied to monitor the community changes of potential toxigenic Microcystis sp. over a period of five years. Two highly specific primers were combined with UPL probes to measure microcystins synthesis gene (mcyB) and phycocyanin intergenic spacer region (cpcB) concentrations in water samples. The copy concentrations of UPL-mcyB and UPL-cpcB correlated well with MC-RR concentrations/water temperature and Microcystis sp. cell numbers in the water samples, respectively. For SMWTP, toxin concentrations were low, but the DGGE bands clearly demonstrated the presence of potential microcystin producers in both water treatment plants and finished water samples. It was demonstrated that toxigenic Microcystis sp. may penetrate through the treatment processes and pose a potential risk to human health in the drinking water systems. PMID:22234317

  11. FIELD DEMONSTRATION OF A MEMBRANE PROCESS TO SEPERATE NITROGEN FROM NATURAL GAS

    SciTech Connect

    Kaaeid Lokhandwala

    2004-01-30

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global. MTR will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid is being built by ABB. NTE has ordered the required compressor and MTR is making the membrane modules. System fabrication was completed in January 2004 and the membrane inserts were loaded. Additional pressure testing and verification will be completed prior to shipment, which is expected in early February 2004.

  12. Individual voxel-based analysis of brain magnetization transfer maps shows great variability of gray matter injury in the first stage of multiple sclerosis.

    PubMed

    Jure, Lorena; Zaaraoui, Wafaa; Rousseau, Celia; Reuter, Françoise; Rico, Audrey; Malikova, Irina; Confort-Gouny, Sylviane; Cozzone, Patrick J; Pelletier, Jean; Ranjeva, Jean-Philippe; Audoin, Bertrand

    2010-08-01

    In multiple sclerosis (MS), it seems likely that the variability of the long-term disability might be partly due to the variability of the early gray matter (GM) injury. In the present study, we assessed the variability of GM injury in early MS, using a method designed to determine individual pathological GM patterns. Eighteen patients presenting with a clinically isolated syndrome and 24 healthy matched control subjects were included in this study. Patients were explored using a 1.5 Tesla MR scanner (Magnetom Vision Plus; Siemens). Brain MR protocol included magnetization transfer ratio imaging (MTR). Statistical mapping analyses were performed to compare each subject's GM MTR maps with those of the whole group of control subjects (SPM5). The statistical threshold was taken to be the maximum P value showing no significant cluster when any control individual was compared with the whole control population. GM abnormalities were observed in 83% of the patients, ranging in size from 0.3 to 125 cm(3). Among the patients with GM abnormalities, 87% had abnormalities located in the temporal cortex, 80% in the frontal cortex, 80% in the limbic cortex, 73% in the posterior fossa, 53% in the deep GM, 47% in the parietal cortex, and 47% in the occipital cortex. Individual statistical mapping of MTR data, which gives a quantitative assessment of individual GM lesions, demonstrates great variability of grey matter injury in the first stage of multiple sclerosis. PMID:20677272

  13. The Kinesio Taping Method for Myofascial Pain Control

    PubMed Central

    Wu, Wei-Ting; Hong, Chang-Zern; Chou, Li-Wei

    2015-01-01

    Many people continue suffering from myofascial pain syndrome (MPS) defined as a regional pain syndrome characterized by muscle pain caused by myofascial trigger points (MTrPs) clinically. Muscle spasm and block of blood circulation can be noticed in the taut bands. In the MTrP region, nociceptors can be sensitized by the peripheral inflammatory factors and contracture of fascia can also be induced. Traditional treatments of MPS include stretching therapy, thermal treatment, electrical stimulation, massage, manipulation, trigger points injection, acupuncture, and medicine. However, the pain syndrome may not be relieved even under multiple therapies. Recently, the Kinesio Taping (KT) method is popularly used in sports injuries, postoperative complications, and various pain problems, but little research is focused on MPS with KT method. In this paper, we review the research studies on the application to KT in treating MPS and other related issues. It appears that the KT application can elevate the subcutaneous space and then increase the blood circulation and lymph fluid drainage to reduce the chemical factors around the MTrP region. Therefore, it is suggested that KT method can be used as a regular treatment or added to the previous treatment for myofascial pain. PMID:26185522

  14. Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections

    PubMed Central

    Jerse, Ann E.; Wu, Hong; Packiam, Mathanraj; Vonck, Rachel A.; Begum, Afrin A.; Garvin, Lotisha E.

    2011-01-01

    Historically, animal modeling of gonorrhea has been hampered by the exclusive adaptation of Neisseria gonorrhoeae to humans. Genital tract infection can be established in female mice that are treated with 17?-estradiol, however, and many features of experimental murine infection mimic human infection. Here we review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, toll-like receptor 4, and T regulatory cells play a role in infection. We also discuss the strengths and limitations of the mouse system and the potential of transgenic mice to circumvent host restrictions. Additionally, we review studies with genetically defined mutants that demonstrated a role for sialyltransferase and the MtrC–MtrD–MtrE active efflux pump in evading innate defenses in vivo, but not for factors hypothesized to protect against the phagocytic respiratory burst and H2O2-producing lactobacilli. Studies using estradiol-treated mice have also revealed the existence of non-host-restricted iron sources in the female genital tract and the influence of hormonal factors on colonization kinetics and selection for opacity (Opa) protein expression. Recent work by others with estradiol-treated mice that are transgenic for human carcinoembryonic adhesion molecules (CEACAMs) supports a role for Opa proteins in enhancing cellular attachment and thus reduced shedding of N. gonorrhoeae. Finally we discuss the use of the mouse model in product testing and a recently developed gonorrhea chlamydia coinfection model. PMID:21747807

  15. Linking land use with pesticides in Dutch surface waters.

    PubMed

    Van't, Zelfde M T; Tamis, W L M; Vijver, M G; De Snoo, G R

    2012-01-01

    Compared with other European countries The Netherlands has a relatively high level of pesticide consumption, particularly in agriculture. Many of the compounds concerned end up in surface waters. Surface water quality is routinely monitored and numerous pesticides are found to be present in high concentrations, with various standards being regularly exceeded. Many standards-breaching pesticides exhibit regional patterns that can be traced back to land use. These patterns have been statistically analysed by correlating surface area per land use category with standards exceedance per pesticide, thereby identifying numerous significant correlations with respect to breaches of both the ecotoxicological standard (Maximum Tolerable Risk, MTR) and the drinking water standard. In the case of the MTR, greenhouse horticulture, floriculture and bulb-growing have the highest number as well as percentage of standard-breaching pesticides, despite these market segments being relatively small in terms of area cropped. Cereals, onions, vegetables, perennial border plants and pulses are also associated with many pesticides that exceed the drinking water standard. When a correction is made for cropped acreage, cereals and potatoes also prove to be a major contributor to monitoring sites where the MTR standard is exceeded. Over the period 1998-2006 the land-use categories with the most and highest percentage of standards-exceeding pesticides (greenhouse horticulture, bulb-growing and flower cultivation) showed an increase in the percentage of standards-exceeding compounds. PMID:23885409

  16. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2007-03-31

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR is working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group found a new site for the project at a North Texas Exploration (NTE) gas processing plant, which met with limited success. MTR then located an alternative testing opportunity and signed a contract with Towne Exploration in the third quarter of 2006, for a demonstration plant in Rio Vista, CA, to be run through May 2007. The demonstration for Towne has already resulted in the sale of two commercial skids to the company; the units will be delivered in mid-2007. Total sales of nitrogen/natural gas membrane separation units from the partnership with ABB are now approaching $4.0 million.

  17. FIELD DEMONSTRATION OF A MEMBRANE PROCESS TO SEPARATE NITROGEN FROM NATURAL GAS

    SciTech Connect

    Kaaeid Lokhandwala

    2004-09-01

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid is being built by ABB. NTE has ordered the required compressor and MTR is making the membrane modules. The membrane skid is scheduled to be completed by December 29. Our target is to have the unit installed and optimized by mid-January.

  18. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2006-09-30

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR is working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group found a new site for the project at a North Texas Exploration (NTE) gas processing plant, and we continue, but have as yet been unsuccessful in our attempts, to negotiate with Atmos Energy for a final test of the original project demonstration unit. In the meantime, MTR has located an alternative testing opportunity and signed a contract with Towne Exploration for a demonstration plant in Rio Vista, CA, to be run through May 2007. Several commercial sales have resulted from the partnership with ABB, and total sales of nitrogen/natural gas membrane separation units are now approaching $2.6 million.

  19. FIELD DEMONSTRATION OF A MEMBRANE PROCESS TO SEPARATE NITROGEN FROM NATURAL GAS

    SciTech Connect

    Andre Da Costa

    2003-11-24

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During precommissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid is being built by ABB. NTE has ordered the required compressor and MTR is making the membrane modules. The membrane skid is scheduled to be completed by December 29. The target is to have the unit installed and optimized by mid-January.

  20. FIELD DEMONSTRATION OF A MEMBRANE PROCESS TO SEPARATE NITROGEN FROM NATURAL GAS

    SciTech Connect

    Kaaeid Lokhandwala

    2005-02-28

    The original proposal described the construction and operation of a 1 MMscfd nitrogen removal/gas treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project field test at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid is being built by ABB. NTE has ordered the required compressor and MTR is making the membrane modules. The membrane skid is scheduled to be completed by December 29. Our target is to have the unit installed and optimized by mid-January.

  1. FIELD DEMONSTRATION OF A MEMBRANE PROCESS TO SEPARATE NITROGEN FROM NATURAL GAS

    SciTech Connect

    Kaaeid Lokhandwala

    2004-11-15

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid is being built by ABB. NTE has ordered the required compressor and MTR is making the membrane modules. The membrane skid is scheduled to be completed by December 29. Our target is to have the unit installed and optimized by mid-January.

  2. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2003-12-31

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global. MTR will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid is being built by ABB. NTE has ordered the required compressor and MTR is making the membrane modules. System fabrication was completed in January 2004 and the membrane inserts were loaded. Additional pressure testing and verification will be completed prior to shipment, which is expected in early February 2004.

  3. Molecular and cellular effects of vitamin B12 in brain, myocardium and liver through its role as co-factor of methionine synthase.

    PubMed

    Guéant, Jean-Louis; Caillerez-Fofou, Maatem; Battaglia-Hsu, Shyuefang; Alberto, Jean-Marc; Freund, Jean-Noel; Dulluc, Isabelle; Adjalla, Charles; Maury, Florence; Merle, Carole; Nicolas, Jean-Pierre; Namour, Fares; Daval, Jean-Luc

    2013-05-01

    Vitamin B12 (cobalamin, cbl) is a cofactor of methionine synthase (MTR) in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAM), which is involved in epigenomic regulatory mechanisms. We have established a neuronal cell model with stable expression of a transcobalamin-oleosin chimer and subsequent decreased cellular availability of vitamin B12, which produces reduced proliferation, increased apoptosis and accelerated differentiation through PP2A, NGF and TACE pathways. Anti-transcobalamin antibody or impaired transcobalamin receptor expression produce also impaired proliferation in other cells. Consistently, the transcription, protein expression and activity of MTR are increased in proliferating cells of skin and intestinal epitheliums, in rat intestine crypts and in proliferating CaCo2 cells, while MTR activity correlates with DNA methylation in rat intestine villi. Exposure to nitrous oxide in animal models identified impairment of MTR reaction as the most important metabolic cause of neurological manifestations of B12 deficiency. Early vitamin B12 and folate deprivation during gestation and lactation of a 'dam-progeny' rat model developed in our laboratory is associated with long-lasting disabilities of behavior and memory capacities, with persisting hallmarks related to increased apoptosis, impaired neurogenesis and altered plasticity. We found also an epigenomic deregulation of energy metabolism and fatty acids beta-oxidation in myocardium and liver, through imbalanced methylation/acetylation of PGC-1alpha and decreased expression of SIRT1. These nutrigenomic effects display similarities with the molecular mechanisms of fetal programming. Beside deficiency, B12 loading increases the expression of MTR through internal ribosome entry sites (IRES) and down-regulates MDR-1 gene expression. In conclusion, vitamin B12 influences cell proliferation, differentiation and apoptosis in brain. Vitamin B12 and folate combined deficiency impairs fatty acid oxidation and energy metabolism in liver and heart through epigenomic mechanisms related to imbalanced acetylation/methylation. Some but not all of these effects reflect the upstream role of vitamin B12 in SAM synthesis. PMID:23415654

  4. Identification and Characterization of MtoA: A Decaheme c-Type Cytochrome of the Neutrophilic Fe(II)-Oxidizing Bacterium Sideroxydans lithotrophicus ES-1.

    PubMed

    Liu, Juan; Wang, Zheming; Belchik, Sara M; Edwards, Marcus J; Liu, Chongxuan; Kennedy, David W; Merkley, Eric D; Lipton, Mary S; Butt, Julea N; Richardson, David J; Zachara, John M; Fredrickson, James K; Rosso, Kevin M; Shi, Liang

    2012-01-01

    The Gram-negative bacterium Sideroxydans lithotrophicus ES-1 (ES-1) grows on FeCO(3) or FeS at oxic-anoxic interfaces at circumneutral pH, and the ES-1-mediated Fe(II) oxidation occurs extracellularly. However, the molecular mechanisms underlying ES-1's ability to oxidize Fe(II) remain unknown. Survey of the ES-1 genome for candidate genes for microbial extracellular Fe(II) oxidation revealed that it contained a three-gene cluster encoding homologs of Shewanella oneidensis MR-1 (MR-1) MtrA, MtrB, and CymA that are involved in extracellular Fe(III) reduction. Homologs of MtrA and MtrB were also previously shown to be involved in extracellular Fe(II) oxidation by Rhodopseudomonas palustris TIE-1. To distinguish them from those found in MR-1, the identified homologs were named MtoAB and CymA(ES-1). Cloned mtoA partially complemented an MR-1 mutant without MtrA with regards to ferrihydrite reduction. Characterization of purified MtoA showed that it was a decaheme c-type cytochrome and oxidized soluble Fe(II). Oxidation of Fe(II) by MtoA was pH- and Fe(II)-complexing ligand-dependent. Under conditions tested, MtoA oxidized Fe(II) from pH 7 to pH 9 with the optimal rate at pH 9. MtoA oxidized Fe(II) complexed with different ligands at different rates. The reaction rates followed the order Fe(II)Cl(2)?>? Fe(II)-citrate?>?Fe(II)-NTA?>?Fe(II)-EDTA with the second-order rate constants ranging from 6.3?×?10(-3)??M(-1)?s(-1) for oxidation of Fe(II)Cl(2) to 1.0?×?10(-3)??M(-1)?s(-1) for oxidation of Fe(II)-EDTA. Thermodynamic modeling showed that redox reaction rates for the different Fe(II)-complexes correlated with their respective estimated reaction-free energies. Collectively, these results demonstrate that MtoA is a functional Fe(II)-oxidizing protein that, by working in concert with MtoB and CymA(ES-1), may oxidize Fe(II) at the bacterial surface and transfer released electrons across the bacterial cell envelope to the quinone pool in the inner membrane during extracellular Fe(II) oxidation by ES-1. PMID:22347878

  5. Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting

    PubMed Central

    Colombo, Giorgio L; Castagna, Antonella; Di Matteo, Sergio; Galli, Laura; Bruno, Giacomo; Poli, Andrea; Salpietro, Stefania; Carbone, Alessia; Lazzarin, Adriano

    2014-01-01

    Objective In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. Methods The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher’s exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. Results A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/?L, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/?L, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71–€33,570.00) and €14,277.00 (range: €5,908.89–€82,310.30) among MTR patients. At multivariate analysis, after adjustment for age, sex, antibody-hepatitis C virus status, HIV risk factors, baseline CD4+, and HIV-RNA, the cost analysis was significantly lower among patients starting an STR treatment than those starting an MTR (adjusted mean: €12,096.00 vs €16,106.00, P=0.0001). Conclusion STR was associated with a lower annual cost per patient than MTR, thus can be considered a cost-saving strategy in the treatment of HIV patients. This analysis is an important tool for policy makers and health care professionals to make short- and long-term cost projections and thus assess the impact of these on available budgets. PMID:24379676

  6. PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION

    SciTech Connect

    J.G. Wijmans; J.O. Stull

    2001-11-07

    The goal of this project was to develop chemical protective clothing for use by DOE decontamination and decommissioning workers that is sufficiently water vapor permeable to keep the workers cool, thereby enhancing their productivity. This report describes the results of Phase II of a two-phase project to complete development of the novel permselective material and to test protective clothing made from the fabric. In Phase I a novel material incorporating a nonporous hydrophilic polyvinylacohol (PVA) layer, which is water vapor permeable but relatively impermeable to organic vapors, was developed. The results of the Phase I tests showed that the chemical resistance of the MTR material is comparable to that of Saranex/Tyvek materials, and that the comfort properties are closer to those of Tyvek (as measured in terms of CLO and permeability). Chemical resistance was measured using permeation tests against liquid dichloromethane. Comfort properties were ascertained by measuring the water vapor transmission of the material and by sweating manikin tests on whole protective suits. In addition, a cost/benefit analysis demonstrated that use of MTR's material technology could result in significant improvements in work productivity and cost savings if protective clothing items made from the new material were used more than once. In Phase II, MTR undertook a program to optimize the performance and production engineering for the new material technology. A partnership was formed with Kimberly-Clark Corporation to assist with a detailed evaluation of the MTR technology, and MTR used the services of Mr. Jeff Stull, President of the consulting firm International Personnel Protection, Inc., who conducted a detailed economic and application analysis for the developed fabric. The protective fabric manufacturing steps were simplified significantly, resulting in a 30% reduction in manufacturing costs and eliminating the necessity for capital investment in production equipment. Protective suits were prepared in collaboration with Kimberly-Clark Corporation and heat stress testing with human test subjects was carried out by the International Union of Operating Engineers (IUOE). The tests confirmed that the MTR protective fabric is significantly more comfortable than non-breathable materials. A cost analysis was developed from the properties of the optimized protective fabric and the results of the of the IUOE field study to determine the potential for the MTR material technology within the chemical protective clothing market. A detailed assessment of the specific chemical protective clothing applications for which the material can be used and its competitiveness with existing material technology, based both on expected performance and material/end item costs, was prepared. Three specific market opportunities identified for the novel protective fabric are: (1) liquid splash protective clothing for hazardous waste site operations, (2) liquid splash protective clothing for emergency response, and (3) Class 3 NFPA 1994-compliant protective clothing for civilian use during chemical terrorism incidents.

  7. Multi-Parametric Spinal Cord MRI as Potential Progression Marker in Amyotrophic Lateral Sclerosis

    PubMed Central

    El Mendili, Mohamed-Mounir; Cohen-Adad, Julien; Pelegrini-Issac, Mélanie; Rossignol, Serge; Morizot-Koutlidis, Régine; Marchand-Pauvert, Véronique; Iglesias, Caroline; Sangari, Sina; Katz, Rose; Lehericy, Stéphane; Benali, Habib; Pradat, Pierre-François

    2014-01-01

    Objective To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. Materials and Methods After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (??, ?//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. Results At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change. Conclusion Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs. PMID:24755826

  8. White matter hyperintensities and normal-appearing white matter integrity in the aging brain

    PubMed Central

    Maniega, Susana Muñoz; Valdés Hernández, Maria C.; Clayden, Jonathan D.; Royle, Natalie A.; Murray, Catherine; Morris, Zoe; Aribisala, Benjamin S.; Gow, Alan J.; Starr, John M.; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.

    2015-01-01

    White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10?9 m2s?1 (area under curve, 0.982; 95% CI, 0.975–0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. PMID:25457555

  9. Melatonin-mediated inhibition of Purkinje neuron P-type Ca²? channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3-kinase-dependent protein kinase C delta pathway.

    PubMed

    Zhang, Yuan; Li, Hua; Pu, Yicheng; Gong, Shan; Liu, Chunfeng; Jiang, Xinghong; Tao, Jin

    2015-04-01

    Although melatonin receptors are widely expressed in the mammalian central nervous system and peripheral tissues, there are limited data regarding the functions of melatonin in cerebellar Purkinje cells. Here, we identified a novel functional role of melatonin in modulating P-type Ca(2+) channels and action-potential firing in rat Purkinje neurons. Melatonin at 0.1 ?m reversibly decreased peak currents (I(Ba)) by 32.9%. This effect was melatonin receptor 1 (MT(R1)) dependent and was associated with a hyperpolarizing shift in the voltage dependence of inactivation. Pertussis toxin pretreatment, intracellular application of QEHA peptide, and a selective antibody raised against the G? subunit prevented the inhibitory effects of melatonin. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitors abolished the melatonin-induced decrease in I(Ba). Surprisingly, melatonin responses were not regulated by Akt, a common downstream target of PI3K. Melatonin treatment significantly increased protein kinase C (PKC) activity 2.1-fold. Antagonists of PKC, but not of protein kinase A, abolished the melatonin-induced decrease in I(Ba). Melatonin application increased the membrane abundance of PKC?, and PKC? inhibition (either pharmacologically or genetically) abolished the melatonin-induced IBa response. Functionally, melatonin increased spontaneous action-potential firing by 53.0%; knockdown of MT(R1) and blockade of P-type channels abolished this effect. Thus, our results suggest that melatonin inhibits P-type channels through MT(R1) activation, which is coupled sequentially to the ?? subunits of G(i/o)-protein and to downstream PI3K-dependent PKC? signaling. This likely contributes to its physiological functions, including spontaneous firing of cerebellar Purkinje neurons. PMID:25707622

  10. Polymorphism in one-carbon metabolism pathway affects survival of gastric cancer patients: Large and comprehensive study.

    PubMed

    Zhao, Tingting; Gu, Dongying; Xu, Zhi; Huo, Xinying; Shen, Lili; Wang, Chun; Tang, Yongfei; Wu, Peng; He, Jason; Gong, Weida; He, Ming-Liang; Chen, Jinfei

    2015-04-20

    Although it has been shown that polymorphisms in one-carbon metabolism (OCM) pathway are associated with gastric cancer (GC), their interactions and contributions for patients' survival are elusive. In this study, we investigated the effects of polymorphisms and their interactions on the survival of GC patients, including genes of Methylenetetrahydrofolate reductase (MTHFR 677C > T, 1298A > C), Methionine synthase reductase (MTRR 66A > G), Methionine synthase (MTR 2756A > G), and Thymidylate synthase (TS 3'-UTR ins6 > del6, 5'-UTR 2R > 3R). We recruited 919 GC patients from 1998 to 2006. The Kaplan-Meier plots, Cox regression analyses and the log-rank tests were carried out in this study. MTHFR 1298CC genotype showed protective effect (HR = 0.444, 95% CI = 0.210-0.940). MTRR 66 GA + GG genotypes decreased the risk of death (HR = 0.793, 95% CI = 0.651-0.967) in general, and in subgroups with more pronounced diffuse type, greater depth of invasion (T2/T3/T4), higher level lymph node metastasis (N1/N2/N3), advanced TNM stages (II/III level) and 5-Fu treatment. However, the improved survival disappeared when GC patients simultaneously had MTR 2756 GA + GG genotypes (HR = 1.063, 95% CI = 0.750-1.507). Although MTRR 66GA genotype was not associated with the survival of GC patients, patients with simultaneous MTRR 66GA and MTR 2756AA genotypes exhibited significant risk reduction of death (HR = 0.773, 95% CI = 0.609-0.981). MTHFR 1298 CA + CC combined with TS 5-UTR 2R3R + 3R3R genotypes (HR = 0.536, 95% CI = 0.315-0.913) also increased patient survival rates. Our results suggest that the MTRR 66A > G and MTHFR 1298A > C polymorphisms may be useful prognostic biomarkers for GC patients. PMID:25840420

  11. Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

    SciTech Connect

    Wang Silun [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tryggestad, Erik [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Zhou Tingting [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Armour, Michael [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Wen Zhibo [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Department of Radiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong (China); Fu Dexue [Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Ford, Eric [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Zijl, Peter C.M. van [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (United States); Zhou Jinyuan, E-mail: jzhou@mri.jhu.edu [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland (United States)

    2012-07-01

    Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T{sub 1}, T{sub 2}, apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Methods and Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 Multiplication-Sign 10 mm{sup 2}) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at {approx}25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. Results: ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T{sub 1}, T{sub 2}, MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T{sub 1}, T{sub 2}, MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. Conclusion: ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.

  12. Manganese sulfide formation via concomitant microbial manganese oxide and thiosulfate reduction.

    SciTech Connect

    Lee, Ji-Hoon; Kennedy, David W.; Dohnalkova, Alice; Moore, Dean A.; Nachimuthu, Ponnusamy; Reed, Samantha B.; Fredrickson, Jim K.

    2011-12-27

    The dissimilatory metal-reducing bacterium, Shewanella oneidensis MR-1 produced ?-MnS (rambergite) nanoparticles under the concurrent reduction of synthetic MnO2 and thiosulfate coupled to H2 oxidation. Using two MR-1 mutants defective in outer membrane c-type cytochromes (?mtrC/?omcA and ?mtrC/?omcA/?mtrF) to eliminate the direct reduction pathway for solid electron acceptors, it was determined that respiratory reduction of MnO2 was dominant relative to chemical reduction by biogenic sulfide generated from bacterial thiosulfate reduction. Although bicarbonate was excluded from the medium, incubations of MR-1 using lactate as the sole electron donor produced MnCO3 (rhodochrosite) as well as MnS in nearly equivalent amounts as estimated by micro X-ray diffraction (micro-XRD) analysis. It was concluded that carbonate released from lactate metabolism promoted MnCO3 formation and that Mn(II) mineralogy was strongly affected by carbonate ions even in the presence of abundant sulfide and weakly alkaline conditions that favor the precipitation of MnS. Formation of the biogenic MnS, as determined by a combination of micro-XRD, transmission electron microscopy, energy dispersive X-ray spectroscopy, and selected area electron diffraction analyses was consistent with equilibrium speciation modeling predictions. Although biogenic MnS likely only forms and is stable over a relatively narrow range of conditions, it may be a significant sink for Mn in anoxic marine basins and terrestrial subsurface sediments where Mn and sulfur compounds are undergoing concurrent reduction.

  13. Multi-modal MRI of mild traumatic brain injury

    PubMed Central

    Narayana, Ponnada A.; Yu, Xintian; Hasan, Khader M.; Wilde, Elisabeth A.; Levin, Harvey S.; Hunter, Jill V.; Miller, Emmy R.; Patel, Vipul Kumar S.; Robertson, Claudia S.; McCarthy, James J.

    2014-01-01

    Multi-modal magnetic resonance imaging (MRI) that included high resolution structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed in mild traumatic brain injury (mTBI) patients with negative computed tomographic scans and in an orthopedic-injured (OI) group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h) and at follow-up (~90 days). DTI data was analyzed using tract based spatial statistics (TBSS). Global and regional atrophies were calculated using tensor-based morphometry (TBM). MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD) was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM) regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE) correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI. PMID:25610770

  14. Propagating waves transverse to the magnetic field in a solar prominence

    NASA Astrophysics Data System (ADS)

    Kucera, Therese; Schmieder, Brigitte; Knizhnik, Kalman; Lopez-Ariste, Arturo; Luna, Manuel; Toot, David

    2014-01-01

    We have observed a quiescent prominence with the Hinode Solar Optical Telescope (SOT) (Ca II and H? lines), Sacramento Peak Dunn Solar Telescope using the Universal Birefringent Filter (DST/UBF, in H?, H? and Sodium-D lines), THEMIS (Télescope Héliographique pour l Etude du Magnétisme et des Instabilités Solaires/MTR (Multi Raies) spectromagnetograph (He D3), and the Solar Dynamics Observatory Atmospheric Imaging Assembly (SDO/AIA) in EUV over a 4 hour period on 2012 October 10. The small fields of view of the SOT, DST, and MTR are centered on a large prominence footpoint extending towards the surface. This feature appears in the larger field of view of the AIA/304 Å filtergram as a large, quasi-vertical pillar with loops on each side. The THEMIS/MTR data indicate that the magnetic field in the pillar is essentially horizontal and the observations in the optical domain show a large number of horizontally aligned features in the pillar. The data are consistent with a model of cool prominence plasma trapped in the dips of horizontal field lines. The SOT and DST data show what appear to be moving wave pulses. These pulses, which include a Doppler signature, move vertically, perpendicular to the field direction, along quasi-vertical columns of horizontal threads in the pillar. The pulses have a velocity of propagation of about 10 km/s, a wavelength about 2000 km in the plane of the sky, and a period about 280 sec. We interpret these waves in terms of fast magnetosonic waves.

  15. Aqueous Alteration at a Delta in Eastern Libya Montes

    NASA Astrophysics Data System (ADS)

    Bishop, Janice L.; Tirsch, Daniela; Tornabene, Livio L.; Seelos, Frank P.; Erkeling, Gino; Hiesinger, Harald; Jaumann, Ralf

    2015-04-01

    Libya Montes hosts ancient Noachian basalt altered by hydrothermal action from the Isidis impact, olivine- and pyroxene-bearing lavas from the Syrtis volcanic outflows, multiple craters that have excavated these geologic units, and numerous Hesperian-Amazonian-aged fluvial features that carved channels across the surface and may have transported material downward towards Isidis. Mineralogical analyses of a delta region in Eastern Libya Montes using recently available MTR3 CRISM images have revealed the presence of carbonate in additional to Al-, Fe-, and Mg-bearing phyllosilicates. We are investigating the origins of these aqueous components through stratigraphical and morphological analyses. We hypothesize that the carbonate and Fe/Mg-phyllosilicates are alteration products of the ancient basalt and that the Al-smectite formed as a result of the delta and more recent lacustrine or fluvial processes. The Al-smectite spectral features are most consistent with beidellite, which forms at elevated temperatures compared to montmorillonite. We seek to determine if the beidellite likely formed in warm delta waters or if it may have formed via burial diagenesis and was then excavated by the delta. Newly developed CRISM parameters are being utilized for analysis of the MTR3 versions of CRISM images FRT0000B0CB and FRT0001E2F2 in the fan and delta region of eastern Libya Montes. The MTR3 images feature joined short-wavelength and long-wavelength images and improved spectral signals through new atmospheric separation and noise removal techniques. This enables better detection of spectral signatures from small outcrops of aqueous components. We have placed these new CRISM mineral maps over HRSC stereo images to evaluate the stratigraphy of the aqueous components in relation to the ancient basalt and Syrtis lavas as in previous analyses of the central Libya Montes region. Coordinated CRISM-HiRISE views are expected to provide insights into the morphologies of the aqueous units as in recent studies of other sites at Libya Montes.

  16. Molecular Assay for Detection of Genetic Markers Associated with Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae.

    PubMed

    Peterson, S W; Martin, I; Demczuk, W; Bharat, A; Hoang, L; Wylie, J; Allen, V; Lefebvre, B; Tyrrell, G; Horsman, G; Haldane, D; Garceau, R; Wong, T; Mulvey, M R

    2015-07-01

    The incidence of antimicrobial-resistant Neisseria gonorrhoeae continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in ponA, mtrR, penA, porB, and one N. gonorrhoeae-specific marker (porA). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24 N. gonorrhoeae-negative NAAT specimens, and 34 N. gonorrhoeae-positive NAAT specimens. Twenty-four of the N. gonorrhoeae-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252 N. gonorrhoeae strains, the agreement between the DNA sequence and real-time PCR was 100% for porA, ponA, and penA, 99.6% for mtrR, and 95.2% for porB. The presence of ?2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for porB, 95.8% for ponA and mtrR, and 91.7% for penA. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in N. gonorrhoeae. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results. PMID:25878350

  17. Effect of cropland management and slope position on soil organic carbon pool at the North Appalachian Experimental Watersheds

    SciTech Connect

    Hao, Yueli; Lal, Rattan; Owens, Lloyd; Izaurralde, R Cesar C.; Post, W M.; Hothem, Daniel

    2002-12-01

    Soil organic matter is strongly related to soil type, landscape morphology, and soil and crop management practices. Therefore, long-term (15-36-years) effects of six cropland management systems on soil organic carbon (SOC) pool in 0-30 cm depth were studied for the period of 1939-1999 at the North Appalachian Experimental Watersheds (<3 ha, Dystric Cambisol, Haplic Luvisol, and Haplic Alisol) near Coshocton, OH, USA. Six management treatments were: (1) no tillage continuous corn with NPK (NC); (2) no tillage continuous corn with NPK and manure (NTC-M); (3) no tillage corn?soybean rotation (NTR); (4) chisel tillage corn?soybean rotation (CTR); (5) moldboard tillage with corn?wheat?meadow?meadow rotation with improved practices (MTR-I); (6) moldboard tillage with corn?wheat?meadow?meadow rotation with prevalent practices (MTR-P). The SOC pool ranged from 24.5Mgha?1 in the 32-years moldboard tillage corn (Zea mays L.)?wheat (Triticum aestivum L.)?meadow?meadow rotation with straight row farming and annual application of fertilizer (N:P:K = 5:9:17) of 56?112 kg ha?1 and cattle (Bos taurus) manure of 9Mg ha?1 as the prevalent system (MTR-P) to 65.5Mgha?1 in the 36-years no tillage continuous corn with contour row farming and annual application of 170?225 kgNha?1 and appropriate amounts of P and K, and 6?11Mgha?1 of cattle manure as the improved system (NTC-M).

  18. Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the fukuoka colorectal cancer study.

    PubMed

    Morita, Makiko; Yin, Guang; Yoshimitsu, Shin-ichiro; Ohnaka, Keizo; Toyomura, Kengo; Kono, Suminori; Ueki, Takashi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Maekawa, Takafumi; Yasunami, Yohichi; Takenaka, Kenji; Ichimiya, Hitoshi; Terasaka, Reiji

    2013-01-01

    One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity. PMID:24377513

  19. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2007-03-31

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR is working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group found a new site for the project at a North Texas Exploration (NTE) gas processing plant, which met with limited success. However, a small test system was installed at a Twin Bottoms Energy well in Kentucky. This unit operated successfully for six months, and demonstrated the technology's reliability on a small scale. MTR then located an alternative test site with much larger gas flow rates and signed a contract with Towne Exploration in the third quarter of 2006, for a demonstration plant in Rio Vista, California, to be run through May 2007. The demonstration for Towne has already resulted in the sale of two commercial skids to the company; both units will be delivered by the end of 2007. Total sales of nitrogen/natural gas membrane separation units from the partnership with ABB are now approaching $4.0 million.

  20. Abbreviated sampling and analysis plan for planning decontamination and decommissioning at Test Reactor Area (TRA) facilities

    SciTech Connect

    NONE

    1994-10-01

    The objective is to sample and analyze for the presence of gamma emitting isotopes and hazardous constituents within certain areas of the Test Reactor Area (TRA), prior to D and D activities. The TRA is composed of three major reactor facilities and three smaller reactors built in support of programs studying the performance of reactor materials and components under high neutron flux conditions. The Materials Testing Reactor (MTR) and Engineering Test Reactor (ETR) facilities are currently pending D/D. Work consists of pre-D and D sampling of designated TRA (primarily ETR) process areas. This report addresses only a limited subset of the samples which will eventually be required to characterize MTR and ETR and plan their D and D. Sampling which is addressed in this document is intended to support planned D and D work which is funded at the present time. Biased samples, based on process knowledge and plant configuration, are to be performed. The multiple process areas which may be potentially sampled will be initially characterized by obtaining data for upstream source areas which, based on facility configuration, would affect downstream and as yet unsampled, process areas. Sampling and analysis will be conducted to determine the level of gamma emitting isotopes and hazardous constituents present in designated areas within buildings TRA-612, 642, 643, 644, 645, 647, 648, 663; and in the soils surrounding Facility TRA-611. These data will be used to plan the D and D and help determine disposition of material by D and D personnel. Both MTR and ETR facilities will eventually be decommissioned by total dismantlement so that the area can be restored to its original condition.

  1. A multicenter phase I study of pazopanib in combination with paclitaxel in first-line treatment of patients with advanced solid tumors.

    PubMed

    Kendra, Kari L; Plummer, Ruth; Salgia, Ravi; O'Brien, Mary E R; Paul, Elaine M; Suttle, A Benjamin; Compton, Natalie; Xu, Chun-Fang; Ottesen, Lone H; Villalona-Calero, Miguel A

    2015-02-01

    This study was designed to evaluate the safety, pharmacokinetics, and clinical activity of pazopanib combined with paclitaxel to determine the recommended phase II dose in the first-line setting in patients with advanced solid tumors. Patients were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated regimen (MTR) of once daily pazopanib plus paclitaxel administered every 3 weeks at four dose levels (DL1-4). Safety, pharmacokinetics, pharmacogenetics, and disease assessments were performed. Twenty-eight patients received treatment. One patient at DL1 had dose-limiting toxicity (DLT) of elevated hepatic enzymes. After pazopanib discontinuation, liver enzyme concentrations remained high until a concurrent medication, simvastatin, was discontinued. This patient had the defective CYP2C8*3*3 genotype. At DL2, 1 patient had DLT of elevated hepatic enzymes with rash and 1 patient had DLT of rash. The MTR was paclitaxel 150 mg/m(2) plus pazopanib 800 mg. The most common toxicities were alopecia, fatigue, hypertension, nausea, diarrhea, dysgeusia, neutropenia, myalgia, hair color changes, and peripheral neuropathy. Coadministration of pazopanib and paclitaxel resulted in a 38% increase in systemic exposure to paclitaxel, relative to administration of paclitaxel alone, at the MTR. Of the 28 patients treated with the combination, 10 achieved a partial response and 10 achieved stable disease of ?12 weeks. Pazopanib 800 mg daily plus paclitaxel 150 mg/m(2) every 3 weeks was the recommended phase II dose, with a manageable safety profile, and with clinical activity in both melanoma and non-small cell lung cancer that suggest further evaluation of this combination is warranted. PMID:25504632

  2. Polymorphism in one-carbon metabolism pathway affects survival of gastric cancer patients: Large and comprehensive study

    PubMed Central

    Huo, Xinying; Shen, Lili; Wang, Chun; Tang, Yongfei; Wu, Peng; He, Jason; Gong, Weida; He, Ming-Liang; Chen, Jinfei

    2015-01-01

    Although it has been shown that polymorphisms in one-carbon metabolism (OCM) pathway are associated with gastric cancer (GC), their interactions and contributions for patients’ survival are elusive. In this study, we investigated the effects of polymorphisms and their interactions on the survival of GC patients, including genes of Methylenetetrahydrofolate reductase (MTHFR 677C > T, 1298A > C), Methionine synthase reductase (MTRR 66A > G), Methionine synthase (MTR 2756A > G), and Thymidylate synthase (TS 3?-UTR ins6 > del6, 5?-UTR 2R > 3R). We recruited 919 GC patients from 1998 to 2006. The Kaplan–Meier plots, Cox regression analyses and the log-rank tests were carried out in this study. MTHFR 1298CC genotype showed protective effect (HR = 0.444, 95% CI = 0.210–0.940). MTRR 66 GA + GG genotypes decreased the risk of death (HR = 0.793, 95% CI = 0.651–0.967) in general, and in subgroups with more pronounced diffuse type, greater depth of invasion (T2/T3/T4), higher level lymph node metastasis (N1/N2/N3), advanced TNM stages (II/III level) and 5-Fu treatment. However, the improved survival disappeared when GC patients simultaneously had MTR 2756 GA + GG genotypes (HR = 1.063, 95% CI = 0.750–1.507). Although MTRR 66GA genotype was not associated with the survival of GC patients, patients with simultaneous MTRR 66GA and MTR 2756AA genotypes exhibited significant risk reduction of death (HR = 0.773, 95% CI = 0.609–0.981). MTHFR 1298 CA + CC combined with TS 5-UTR 2R3R + 3R3R genotypes (HR = 0.536, 95% CI = 0.315–0.913) also increased patient survival rates. Our results suggest that the MTRR 66A > G and MTHFR 1298A > C polymorphisms may be useful prognostic biomarkers for GC patients. PMID:25840420

  3. Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

    PubMed Central

    Akintola, Abimbola A.; van den Berg, Annette; van Buchem, Mark A.; Jansen, Steffy W.; Slagboom, Eline P.; Westendorp, Rudi G.; van der Grond, Jeroen; van Heemst, Diana

    2015-01-01

    Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families (“offspring”) and controls; and age categories thereof. From the Leiden Longevity Study (LLS), 132 participants underwent an oral glucose tolerance test (OGTT) to assess glycemia [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR) peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age. In the full offspring group only, reduced MTR peak-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p < 0.01). When dichotomized for age (?65 years and >65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction < 0.05). Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age. PMID:26074813

  4. MEMBRANE PROCESS TO SEQUESTER CO2 FROM POWER PLANT FLUE GAS

    SciTech Connect

    Tim Merkel; Karl Amo; Richard Baker; Ramin Daniels; Bilgen Friat; Zhenjie He; Haiqing Lin; Adrian Serbanescu

    2009-03-31

    The objective of this project was to assess the feasibility of using a membrane process to capture CO2 from coal-fired power plant flue gas. During this program, MTR developed a novel membrane (Polaris™) with a CO2 permeance tenfold higher than commercial CO2-selective membranes used in natural gas treatment. The Polaris™ membrane, combined with a process design that uses a portion of combustion air as a sweep stream to generate driving force for CO2 permeation, meets DOE post-combustion CO2 capture targets. Initial studies indicate a CO2 separation and liquefaction cost of $20 - $30/ton CO2 using about 15% of the plant energy at 90% CO2 capture from a coal-fired power plant. Production of the Polaris™ CO2 capture membrane was scaled up with MTR’s commercial casting and coating equipment. Parametric tests of cross-flow and countercurrent/sweep modules prepared from this membrane confirm their near-ideal performance under expected flue gas operating conditions. Commercial-scale, 8-inch diameter modules also show stable performance in field tests treating raw natural gas. These findings suggest that membranes are a viable option for flue gas CO2 capture. The next step will be to conduct a field demonstration treating a realworld power plant flue gas stream. The first such MTR field test will capture 1 ton CO2/day at Arizona Public Service’s Cholla coal-fired power plant, as part of a new DOE NETL funded program.

  5. Myofascial low back pain.

    PubMed

    Ramsook, Ryan R; Malanga, Gerard A

    2012-10-01

    Low back pain is a common condition that is encountered by both primary care physicians as well as various specialists, which include: orthopedic surgeons, physical medicine and rehabilitation specialists, neurologists, rheumatologists, and pain management specialists. Associated muscular pain is very common and often a reactive response from nociception from other structures. Myofascial pain may arise, which is characterized by the presence of myofascial trigger points (MTrPs) that are located in fascia, tendons, and/or muscle. This article reviews the current evidence regarding the pathophysiology, assessment, and recommended treatment options for myofascial low back pain. PMID:22945480

  6. Effects of high density dispersion fuel loading on the uncontrolled reactivity insertion transients of a low enriched uranium fueled material test research reactor

    Microsoft Academic Search

    Farhan Muhammad; Asad Majid

    2009-01-01

    The effects of using high density low enriched uranium on the uncontrolled reactivity insertion transients of a material test research reactor were studied. For this purpose, the low density LEU fuel of an MTR was replaced with high density U–Mo (9w\\/o) LEU fuels currently being developed under the RERTR program having uranium densities of 6.57gU\\/cm3, 7.74gU\\/cm3 and 8.57gU\\/cm3. Simulations were

  7. HOT CELL BUILDING, TRA632. CONTEXTUAL VIEW ALONG WALLEYE AVENUE, CAMERA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    HOT CELL BUILDING, TRA-632. CONTEXTUAL VIEW ALONG WALLEYE AVENUE, CAMERA FACING EASTERLY. HOT CELL BUILDING IS AT CENTER LEFT OF VIEW; THE LOW-BAY PROJECTION WITH LADDER IS THE TEST TRAIN ASSEMBLY FACILITY, ADDED IN 1968. MTR BUILDING IS IN LEFT OF VIEW. HIGH-BAY BUILDING AT RIGHT IS THE ENGINEERING TEST REACTOR BUILDING, TRA-642. INL NEGATIVE NO. HD46-32-1. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. Identification and initial characterization of circadian clock mutants in Neurospora crassa

    E-print Network

    March, Irene Jennifer

    2002-01-01

    will be selected by their ability to grow under conditions thai are inappropriate for wild type. For example, in a FRQ strain, mtr under control of the ccg-1 promoter should be low and the strain will grow on media with FPA and anthranilate but not on media... will also be low, and the strain will grow on media containing FPA and anthranilate. In FRQ strains, ccg-1 levels are high, therefore mtv expression will also be high, and the strain will grow on media containing tryptophan and arginine. Following...

  9. Bell pepper endornavirus: molecular and biological properties, and occurrence in the genus Capsicum.

    PubMed

    Okada, Ryo; Kiyota, Eri; Sabanadzovic, Sead; Moriyama, Hiromitsu; Fukuhara, Toshiyuki; Saha, Prasenjit; Roossinck, Marilyn J; Severin, Ake; Valverde, Rodrigo A

    2011-11-01

    Bell peppers (Capsicum annuum) harbour a large dsRNA virus. The linear genome (14.7 kbp) of two isolates from Japanese and USA bell pepper cultivars were completely sequenced and compared. They shared extensive sequence identity and contained a single, long ORF encoding a 4815 aa protein. This polyprotein contained conserved motifs of putative viral methyltransferase (MTR), helicase 1 (Hel-1), UDP-glycosyltransferase and RNA-dependent RNA polymerase. This unique arrangement of conserved domains has not been reported in any of the known endornaviruses. Hence this virus, for which the name Bell pepper endornavirus (BPEV) is proposed, is a distinct species in the genus Endornavirus (family Endornaviridae). The BPEV-encoded polyprotein contains a cysteine-rich region between the MTR and Hel-1 domains, with conserved CXCC motifs shared among several endornaviruses, suggesting an additional functional domain. In agreement with general endornavirus features, BPEV contains a nick in the positive-strand RNA molecule. The virus was detected in all bell pepper cultivars tested and transmitted through seed but not by graft inoculations. Analysis of dsRNA patterns and RT-PCR using degenerate primers revealed putative variants of BPEV, or closely related species, infecting other C. annuum genotypes and three other Capsicum species (C. baccatum, C. chinense and C. frutescens). PMID:21775578

  10. Audibility-based annoyance prediction modeling

    NASA Astrophysics Data System (ADS)

    Fidell, Sanford; Finegold, Lawrence S.

    1992-04-01

    The effects of rapid onset times and high absolute sound pressures near military training routes (MTR's) including possible startle effects and increased annoyance due to the unpredictable nature of these flights, have been of longstanding concern. A more recent concern is the possibility of increased annoyance due to low ambient noise levels near military flight training operations and differences in expectations about noise exposure in high and low population density areas. This paper describes progress in developing audibility-based methods for predicting the annoyance of noise produced at some distance from aircraft flight tracks. Audibility-based models which take into account near-ground acoustic propagation and ambient noise levels may be useful in assessing environmental impacts of MTR's and Military Operating Areas (MOA's) under some conditions. A prototype Single Event Annoyance Prediction Model (SEAPM) has been developed under USAF sponsorship as an initial effort to address these issues, and work has progressed on a geographic information system (GIS) to produce cartographically referenced representations of aircraft audibility.

  11. Expression of equine morbillivirus (EMV) matrix and fusion proteins and their evaluation as diagnostic reagents.

    PubMed

    Wang, L F; Gould, A R; Selleck, P W

    1997-01-01

    Full-length cDNA clones coding for the matrix (M) and fusion (F) proteins of equine morbillivirus (EMV) were isolated by RT-PCR, and expressed in Escherichia coli using two different expression systems. Western blot analysis indicated that the M and F proteins, expressed either by itself or as fusion proteins with glutathione S-transferase (GST), were insoluble and degraded after expression. Analysis of the degradation pattern of recombinant M protein suggested that the N-terminus of the matrix protein might be more stable and antigenic than the C-terminal region. Therefore a third system was used to express a truncated M protein, composed of the N-terminal amino acid residues 1-197, with a (His)6-tag attached at the N-terminus. This recombinant protein [(His)6-Mtr], was stable but was also insoluble. After one-step affinity purification under denaturing conditions, (His)6-Mtr was used to monitor the antibody response to EMV infection by Western blot and ELISA. We obtained a 100% correlation between Western blot and virus neutralisation testing although the number of positive sera available for testing was very limited, which included seven horse, two rabbit and one human sera. PMID:9672592

  12. A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice

    PubMed Central

    Frescas, David; de Lange, Titia

    2014-01-01

    The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations affect telomere function, we generated mice with the equivalent of the TIN2 K280E DC allele (TIN2DC) by gene targeting. Whereas homozygous TIN2DC/DC mice were not viable, first-generation TIN2+/DC mice were healthy and fertile. In the second and third generations, the TIN2+/DC mice developed mild pancytopenia, consistent with hematopoietic dysfunction in DC, as well as diminished fecundity. Bone marrow telomeres of TIN2+/DC mice shortened over the generations, and immortalized TIN2+/DC mouse embryonic fibroblasts (MEFs) showed telomere shortening with proliferation. Unexpectedly, telomere shortening was accelerated in TIN2+/DC mTR?/? mice and MEFs compared with TIN2+/+ mTR?/? controls, establishing that the TIN2DC telomere maintenance defect was not solely due to diminished telomerase action. The TIN2DC allele induced mild ATR kinase signaling at telomeres and a fragile telomere phenotype, suggestive of telomere replication problems. These data suggest that this TIN2-DC mutation could induce telomeric dysfunction phenotypes in telomerase-negative somatic cells and tissues that further exacerbate the telomere maintenance problems in telomerase-positive stem cell compartments. PMID:24449270

  13. Radioisotopic data of sediment collected in Mobile and Bon Secour Bays, Alabama

    USGS Publications Warehouse

    Marot, Marci E.; Smith, Christopher G.

    2012-01-01

    The focus of this study was to determine the extent of natural and (or) anthropogenic impacts on the sedimentary records of Mobile and Bon Secour Bays, Alabama during the last 150 years. These bays are unique in that anthropogenic activities are generally widespread and span both the eastern and western shorelines. However, there is a clear distinction in the types of human development and infrastructure between the western and eastern shorelines. These activities and the differences in land-use and -change influence the overall supply and remobilization of sediment to and within the bay. These factors could subsequently threaten the health and integrity of these environments and their ability to mitigate against long-term processes associated with climate change. In an attempt to characterize long-term accretion rates within the Mobile Bay Estuarine System (MBES), seven box cores were collected and analyzed for excess lead-210 (210Pbxs, the difference between total and supported 210Pb) and cesium-137 (137Cs) activities. The MBES receives sediment and water from the Alabama and Tombigbee River watersheds, which converge into the Mobile-Tensaw River (MTR) system just prior to discharging into Mobile Bay. Riverine discharge from the MTR system to the bay is second only to the Mississippi River discharge to the Gulf of Mexico for the conterminous United States.

  14. A yeast acetyl coenzyme A carboxylase mutant links very-long-chain fatty acid synthesis to the structure and function of the nuclear membrane-pore complex.

    PubMed Central

    Schneiter, R; Hitomi, M; Ivessa, A S; Fasch, E V; Kohlwein, S D; Tartakoff, A M

    1996-01-01

    The conditional mRNA transport mutant of Saccharomyces cerevisiae, acc1-7-1 (mtr7-1), displays a unique alteration of the nuclear envelope. Unlike nucleoporin mutants and other RNA transport mutants, the intermembrane space expands, protuberances extend from the inner membrane into the intermembrane space, and vesicles accumulate in the intermembrane space. MTR7 is the same gene as ACC1, encoding acetyl coenzyme A (CoA) carboxylase (Acc1p), the rate-limiting enzyme of de novo fatty acid synthesis. Genetic and biochemical analyses of fatty acid synthesis mutants and acc1-7-1 indicate that the continued synthesis of malonyl-CoA, the enzymatic product of acetyl-CoA carboxylase, is required for an essential pathway which is independent from de novo synthesis of fatty acids. We provide evidence that synthesis of very-long-chain fatty acids (C26 atoms) is inhibited in acc1-7-1, suggesting that very-long-chain fatty acid synthesis is required to maintain a functional nuclear envelope. PMID:8943372

  15. Field Demonstration of a Membrane Process to Recover Heavy Hydrocarbons and to Remove Water from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2007-03-30

    The objective of this project was to design, construct and field demonstrate a membrane system to recover natural gas liquids (NGL) and remove water from raw natural gas. An extended field test to demonstrate system performance under real-world high-pressure conditions was conducted to convince industry users of the efficiency and reliability of the process. The system was designed and fabricated by Membrane Technology and Research, Inc. (MTR) and installed and operated at BP Amoco's Pascagoula, MS plant. The Gas Research Institute partially supported the field demonstration and BP-Amoco helped install the unit and provide onsite operators and utilities. The gas processed by the membrane system meets pipeline specifications for dew point and BTU value and can be delivered without further treatment to the pipeline. During the course of this project, MTR has sold thirteen commercial units related to the field test technology. Revenue generated from new business is already more than four times the research dollars invested in this process by DOE. The process is ready for broader commercialization and the expectation is to pursue the commercialization plans developed during this project, including collaboration with other companies already servicing the natural gas processing industry.

  16. Evaluation of Bioreactor-Cultivated Bone by Magnetic Resonance Microscopy and FTIR Microspectroscopy

    PubMed Central

    Chesnick, Ingrid E.; Avallone, Frank; Leapman, Richard D.; Landis, William J.; Eidelman, Naomi; Potter, Kimberlee

    2007-01-01

    We present a three-dimensional mineralizing model based on a hollow fiber bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the growth and development of the mineralized tissue around the individual fibers were monitored over a period of nine weeks. Spatial maps of the water proton MRM properties of the intact tissue, with 78 ?m resolution, were used to determine changes in tissue composition with development. Unique changes in the mineral and collagen content of the tissue were detected with high specificity by proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At the end of the growth period, the presence of a bone-like tissue was verified by histology and the formation of poorly crystalline apatite was verified by selected area electron diffraction and electron probe X-ray microanalysis. FTIR microspectroscopy confirmed the heterogeneous nature of the bone-like tissue formed. FTIR-derived phosphate maps confirmed that those locations with the lowest PD values contained the most mineral, and FTIR-derived collagen maps confirmed that bright pixels on MTR maps corresponded to regions of high collagen content. In conclusion, the spatial mapping of tissue constituents by FTIR microspectroscopy corroborated the findings of non-invasive MRM measurements and supported the role of MRM in monitoring the bone formation process in vitro. PMID:17174620

  17. Polymorphisms in folate pathway genes are not associated with somatic nondisjunction in turner syndrome.

    PubMed

    Bispo, Adriana Valéria Sales; Dos Santos, Luana Oliveira; de Barros, Juliana Vieira; Duarte, Andrea Rezende; Araújo, Jacqueline; Muniz, Maria Tereza Cartaxo; Santos, Neide

    2015-07-01

    Folate metabolism dysfunction can lead to DNA hypomethylation and abnormal chromosomal segregation. Previous investigations of this association have produced controversial results. Here we performed a case-control study in patients with Turner syndrome (TS) to determine the effects of genetic polymorphisms of folate pathway genes as potential risk factors for somatic chromosomal nondisjunction. TS is a useful model for this investigation because patients with TS show a high frequency of chromosome mosaicism. Here we investigated the possible association of polymorphisms of the MTHFR gene with TS risk, which has been previously investigated with controversial results. We also examined the effects of MTR, RFC1, and TYMS gene polymorphisms in TS for the first time. The risk was evaluated according to allelic and genotype (independent and combined) frequencies among 70 patients with TS and 144 age-matched healthy control subjects. Polymorphism genotyping was performed by PCR, PCR-RFLP, and PCR-ASA. The polymorphisms MTHFR 677C>T and 1298A>C, MTR 2756A>G, RFC1 80G>A, and TYMS 2R/3R-alone or in combinations-were not associated with the risk of chromosomal aneuploidy in TS. In conclusion, our present findings did not support a link between impaired folate metabolism and abnormal chromosome segregation leading to somatic nondisjunction in TS patients. © 2015 Wiley Periodicals, Inc. PMID:25858821

  18. Tackling codon usage bias for heterologous expression in Rhodobacter sphaeroides by supplementation of rare tRNAs.

    PubMed

    Cheng, Danhui; Wang, Ri; Prather, Kristala Jones; Chow, King Lau; Hsing, I-Ming

    2015-05-01

    The photosynthetic Rhodobacter species are promising alternative expression hosts in bioproduction and biorefinery due to their unique metabolic capacities. With prominent inner membrane areas and efficient endogenous translocation machineries, they are especially attractive for membrane protein expression. However, codon usage bias could be a limitation in the engineering of Rhodobacter species and has seldom been investigated. In this study, we tackled the codon bias of Rhodobacter by functionally expressing 8 rare tRNAs of Rhodobacter sphaeroides with a multi-copy vector. The impact of tRNA supplementation was evaluated through monitoring expression levels of two heterologous proteins with different phylogenetic origins, a membrane subunit of the riboflavin transporter, RibU, from Lactobacillus acidophilus La-14 and a decaheme cytochrome, MtrA, from Shewanella oneidensis. Our results showed that the performances were closely related to medium composition and rare codon percentages of raw DNA sequences. Provision of rare tRNAs has increased RibU production by 7.7-folds and 2.86-fold in minimal medium and rich medium, respectively, while MtrA levels were increased by 1-fold in minimal medium. The present study confirms the presence of codon bias in R. sphaeroides and offers a facile tool for improving heterologous expression of rare-codon containing genes. We anticipate that this tRNA supplementation system can be further extended to other species of Rhodobacter, and thus will facilitate the engineering of purple bacteria for interesting applications in microbial technology. PMID:25837504

  19. Remote Effect of Lower Limb Acupuncture on Latent Myofascial Trigger Point of Upper Trapezius Muscle: A Pilot Study

    PubMed Central

    Chen, Kai-Hua; Hsiao, Kuang-Yu; Lin, Chu-Hsu; Chang, Wen-Ming; Hsu, Hung-Chih; Hsieh, Wei-Chi

    2013-01-01

    Objectives. To demonstrate the use of acupuncture in the lower limbs to treat myofascial pain of the upper trapezius muscles via a remote effect. Methods. Five adults with latent myofascial trigger points (MTrPs) of bilateral upper trapezius muscles received acupuncture at Weizhong (UB40) and Yanglingquan (GB34) points in the lower limbs. Modified acupuncture was applied at these points on a randomly selected ipsilateral lower limb (experimental side) versus sham needling on the contralateral lower limb (control side) in each subject. Each subject received two treatments within a one-week interval. To evaluate the remote effect of acupuncture, the range of motion (ROM) upon bending the contralateral side of the cervical spine was assessed before and after each treatment. Results. There was significant improvement in cervical ROM after the second treatment (P = 0.03) in the experimental group, and the increased ROM on the modified acupuncture side was greater compared to the sham needling side (P = 0.036). Conclusions. A remote effect of acupuncture was demonstrated in this pilot study. Using modified acupuncture needling at remote acupuncture points in the ipsilateral lower limb, our treatments released tightness due to latent MTrPs of the upper trapezius muscle. PMID:23710218

  20. Genetic variation in genes involved in folate and drug metabolism in a south Indian population

    PubMed Central

    Rai, Padmalatha S; Murali, T. S; Vasudevan, T. G; Prasada, Shama K.; Bhagavath, Ashok Kumar; Pai, Pranita; Gopinath, P. M.; Satyamoorthy, K.

    2011-01-01

    BACKGROUND: Genetic variations represented as single nucleotide polymorphisms (SNPs) vary across the world population. This genetic polymorphism (such as SNPs) plays an important role in pharmacogenomics. SNPs that affects cellular metabolism, by altering the enzyme activity, have an important role in therapeutic outcome. Allele frequencies in number of clinically relevant SNPs within south Indian populations are not yet known. Hence, we genotyped randomly selected unrelated south Indian subjects from different locations of south India representing the heterogeneous ethnic background of the population. MATERIALS AND METHODS: Common variants of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULT1A1 gene polymorphisms were screened from healthy unrelated south Indian volunteers. Genotypes were determined using RFLP analysis of polymerase chain reaction-amplified products and confirmed by DNA sequencing. Chi-square test was performed to test for deviation from the Hardy-Weinberg equilibrium for each locus. RESULTS: Gene allele frequency for several polymorphisms in our study differed significantly between the populations of other nations reported for several of the SNPs. These results demonstrate that the populations in different geographic regions may have widely varying genetic allele frequencies for clinically relevant SNPs. CONCLUSION: The present study reports, for the first time, the frequency distribution of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULTIA1 gene polymorphisms in a south Indian population. Population-specific genetic polymorphism studies will help in practicing pharmacogenomic principles in the clinics. PMID:21747588

  1. THERMAL MODELING ANALYSIS OF SRS 70 TON CASK

    SciTech Connect

    Lee, S.; Jordan, J.; Hensel, S.

    2011-03-08

    The primary objective of this work was to perform the thermal calculations to evaluate the Material Test Reactor (MTR) fuel assembly temperatures inside the SRS 70-Ton Cask loaded with various bundle powers. MTR fuel consists of HFBR, MURR, MIT, and NIST. The MURR fuel was used to develop a bounding case since it is the fuel with the highest heat load. The results will be provided for technical input for the SRS 70 Ton Cask Onsite Safety Assessment. The calculation results show that for the SRS 70 ton dry cask with 2750 watts total heat source with a maximum bundle heat of 670 watts and 9 bundles of MURR bounding fuel, the highest fuel assembly temperatures are below about 263 C. Maximum top surface temperature of the plastic cover is about 112 C, much lower than its melting temperature 260 C. For 12 bundles of MURR bounding fuel with 2750 watts total heat and a maximum fuel bundle of 482 watts, the highest fuel assembly temperatures are bounded by the 9 bundle case. The component temperatures of the cask were calculated by a three-dimensional computational fluid dynamics approach. The modeling calculations were performed by considering daily-averaged solar heat flux.

  2. Neutron beam studies for a medical therapy reactor.

    PubMed

    Neuman, W A

    1990-01-01

    A conceptual design of a Medical Therapy Reactor (MTR) for neutron capture therapy (NCT) has been performed at the Idaho National Engineering Laboratory (INEL). The initial emphasis of the conceptual design was toward the treatment of glioblastoma multiforme and other presently incurable cancers. The design goal of the facility is to provide routine patient treatments both in brief time intervals (approximately 10 minutes) and inexpensively. The conceptual study has shown this goal to be achievable by locating an MTR at a major medical facility. This paper addresses the next step in the conceptual design process: a guide to the optimization of the epithermal-neutron filter and collimator assembly for the treatment of brain tumors. The current scope includes the sensitivity of the treatment beam to variations in filter length, gamma shield length, and collimator lengths as well as exit beam aperture size. The study shows the areas which can provide the greatest latitude in improving beam intensity and quality. Suggestions are given for future areas of optimization of beam filtering and collimation. PMID:2268234

  3. Hippocampal Volume Is Related to Cognitive Decline and Fornicial Diffusion Measures in Multiple Sclerosis

    PubMed Central

    Koenig, Katherine A.; Sakaie, Ken E.; Lowe, Mark J.; Lin, Jian; Stone, Lael; Bermel, Robert A.; Beall, Erik B.; Rao, Stephen M.; Trapp, Bruce D.; Phillips, Micheal D.

    2014-01-01

    Purpose To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls. Materials and Methods A total of 53 patients with MS and 20 age- and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks. Results In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P < 7 × 10?4) and to measures of verbal (P = 0.030) and visual spatial (P = 0.004) episodic memory and a measure of information processing speed (P < 0.037). Discussion These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression. PMID:24512796

  4. The bacterial stressosome: a modular system that has been adapted to control secondary messenger signaling.

    PubMed

    Quin, Maureen B; Berrisford, John M; Newman, Joseph A; Baslé, Arnaud; Lewis, Richard J; Marles-Wright, Jon

    2012-02-01

    The stressosome complex regulates downstream effectors in response to environmental signals. In Bacillus subtilis, it activates the alternative sigma factor ?(B), leading to the upregulation of the general stress regulon. Herein, we characterize a stressosome-regulated biochemical pathway in Moorella thermoacetica. We show that the presumed sensor, MtR, and the scaffold, MtS, form a pseudo-icosahedral structure like that observed in B. subtilis. The N-terminal domain of MtR is structurally homologous to B. subtilis RsbR, despite low sequence identity. The affinity of the switch kinase, MtT, for MtS decreases following MtS phosphorylation and not because of structural reorganization. Dephosphorylation of MtS by the PP2C type phosphatase MtX permits the switch kinase to rebind the stressosome to reset the response. We also show that MtT regulates cyclic di-GMP biosynthesis through inhibition of a GG(D/E)EF-type diguanylate cyclase, demonstrating that secondary messenger levels are regulated by the stressosome. PMID:22325782

  5. CORROSION OF ALUMINUM CLAD SPENT NUCLEAR FUEL IN THE 70 TON CASK DURING TRANSFER FROM L AREA TO H-CANYON

    SciTech Connect

    Mickalonis, J.

    2014-06-01

    Aluminum-clad spent nuclear fuel will be transported for processing in the 70-ton nuclear fuel element cask from L Basin to H-canyon. During transport these fuels would be expected to experience high temperature aqueous corrosion from the residual L Basin water that will be present in the cask. Cladding corrosion losses during transport were calculated for material test reactor (MTR) and high flux isotope reactors (HFIR) fuels using literature and site information on aqueous corrosion at a range of time/temperature conditions. Calculations of the cladding corrosion loss were based on Arrhenius relationships developed for aluminum alloys typical of cladding material with the primary assumption that an adherent passive film does not form to retard the initial corrosion rate. For MTR fuels a cladding thickness loss of 33 % was found after 1 year in the cask with a maximum temperature of 260 {degrees}C. HFIR fuels showed a thickness loss of only 6% after 1 year at a maximum temperature of 180 {degrees}C. These losses are not expected to impact the overall confinement function of the aluminum cladding.

  6. Magnetization transfer imaging of the brain: A quantitative comparison of results obtained at 1.5 and 4.0 T.

    PubMed

    Duvvuri, U; Roberts, D A; Leigh, J S; Bolinger, L

    1999-10-01

    The preliminary results of magnetization transfer (MT) imaging on a whole body 4.0 T system are presented. Cooked egg phantoms and several volunteers were imaged on 1.5 and 4.0 T magnets interfaced to GE Signa scanners. The MT ratio (MTR), signal difference to noise ratio (SDNR), and contrast parameters were measured at both fields and compared. Furthermore, single-shot Z-spectroscopy was used to characterize the frequency dependence of the MT phenomenon. The results show that MT imaging can be safely performed at 4.0 T without exceeding limitations of radio frequency power. The MT effect is more pronounced at the higher field, leading to better quality images with higher contrast and SDNR. The Z-spectra are not markedly different at the higher field although the MTR is greater. The potential applications of this technique to study neurodegenerative diseases, as well as, perfusion imaging and angiography are discussed. J. Magn. Reson. Imaging 1999;10:527-532. PMID:10508319

  7. Damage to the Optic Radiation in Multiple Sclerosis Is Associated with Retinal Injury and Visual Disability

    PubMed Central

    Reich, Daniel S.; Smith, Seth A.; Gordon-Lipkin, Eliza M.; Ozturk, Arzu; Caffo, Brian S.; Balcer, Laura J.; Calabresi, Peter A.

    2009-01-01

    Objective We investigated whether damage to the optic radiation (OR) in multiple sclerosis (MS) is associated with optic nerve injury and visual dysfunction. Design Case-control. Setting Referral center. Patients 90 referred MS participants and 29 healthy volunteers. Main outcome measures MRI indices along the OR were reconstructed with diffusion tensor tractography. Retinal nerve fiber layer (RNFL) thickness and visual acuity at high and low contrast were measured in a subset of the MS group (n=36). Results All tested MRI indices (fractional anisotropy [FA]; mean, parallel, and perpendicular [??] diffusivity; T2 relaxation time; and magnetization transfer ratio [MTR]) were significantly abnormal in MS. Average RNFL thickness was significantly correlated with FA (r=0.55, p<0.001) and ?? (r=?0.37, p=0.001). RNFL thickness in the nasal retinal quadrant was also specifically correlated with FA and ?? in the synaptically connected contralateral optic radiation. In individuals with less severely damaged optic nerves (average RNFL thickness >80?m), letter acuity scores at 2.5% contrast were correlated with OR-specific FA (r=0.55, p=0.004), ?? (r=?0.40, p=0.044), and MTR (r=0.54, p=0.011), as well as the fraction of OR volume made up of lesions (r=?0.69, p<0.001). Conclusions FA and ?? are potentially useful quantitative imaging biomarkers of OR-specific damage in MS. Such damage is associated with retinal injury and visual disability. PMID:19667222

  8. Genome-Wide Investigation of the Role of the tRNA Nuclear-Cytoplasmic Trafficking Pathway in Regulation of the Yeast Saccharomyces cerevisiae Transcriptome and Proteome

    PubMed Central

    Chu, Hui-Yi

    2013-01-01

    In eukaryotic cells, tRNAs are transcribed and partially processed in the nucleus before they are exported to the cytoplasm, where they have an essential role in protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm, and tRNA subcellular distribution is nutrient dependent. At least three members of the ?-importin family, Los1, Mtr10, and Msn5, function in tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the tRNA retrograde pathway regulates the translation of particular transcripts, we compared the expression profiles from nontranslating mRNAs and polyribosome-associated translating mRNAs collected from msn5?, mtr10?, and wild-type cells under fed or acute amino acid depletion conditions. Our microarray data revealed that the methionine, arginine, and leucine biosynthesis pathways are targets of the tRNA retrograde process. We confirmed the microarray data by Northern and Western blot analyses. The levels of some of the particular target mRNAs were reduced, while others appeared not to be affected. However, the protein levels of all tested targets in these pathways were greatly decreased when tRNA nuclear import or reexport to the cytoplasm was disrupted. This study provides information that tRNA nuclear-cytoplasmic dynamics is connected to the biogenesis of proteins involved in amino acid biosynthesis. PMID:23979602

  9. Folate metabolism-related gene polymorphisms and susceptibility to primary liver cancer in North China.

    PubMed

    Cui, Lian-Hua; Song, Yang; Si, Hongzong; Shen, Fangzhen; Shin, Min-Ho; Kim, Hee Nam; Choi, Jin-Su

    2012-09-01

    Genetic factors may contribute to individual differences in cancer susceptibility. This study was designed to investigate the effects of the polymorphisms of methylenetetrahydrofolate reductase 677 C ? T (MTHFR 677 C ? T), methylenetetrahydrofolate reductase 1298 A ? C (MTHFR 1298A ? C), thymidylate synthase (TYMS 3R ? 2R), and methionine synthase 2756 A ? G (MTR 2756 A ? G) on the risk of primary liver cancer (PLC). We conducted a case-control study involving 356 PLC cases and 641 healthy controls in North China. Compared with the MTHFR 677CC genotype, the MTHFR 677TT genotype showed an increased risk for PLC (TT vs. CC: adjusted odds ratio (OR) = 1.56; 95% confidence interval (CI): 1.02-2.40; P = 0.043) after adjusting for gender and age, whereas the MTHFR 1298CC genotype showed a significantly decreased risk for PLC (CC vs. AA: adjusted OR = 0.23; 95% CI: 0.08-0.70; P = 0.010). However, no significant association was found between the TYMS 3R ? 2R or the MTR 2756 A ? G polymorphism and the risk of PLC. Our results suggest that the MTHFR 677 C ? T and the MTHFR 1298A ? C genetic polymorphisms might play important role in hepatic carcinogenesis. Further studies with larger sample sizes are required to validate this association. PMID:21956592

  10. Pronounced and extensive microtubule defects in a Saccharomyces cerevisiae DIS3 mutant.

    PubMed

    Smith, Sarah B; Kiss, Daniel L; Turk, Edward; Tartakoff, Alan M; Andrulis, Erik D

    2011-11-01

    Subunits of the RNA processing exosome assemble into structurally distinct protein complexes that function in disparate cellular compartments and RNA metabolic pathways. Here, in a genetic, cell biological and transcriptomic analysis, we examined the role of Dis3, an essential polypeptide with endo- and 3'?5' exo-ribonuclease activity, in cell cycle progression. We present several lines of evidence that perturbation of DIS3 affects microtubule (MT) localization and structure in Saccharomyces cerevisiae. Cells with a DIS3 mutant: (a) accumulate anaphase and pre-anaphase mitotic spindles; (b) exhibit spindles that are misorientated and displaced from the bud neck; (c) harbour elongated spindle-associated astral MTs; (d) have an increased G1 astral MT length and number; and (e) are hypersensitive to MT poisons. Mutations in the core exosome genes RRP4 and MTR3 and the exosome cofactor gene MTR4, but not other exosome subunit gene mutants, also elicit MT phenotypes. RNA deep sequencing analysis (RNA-seq) shows broad changes in the levels of cell cycle- and MT-related transcripts in mutant strains. Collectively, the data presented in this study suggest an evolutionarily conserved role for Dis3 in linking RNA metabolism, MTs and cell cycle progression. PMID:21919057

  11. NTF2-like domain of Tap plays a critical role in cargo mRNA recognition and export

    PubMed Central

    Katahira, Jun; Dimitrova, Lyudmila; Imai, Yumiko; Hurt, Ed

    2015-01-01

    Metazoan Tap-p15 (also called Nxf1-Nxt1) and yeast Mex67-Mtr2 heterodimers are the general mRNA export receptors. The RNA binding activity of Tap-p15, which is essential for mRNA nuclear export, has been attributed to the amino-terminal RNA binding module of Tap consists of RNA recognition motif (RRM) and leucine-rich repeat. In this study, we identified a novel RNA interaction surface in the NTF2-like (NTF2L) domain of Tap, which is analogous to the rRNA binding platform of Mex67-Mtr2. Tap-p15 uses the three domains to tightly bind the retroviral constitutive transport element. The RNA binding through the NTF2L domain is functionally relevant as introduction of mutations in this region reduced CTE-containing mRNA export activity. In contrast, only when the RRM and NTF2L domains were mutated simultaneously, bulk poly (A)+ RNA export and in vivo poly (A)+ RNA binding activities of Tap-p15 were significantly attenuated. Moreover, an engineered human cell line harboring the NTF2L domain mutation in the NXF1 gene showed a synthetic growth phenotype and severe mRNA export defect under Aly/REF and Thoc5 depleted condition. These data suggest that Tap-p15 recognizes bulk mRNAs through combinatorial use of the distinct RNA binding domains. PMID:25628355

  12. Redox Linked Flavin Sites in Extracellular Decaheme Proteins Involved in Microbe-Mineral Electron Transfer.

    PubMed Central

    Edwards, Marcus J.; White, Gaye F.; Norman, Michael; Tome-Fernandez, Alice; Ainsworth, Emma; Shi, Liang; Fredrickson, Jim K.; Zachara, John M.; Butt, Julea N.; Richardson, David J.; Clarke, Thomas A.

    2015-01-01

    Extracellular microbe-mineral electron transfer is a major driving force for the oxidation of organic carbon in many subsurface environments. Extracellular multi-heme cytochromes of the Shewenella genus play a major role in this process but the mechanism of electron exchange at the interface between cytochrome and acceptor is widely debated. The 1.8?Å x-ray crystal structure of the decaheme MtrC revealed a highly conserved CX8C disulfide that, when substituted for AX8A, severely compromised the ability of S. oneidensis to grow under aerobic conditions. Reductive cleavage of the disulfide in the presence of flavin mononucleotide (FMN) resulted in the reversible formation of a stable flavocytochrome. Similar results were also observed with other decaheme cytochromes, OmcA, MtrF and UndA. The data suggest that these decaheme cytochromes can transition between highly reactive flavocytochromes or less reactive cytochromes, and that this transition is controlled by a redox active disulfide that responds to the presence of oxygen. PMID:26126857

  13. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas

    SciTech Connect

    Kaaeid Lokhandwala

    2006-03-20

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group found a new site for the project at a North Texas Exploration (NTE) gas processing plant, and we are now negotiating with Atmos Energy for a final test of the project demonstration unit. Several commercial sales have also resulted from the partnership with ABB, and sales of nitrogen/natural gas membrane separation units now total $2.3 million.

  14. Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas: Nineteenth Quarterly Progress Report (Second Quarter 2006)

    SciTech Connect

    Kaaeid Lokhandwala

    2006-06-30

    The original proposal described the construction and operation of a 1 MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation, and is working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group found a new site for the project at a North Texas Exploration (NTE) gas processing plant, and we continue, but have as yet been unsuccessful in our attempts, to negotiate with Atmos Energy for a final test of the project demonstration unit. In the meantime, MTR has located an alternative testing opportunity and signed a contract for a demonstration plant in Rio Vista, CA. Several commercial sales have resulted from the partnership with ABB, and total sales of nitrogen/natural gas membrane separation units are now approaching $2.6 million.

  15. FIELD DEMONSTRATION OF A MEMBRANE PROCESS TO SEPARATE NITROGEN FROM NATURAL GAS

    SciTech Connect

    Kaaeid Lokhandwala

    2004-04-30

    The original proposal described the construction and operation of a 1-MMscfd treatment system to be operated at a Butcher Energy gas field in Ohio. The gas produced at this field contained 17% nitrogen. During pre-commissioning of the project, a series of well tests showed that the amount of gas in the field was significantly smaller than expected and that the nitrogen content of the wells was very high (25 to 30%). After evaluating the revised cost of the project, Butcher Energy decided that the plant would not be economical and withdrew from the project. Since that time, Membrane Technology and Research, Inc. (MTR) has signed a marketing and sales partnership with ABB Lummus Global, a large multinational corporation. MTR will be working with the company's Randall Gas Technologies group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The system has been installed in the field and initial startup activities have been completed. The system has not yet produced the flow rate required for continuous stable operation. NTE, the company hosting this test site/pilot plant, will drill additional wells to increase the inlet flow rate. The system is expected to be in full continuous operation by May 2004.

  16. Identification and Characterization of MtoA: a Decaheme c-Type Cytochrome of the Neutrophilic Fe(II)-oxidizing Bacterium Sideroxydans lithotrophicus ES-1

    SciTech Connect

    Liu, Juan; Wang, Zheming; Belchik, Sara M.; Edwards, Marcus; Liu, Chongxuan; Kennedy, David W.; Merkley, Eric D.; Lipton, Mary S.; Butt, Julea N.; Richardson, David; Zachara, John M.; Fredrickson, Jim K.; Rosso, Kevin M.; Shi, Liang

    2012-02-08

    The Gram-negative bacterium Sideroxydans lithotrophicus ES-1 (ES-1) grows on FeCO{sub 3} or FeS at oxic-anoxic interfaces at circumneutral pH, and the ES-1-mediated Fe(II) oxidation occurs extracellularly. However, the molecular mechanisms underlying ES-1's ability to oxidize Fe(II) remain unknown. Survey of the ES-1 genome for the genes known for microbial extracellular Fe(II) oxidation revealed that it contained a three-gene cluster encoding an MtrA homologue, an MtrB homologue and a CymA homologue. The homologues of MtrA, MtrB and/or CymA were previously shown to be involved in extracellular Fe(II) oxidation by Rhodopseudomonas palustris TIE-1 and in extracellular Fe(III) reduction by Shewanella oneidensis MR-1 (MR-1). To distinguish them from those found in MR-1, the identified homologues were named MtoAB and CymA{sub ES-1}, respectively. The gene for MtoA was cloned, and cloned mtoA partially complemented an MR-1 mutant without MtrA in ferrihydrite reduction. Following overexpression in MR-1 cells, recombinant MtoA was purified. Characterization of purified MtoA showed that it was a decaheme c-type cytochrome and oxidized soluble Fe(II). Oxidation of Fe(II) by MtoA was pH- and Fe(II)-complexing ligand-dependent. Under conditions tested, MtoA oxidized Fe(II) at pH ranging from 7-9, and optimal oxidation occurred at pH 9, possibly because of the attendant net increase of [Fe(OH){sup +}] at higher pH. MtoA oxidized Fe(II) complexed with different ligands at different rates. The reaction rates followed the order Fe(II)Cl2 > Fe(II)-citrate > Fe(III)-NTA > Fe(II)-EDTA with the second-order rate constants ranging from 5.5 x 10{sup -3} {micro}M{sup -1}s{sup -1} for oxidation of Fe(II)Cl{sub 2} to 1.0 x 10{sup -3} {micro}M{sup -1}s{sup -1} for oxidation of Fe(II)-EDTA. Thermodynamic modeling shows that redox reaction rate differences for the different Fe(II)-complexes correlated with estimated reaction-free energies. Collectively, these results suggest that MtoA is a functional Fe(II)-oxidizing protein that, by working in concert with MtoB and CymAES 1, may oxidize the Fe(II) on the bacterial surface and transfer released electrons across the bacterial cell envelope to the quinone pool in the inner membrane during extracellular Fe(II) oxidation by ES-1.

  17. A Modular Re-configurable Rover System

    NASA Astrophysics Data System (ADS)

    Bouloubasis, A.; McKee, G.; Active Robotics Lab

    In this paper we present the novel concepts incorporated in a planetary surface exploration rover design that is currently under development. The Multitasking Rover (MTR) aims to demonstrate functionality that will cover many of the current and future needs such as rough-terrain mobility, modularity and upgradeability [1]. The rover system has enhanced mobility characteristics. It operates in conjunction with Science Packs (SPs) and Tool Packs (TPs) - modules attached to the main frame of the rover, which are either special tools or science instruments and alter the operation capabilities of the system. To date, each rover system design is very much task driven for example, the scenario of cooperative transportation of extended payloads [2], comprises two rovers each equipped with a manipulator dedicated to the task [3]. The MTR approach focuses mostly on modularity and upgradeability presenting at the same time a fair amount of internal re-configurability for the sake of rough terrain stability. The rover itself does not carry any scientific instruments or tools. To carry out the scenario mentioned above, the MTR would have to locate and pick-up a TP with the associated manipulator. After the completion of the task the TP could be put away to a storage location enabling the rover to utilize a different Pack. The rover will not only offer mobility to these modules, but also use them as tools, transforming its role and functionality. The advantage of this approach is that instead of sending a large number of rovers to perform a variety of tasks, a smaller number of MTRs could be deployed with a large number of SPs/TPs, offering multiples of the functionality at a reduced payload. Two SPs or TPs (or a combination of) can be carried and deployed. One of the key elements in the design of the four wheeled rover, lies within its suspension system. It comprises a linear actuator located within each leg and also an active differential linking the two shoulders. This novel design allows the MTR to lift, lower, roll or tilt its body. It also provides the ability to lift any of the legs by nearly 300mm, enhancing internal re-configurability and therefore rough terrain stability off the robotic vehicle. A modular software and control architecture will be used so that integration to, and operation through the MTR, of different Packs can be demonstrated. An on-board high-level controller [4] will communicate with a small network of micro-controllers through an RS485 bus. Additional processing power could be obtained through a Pack with equivalent or higher computational capabilities. 1 The nature of the system offers many opportunities for behavior based control. The control system must accommodate not only rover based behaviors like obstacle avoidance and vehicle stabilization, but also any additional behaviors that different Packs may introduce. The Ego-Behavior Architecture (EBA) [5] comprises a number of behaviors which operate autonomously and independent of each other. This facilitates the design and suits the operation of the MTR since it fulfills the need for uncomplicated assimilation of new behaviors in the existing architecture. Our work at the moment focuses on the design and construction of the mechanical and electronic systems for the MTR and an associated Pack. References [1] NASA, Human Exploration of Mars: The Reference Mission (Version 3.0 with June, 1998 Addendum) of the NASA Mars Exploration Study Team, Exploration Office, Advanced Development Office, Lyndon B. Johnson Space Center, Houston, TX 77058, June, 1998. [2] A. Trebi-Ollennu, H Das Nayer, H Aghazarian, A ganino, P Pirjanian, B Kennedy, T Huntsberger and P Schenker, Mars Rover Pair Cooperatively Transporting a Long Payload, in Proceedings of the 2002 IEEE International Conference on Robotics and Automation, May 2002, pp. 3136-3141. [3] A. K. Bouloubasis, G. T McKee, P. S. Schenker, A Behavior-Based Manipulator for Multi-Robot Transport Tasks, in proceedings of the IEEE International Conference on Robotics and Automation (ICRA) 2003, Taipei, Taiwan, Septembe

  18. Characterizing streamflow response of a mountaintop mined watershed to changing landuse and climate

    NASA Astrophysics Data System (ADS)

    Zegre, N.; Maxwell, A.; Lamont, S.

    2012-12-01

    Mountaintop removal mining (MTR) is a dominant driver of land use/land cover changes in the Appalachian Region of the eastern United States and is expected to increase in scale in the coming decades. The U.S. EPA estimates that, by 2012, MTR will have impacted 6.8% of the largely forested 4.86 million hectares portion of the Appalachian Coalfield region within West Virginia (WV), Kentucky, Virginia, and Tennessee. Between 1992 and 2002, approximately 1,994 km of headwater streams have been buried, and this number is expected to double to almost 4,000 km in 2012. Several devastating floods in this region have been attributed to this practice and recent studies have demonstrated cumulative aquatic degradation downstream of MTR. Despite its scale and extent, its impact on runoff, particularly at larger spatial scales (10^3 - 10^4 km^2), is poorly understood due to the complex relationships between climate, land use, and hydrology. To explore the impacts of this practice at larger scales, we estimated land use/land cover changes using Landsat 5 TM imagery over five periods between 1994-2010; conducted non-parametric trend analyses on annual streamflow, precipitation, and air temperature; and used a simple rainfall-runoff model to estimate hydrologic response time for the Big Coal River watershed (1,011 km^2) located in the southern WV coalfields. Though not statistically significant, annual streamflow decreased, hydrologic response time increased, air temperature increased, and annual precipitation was geographically variable across the area. Correlation analyses reveals that the decreasing trend in streamflow at annual timescales is likely related to changes in precipitation rather than land use/land cover changes. The lack of statistically detectable trends and correlations between land use change and hydrology at this scale are not entirely unexpected due to the long history and the mosaic of anthropogenic and natural processes and disturbances that span large timescales. In order to better understand the hydrologic impacts of this practice, future research should include multiple spatial (headwater to basin-scale) and temporal (annual to hourly) scales and process-level studies to understand the mechanisms that govern streamflow and flood generation in these heavily disturbed catchments.

  19. Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system.

    PubMed

    Lehmann, Joerg; Hartmann Siantar, Christine; Wessol, Daniel E; Wemple, Charles A; Nigg, David; Cogliati, Josh; Daly, Tom; Descalle, Marie-Anne; Flickinger, Terry; Pletcher, David; Denardo, Gerald

    2005-03-01

    The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4-2%, MCNP-10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of the drug pharmacokinetics in MTR can only be properly accounted for by image-based, patient-specific treatment planning, as has been common in external beam radiation therapy for many years. MINERVA offers 3D Monte Carlo-based MTR treatment planning as its first integrated operational capability. The new MINERVA system will ultimately incorporate capabilities for a comprehensive list of radiation therapies. In progress are modules for external beam photon-electron therapy and boron neutron capture therapy (BNCT). Brachytherapy and proton therapy are planned. Through the open application programming interface (API), other groups can add their own modules and share them with the community. PMID:15798267

  20. Monte Carlo Treatment Planning for Molecular Targeted Radiotherapy within the MINERVA System

    SciTech Connect

    Lehmann, J; Siantar, C H; Wessol, D E; Wemple, C A; Nigg, D; Cogliati, J; Daly, T; Descalle, M; Flickinger, T; Pletcher, D; DeNardo, G

    2004-09-22

    The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry, and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU), and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo-based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (Modality Inclusive Environment for Radiotherapeutic Variable Analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plug-in architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4 - 2%, MCNP - 10%)(Descalle et al. 2003). The code is currently being benchmarked against experimental data. The interpatient variability of the drug pharmacokinetics in MTR can only be properly accounted for by image-based, patient-specific treatment planning as has been common in external beam radiation therapy for many years. MINERVA offers 3D Monte Carlo based MTR treatment planning as its first integrated operational capability. The new MINERVA system will ultimately incorporate capabilities for a comprehensive list of radiation therapies. In progress are modules for external beam photon-electron therapy and Boron Neutron Capture Therapy (BNCT). Brachytherapy and Protontherapy are planned. Through the open Application Programming Interface (API) other groups can add their own modules and share them with the community.

  1. Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system

    NASA Astrophysics Data System (ADS)

    Lehmann, Joerg; Hartmann Siantar, Christine; Wessol, Daniel E.; Wemple, Charles A.; Nigg, David; Cogliati, Josh; Daly, Tom; Descalle, Marie-Anne; Flickinger, Terry; Pletcher, David; DeNardo, Gerald

    2005-03-01

    The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4—2%, MCNP—10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of the drug pharmacokinetics in MTR can only be properly accounted for by image-based, patient-specific treatment planning, as has been common in external beam radiation therapy for many years. MINERVA offers 3D Monte Carlo-based MTR treatment planning as its first integrated operational capability. The new MINERVA system will ultimately incorporate capabilities for a comprehensive list of radiation therapies. In progress are modules for external beam photon-electron therapy and boron neutron capture therapy (BNCT). Brachytherapy and proton therapy are planned. Through the open application programming interface (API), other groups can add their own modules and share them with the community.

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

    PubMed

    Zeng, Xian-Tao; Lu, Jun-Ti; Tang, Xiang-Jun; Weng, Hong; Luo, Jie

    2014-05-01

    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

  3. Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from Vietnam, 2011

    PubMed Central

    2013-01-01

    Background Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. In Vietnam, knowledge regarding N. gonorrhoeae prevalence and AMR is limited, and data concerning genetic characteristics of N. gonorrhoeae is totally lacking. Herein, we investigated the phenotypic AMR (previous, current and possible future treatment options), genetic resistance determinants for extended-spectrum cephalosporins (ESCs), and genotypic distribution of N. gonorrhoeae isolated in 2011 in Hanoi, Vietnam. Methods N. gonorrhoeae isolates from Hanoi, Vietnam isolated in 2011 (n?=?108) were examined using antibiograms (Etest for 10 antimicrobials), Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST), and sequencing of ESC resistance determinants (penA, mtrR and penB). Results The levels of in vitro resistance were as follows: ciprofloxacin 98%, tetracycline 82%, penicillin G 48%, azithromycin 11%, ceftriaxone 5%, cefixime 1%, and spectinomycin 0%. The MICs of gentamicin (0.023-6?mg/L), ertapenem (0.002-0.125?mg/L) and solithromycin (<0.016-0.25?mg/L) were relatively low. No penA mosaic alleles were found, however, 78% of the isolates contained an alteration of amino acid A501 (A501V (44%) and A501T (34%)) in the encoded penicillin-binding protein 2. A single nucleotide (A) deletion in the inverted repeat of the promoter region of the mtrR gene and amino acid alterations in MtrR was observed in 91% and 94% of the isolates, respectively. penB resistance determinants were detected in 87% of the isolates. Seventy-five different NG-MAST STs were identified, of which 59 STs have not been previously described. Conclusions In Vietnam, the highly diversified gonococcal population displayed high in vitro resistance to antimicrobials previously recommended for gonorrhoea treatment (with exception of spectinomycin), but resistance also to the currently recommended ESCs were found. Nevertheless, the MICs of three potential future treatment options were low. It is essential to strengthen the diagnostics, case reporting, and epidemiologic surveillance of gonorrhoea in Vietnam. Furthermore, the surveillance of gonococcal AMR and gonorrhoea treatment failures is imperative to reinforce. Research regarding novel antimicrobial treatment strategies (e.g., combination therapy) and new antimicrobials is crucial for future treatment of gonorrhoea. PMID:23351067

  4. Selenite reduction by Shewanella oneidensis MR-1 is mediated by fumarate reductase in periplasm

    NASA Astrophysics Data System (ADS)

    Li, Dao-Bo; Cheng, Yuan-Yuan; Wu, Chao; Li, Wen-Wei; Li, Na; Yang, Zong-Chuang; Tong, Zhong-Hua; Yu, Han-Qing

    2014-01-01

    In situ reduction of selenite to elemental selenium (Se(0)), by microorganisms in sediments and soils is an important process and greatly affects the environmental distribution and the biological effects of selenium. However, the mechanism behind such a biological process remains unrevealed yet. Here we use Shewanella oneidensis MR-1, a widely-distributed dissimilatory metal-reducing bacterium with a powerful and diverse respiration capability, to evaluate the involvement of anaerobic respiration system in the microbial selenite reduction. With mutants analysis, we identify fumarate reductase FccA as the terminal reductase of selenite in periplasm. Moreover, we find that such a reduction is dependent on central respiration c-type cytochrome CymA. In contrast, nitrate reductase, nitrite reductase, and the Mtr electron transfer pathway do not work as selenite reductases. These findings reveal a previously unrecognized role of anaerobic respiration reductases of S. oneidensis MR-1 in selenite reduction and geochemical cycles of selenium in sediments and soils.

  5. Functional and anatomical properties of human visual cortical fields.

    PubMed

    Zhang, Shouyu; Cate, Anthony D; Herron, Timothy J; Kang, Xiaojian; Yund, E William; Bao, Shanglian; Woods, David L

    2015-04-01

    Human visual cortical fields (VCFs) vary in size and anatomical location across individual subjects. Here, we used functional magnetic resonance imaging (fMRI) with retinotopic stimulation to identify VCFs on the cortical surface. We found that aligning and averaging VCF activations across the two hemispheres provided clear delineation of multiple retinotopic fields in visual cortex. The results show that VCFs have consistent locations and extents in different subjects that provide stable and accurate landmarks for functional and anatomical mapping. Interhemispheric comparisons revealed minor differences in polar angle and eccentricity tuning in comparable VCFs in the left and right hemisphere, and somewhat greater intersubject variability in the right than left hemisphere. We then used the functional boundaries to characterize the anatomical properties of VCFs, including fractional anisotropy (FA), magnetization transfer ratio (MTR) and the ratio of T1W and T2W images and found significant anatomical differences between VCFs and between hemispheres. PMID:25661165

  6. Investigation of the C-Terminal Redox Center of High Mr Thioredoxin Reductase by Protein Engineering and Semisynthesis†

    PubMed Central

    Eckenroth, Brian E.; Lacey, Brian M.; Lothrop, Adam P.; Harris, Katharine M.; Hondal, Robert J.

    2013-01-01

    High molecular weight thioredoxin reductases (TRs) catalyze the reduction of the redoxactive disulfide bond of thioredoxin, but an important difference in the TR family is the sequence of the C-terminal redox-active tetrapeptide that interacts directly with thioredoxin, especially the presence or absence of a selenocysteine (Sec) residue in this tetrapeptide. In this study we have employed protein engineering techniques to investigate the C-terminal redox active tetrapeptides of three different TRs: mouse mitochondrial TR (mTR3), Drosophila melanogaster TR (DmTR), and the mitochondrial TR from C. elegans (CeTR2), which have C-terminal tetrapeptide sequences of Gly-Cys-Sec-Gly, Ser-Cys-Cys-Ser, and Gly-Cys-Cys-Gly, respectively. PMID:17661444

  7. Cr precipitation in neutron irradiated industrial purity Fe-Cr model alloys

    NASA Astrophysics Data System (ADS)

    Kuksenko, V.; Pareige, C.; Pareige, P.

    2013-01-01

    The microstructure of four neutron irradiated Fe-Cr model alloys of industrial purity (Fe-2.5%Cr, Fe-5%Cr, Fe-9%Cr and Fe-12%Cr) has been characterized by atom probe tomography (APT). Irradiation has been performed at 300 °C up to 0.6 dpa in MTR reactor. APT investigations confirmed the enhanced precipitation of ?' clusters as these clusters have only been observed in supersaturated model alloys. In addition a nonexpected family of clusters has been revealed due to irradiation induced segregation of impurities: NiSiPCr-enriched clusters. They might be associated to defect clusters invisible by transmission electron microscopy (TEM). A quantitative description of these objects is presented in this paper and results are compared with TEM and SANS data of the literature obtained on the same model alloy.

  8. Genetic variation in homocysteine metabolism, cognition, and white matter lesions.

    PubMed

    de Lau, Lonneke M L; van Meurs, Joyce B J; Uitterlinden, André G; Smith, A David; Refsum, Helga; Johnston, Carole; Breteler, Monique M B

    2010-11-01

    Several studies have shown an association between homocysteine concentration and cognitive performance or cerebral white matter lesions. However, variations in genes encoding for enzymes and other proteins that play a role in homocysteine metabolism have hardly been evaluated in relation to these outcome measures. In the population-based Rotterdam Scan Study, we examined the association of seven polymorphisms of genes involved in homocysteine metabolism (MTHFR 677C>T, MTHFR 1298A>C, RFC 80G>A, TC 776C>G, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68) with plasma total homocysteine, cognitive performance, and cerebral white matter lesions among 1011 non-demented elderly participants. Of all the studied polymorphisms, only MTHFR 677C>T was associated with homocysteine concentration. No significant relationship was observed for any of the polymorphisms with cognitive performance or severity of cerebral white matter lesions. PMID:19019492

  9. Arx1 functions as an unorthodox nuclear export receptor for the 60S preribosomal subunit.

    PubMed

    Bradatsch, Bettina; Katahira, Jun; Kowalinski, Eva; Bange, Gert; Yao, Wei; Sekimoto, Toshihiro; Baumgärtel, Viola; Boese, Guido; Bassler, Jochen; Wild, Klemens; Peters, Reiner; Yoneda, Yoshihiro; Sinning, Irmi; Hurt, Ed

    2007-09-01

    Shuttling transport receptors carry cargo through nuclear pore complexes (NPCs) via transient interactions with Phe-Gly (FG)-rich nucleoporins. Here, we identify Arx1, a factor associated with a late 60S preribosomal particle in the nucleus, as an unconventional export receptor. Arx1 binds directly to FG nucleoporins and exhibits facilitated translocation through NPCs. Moreover, Arx1 functionally overlaps with the other 60S export receptors, Xpo1 and Mex67-Mtr2, and is genetically linked to nucleoporins. Unexpectedly, Arx1 is structurally unrelated to known shuttling transport receptors but homologous to methionine aminopeptidases (MetAPs), however, without enzymatic activity. Typically, the MetAP fold creates a central cavity that binds the methionine. In contrast, the predicted central cavity of Arx1 is involved in the interaction with FG repeat nucleoporins and 60S subunit export. Thus, an ancient enzyme fold has been adopted by Arx1 to function as a nuclear export receptor. PMID:17803941

  10. Dependence of positive and negative sprite morphology on lightning characteristics and upper atmospheric ambient conditions

    NASA Astrophysics Data System (ADS)

    Qin, Jianqi; Celestin, Sebastien; Pasko, Victor P.

    2013-05-01

    Carrot sprites, exhibiting both upward and downward propagating streamers, and columniform sprites, characterized by predominantly vertical downward streamers, represent two distinct morphological classes of lightning-driven transient luminous events in the upper atmosphere. It is found that positive cloud-to-ground lightning discharges (+CGs) associated with large charge moment changes (QhQ) tend to produce carrot sprites with the presence of a mesospheric region where the electric field exceeds the value 0.8Ek and persists for <mtr columnalign="center">>mtr> columnalign="center">˜mtr>2 ms, whereas those associated with small QhQ are only able to produce columniform sprites. Columniform sprites may also appear in the periphery of a sprite halo produced by +CGs associated with large QhQ. For a sufficiently large QhQ, the time dynamics of the QhQ determines the specific shape of the carrot sprites. In the case when the sufficiently large QhQ is produced mainly by an impulsive return stroke, strong electric field is produced at high altitudes and manifests as a bright halo, and the corresponding conductivity enhancement lowers/enhances the probability of streamer initiation inside/below the sprite halo. A more impulsive return stroke leads to a more significant conductivity enhancement (i.e., a brighter halo). This conductivity enhancement also leads to fast decay and termination of the upper diffuse region of carrot sprites because it effectively screens out the electric field at high altitudes. On the contrary, if the sufficiently large QhQ is produced by a weak return stroke (i.e., a dim halo) accompanied by intense continuing current, the lightning-induced electric field at high altitudes persists at a level that is comparable to Ek, and therefore an extensive upper diffuse region can develop. Furthermore, we demonstrate that `negative sprites' (produced by -CGs) should be necessarily carrot sprites and most likely accompanied by a detectable halo, since the initiation of upward positive streamers is always easier than that of downward negative streamers, and -CGs are usually associated with impulsive return stroke with no continuing current. We also conjecture that in some cases, fast decaying single-headed upward positive streamers produced by -CGs may appear as bright spots/patches. We show that the threshold charge moment changes of positive and negative sprites are, respectively, ~320 and ~500 C km under typical nighttime conditions assumed in this study. These different initiation thresholds, along with the different applied electric field required for stable propagation of positive and negative streamers and the fact that +CGs much more frequently produce large charge moment changes, represent three major factors in the polarity asymmetry of +CGs and -CGs in producing sprite streamers. We further demonstrate that lower mesospheric ambient conductivity leads to smaller threshold charge moment change required for the production of carrot sprites. We suggest that geographical and temporal conductivity variations in the lower ionosphere documented in earlier studies, along with the seasonal and inter-annual variations of thunderstorm activity that lead to different lightning characteristics in the troposphere, account for the different morphological features of sprites observed in different observation campaigns.

  11. Thermal property measurement of solder joints fabricated by self-propagating exothermic reaction in Al/Ni multilayer film

    NASA Astrophysics Data System (ADS)

    Miyake, Shugo; Kanetsuki, Shunsuke; Morino, Katsuya; Kuroishi, Junki; Namazu, Takahiro

    2015-06-01

    To realize the application of reactive joint process to electronic packaging, we analyze thermal resistance for solder joints fabricated by using Al/Ni self-propagating exothermic reaction. Laser flash method with response function analysis is used for thermal resistance measurement. The specimens with 4–8-µm-thick Sn–3.5Ag solder joint have thermal resistances ranging from 5.0 × 10?6 to 8.1 × 10?6 m2 K/W. In the specimen with 12-µm-thick SnAg solder joint, periodical heating analysis suggests that high and low thermal resistance areas happen to coexist due to incomplete bonding. Micro thermo-reflectance (m-TR) analysis suggests that thermal effusivity of reacted NiAl layer is lower than expected. Thermal resistance of the joints will be influenced by voids, cracks, and grain boundaries in reacted NiAl layer.

  12. Application of derivative spectrophotometry under orthogonal polynomial at unequal intervals: determination of metronidazole and nystatin in their pharmaceutical mixture.

    PubMed

    Korany, Mohamed A; Abdine, Heba H; Ragab, Marwa A A; Aboras, Sara I

    2015-05-15

    This paper discusses a general method for the use of orthogonal polynomials for unequal intervals (OPUI) to eliminate interferences in two-component spectrophotometric analysis. In this paper, a new approach was developed by using first derivative D1 curve instead of absorbance curve to be convoluted using OPUI method for the determination of metronidazole (MTR) and nystatin (NYS) in their mixture. After applying derivative treatment of the absorption data many maxima and minima points appeared giving characteristic shape for each drug allowing the selection of different number of points for the OPUI method for each drug. This allows the specific and selective determination of each drug in presence of the other and in presence of any matrix interference. The method is particularly useful when the two absorption spectra have considerable overlap. The results obtained are encouraging and suggest that the method can be widely applied to similar problems. PMID:25748283

  13. Far field tsunami simulations of the 1755 Lisbon earthquake: Implications for tsunami hazard to the U.S. East Coast and the Caribbean

    USGS Publications Warehouse

    Barkan, R.; ten Brink, U.S.; Lin, J.

    2009-01-01

    The great Lisbon earthquake of November 1st, 1755 with an estimated moment magnitude of 8.5-9.0 was the most destructive earthquake in European history. The associated tsunami run-up was reported to have reached 5-15??m along the Portuguese and Moroccan coasts and the run-up was significant at the Azores and Madeira Island. Run-up reports from a trans-oceanic tsunami were documented in the Caribbean, Brazil and Newfoundland (Canada). No reports were documented along the U.S. East Coast. Many attempts have been made to characterize the 1755 Lisbon earthquake source using geophysical surveys and modeling the near-field earthquake intensity and tsunami effects. Studying far field effects, as presented in this paper, is advantageous in establishing constraints on source location and strike orientation because trans-oceanic tsunamis are less influenced by near source bathymetry and are unaffected by triggered submarine landslides at the source. Source location, fault orientation and bathymetry are the main elements governing transatlantic tsunami propagation to sites along the U.S. East Coast, much more than distance from the source and continental shelf width. Results of our far and near-field tsunami simulations based on relative amplitude comparison limit the earthquake source area to a region located south of the Gorringe Bank in the center of the Horseshoe Plain. This is in contrast with previously suggested sources such as Marqu??s de Pombal Fault, and Gulf of C??diz Fault, which are farther east of the Horseshoe Plain. The earthquake was likely to be a thrust event on a fault striking ~ 345?? and dipping to the ENE as opposed to the suggested earthquake source of the Gorringe Bank Fault, which trends NE-SW. Gorringe Bank, the Madeira-Tore Rise (MTR), and the Azores appear to have acted as topographic scatterers for tsunami energy, shielding most of the U.S. East Coast from the 1755 Lisbon tsunami. Additional simulations to assess tsunami hazard to the U.S. East Coast from possible future earthquakes along the Azores-Iberia plate boundary indicate that sources west of the MTR and in the Gulf of Cadiz may affect the southeastern coast of the U.S. The Azores-Iberia plate boundary west of the MTR is characterized by strike-slip faults, not thrusts, but the Gulf of Cadiz may have thrust faults. Southern Florida seems to be at risk from sources located east of MTR and South of the Gorringe Bank, but it is mostly shielded by the Bahamas. Higher resolution near-shore bathymetry along the U.S. East Coast and the Caribbean as well as a detailed study of potential tsunami sources in the central west part of the Horseshoe Plain are necessary to verify our simulation results. ?? 2008 Elsevier B.V.

  14. Development and experimental validation of a calculation scheme for nuclear heating evaluation in the core of the OSIRIS material testing reactor

    SciTech Connect

    Malouch, F. [Saclay Center CEA, DEN/DANS/DM2S/SERMA, F-91191 Gif-sur-Yvette Cedex (France)

    2011-07-01

    The control of the temperature in material samples irradiated in a material testing reactor requires the knowledge of the nuclear heating caused by the energy deposition by neutrons and photons interacting in the irradiation device structures. Thus, a neutron-photonic three-dimensional calculation scheme has been developed to evaluate the nuclear heating in experimental devices irradiated in the core of the OSIRIS MTR reactor (CEA/Saclay Center). The aim is to obtain a predictive tool for the nuclear heating estimation in irradiation devices. This calculation scheme is mainly based on the TRIPOLI-4 three-dimensional continuous-energy Monte Carlo transport code, developed by CEA (Saclay Center). An experimental validation has been carried out on the basis of nuclear heating measurements performed in the OSIRIS core. After an overview of the experimental devices irradiated in the OSIRIS reactor, we present the calculation scheme and the first results of the experimental validation. (authors)

  15. Preliminary neutronic analysis of a cavity test reactor

    NASA Technical Reports Server (NTRS)

    Whitmarsh, C. L., Jr.

    1973-01-01

    A reference configuration was calculated for a cavity test reactor to be used for testing the gascore nuclear rocket concept. A thermal flux of 4.1 x 10 to the 14th power neutrons per square centimeter per second in the cavity was provided by a driver fuel loading of 6.4 kg of enriched uranium in MTR fuel elements. The reactor was moderated and cooled by heavy water and reflected with 25.4 cm of beryllium. Power generation of 41.3 MW in the driver fuel is rejected to a heat sink. Design effort was directed toward minimization of driver power while maintaining 2.7 MW in the cavity during a test run. Ancillary data on material reactivity worths, reactivity coefficients, flux spectra, and power distributions are reported.

  16. Detailed Sunyaev-Zel'dovich study with AMI of 19 LoCuSS galaxy clusters: masses and temperatures out to the virial radius

    NASA Astrophysics Data System (ADS)

    AMI Consortium; Rodríguez-Gonzálvez, Carmen; Shimwell, Timothy W.; Davies, Matthew L.; Feroz, Farhan; Franzen, Thomas M. O.; Grainge, Keith J. B.; Hobson, Michael P.; Hurley-Walker, Natasha; Lasenby, Anthony N.; Olamaie, Malak; Pooley, Guy; Saunders, Richard D. E.; Scaife, Anna M. M.; Schammel, Michel P.; Scott, Paul F.; Titterington, David J.; Waldram, Elizabeth M.

    2012-09-01

    We present detailed 16-GHz interferometric observations using the Arcminute Microkelvin Imager (AMI) of 19 clusters with LX > 7 × 1037 W (h50 = 1) selected from the Local Cluster Substructure Survey (LoCuSS; 0.142 ? z ? 0.295) and of Abell 1758b, which is in the field of view of Abell 1758a. We detect and resolve Sunyaev-Zel'dovich (SZ) signals towards 17 clusters, with peak surface brightnesses between 5? and 23?. We use a fast, Bayesian cluster analysis to obtain cluster parameter estimates in the presence of radio point sources, receiver noise and primordial cosmic microwave background (CMB) anisotropy. We fit isothermal ?-models to our data and assume the clusters are virialized (with all the kinetic energy in gas internal energy). Our gas temperature, TAMI, is derived from AMI SZ data and not from X-ray spectroscopy. Cluster parameters internal to r500 are derived under the assumption of hydrostatic equilibrium. We find the following. (i) Different generalized Navarro-Frenk-White (gNFW) parametrizations yield significantly different parameter degeneracies. (ii) For h70 = 1, we find the classical virial radius, r200, to be typically 1.6 ± 0.1 Mpc and the total mass MT(r200) typically to be 2.0-2.5× MT(r500). (iii) Where we have found MT(r500) and MT(r200) X-ray and weak-lensing values in the literature, there is good agreement between weak-lensing and AMI estimates (with MT, AMI/MT, WL =1.2-0.3+0.2 and 1.0 ± 0.1 for r500 and r200, respectively). In comparison, most Suzaku/Chandra estimates are higher than for AMI (with MT, X/MT, AMI = 1.7 ± 0.2 within r500), particularly for the stronger mergers. (iv) Comparison of TAMI to TX sheds light on high X-ray masses: even at large radius, TX can substantially exceed TAMI in mergers. The use of these higher TX values will give higher X-ray masses. We stress that large-radius TAMI and TX data are scarce and must be increased. (v) Despite the paucity of data, there is an indication of a relation between merger activity and SZ ellipticity. (vi) At small radius (but away from any cooling flow) the SZ signal (and TAMI) is less sensitive to intracluster medium disturbance than the X-ray signal (and TX) and, even at high radius, mergers affect n2-weighted X-ray data more than n-weighted SZ, implying that significant shocking or clumping or both occur in even the outer parts of mergers. We request that any reference to this paper cites 'AMI Consortium: Rodríguez-Gonzálvez et al. 2012'.

  17. Effective delayed neutron fraction and prompt neutron lifetime of Tehran research reactor mixed-core.

    PubMed

    Lashkari, A; Khalafi, H; Kazeminejad, H

    2013-05-01

    In this work, kinetic parameters of Tehran research reactor (TRR) mixed cores have been calculated. The mixed core configurations are made by replacement of the low enriched uranium control fuel elements with highly enriched uranium control fuel elements in the reference core. The MTR_PC package, a nuclear reactor analysis tool, is used to perform the analysis. Simulations were carried out to compute effective delayed neutron fraction and prompt neutron lifetime. Calculation of kinetic parameters is necessary for reactivity and power excursion transient analysis. The results of this research show that effective delayed neutron fraction decreases and prompt neutron lifetime increases with the fuels burn-up. Also, by increasing the number of highly enriched uranium control fuel elements in the reference core, the prompt neutron lifetime increases, but effective delayed neutron fraction does not show any considerable change. PMID:24976672

  18. Effective delayed neutron fraction and prompt neutron lifetime of Tehran research reactor mixed-core

    PubMed Central

    Lashkari, A.; Khalafi, H.; Kazeminejad, H.

    2013-01-01

    In this work, kinetic parameters of Tehran research reactor (TRR) mixed cores have been calculated. The mixed core configurations are made by replacement of the low enriched uranium control fuel elements with highly enriched uranium control fuel elements in the reference core. The MTR_PC package, a nuclear reactor analysis tool, is used to perform the analysis. Simulations were carried out to compute effective delayed neutron fraction and prompt neutron lifetime. Calculation of kinetic parameters is necessary for reactivity and power excursion transient analysis. The results of this research show that effective delayed neutron fraction decreases and prompt neutron lifetime increases with the fuels burn-up. Also, by increasing the number of highly enriched uranium control fuel elements in the reference core, the prompt neutron lifetime increases, but effective delayed neutron fraction does not show any considerable change. PMID:24976672

  19. Conversion and Evaluation of the University of Massachusetts Lowell Research Reactor From High-Enriched To Low-Enriched Uranium Fuel

    SciTech Connect

    Leo M. Bobek

    2003-11-19

    The process for converting the University of Massachusetts Lowell Research Reactor (UMLRR) from high-enrichment uranium (HEU) fuel to low-enrichment uranium (LEU) fuel began in 1988. Several years of design reviews, computational modeling, and thermal hydraulic analyses resulted in a preliminary reference core design and configuration based on 20 standard, MTR-type, flat-plate, 19.75% enriched, uranium silicide (u3Si2) fuel elements. A final safety analysis for the fuel conversion was submitted to the Nuclear Regulatory Commission (NRC) in 1993. The NRC made two additional requests for additional information and supplements were submitted in 1994 and 1997. The new UMLRR Reactor Supervisor initiated an effort to change the LEU reference core configuration to eliminate a complicated control rod modification needed for the smaller core.

  20. An Advanced Reader in Chinese Literature

    E-print Network

    Johnson, Wallace

    1978-01-01

    ^^^^ai '^TC763- 7 6 4? 8. 21-^M^ r fv ^ lE^S^M-ii > *fiafc-ftMfcf _?^ 26 mm ? & 21mm ^$- Ho 9. 1.MT |,f. ^T ? *?*? ffit> mm o zimMmm ^ ^ % MTR 9. 13...* & /- 2. .^ #g ^ ^g #j? ? % % mm ^ m ? i2a|ifBJI? rH'1 g a A?g B A o 12. 6. m l * ffil& o SiifbT flff^tBWlfr ? 12 7.- SfcM -- |v 5- *N 3cI??!J^ nJ^fetfttik # o 4t f' ^ j@ fl^J o 12 m&m r^ Si?^W? 92 at era PR! H i.nmtt%igM]rto?.2E ? Mm ? 93...

  1. Application of derivative spectrophotometry under orthogonal polynomial at unequal intervals: Determination of metronidazole and nystatin in their pharmaceutical mixture

    NASA Astrophysics Data System (ADS)

    Korany, Mohamed A.; Abdine, Heba H.; Ragab, Marwa A. A.; Aboras, Sara I.

    2015-05-01

    This paper discusses a general method for the use of orthogonal polynomials for unequal intervals (OPUI) to eliminate interferences in two-component spectrophotometric analysis. In this paper, a new approach was developed by using first derivative D1 curve instead of absorbance curve to be convoluted using OPUI method for the determination of metronidazole (MTR) and nystatin (NYS) in their mixture. After applying derivative treatment of the absorption data many maxima and minima points appeared giving characteristic shape for each drug allowing the selection of different number of points for the OPUI method for each drug. This allows the specific and selective determination of each drug in presence of the other and in presence of any matrix interference. The method is particularly useful when the two absorption spectra have considerable overlap. The results obtained are encouraging and suggest that the method can be widely applied to similar problems.

  2. Simulations of MATROSHKA experiments at ISS using PHITS

    E-print Network

    Sihver, L; Puchalska, M; Reitz, G

    2010-01-01

    Concerns about the biological effects of space radiation are increasing rapidly due to the perspective of long-duration manned missions, both in relation to the International Space Station (ISS) and to manned interplanetary missions to Moon and Mars in the future. As a preparation for these long duration space missions it is important to ensure an excellent capability to evaluate the impact of space radiation on human health in order to secure the safety of the astronauts/cosmonauts and minimize their risks. It is therefore necessary to measure the radiation load on the personnel both inside and outside the space vehicles and certify that organ and tissue equivalent doses can be simulated as accurate as possible. In this paper we will present simulations using the three-dimensional Monte Carlo Particle and Heavy Ion Transport code System (PHITS) of long term dose measurements performed with the ESA supported experiment MATROSHKA (MTR), which is an anthropomorphic phantom containing over 6000 radiation detecto...

  3. The CCR4-NOT Complex Physically and Functionally Interacts with TRAMP and the Nuclear Exosome

    PubMed Central

    Azzouz, Nowel; Panasenko, Olesya O.; Colau, Geoffroy; Collart, Martine A.

    2009-01-01

    Background Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. Methodology/Principal Findings In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. Conclusions/Significance We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation. PMID:19707589

  4. Exploring the molecular mechanisms of electron shuttling across the microbe/metal space

    PubMed Central

    Paquete, Catarina M.; Fonseca, Bruno M.; Cruz, Davide R.; Pereira, Tiago M.; Pacheco, Isabel; Soares, Cláudio M.; Louro, Ricardo O.

    2014-01-01

    Dissimilatory metal reducing organisms play key roles in the biogeochemical cycle of metals as well as in the durability of submerged and buried metallic structures. The molecular mechanisms that support electron transfer across the microbe-metal interface in these organisms remain poorly explored. It is known that outer membrane proteins, in particular multiheme cytochromes, are essential for this type of metabolism, being responsible for direct and indirect, via electron shuttles, interaction with the insoluble electron acceptors. Soluble electron shuttles such as flavins, phenazines, and humic acids are known to enhance extracellular electron transfer. In this work, this phenomenon was explored. All known outer membrane decaheme cytochromes from Shewanella oneidensis MR-1 with known metal terminal reductase activity and a undecaheme cytochrome from Shewanella sp. HRCR-6 were expressed and purified. Their interactions with soluble electron shuttles were studied using stopped-flow kinetics, NMR spectroscopy, and molecular simulations. The results show that despite the structural similarities, expected from the available structural data and sequence homology, the detailed characteristics of their interactions with soluble electron shuttles are different. MtrC and OmcA appear to interact with a variety of different electron shuttles in the close vicinity of some of their hemes, and with affinities that are biologically relevant for the concentrations typical found in the medium for this type of compounds. All data support a view of a distant interaction between the hemes of MtrF and the electron shuttles. For UndA a clear structural characterization was achieved for the interaction with AQDS a humic acid analog. These results provide guidance for future work of the manipulation of these proteins toward modulation of their role in metal attachment and reduction. PMID:25018753

  5. Efficacy and side effects of diclofenac patch in treatment of patients with myofascial pain syndrome of the upper trapezius.

    PubMed

    Hsieh, Lin-Fen; Hong, Chang-Zern; Chern, Shiuan-Horng; Chen, Chen-Chiao

    2010-01-01

    Locally administered nonsteroidal anti-inflammatory drugs have been widely used in acute soft-tissue damage and articular musculoskeletal pain. This double-blind, placebo-controlled, randomized study was designed to evaluate the efficacy and safety of a topical diclofenac sodium patch in the relief of pain and inflammation as a result of myofascial pain syndrome (MPS) in the upper trapezius. After sample size calculations indicated that 147 patients would be needed to detect a 25% difference between drug and control, 153 patients with MPS were recruited and randomized to receive either a diclofenac sodium patch or control (menthol) patch. Visual analog scale (VAS), cervical active range of motion, pressure pain threshold of the myofascial trigger point (MTrP), patient global assessment, Neck Disability Index, and the occurrence of adverse events were assessed on Day 0 (baseline), Day 4, and Day 8. Use of the diclofenac sodium patch elicited favorable responses for the VAS, cervical active range of motion, and Neck Disability Index by the end of the treatment course (P<0.05), and was consistently superior to the control patch at all time intervals. No significant differences were observed for the pressure pain threshold of the MTrP for either patch. Tolerability assessment similarly showed the diclofenac patch to be comparatively superior. When assessed at the end of the study, 20 diclofenac patch patients, but only four control patients, considered the tolerability of treatment to be "very good." Significant differences in adverse reactions were observed between the diclofenac and control patches, with the control patch more likely to produce overall skin irritation. This study demonstrate that the diclofenac sodium patch was superior to the control patch in terms of reducing pain and improving functional outcomes, and did not result in significant adverse effects. PMID:19822404

  6. Jules Horowitz Reactor: a high performance material testing reactor

    NASA Astrophysics Data System (ADS)

    Iracane, Daniel; Chaix, Pascal; Alamo, Ana

    2008-04-01

    The physical modelling of materials' behaviour under severe conditions is an indispensable element for developing future fission and fusion systems: screening, design, optimisation, processing, licensing, and lifetime assessment of a new generation of structure materials and fuels, which will withstand high fast neutron flux at high in-service temperatures with the production of elements like helium and hydrogen. JANNUS and other analytical experimental tools are developed for this objective. However, a purely analytical approach is not sufficient: there is a need for flexible experiments integrating higher scales and coupled phenomena and offering high quality measurements; these experiments are performed in material testing reactors (MTR). Moreover, complementary representative experiments are usually performed in prototypes or dedicated facilities such as IFMIF for fusion. Only such a consistent set of tools operating on a wide range of scales, can provide an actual prediction capability. A program such as the development of silicon carbide composites (600-1200 °C) illustrates this multiscale strategy. Facing the long term needs of experimental irradiations and the ageing of present MTRs, it was thought necessary to implement a new generation high performance MTR in Europe for supporting existing and future nuclear reactors. The Jules Horowitz Reactor (JHR) project copes with this context. It is funded by an international consortium and will start operation in 2014. JHR will provide improved performances such as high neutron flux ( 10 n/cm/s above 0.1 MeV) in representative environments (coolant, pressure, temperature) with online monitoring of experimental parameters (including stress and strain control). Experimental devices designing, such as high dpa and small thermal gradients experiments, is now a key objective requiring a broad collaboration to put together present scientific state of art, end-users requirements and advanced instrumentation. To cite this article: D. Iracane et al., C. R. Physique 9 (2008).

  7. Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia

    PubMed Central

    Roffman, Joshua L.; Brohawn, David G.; Nitenson, Adam Z.; Macklin, Eric A.; Smoller, Jordan W.; Goff, Donald C.

    2013-01-01

    Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients. PMID:22021659

  8. Transcriptional and proteomic analyses of two-component response regulators in multidrug-resistant Mycobacterium tuberculosis.

    PubMed

    Zhou, Lei; Yang, Liu; Zeng, Xianfei; Danzheng, Jiacuo; Zheng, Qing; Liu, Jiayun; Liu, Feng; Xin, Yijuan; Cheng, Xiaodong; Su, Mingquan; Ma, Yueyun; Hao, Xiaoke

    2015-07-01

    Two-component systems (TCSs) have been reported to exhibit a sensing and responding role under drug stress that induces drug resistance in several bacterial species. However, the relationship between TCSs and multidrug resistance in Mycobacterium tuberculosis has not been comprehensively analysed to date. In this study, 90 M. tuberculosis clinical isolates were analysed using 15-loci mycobacterial interspersed repetitive unit (MIRU)-variable number tandem repeat (VNTR) typing and repetitive extragenic palindromic (rep)-PCR-based DNA fingerprinting. The results showed that all of the isolates were of the Beijing lineage, and strains with a drug-susceptible phenotype had not diverged into similar genotype clusters. Expression analysis of 13 response regulators of TCSs using real-time PCR and tandem mass spectrometry (MS/MS) proteomic analysis demonstrated that four response regulator genes (devR, mtrA, regX3 and Rv3143) were significantly upregulated in multidrug-resistant (MDR) strains compared with the laboratory strain H37Rv as well as drug-susceptible and isoniazid-monoresistant strains (P<0.05). DNA sequencing revealed that the promoter regions of devR, mtrA, regX3 and Rv3143 did not contain any mutations. Moreover, expression of the four genes could be induced by most of the four first-line antitubercular agents. In addition, either deletion or overexpression of devR in Mycobacterium bovis BCG did not alter its sensitivity to the four antitubercular drugs. This suggests that upregulation of devR, which is common in MDR-TB strains, might be induced by drug stress and hypoxic adaptation following the acquisition of multidrug resistance. PMID:25937537

  9. Effect of yoga on the Myofascial Pain Syndrome of neck.

    PubMed

    Sharan, D; Manjula, M; Urmi, D; Ajeesh, Ps

    2014-01-01

    Myofascial Pain Syndrome (MPS) refers to pain attributed to muscle and its surrounding fascia, which is associated with "myofascial trigger points" (MTrPs). MTrPs in the trapezius has been proposed as the main cause of temporal and cervicogenic headache and neck pain. Literature shows that the prevalence of various musculoskeletal disorders (MSD) among physiotherapists is high. Yoga has traditionally been used to treat MSDs in various populations. But there is scarcity of literature which explains the effects of yoga on reducing MPS of the neck in terms of various physical parameters and subjective responses. Therefore, a pilot study was done among eight physiotherapists with minimum six months of experience. A structured yoga protocol was designed and implemented for five days in a week for four weeks. The outcome variables were Disability of Arm, Shoulder and Hands (DASH) score, Neck Disability Index (NDI), Visual Analogue Scale (VAS), Pressure Pain Threshold (PPT) for Trigger Points, Cervical Range of Motion (CROM) - active & passive, grip and pinch strengths. The variables were compared before and after the intervention. Finally, the result revealed that all the variables (DASH: P<0.00, NDI: P<0.00, VAS: P<0.00, PPT: Left: P<0.00, PPT: Right: P<0.00, Grip strength: left: P<0.00, Grip strength: right: P<0.01, Key pinch: left: P<0.01, Key pinch: right: P<0.01, Palmar pinch: left: P<0.01, Palmar pinch: right: P<0.00, Tip pinch: left: P<0.01, Tip pinch: Right: P<0.01) improved significantly after intervention. PMID:25035608

  10. Shewanella oneidensis MR-1 Uses Overlapping Pathways for Iron Reduction at a Distance and by Direct Contact under Conditions Relevant for Biofilms

    PubMed Central

    Lies, Douglas P.; Hernandez, Maria E.; Kappler, Andreas; Mielke, Randall E.; Gralnick, Jeffrey A.; Newman, Dianne K.

    2005-01-01

    We developed a new method to measure iron reduction at a distance based on depositing Fe(III) (hydr)oxide within nanoporous glass beads. In this “Fe-bead” system, Shewanella oneidensis reduces at least 86.5% of the iron in the absence of direct contact. Biofilm formation accompanies Fe-bead reduction and is observable both macro- and microscopically. Fe-bead reduction is catalyzed by live cells adapted to anaerobic conditions, and maximal reduction rates require sustained protein synthesis. The amount of reactive ferric iron in the Fe-bead system is available in excess such that the rate of Fe-bead reduction is directly proportional to cell density; i.e., it is diffusion limited. Addition of either lysates prepared from anaerobic cells or exogenous electron shuttles stimulates Fe-bead reduction by S. oneidensis, but iron chelators or additional Fe(II) do not. Neither dissolved Fe(III) nor electron shuttling activity was detected in culture supernatants, implying that the mediator is retained within the biofilm matrix. Strains with mutations in omcB or mtrB show about 50% of the wild-type levels of reduction, while a cymA mutant shows less than 20% of the wild-type levels of reduction and a menF mutant shows insignificant reduction. The Fe-bead reduction defect of the menF mutant can be restored by addition of menaquinone, but menaquinone itself cannot stimulate Fe-bead reduction. Because the menF gene encodes the first committed step of menaquinone biosynthesis, no intermediates of the menaquinone biosynthetic pathway are used as diffusible mediators by this organism to promote iron reduction at a distance. CymA and menaquinone are required for both direct and indirect mineral reduction, whereas MtrB and OmcB contribute to but are not absolutely required for iron reduction at a distance. PMID:16085832

  11. Quantitative multi-modal MRI of the Hippocampus and cognitive ability in community-dwelling older subjects

    PubMed Central

    Aribisala, Benjamin S.; Royle, Natalie A.; Maniega, Susana Muñoz; Valdés Hernández, Maria C.; Murray, Catherine; Penke, Lars; Gow, Alan; Starr, John M.; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.

    2014-01-01

    Hippocampal structural integrity is commonly quantified using volumetric measurements derived from brain magnetic resonance imaging (MRI). Previously reported associations with cognitive decline have not been consistent. We investigate hippocampal integrity using quantitative MRI techniques and its association with cognitive abilities in older age. Participants from the Lothian Birth Cohort 1936 underwent brain MRI at mean age 73 years. Longitudinal relaxation time (T1), magnetization transfer ratio (MTR), fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampus. General factors of fluid-type intelligence (g), cognitive processing speed (speed) and memory were obtained at age 73 years, as well as childhood IQ test results at age 11 years. Amongst 565 older adults, multivariate linear regression showed that, after correcting for ICV, gender and age 11 IQ, larger left hippocampal volume was significantly associated with better memory ability (? = .11, p = .003), but not with speed or g. Using quantitative MRI and after correcting for multiple testing, higher T1 and MD were significantly associated with lower scores of g (? range = ?.11 to ?.14, p < .001), speed (? range = ?.15 to ?.20, p < .001) and memory (? range = ?.10 to ?.12, p < .001). Higher MTR and FA in the hippocampus were also significantly associated with higher scores of g (? range = .17 to .18, p < .0001) and speed (? range = .10 to .15, p < .0001), but not memory. Quantitative multi-modal MRI assessments were more sensitive at detecting cognition-hippocampal integrity associations than volumetric measurements, resulting in stronger associations between MRI biomarkers and age-related cognition changes. PMID:24561387

  12. Joint effects between urinary selenium and polymorphisms in methylation related genes on breast cancer risk.

    PubMed

    Lin, W; Cen, Y L; Lin, Y; Su, F X; Wu, B H; Tang, L Y; Ren, Z F

    2015-01-01

    The aim of this study was to explore the associations of urinary selenium and polymorphisms in methylation related genes with breast cancer risk and the interactions on the risk. The present study involved in 240 female patients with incident breast cancer and 246 age-matched controls in two affiliated hospitals of Sun Yat-sen University in Guangzhou, China, from October 2009 to July 2010. DNMT1 rs2228611, MTHFR rs1801133, and MTR rs1805087 were genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Urinary concentration of selenium was measured by inductively coupled plasma mass spectrometry. Women with urinary selenium in the second tertile had a significant reduced breast cancer risk compared to those with urinary selenium in the lowest tertile [OR (95%CI): 0.50 (0.30, 0.81)]. DNMT1 rs2228611, MTHFR rs1801133, and MTR rs1805087 were not associated with breast cancer risk. Women with the third tertile of urinary selenium had a significant reduced breast cancer risk compared to those with the lowest tertile among women only with CC genotype [OR (95%CI): 0.55 (0.30, 1.00)] but not CT/TT genotypes [OR (95%CI): 1.58 (0.73, 3.42)] of MTHFR rs1801133 (P for interaction=0.044). Our results suggested that selenium was associated with a decreased risk of breast cancer and this beneficial effect was limited to women with CC genotype of MTHFR rs1801133. PMID:25869796

  13. ADvanced IMage Algebra (ADIMA): a novel method for depicting multiple sclerosis lesion heterogeneity, as demonstrated by quantitative MRI

    PubMed Central

    Tozer, Daniel J; Schmierer, Klaus; Chard, Declan T; Anderson, Valerie M; Altmann, Daniel R; Miller, David H; Wheeler-Kingshott, Claudia AM

    2013-01-01

    Background: There are modest correlations between multiple sclerosis (MS) disability and white matter lesion (WML) volumes, as measured by T2-weighted (T2w) magnetic resonance imaging (MRI) scans (T2-WML). This may partly reflect pathological heterogeneity in WMLs, which is not apparent on T2w scans. Objective: To determine if ADvanced IMage Algebra (ADIMA), a novel MRI post-processing method, can reveal WML heterogeneity from proton-density weighted (PDw) and T2w images. Methods: We obtained conventional PDw and T2w images from 10 patients with relapsing–remitting MS (RRMS) and ADIMA images were calculated from these. We classified all WML into bright (ADIMA-b) and dark (ADIMA-d) sub-regions, which were segmented. We obtained conventional T2-WML and T1-WML volumes for comparison, as well as the following quantitative magnetic resonance parameters: magnetisation transfer ratio (MTR), T1 and T2. Also, we assessed the reproducibility of the segmentation for ADIMA-b, ADIMA-d and T2-WML. Results: Our study’s ADIMA-derived volumes correlated with conventional lesion volumes (p < 0.05). ADIMA-b exhibited higher T1 and T2, and lower MTR than the T2-WML (p < 0.001). Despite the similarity in T1 values between ADIMA-b and T1-WML, these regions were only partly overlapping with each other. ADIMA-d exhibited quantitative characteristics similar to T2-WML; however, they were only partly overlapping. Mean intra- and inter-observer coefficients of variation for ADIMA-b, ADIMA-d and T2-WML volumes were all < 6 % and < 10 %, respectively. Conclusion: ADIMA enabled the simple classification of WML into two groups having different quantitative magnetic resonance properties, which can be reproducibly distinguished. PMID:23037551

  14. Association of dietary and genetic factors related to one-carbon metabolism with global methylation level of leukocyte DNA.

    PubMed

    Ono, Hiroe; Iwasaki, Motoki; Kuchiba, Aya; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Ohnami, Sumiko; Sakamoto, Hiromi; Yoshida, Teruhiko; Tsugane, Shoichiro

    2012-12-01

    Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one-carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross-sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03-0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (P(interaction)  = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females. PMID:22957669

  15. Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.

    PubMed

    Roffman, Joshua L; Brohawn, David G; Nitenson, Adam Z; Macklin, Eric A; Smoller, Jordan W; Goff, Donald C

    2013-03-01

    Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients. PMID:22021659

  16. Quantitative multi-modal MRI of the Hippocampus and cognitive ability in community-dwelling older subjects.

    PubMed

    Aribisala, Benjamin S; Royle, Natalie A; Maniega, Susana Muñoz; Valdés Hernández, Maria C; Murray, Catherine; Penke, Lars; Gow, Alan; Starr, John M; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

    2014-04-01

    Hippocampal structural integrity is commonly quantified using volumetric measurements derived from brain magnetic resonance imaging (MRI). Previously reported associations with cognitive decline have not been consistent. We investigate hippocampal integrity using quantitative MRI techniques and its association with cognitive abilities in older age. Participants from the Lothian Birth Cohort 1936 underwent brain MRI at mean age 73 years. Longitudinal relaxation time (T1), magnetization transfer ratio (MTR), fractional anisotropy (FA) and mean diffusivity (MD) were measured in the hippocampus. General factors of fluid-type intelligence (g), cognitive processing speed (speed) and memory were obtained at age 73 years, as well as childhood IQ test results at age 11 years. Amongst 565 older adults, multivariate linear regression showed that, after correcting for ICV, gender and age 11 IQ, larger left hippocampal volume was significantly associated with better memory ability (? = .11, p = .003), but not with speed or g. Using quantitative MRI and after correcting for multiple testing, higher T1 and MD were significantly associated with lower scores of g (? range = -.11 to -.14, p < .001), speed (? range = -.15 to -.20, p < .001) and memory (? range = -.10 to -.12, p < .001). Higher MTR and FA in the hippocampus were also significantly associated with higher scores of g (? range = .17 to .18, p < .0001) and speed (? range = .10 to .15, p < .0001), but not memory. Quantitative multi-modal MRI assessments were more sensitive at detecting cognition-hippocampal integrity associations than volumetric measurements, resulting in stronger associations between MRI biomarkers and age-related cognition changes. PMID:24561387

  17. Metagenomic Insights into Anaerobic Metabolism along an Arctic Peat Soil Profile

    PubMed Central

    Lipson, David A.; Haggerty, John Matthew; Srinivas, Archana; Raab, Theodore K.; Sathe, Shashank; Dinsdale, Elizabeth A.

    2013-01-01

    A metagenomic analysis was performed on a soil profile from a wet tundra site in northern Alaska. The goal was to link existing biogeochemical knowledge of the system with the organisms and genes responsible for the relevant metabolic pathways. We specifically investigated how the importance of iron (Fe) oxides and humic substances (HS) as terminal electron acceptors in this ecosystem is expressed genetically, and how respiratory and fermentative processes varied with soil depth into the active layer and into the upper permafrost. Overall, the metagenomes reflected a microbial community enriched in a diverse range of anaerobic pathways, with a preponderance of known Fe reducing species at all depths in the profile. The abundance of sequences associated with anaerobic metabolic processes generally increased with depth, while aerobic cytochrome c oxidases decreased. Methanogenesis genes and methanogen genomes followed the pattern of CH4 fluxes : they increased steeply with depth into the active layer, but declined somewhat over the transition zone between the lower active layer and the upper permafrost. The latter was relatively enriched in fermentative and anaerobic respiratory pathways. A survey of decaheme cytochromes (MtrA, MtrC and their homologs) revealed that this is a promising approach to identifying potential reducers of Fe(III) or HS, and indicated a possible role for Acidobacteria as Fe reducers in these soils. Methanogens appear to coexist in the same layers, though in lower abundance, with Fe reducing bacteria and other potential competitors, including acetogens. These observations provide a rich set of hypotheses for further targeted study. PMID:23741360

  18. Clonally Related Neisseria gonorrhoeae Isolates with Decreased Susceptibility to the Extended-Spectrum Cephalosporin Cefotaxime in Amsterdam, the Netherlands

    PubMed Central

    Heymans, Raymond; Bruisten, Sylvia M.; Golparian, Daniel; Unemo, Magnus; de Vries, Henry J. C.

    2012-01-01

    From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 ?g/ml (group A), 54 with a cefotaxime MIC of 0.125 ?g/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 ?g/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial. PMID:22214779

  19. Clonally related Neisseria gonorrhoeae isolates with decreased susceptibility to the extended-spectrum cephalosporin cefotaxime in Amsterdam, the Netherlands.

    PubMed

    Heymans, Raymond; Bruisten, Sylvia M; Golparian, Daniel; Unemo, Magnus; de Vries, Henry J C; van Dam, Alje P

    2012-03-01

    From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 ?g/ml (group A), 54 with a cefotaxime MIC of 0.125 ?g/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 ?g/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial. PMID:22214779

  20. Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case-control study in Thai women.

    PubMed

    Sangrajrang, Suleeporn; Sato, Yasunori; Sakamoto, Hiromi; Ohnami, Sumiko; Khuhaprema, Thiravud; Yoshida, Teruhiko

    2010-10-01

    Dietary folate as well as polymorphic variants in one-carbon metabolism genes may modulate risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and repair. Alcohol is well recognized as a risk factor for breast cancer, and interactions with one-carbon metabolism has also been suggested. The purpose of this study is to test the hypothesis that genetic polymorphisms in the folate and alcohol metabolic pathway are associated with breast cancer risk. Twenty-seven single nucleotide polymorphisms (SNPs) in the MTR, MTRR, MTHFR, TYMS, ADH1C, ALDH2, GSTP1, NAT1, NAT2, CYP2E1 DRD2, DRD3, and SLC6A4 were genotyped. Five hundred and seventy patients with histopathogically confirmed breast cancer and 497 controls were included in the present study. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95% CI). Increased risk was observed for homozygotes at the MTR SNPs (rs1770449 and rs1050993) with the OR = 2.21 (95% CI 1.18-4.16) and OR = 2.24 (95% CI 1.19-4.22), respectively. A stratified analysis by menopausal status indicated the association between the NAT2 SNP (rs1799930) and breast cancer was mainly evident in premenopausal women (OR 2.70, 95% CI 1.20-6.07), while the MTRR SNP (rs162049) was significant in postmenopausal women (OR 1.61, 95% CI 1.07-2.44). Furthermore, SNPs of the genes that contribute to alcohol behavior, DRD3 (rs167770), DRD2 (rs10891556), and SLC6A4 (rs140701), were also associated with an increased risk of breast cancer. No gene-gene or gene-environment interactions were observed in this study. Our results suggest that genetic polymorphisms in folate and alcohol metabolic pathway influence the risk of breast cancer in Thai population. PMID:20180013

  1. Dry needling: a literature review with implications for clinical practice guidelines1

    PubMed Central

    Dunning, James; Butts, Raymond; Mourad, Firas; Young, Ian; Flannagan, Sean; Perreault, Thomas

    2014-01-01

    Background: Wet needling uses hollow-bore needles to deliver corticosteroids, anesthetics, sclerosants, botulinum toxins, or other agents. In contrast, dry needling requires the insertion of thin monofilament needles, as used in the practice of acupuncture, without the use of injectate into muscles, ligaments, tendons, subcutaneous fascia, and scar tissue. Dry needles may also be inserted in the vicinity of peripheral nerves and/or neurovascular bundles in order to manage a variety of neuromusculoskeletal pain syndromes. Nevertheless, some position statements by several US State Boards of Physical Therapy have narrowly defined dry needling as an ‘intramuscular’ procedure involving the isolated treatment of ‘myofascial trigger points’ (MTrPs). Objectives: To operationalize an appropriate definition for dry needling based on the existing literature and to further investigate the optimal frequency, duration, and intensity of dry needling for both spinal and extremity neuromusculoskeletal conditions. Major findings: According to recent findings in the literature, the needle tip touches, taps, or pricks tiny nerve endings or neural tissue (i.e. ‘sensitive loci’ or ‘nociceptors’) when it is inserted into a MTrP. To date, there is a paucity of high-quality evidence to underpin the use of direct dry needling into MTrPs for the purpose of short and long-term pain and disability reduction in patients with musculoskeletal pain syndromes. Furthermore, there is a lack of robust evidence validating the clinical diagnostic criteria for trigger point identification or diagnosis. High-quality studies have also demonstrated that manual examination for the identification and localization of a trigger point is neither valid nor reliable between-examiners. Conclusions: Several studies have demonstrated immediate or short-term improvements in pain and/or disability by targeting trigger points (TrPs) using in-and-out techniques such as ‘pistoning’ or ‘sparrow pecking’; however, to date, no high-quality, long-term trials supporting in-and-out needling techniques at exclusively muscular TrPs exist, and the practice should therefore be questioned. The insertion of dry needles into asymptomatic body areas proximal and/or distal to the primary source of pain is supported by the myofascial pain syndrome literature. Physical therapists should not ignore the findings of the Western or biomedical ‘acupuncture’ literature that have used the very same ‘dry needles’ to treat patients with a variety of neuromusculoskeletal conditions in numerous, large scale randomized controlled trials. Although the optimal frequency, duration, and intensity of dry needling has yet to be determined for many neuromusculoskeletal conditions, the vast majority of dry needling randomized controlled trials have manually stimulated the needles and left them in situ for between 10 and 30 minute durations. Position statements and clinical practice guidelines for dry needling should be based on the best available literature, not a single paradigm or school of thought; therefore, physical therapy associations and state boards of physical therapy should consider broadening the definition of dry needling to encompass the stimulation of neural, muscular, and connective tissues, not just ‘TrPs’. PMID:25143704

  2. Fibre optic extensometer for high radiation and high temperature nuclear applications

    SciTech Connect

    Cheymol, G. [CEA, French Nuclear Energy Commission, Nuclear Energy Div. DEN, 91191 Gif/Yvette Cedex (France); Villard, J. F. [CEA, Nuclear Energy Div. DEN, Reactors Studies Dept., Cadarache, 13108 St Paul Lez Durance (France); Gusarov, A.; Brichard, B. [SCK.CEN, ANS/ARI, Boeretang 200, 2400 Mol (Belgium)

    2011-07-01

    In the framework of the Joint Instrumentation Laboratory (LCI), gathering resources from SCK-CEN (Belgium) and CEA (France), we are developing an optical sensor in order to accurately measure radiation-induced elongation of material placed in the core of a Material Testing Reactor (MTR). This extensometer displays common advantages of Fibre Optic (FO) sensors: high resolution, easy remote sensing and multiplexing, and also compact size which is of particular interest for in pile experiments with little room available. In addition, light weight reduces gamma heating hence limiting the thermal effect. In accordance with the specifications, the sensor has preferably two fixing points defining a gauge length of 10 to 15 mm (as a minimum). The diameter is less than 2 mm. Intense gamma and neutron irradiation as well as high temperatures are the most difficult environment conditions to withstand. Reactor radiation produces huge losses in common optical fibre. The losses can be limited by selecting the fibres (mainly with high purity silica core), the wavelength range (800-1200 nm), and a measurement based on interferometry (largely insensitive to losses in the fibre thanks to the wavelength encoding of the useful signal). Heavy neutron - mainly - and gamma flux such as in MTR, also produce compaction of silica, resulting in a significant drift and preventing the use of commercial FO sensors in such environment. Knowing this issue we revised the basic scheme of Extrinsic Fabry Perot Interferometer (EFPI) in order to limit the effects of compaction. A first sensor prototype fixed on a stainless steel support was tested in the Smirnof test facility in the BR2 MTR in Mol (Belgium). The support was subject to a constant mechanical and thermal stress, and his dimensions were not supposed to vary. This test showed a very low drift of the revisited EPFI design under high irradiation field in comparison with a commercial EFPI. This result has to be confirmed with second generation sensors with an increased robustness. The other difficulty to face is high temperature. Fibre optics with metal coating allows safe operation under temperatures up to 400 deg.C and even higher. But differential dilatation between silica and typical metallic material produces differential elongation in the range of 0.5 10{sup -2} i.e 5000{mu}{epsilon} for an increase in temperature of 300-400 deg. C. Such large elongation has to be considered carefully in the sensor design and its fixing on the sample. Laboratory tests with a second generation of adapted sensors demonstrated their good accuracy: less than 1% error over a displacement of 100{mu}m (< 1 {mu}m error), at room temperature. The displacement measured can reach 250{mu}m (20000{mu}{epsilon} with a gauge length of 12.5 mm) or more. We are currently implementing metal-coated fibre and we are preparing the next in pile irradiation on the BR2 reactor scheduled for mid-2011. Other applications of the sensor can be considered. (authors)

  3. Modelling tools to support the harmonization of Water Framework Directive and Common Agricultural Policy

    NASA Astrophysics Data System (ADS)

    Tediosi, A.; Bulgheroni, C.; Sali, G.; Facchi, A.; Gandolfi, C.

    2009-04-01

    After a few years from the delivery of the EU Water Framework Directive (WFD) the need to link agriculture and WFD has emerged as one of the highest priorities; therefore, it is important to discuss on how the EU Common Agricultural Policy (CAP) can contribute to the achievements of the WFD objectives. The recent CAP reform - known as Mid Term Review (MTR) or Fischler Reform - has increased the opportunities, offering to farmers increased support to address some environmental issues. The central novelty coming from the MTR is the introduction of a farm single payment which aims to the Decoupling of EU Agricultural Support from production. Other MTR important topics deal with the Modulation of the payments, the Cross-Compliance and the strengthening of the Rural Development policy. All these new elements will affect the farmers' behaviour, steering their productive choices for the future, which, in turn, will have consequences on the water demand for irrigation. Indeed, from the water quantity viewpoint, agriculture is a large consumer and improving water use efficiency is one of the main issues at stake, following the increasing impacts of water scarcity and droughts across Europe in a context of climate change. According to a recent survey of the European Commission the saving potential in the agricultural sector is 43% of present abstraction and 95% of it is concentrated in southern europe. Many models have been developed to forecast the farmers' behaviour as a consequence of agricultural policies, both at sector and regional level; all of them are founded on Mathematical Programming techniques and many of them use the Positive approach, which better fits the territorial dimension. A large body of literature also exists focusing on the assessment of irrigation water requirements. The examples of conjunctive modelling of the two aspects are however much more limited. The work presented has got some innovative aspects: not only does it couple an economical model and a spatially distributed hydrologic model, but also embodies the two models in a wider procedure aiming at supporting the process of water resources planning at basin scale, based on the IWRM (Integrated Water Resources Management) paradigm. In practice, the economical model defines different land use scenarios deriving from the effects of the CAP on the farmers' productive choices; the hydrological model assesses the crop water requirements and determines the consequent variations of irrigation water demand at the basin scale; finally, the modified pattern of irrigation demand of each land use scenario is incorporated into a multi-objective optimisation procedure, which generates a set of efficient water management policies. Stakeholders involvement is a central component in all the phases of the procedure, including setting the optimization objectives and selecting the performance indicators for the different uses of the water resources within the basin. The presentation will focus on the first two phases of the process, describing the characteristics of the economical and hydrological models; moreover it will illustrate the results of their application to a pilot study basin in Northern Italy, the 6,500 sqaure kilometers wide Adda river basin, which includes the regulated Como lake and is characterized by a broad range of conflicting water related issues: irrigation of a 3,500 square kilometers wide district, navigation and tourism, environment protection, flood protection, hydropower production.

  4. Characterization of an Archaeal Two-Component System That Regulates Methanogenesis in Methanosaeta harundinacea

    PubMed Central

    Guo, Xiaopeng; Qi, Lei; Dong, Xiuzhu

    2014-01-01

    Two-component signal transduction systems (TCSs) are a major mechanism used by bacteria in response to environmental changes. Although many sequenced archaeal genomes encode TCSs, they remain poorly understood. Previously, we reported that a methanogenic archaeon, Methanosaeta harundinacea, encodes FilI, which synthesizes carboxyl-acyl homoserine lactones, to regulate transitions of cellular morphology and carbon metabolic fluxes. Here, we report that filI, the cotranscribed filR2, and the adjacent filR1 constitute an archaeal TCS. FilI possesses a cytoplasmic kinase domain (histidine kinase A and histidine kinase-like ATPase) and its cognate response regulator. FilR1 carries a receiver (REC) domain coupled with an ArsR-related domain with potential DNA-binding ability, while FilR2 carries only a REC domain. In a phosphorelay assay, FilI was autophosphorylated and specifically transferred the phosphoryl group to FilR1 and FilR2, confirming that the three formed a cognate TCS. Through chromatin immunoprecipitation–quantitative polymerase chain reaction (ChIP-qPCR) using an anti-FilR1 antibody, FilR1 was shown to form in vivo associations with its own promoter and the promoter of the filI-filR2 operon, demonstrating a regulatory pattern common among TCSs. ChIP-qPCR also detected FilR1 associations with key genes involved in acetoclastic methanogenesis, acs4 and acs1. Electrophoretic mobility shift assays confirmed the in vitro tight binding of FilR1 to its own promoter and those of filI-filR2, acs4, and mtrABC. This also proves the DNA-binding ability of the ArsR-related domain, which is found primarily in Archaea. The archaeal promoters of acs4, filI, acs1, and mtrABC also initiated FilR1-modulated expression in an Escherichia coli lux reporter system, suggesting that FilR1 can up-regulate both archaeal and bacterial transcription. In conclusion, this work identifies an archaeal FilI/FilRs TCS that regulates the methanogenesis of M. harundinacea. PMID:24748383

  5. The effect of commuting microenvironment on commuter exposures to vehicular emission in Hong Kong

    NASA Astrophysics Data System (ADS)

    Chan, L. Y.; Chan, C. Y.; Qin, Y.

    Vehicular exhaust emission has gradually become the major air pollution source in modern cities and traffic related exposure is found to contribute significantly to total human exposure level. A comprehensive survey was conducted from November 1995 to July 1996 in Hong Kong to assess the effect of traffic-induced air pollution inside different commuting microenvironments on commuter exposure. Microenvironmental monitoring is performed for six major public commuting modes (bus, light bus, MTR, railway, tram, ferry), plus private car and roadside pavement. Traffic-related pollutants, CO, NO x, THC and O 3 were selected as the target pollutants. The results indicate that commuter exposure is highly influenced by the choice of commuting microenvironment. In general, the exposure level in decreasing order of measured pollutant level for respective commuting microenvironments are: private car, the group consisting light bus, bus, tram and pavement, MTR and train, and finally ferry. In private car, the CO level is several times higher than that in the other microenvironments with a trip averaged of 10.1 ppm and a maximum of 24.9 ppm. Factors such as the body position of the vehicle, intake point of the ventilation system, fuel used, ventilation, transport mode, road and driving conditions were used in the analysis. Inter-microenvironment, intra-microenvironment and temporal variation of CO concentrations were used as the major indicator. The low body position and low intake point of the ventilation system of the private car are believed to be the cause of higher intake of exhaust of other vehicles and thus result in high pollution level in this microenvironment. Compared with other metropolis around the world and the Hong Kong Air Quality Objectives (HKAQO), exposure levels of commuter to traffic-related air pollution in Hong Kong are relatively low for most pollutants measured. Only several cases of exceedence of HKAQO by NO 2 were recorded. The strong prevailing wind plus the channeling effect created by the harbor, the fuel used, the relative abundance of new cars and the successful implementation of the vehicle emission control program are factors that compensate the effect of the emission source strength and thus lead to low exposure levels.

  6. Enhanced protein loading on a planar Si(111)-H surface with second generation NTA

    NASA Astrophysics Data System (ADS)

    Liu, Xiang; Han, Huan-Mei; Liu, Hong-Bo; Xiao, Shou-jun

    2010-08-01

    A Si(111)-H surface was modified via a direct reaction between Si-H and 1-undecylenic acid (UA) under microwave irradiation to form molecular monolayers with terminal carboxyl groups. After esterifying carboxylic acid being esterified with N-hydroxysuccinimide (NHS), aminobutyl nitrilotriacetic acid (ANTA) was bound to the silicon surface through amidation (pH = 8.0) between its primary amino group and NHS-ester, producing nitrilotriacetic acid (NTA) anions. Then hexa-histidine tagged thioredoxin-urodilatin (his-tagged protein) and FITC-labeled hexa-histidine tagged thioredoxin-urodilatin (FITC-his-tagged protein) can be anchored after NTA was coordinated with Ni 2+. Furthermore, the NTA-terminated chip was acidified with 0.1 M HCl and subsequently esterified with NHS and then amidated with ANTA again to produce a second generation NTA. Thus the surface density of nitrilotriacetic acid anions was improved and resultantly that of anchored proteins was also enhanced through the iterative reactions. Both multiple transmission-reflection infrared spectroscopy (MTR-IR) and fluorescence scanning measurements demonstrated a proximate 1.63 times of anchored proteins on the second generation NTA/Ni 2+ as that on the first generation NTA/Ni 2+ monolayer.

  7. Impacts of Shewanella oneidensis c-type cytochromes on aerobic and anaerobic respiration

    SciTech Connect

    Gao, Haichun; Barua, Soumitra; Liang, Yili; Wu, Lianming; Dong, Yangyang; Reed, Samantha B.; Chen, Jingrong; Culley, David E.; Kennedy, David W.; Yang, Yunfeng; He, Zhili; Nealson, Kenneth H.; Fredrickson, Jim K.; Tiedje, James M.; Romine, Margaret F.; Zhou, Jizhong

    2010-06-24

    Shewanella are renowned for their ability to utilize a wide range of electron acceptors (EA) for respiration, which has been partially accredited to the presence of a large number of the c-type cytochromes. To investigate the involvement of c-type cytochrome proteins in aerobic and anaerobic respiration of Shewanella oneidensis Mr -1, 36 in-frame deletion mutants, among possible 41 predicted, c-type cytochrome genes were obtained. The potential involvement of each individual c-type cytochrome in the reduction of a variety of EAs was assessed individually as well as in competition experiments. While results on the wellstudied c-type cytochromes CymA(SO4591) and MtrC(SO1778) were consistent with previous findings, collective observations were very interesting: the responses of S. oneidensis Mr -1 to low and highly toxic metals appeared to be significantly different; CcoO, CcoP and PetC, proteins involved in aerobic respiration in various organisms, played critical roles in both aerobic and anaerobic respiration with highly toxic metals as EA. In addition, these studies also suggested that an uncharacterized c-type cytochrome (SO4047) may be important to both aerobiosis and anaerobiosis.

  8. Pre-design of MYRRHA, A Multipurpose Accelerator Driven System for Research and Development

    SciTech Connect

    D'hondt, P.; Abderrahim, H. Aiet; Kupschus, P.; Malambu, E.; Aoust, Th.; Benoit, Ph.; Sobolev, V.; Tichelen, K. van; Arien, B.; Vermeersch, F.; Jongen, Y.; Ternier, S.; Vandeplassche, D. [Belgian Nuclear Research Centre SCKCEN, Boeretang 200, B-2400 Mol (Belgium); IBA, Chemin du Cyclotron, rue J.E. Lenoir 6, B-1348 Louvain-la-Neuve (Belgium)

    2003-08-26

    One of the main SCKCEN research facility, namely BR2, is nowadays arriving at an age of 40 years just like the major materials testing reactors (MTR) in the world and in Europe (i.e. BR2 (B-Mol), HFR (EU-Petten), OSIRIS (F-Saclay), R2 (S-Studsvik)). The MYRRHA facility in planning has been conceived as potentially replacing BR2 and to be a fast spectrum facility complementary to the thermal spectrum RJH (Reacteur Jules Horowitz) facility, in planning in France. This situation would give Europe a full research capability in terms of nuclear R and D. Furthermore, the disposal of radioactive wastes resulting from industrial nuclear energy production has still to find a fully satisfactory solution, especially in terms of environmental and social acceptability. Scientists are looking for ways to drastically reduce (by a factor of 100 or more) the radio-toxicity of the High Level Waste (HLW) to be stored in a deep geological repository. This can be achieved via burning of minor actinides (MA) and to a less extent of long-lived fission products (LLFP) in Accelerator Driven Systems. The MYRRHA project contribution will be in helping to demonstrate the ADS concept at reasonable power level and the demonstration of the technological feasibility of MA and LLFP transmutation under real conditions.

  9. Botulinum Toxin for the Treatment of Myofascial Pain Syndromes Involving the Neck and Back: A Review from a Clinical Perspective

    PubMed Central

    Climent, José M.; Fenollosa, Pedro; Martin-del-Rosario, Francisco

    2013-01-01

    Introduction. Botulinum toxin inhibits acetylcholine (ACh) release and probably blocks some nociceptive neurotransmitters. It has been suggested that the development of myofascial trigger points (MTrP) is related to an excess release of ACh to increase the number of sensitized nociceptors. Although the use of botulinum toxin to treat myofascial pain syndrome (MPS) has been investigated in many clinical trials, the results are contradictory. The objective of this paper is to identify sources of variability that could explain these differences in the results. Material and Methods. We performed a content analysis of the clinical trials and systematic reviews of MPS. Results and Discussion. Sources of differences in studies were found in the diagnostic and selection criteria, the muscles injected, the injection technique, the number of trigger points injected, the dosage of botulinum toxin used, treatments for control group, outcome measures, and duration of followup. The contradictory results regarding the efficacy of botulinum toxin A in MPS associated with neck and back pain do not allow this treatment to be recommended or rejected. There is evidence that botulinum toxin could be useful in specific myofascial regions such as piriformis syndrome. It could also be useful in patients with refractory MPS that has not responded to other myofascial injection therapies. PMID:23533477

  10. Electrical transport along bacterial nanowires from Shewanella oneidensis MR-1

    PubMed Central

    El-Naggar, Mohamed Y.; Wanger, Greg; Leung, Kar Man; Yuzvinsky, Thomas D.; Southam, Gordon; Yang, Jun; Lau, Woon Ming; Nealson, Kenneth H.; Gorby, Yuri A.

    2010-01-01

    Bacterial nanowires are extracellular appendages that have been suggested as pathways for electron transport in phylogenetically diverse microorganisms, including dissimilatory metal-reducing bacteria and photosynthetic cyanobacteria. However, there has been no evidence presented to demonstrate electron transport along the length of bacterial nanowires. Here we report electron transport measurements along individually addressed bacterial nanowires derived from electron-acceptor–limited cultures of the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1. Transport along the bacterial nanowires was independently evaluated by two techniques: (i) nanofabricated electrodes patterned on top of individual nanowires, and (ii) conducting probe atomic force microscopy at various points along a single nanowire bridging a metallic electrode and the conductive atomic force microscopy tip. The S. oneidensis MR-1 nanowires were found to be electrically conductive along micrometer-length scales with electron transport rates up to 109/s at 100 mV of applied bias and a measured resistivity on the order of 1 ?·cm. Mutants deficient in genes for c-type decaheme cytochromes MtrC and OmcA produce appendages that are morphologically consistent with bacterial nanowires, but were found to be nonconductive. The measurements reported here allow for bacterial nanowires to serve as a viable microbial strategy for extracellular electron transport. PMID:20937892

  11. Underwater Coatings Testing for INEEL Fuel Basin Applications

    SciTech Connect

    Julia L. Tripp

    2004-01-01

    The Idaho National Engineering and Environmental Laboratory (INEEL) is deactivating several fuel storage basins. Airborne contamination is a concern when the sides of the basins are exposed and allowed to dry during water removal. One way of controlling this airborne contamination is to fix the contamination in place while the pool walls are still submerged. There are many underwater coatings available on the market that are used in marine, naval and other applications. A series of tests were run to determine whether the candidate underwater fixatives are easily applied and adhere well to the substrates (pool wall materials) found in INEEL fuel pools. The four pools considered included (1) Test Area North (TAN-607) with epoxy painted concrete walls; (2) Idaho Nuclear Technology and Engineering Center (INTEC) (CPP-603) with bare concrete walls; (3) Materials Test Reactor (MTR) Canal with stainless steel lined concrete walls; and (4) Power Burst Facility (PBF-620) with stainless steel lined concrete walls on the bottom and epoxy painted carbon steel lined walls on the upper portions. Therefore, the four materials chosen for testing included bare concrete, epoxy painted concrete, epoxy painted carbon steel, and stainless steel. The typical water temperature of the pools varies from 55 F to 80 F dependent on the pool and the season. These tests were done at room temperature.

  12. Thermal study of a non adiabatic differential calorimeter used for nuclear heating measurements inside an experimental channel of the Jules Horowitz Reactor

    NASA Astrophysics Data System (ADS)

    Reynard-Carette, C.; Lyoussi, A.; Brun, J.; Muraglia, M.; Carette, M.; Janulyte, A.; Zerega, Y.; André, J.; Bignan, G.; Chauvin, J.-P.; Fourmentel, D.; Gonnier, C.; Guimbal, P.; Malo, J.-Y.; Villard, J.-F.

    2012-11-01

    New online in-pile measurement methods are crucial during irradiations in Material Testing Reactors (MTR) for a better understanding of accelerated material ageing and nuclear fuel behaviour. In particular, instrumentation for measurements of one relevant parameter: nuclear heat deposition rate, called nuclear heating, has to be improved. The knowledge of this quantity is a great interest for various safety, scientist and end-user requirements (design of specific irradiation devices and associated cooling systems with imposed conditions). This paper focuses on thermal experimental and numerical studies carried out under non irradiation conditions on an in-pile calorimeter dedicated to nuclear heating quantification inside a new experimental device which will be dedicated to the experimental condition mapping (neutron and photon fluxes and nuclear heating) inside the JHR experimental channels. Experimental results concerning the calorimeter response during its electrical calibration (<3W) under laminar forced convection conditions show that its sensitivity does not depend on the cooling flow. Temperature and heat flux density measurements lead to the conclusion of a good directional conductive heat flow design (increased with a higher Reynolds number). A parametric numerical stationary study highlights a sensor sensitivity increasing. At last, the usual calorimeter design is compared to a single calorimeter which gives promising results (miniaturization, higher sensitivity).

  13. Pre-design of MYRRHA, A Multipurpose Accelerator Driven System for Research and Development

    NASA Astrophysics Data System (ADS)

    D'hondt, P.; Abderrahim, H. Aït; Kupschus, P.; Malambu, E.; Aoust, Th.; Benoit, Ph.; Sobolev, V.; Van Tichelen, K.; Arien, B.; Vermeersch, F.; Jongen, Y.; Ternier, S.; Vandeplassche, D.

    2003-08-01

    One of the main SCK•CEN research facility, namely BR2, is nowadays arriving at an age of 40 years just like the major materials testing reactors (MTR) in the world and in Europe (i.e. BR2 (B-Mol), HFR (EU-Petten), OSIRIS (F-Saclay), R2 (S-Studsvik)). The MYRRHA facility in planning has been conceived as potentially replacing BR2 and to be a fast spectrum facility complementary to the thermal spectrum RJH (Réacteur Jules Horowitz) facility, in planning in France. This situation would give Europe a full research capability in terms of nuclear R&D. Furthermore, the disposal of radioactive wastes resulting from industrial nuclear energy production has still to find a fully satisfactory solution, especially in terms of environmental and social acceptability. Scientists are looking for ways to drastically reduce (by a factor of 100 or more) the radio-toxicity of the High Level Waste (HLW) to be stored in a deep geological repository. This can be achieved via burning of minor actinides (MA) and to a less extent of long-lived fission products (LLFP) in Accelerator Driven Systems. The MYRRHA project contribution will be in helping to demonstrate the ADS concept at reasonable power level and the demonstration of the technological feasibility of MA and LLFP transmutation under real conditions.

  14. Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: results from the German Investigation on Neurobiology in Alcoholism (GINA).

    PubMed

    Semmler, Alexander; Heese, Peter; Stoffel-Wagner, Birgit; Muschler, Marc; Heberlein, Annemarie; Bigler, Laurent; Prost, Jean-Christophe; Frieling, Helge; Kornhuber, Johannes; Banger, Markus; Bleich, Stefan; Hillemacher, Thomas; Linnebank, Michael

    2015-03-01

    Recent studies have shown that smoking and alcoholism may be associated with altered DNA methylation and that alcohol consumption might induce changes in DNA methylation by altering homocysteine metabolism. In this monocenter study, we included 363 consecutive patients referred for hospitalization for alcohol detoxification treatment. Blood samples were obtained on treatment days 1, 3, and 7 for measurement of global DNA methylation in leukocytes by liquid chromatography tandem mass spectrometry. Genomic DNA was used for genotyping the following seven genetic variants of homocysteine metabolism: cystathionine beta-synthase (CBS) c.844_855ins68, dihydrofolate-reductase (DHFR) c.594 + 59del19bp, methylenetetrahydrofolate-reductase (MTHFR) c.677C > T and c.1298A > C, methyltetrahydrofolate-transferase (MTR) c.2756A > G, reduced folate carrier 1 (RFC1) c.80G > A, and transcobalamin 2 c.776C > G. Multivariate linear regression showed a positive correlation of global DNA methylation with alcohol consumption and smoking on day 1 of hospitalization. DNA methylation was not correlated with homocysteine or vitamin plasma levels, nor with the tested genetic variants of homocysteine metabolism. This suggests a direct effect of alcohol consumption and smoking on DNA methylation, which is not mediated by effects of alcohol on homocysteine metabolism. PMID:25702197

  15. Structure of a bacterial cell surface decaheme electron conduit

    PubMed Central

    Clarke, Thomas A.; Edwards, Marcus J.; Gates, Andrew J.; Hall, Andrea; White, Gaye F.; Bradley, Justin; Reardon, Catherine L.; Shi, Liang; Beliaev, Alexander S.; Marshall, Matthew J.; Wang, Zheming; Watmough, Nicholas J.; Fredrickson, James K.; Zachara, John M.; Butt, Julea N.; Richardson, David J.

    2011-01-01

    Some bacterial species are able to utilize extracellular mineral forms of iron and manganese as respiratory electron acceptors. In Shewanella oneidensis this involves decaheme cytochromes that are located on the bacterial cell surface at the termini of trans-outer-membrane electron transfer conduits. The cell surface cytochromes can potentially play multiple roles in mediating electron transfer directly to insoluble electron sinks, catalyzing electron exchange with flavin electron shuttles or participating in extracellular intercytochrome electron exchange along “nanowire” appendages. We present a 3.2-? crystal structure of one of these decaheme cytochromes, MtrF, that allows the spatial organization of the 10 hemes to be visualized for the first time. The hemes are organized across four domains in a unique crossed conformation, in which a staggered 65-? octaheme chain transects the length of the protein and is bisected by a planar 45-? tetraheme chain that connects two extended Greek key split ?-barrel domains. The structure provides molecular insight into how reduction of insoluble substrate (e.g., minerals), soluble substrates (e.g., flavins), and cytochrome redox partners might be possible in tandem at different termini of a trifurcated electron transport chain on the cell surface. PMID:21606337

  16. Structure of a Bacterial Cell Surface Decaheme Electron Conduit

    SciTech Connect

    Clarke, Thomas A.; Edwards, Marcus; Gates, Andrew J.; Hall, Andrea; White, Gaye; Bradley, Justin; Reardon, Catherine L.; Shi, Liang; Beliaev, Alex S.; Marshall, Matthew J.; Wang, Zheming; Watmough, Nicholas; Fredrickson, Jim K.; Zachara, John M.; Butt, Julea N.; Richardson, David J.

    2011-05-23

    Some bacterial species are able to utilize extracellular mineral forms of iron and manganese as respiratory electron acceptors. In Shewanella oneidensis this involves deca-heme cytochromes that are located on the bacterial cell surface at the termini of trans-outermembrane (OM) electron transfer conduits. The cell surface cytochromes can potentially play multiple roles in mediating electron transfer directly to insoluble electron sinks, catalyzing electron exchange with flavin electron shuttles or participating in extracellular inter-cytochrome electron exchange along ‘nanowire’ appendages. We present a 3.2 Å crystal structure of one of these deca-heme cytochromes, MtrF, that allows the spatial organization of the ten hemes to be visualized for the first time. The hemes are organized across four domains in a unique crossed conformation, in which a staggered 65 Å octa-heme chain transects the length of the protein and is bisected by a planar 45 Å tetra-heme chain that connects two extended Greek key split ?-barrel domains. The structure provides molecular insight into how reduction of insoluble substrate (e.g. minerals), soluble substrates (e.g. flavins) and cytochrome redox partners might be possible in tandem at different termini of a trifurcated electron transport chain on the cell surface.

  17. Power transient analyses of experimental in-reflector devices during safety shutdown in Jules Horowitz Reactor (JHR)

    SciTech Connect

    Camprini, P. C.; Sumini, M. [Univ. of Bologna (Italy); Artioli, C. [National Agency for New Technologies, Energy and Sustainable Economic Development ENEA (Italy); Gonnier, C.; Pouchin, B.; Bourdon, S. [Atomic Energy Commission CEA (France)

    2012-07-01

    The Jules Horowitz Reactor (JHR) is designed to be a 100 MW material testing reactor (MTR) and it is expected to become the reference facility in the framework of European nuclear research activity. As the core neutron spectrum is quite fast, several experimental devices concerning fuel studies have been conceived to be placed in the reflector in order to exploit a proper thermal neutron flux irradiation. Since the core power is relatively high, the neutronic coupling between the reactor core and the reflector devices has to be taken into account for different rod insertions. In fact the thermal power produced within the fuel samples is considerable. Heat removal during shutdown is a main topic in nuclear safety and it is worth to analyse thermal power transients in fuel samples as well. Here a thermal hydraulic model for JHR core is proposed aiming at a simple and representative description as far as reactivity feedbacks are concerned. Then it is coupled with a neutronic pointwise kinetics analysis by means of the DULCINEE code to compute core power transient calculations. Moreover, some reflector-core coupling evaluations are performed through Monte Carlo method using the TRIPOLI 4.7 code. The JHR equilibrium cycle is considered with respect to four fuel compositions namely Beginning of Cycle (BOC), Xenon Saturation Point (XSP), Middle of Cycle (MOC) and End of Cycle (EOC). Then thermal power transients in the experimental reflector devices are evaluated during safety shutdowns and they are verified for all these cycle steps. (authors)

  18. Association of Genetic Variation in Cystathionine-?-Synthase and Arsenic Metabolism

    PubMed Central

    Porter, Kristin E.; Basu, Anamika; Hubbard, Alan E.; Bates, Michael N.; Kalman, David; Rey, Omar; Smith, Allan; Smith, Martyn T.; Steinmaus, Craig; Skibola, Christine F.

    2010-01-01

    Variation in individual susceptibility to arsenic-induced disease may be partially explained by genetic differences in arsenic metabolism. Mounting epidemiological evidence and in vitro studies suggest that methylated arsenic metabolites, particularly monomethylarsonic (MMA3), are more acutely toxic than inorganic arsenic; thus, MMA3 may be the primary toxic arsenic species. To test the role of genetic variation in arsenic metabolism, polymorphisms in genes involved in one-carbon metabolism [methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), cystathionine-?-synthase (CBS), thymidylate synthase (TYMS), dihydrofolate reductase (DHFR), serine hydroxymethyltransferase 1 (SHMT1] and glutathione biosynthesis [glutathione S-transferase omega 1 (GSTO1)] were examined in an arsenic exposed population to determine their influence in urinary arsenic metabolite patterns. In 142 subjects in Cordoba Province, Argentina, variant genotypes for CBS rs234709 and rs4920037 SNPs compared with wild-type homozygotes were associated with 24% and 26% increases, respectively, in the mean proportion of arsenic excreted as monomethylarsonic acid (%MMA). This difference is within the range of differences in %MMA seen between people with arsenic-related disease and those without such disease in other studies. Small inverse associations with CBS rs234709 and rs4920037 variants were also found for the mean levels of the proportion of arsenic excreted as dimethylarsinous acid (%DMA). No other genetic associations were found. These findings are the first to suggest that CBS polymorphisms may influence arsenic metabolism in humans and susceptibility to arsenic-related disease. PMID:20670920

  19. Redox reactions of reduced flavin mononucleotide (FMN), riboflavin (RBF), and anthraquinone-2,6-disulfonate (AQDS) with ferrihydrite and lepidocrocite

    SciTech Connect

    Shi, Zhi; Zachara, John M.; Shi, Liang; Wang, Zheming; Moore, Dean A.; Kennedy, David W.; Fredrickson, Jim K.

    2012-11-01

    Flavins are secreted by the dissimilatory iron-reducing bacterium Shewanella and can function as endogenous electron transfer mediators (ETM). In order to assess the potential importance of flavins in Fe(III) bioreduction, we investigated the redox reaction kinetics of reduced flavins (FMNH2 and RBFH2) with ferrihydrite and lepidocrocite. The organic reductants rapidly reduced and dissolved ferrihydrite and lepidocrocite in the pH range 4-8. The rate constant k for 2-line ferrihydrite reductive dissolution by FMNH2 was 87.5 ? 3.5 M-1?s-1 at pH 7.0 in batch reactors, and the k was similar for RBFH2. For lepidocrocite, the k was 500 ? 61 M-1?s-1 for FMNH2, and 236 ? 22 M-1?s-1 for RBFH2. The surface area normalized initial reaction rates (ra) were between 0.08 and 77 ?moles?m-2?s-1 for various conditions in stopped-flow experiments. Initial rates (ro) were first-order with respect to Fe(III) oxide concentration, and ra increased with decreasing pH. Poorly crystalline 2-line ferrihydrite yielded the highest ra, followed by more crystalline 6-line ferrihydrite, and crystalline lepidocrocite. Compared to a previous whole-cell study with Shewanella oneidensis strain MR-1, our findings suggest that ETM reduction by the Mtr pathway coupled to lactate oxidation are rate limiting, rather than heterogeneous electron transfer to the Fe(III) oxide.

  20. Calibration of dimensional change in finite element models using AGR moderator brick measurements

    NASA Astrophysics Data System (ADS)

    McNally, K.; Hall, G.; Tan, E.; Marsden, B. J.; Warren, N.

    2014-08-01

    Physically based models, resolved using the finite element (FE) method, are often used to model changes in geometry and the associated stress fields of graphite moderator bricks within a reactor. These models require inputs that describe the loading conditions (field variables), and coded relationships describing the behaviour of material properties. Historically, behaviour on material properties have been obtained from Materials Test Reactor (MTR) experiments, however data relating to samples trepanned from operating reactors are increasingly being used to improve models. Geometry measurements from operating reactors offer the potential for improving the coded relationship for dimensional change in FE models. A non-linear mixed-effect model is presented for calibrating the parameters of FE models that are sensitive to mid-brick diameter, using channel geometry measurements obtained from inspection campaigns. The work makes use of a novel technique: the development of a Bayesian emulator, which is a surrogate for the FE model. The use of an emulator allows the influence of the inputs to the finite element model to be evaluated, and delivers a substantial reduction in the computational burden of calibration.

  1. FIELD DEMONSTRATION OF A MEMBRANE PROCESS TO RECOVER HEAVY HYDROCARBONS AND TO REMOVE WATER FROM NATURAL GAS

    SciTech Connect

    R. Baker; T. Hofmann; J. Kaschemekat; K.A. Lokhandwala; Membrane Group; Module Group; Systems Group

    2001-01-11

    The objective of this project is to design, construct and field demonstrate a 3-MMscfd membrane system to recover natural gas liquids (NGL) and remove water from raw natural gas. An extended field test to demonstrate system performance under real-world conditions is required to convince industry users of the efficiency and reliability of the process. The system will be designed and fabricated by Membrane Technology and Research, Inc. (MTR) and then installed and operated at British Petroleum (BP)-Amoco's Pascagoula, MS plant. The Gas Research Institute will partially support the field demonstration and BP-Amoco will help install the unit and provide onsite operators and utilities. The gas processed by the membrane system will meet pipeline specifications for dewpoint and Btu value and can be delivered without further treatment to the pipeline. Based on data from prior membrane module tests, the process is likely to be significantly less expensive than glycol dehydration followed by propane refrigeration, the principal competitive technology. At the end of this demonstration project the process will be ready for commercialization. The route to commercialization will be developed during this project and may involve collaboration with other companies already servicing the natural gas processing industry.

  2. Pot1b Deletion and Telomerase Haploinsufficiency in Mice Initiate an ATR-Dependent DNA Damage Response and Elicit Phenotypes Resembling Dyskeratosis Congenita? †

    PubMed Central

    He, Hua; Wang, Yang; Guo, Xiaolan; Ramchandani, Sonal; Ma, Jin; Shen, Mei-Feng; Garcia, Dennis A.; Deng, Yibin; Multani, Asha S.; You, Mingjian James; Chang, Sandy

    2009-01-01

    The Protection of telomeres 1 (POT1) protein is a single-stranded telomere binding protein that is essential for proper maintenance of telomere length. Disruption of POT1 function leads to chromosome instability and loss of cellular viability. Here, we show that targeted deletion of the mouse Pot1b gene results in increased apoptosis in highly proliferative tissues. In the setting of telomerase haploinsufficiency, loss of Pot1b results in depletion of germ cells and complete bone marrow failure due to increased apoptosis, culminating in premature death. Pot1b?/? mTR+/? hematopoietic progenitor and stem cells display markedly reduced survival potential in vitro. Accelerated telomere shortening, increased G overhang and elevated number of chromosome end-to-end fusions that initiate an ATR-dependent DNA damage response were also observed. These results indicate an essential role for Pot1b in the maintenance of genome integrity and the long-term viability of proliferative tissues in the setting of telomerase deficiency. Interestingly, these phenotypes closely resemble those found in the human disease dyskeratosis congenita (DC), an inherited syndrome characterized by bone marrow failure, hyperpigmentation, and nail dystrophy. We anticipate that this mouse will serve as a useful model to further understand the pathophysiology of DC. PMID:18936156

  3. Analysis of MNSR core composition changes using the codes WIMSD-4 and CITATION.

    PubMed

    Haj Hassan, H; Ghazi, N; Hainoun, A

    2008-10-01

    The codes WIMSD/4 and BORGES--part of the MTR-PC code package--have been applied to prepare the microscopic cross-section library for the main elements of miniature neutron source reactor (MNSR) core for six neutron energy groups. The generated library has been utilized by the 3D code CITATION to perform the calculation of fuel burn-up including the identification of main fission products and their impacts on the multiplication factor. In this regard some modifications have been introduced to the subroutine NUCY in CITATION to incorporate estimating the concentration of the related actinides and fission products. The burn-up results have indicated that the core life-time of MNSR is being mainly estimated by Sm(149) followed by Gd(157) and Cd(113). The accumulation of these fission products during 100 continuous operation days caused a reduction of about 4.3 mk for the excess reactivity. This result seems to be in good agreement with the available empirical value of 3.5 mk, which relates to the whole discontinuous operation period of the reactor since its start up to now. The calculation procedure simulates the sporadic operation with an equivalent continuous operation period. This approximation is valid for the long-lived fission products that mainly dictate the core life-time. However, it is an overestimation for the concentration of short-lived radioactive products like Xe(135). PMID:18547812

  4. Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.

    PubMed

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W; van Buchem, Mark A; Slagboom, P Eline; Westendorp, Rudi G; van Heemst, Diana; van der Grond, Jeroen

    2015-08-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P < 0.001). Similar significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging. PMID:26178969

  5. Matrin 3 as a key regulator of endothelial cell survival

    SciTech Connect

    Przygodzka, Patrycja; Boncela, Joanna [Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland)] [Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland); Cierniewski, Czeslaw S., E-mail: czeslaw.cierniewski@umed.lodz.pl [Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland); Department of Molecular and Medical Biophysics, Medical University in Lodz, Lodz (Poland)

    2011-04-01

    Matrin 3 is an integral component of nuclear matrix architecture that has been implicated in interacting with other nuclear proteins and thus modulating the activity of proximal promoters. In this study, we evaluated the contribution of this protein to proliferation of endothelial cells. To selectively modulate matrin 3 expression, we used siRNA oligonucleotides and transfection of cells with a pEGFP-N1-Mtr3. Our data indicate that downregulation of matrin 3 is responsible for reduced proliferation and leads to necrosis of endothelial cells. This conclusion is supported by observations that reducing matrin 3 expression results in (a) producing signs of necrosis detected by PI staining, LDH release, and scatter parameters in flow cytometry, (b) affecting cell cycle progression. It does not cause (c) membrane asymmetry of cells as indicated by lack of Annexin V binding as well as (d) activation of caspase 3 and cleavage of PARP. We conclude that matrin 3 plays a significant role in controlling cell growth and proliferation, probably via formation of complexes with nuclear proteins that modulate pro- and antiapoptotic signaling pathways. Thus, degradation of matrin 3 may be a switching event that induces a shift from apoptotic to necrotic death of cells.

  6. Irradiation Facilities at the Advanced Test Reactor

    SciTech Connect

    S. Blaine Grover

    2005-12-01

    The Advanced Test Reactor (ATR) is the third generation and largest test reactor built in the Reactor Technology Complex (RTC – formerly known as the Test Reactor Area), located at the Idaho National Laboratory (INL), to study the effects of intense neutron and gamma radiation on reactor materials and fuels. The RTC was established in the early 1950s with the development of the Materials Testing Reactor (MTR), which operated until 1970. The second major reactor was the Engineering Test Reactor (ETR), which operated from 1957 to 1981, and finally the ATR, which began operation in 1967 and will continue operation well into the future. These reactors have produced a significant portion of the world’s data on materials response to reactor environments. The wide range of experiment facilities in the ATR and the unique ability to vary the neutron flux in different areas of the core allow numerous experiment conditions to co-exist during the same reactor operating cycle. Simple experiments may involve a non-instrumented capsule containing test specimens with no real-time monitoring or control capabilities1. More sophisticated testing facilities include inert gas temperature control systems and pressurized water loops that have continuous chemistry, pressure, temperature, and flow control as well as numerous test specimen monitoring capabilities. There are also apparatus that allow for the simulation of reactor transients on test specimens.

  7. Extracellular Polymeric Substances from Shewanella sp. HRCR-1 Biofilms: Characterization by Infrared Spectroscopy and Proteomics

    SciTech Connect

    Cao, Bin; Shi, Liang; Brown, Roslyn N.; Xiong, Yijia; Fredrickson, Jim K.; Romine, Margaret F.; Marshall, Matthew J.; Lipton, Mary S.; Beyenal, Haluk

    2011-04-01

    This study characterizes the composition of extracellular polymeric substances (EPS) from Shewanella sp. HRCR-1 biofilms to provide insight into potential interactions of EPS with redox-active metals and radionuclides. Both bound and loosely associated EPS were extracted from Shewanella sp. HRCR-1 biofilms prepared using a hollow-fiber membrane biofilm reactor (HfMBR). FTIR spectra revealed the presence of proteins, polysaccharides, nucleic acids, membrane lipids, and fatty acids in both bound and loosely associated EPS. Using a global proteomic approach, a total of 58 extracellular and outer membrane proteins were identified in the EPS. These included homologues of multiple S. oneidensis MR-1 proteins that potentially contribute to key physiological biofilm processes, such as biofilm-promoting protein BpfA, surface-associated serine protease, nucleotidases (CpdB and UshA), an extracellular lipase, and oligopeptidases (PtrB and a M13 family oligopeptidase lipoprotein). In addition, 20 redox proteins were found in extracted EPS. Among the detected redox proteins were the homologues of two S. oneidensis MR-1 c-type cytochromes, MtrC and OmcA, which have been implicated in extracellular electron transfer. Given their detection in the EPS of Shewanella sp. HRCR 1 biofilms, c-type cytochromes may contribute to the possible redox activity of the biofilm matrix and play important roles in extracellular electron transfer reactions.

  8. Towards a Computational Model of a Methane Producing Archaeum

    PubMed Central

    Peterson, Joseph R.; Ellermeier, Jeremy R.; Kohler, Petra R. A.; Ha, Taekjip; Metcalf, William W.; Luthey-Schulten, Zaida

    2014-01-01

    Progress towards a complete model of the methanogenic archaeum Methanosarcina acetivorans is reported. We characterized size distribution of the cells using differential interference contrast microscopy, finding them to be ellipsoidal with mean length and width of 2.9??m and 2.3??m, respectively, when grown on methanol and 30% smaller when grown on acetate. We used the single molecule pull down (SiMPull) technique to measure average copy number of the Mcr complex and ribosomes. A kinetic model for the methanogenesis pathways based on biochemical studies and recent metabolic reconstructions for several related methanogens is presented. In this model, 26 reactions in the methanogenesis pathways are coupled to a cell mass production reaction that updates enzyme concentrations. RNA expression data (RNA-seq) measured for cell cultures grown on acetate and methanol is used to estimate relative protein production per mole of ATP consumed. The model captures the experimentally observed methane production rates for cells growing on methanol and is most sensitive to the number of methyl-coenzyme-M reductase (Mcr) and methyl-tetrahydromethanopterin:coenzyme-M methyltransferase (Mtr) proteins. A draft transcriptional regulation network based on known interactions is proposed which we intend to integrate with the kinetic model to allow dynamic regulation. PMID:24729742

  9. Impacts of Shewanella oneidensis c?type cytochromes on aerobic and anaerobic respiration

    PubMed Central

    Gao, Haichun; Barua, Soumitra; Liang, Yili; Wu, Lin; Dong, Yangyang; Reed, Samantha; Chen, Jingrong; Culley, Dave; Kennedy, David; Yang, Yunfeng; He, Zhili; Nealson, Kenneth H.; Fredrickson, James K.; Tiedje, James M.; Romine, Margaret; Zhou, Jizhong

    2010-01-01

    Summary Shewanella are renowned for their ability to utilize a wide range of electron acceptors (EA) for respiration, which has been partially accredited to the presence of a large number of the c?type cytochromes. To investigate the involvement of c?type cytochrome proteins in aerobic and anaerobic respiration of Shewanella oneidensis Mr ?1, 36 in?frame deletion mutants, among possible 41 predicted, c?type cytochrome genes were obtained. The potential involvement of each individual c?type cytochrome in the reduction of a variety of EAs was assessed individually as well as in competition experiments. While results on the well?studied c?type cytochromes CymA(SO4591) and MtrC(SO1778) were consistent with previous findings, collective observations were very interesting: the responses of S. oneidensis Mr ?1 to low and highly toxic metals appeared to be significantly different; CcoO, CcoP and PetC, proteins involved in aerobic respiration in various organisms, played critical roles in both aerobic and anaerobic respiration with highly toxic metals as EA. In addition, these studies also suggested that an uncharacterized c?type cytochrome (SO4047) may be important to both aerobiosis and anaerobiosis. PMID:21255343

  10. Processing of historic high radioactive waste coming from nuclear applications

    SciTech Connect

    Van Velzen, L.P.M.; Vos, R.M. de; Roobol, L.P. [Nuclear Research and consultancy Group - NRG, PO Box 25, NL-1755 ZG Petten (Netherlands); IJpelaan, R.; Van Tongeren, R. [Energy research Centre of the Netherlands (ECN), P.O. Box 1, 1755 ZG Petten (Netherlands)

    2007-07-01

    At ECN-NRG irradiations of materials have been performed with the aid of the High Flux Reactor at the site for investigations of their properties under different conditions as well for nuclear isotope productions since 1967 e.g. molybdenum. The high radioactive waste (HRW) coming from these nuclear applications are stored since the start in an interim storage facility located at the site. Due to the site license the HRW has to be transported to COVRA. Therefore a project has been set-up to transport all the HRW to COVRA. However, COVRA accepts a limited number of HLW containers among the CASTOR{sup R} MTR-2 container and thus all temporary stored drums have to be over packed. As the existing infra structure at the site is not suited a new facility has to be build. This also creates the opportunity to minimize, by separation of the HRW in low- and intermediate level waste, the amount of waste that has to be classified as HLW. The applied methodology, design and specifications of the HRW-ILW non-destructive assay characterization and separation system will be described. (authors)

  11. Methionine synthase reductase A66G polymorphism and leukemia risk: evidence from published studies.

    PubMed

    Fang, Dai-Hua; Ji, Qiang; Fan, Cong-Hai; An, Qi; Li, Juan

    2014-08-01

    Methionine synthase reductase (MTRR) is required for the reductive methylation of cobalamin, which is the functional cofactorial form of methionine synthase (MS) in the remethylation of homocysteine to methionine. The MTRR A66G (rs1801394) polymorphism is found to be associated with decreased enzyme affinity for MTR, the gene that encodes MS, and has been widely investigated for cancer risk, including leukemia. However, the conclusions of epidemiological studies have always been contradictory. To further clarify the association of MTRR A66G polymorphism with the risk of leukemia, this meta-analysis was performed for 2913 cases and 4764 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Pooled ORs were determined for the co-dominant model (GG vs. AA, AG vs. AA), dominant model (GG + AG vs. AA) and recessive model (GG vs. AA+ AG), respectively. No significant associations were found for all comparisons in the overall pooled analysis. However, the results of stratified analyses revealed that MTRR A66G GG genotype was associated with decreased leukemia risk in the Caucasian population, in children and for acute lymphoblastic leukemia (ALL). In contrast, increased risk was observed in the Asian population and for acute myeloid leukemia (AML). This meta-analysis suggests that MTRR A66G GG is associated with decreased risk of leukemia in a Caucasian population and in children, especially for ALL. PMID:24261678

  12. Development and application of procedures to evaluate air quality and visibility impacts of low-altitude flying operations

    SciTech Connect

    Liebsch, E.J.

    1990-08-01

    This report describes the development and application of procedures to evaluate the effects of low-altitude aircraft flights on air quality and visibility. The work summarized in this report was undertaken as part of the larger task of assessing the various potential environmental impacts associated with low-altitude military airspaces. Accomplishing the air quality/visibility analysis for the GEIS included (1) development and application of an integrated air quality model and aircraft emissions database specifically for Military Training Route (MTR) or similar flight operations, (2) selection and application of an existing air quality model to analyze the more widespread and less concentrated aircraft emissions from military Operations Areas (MOAs) and Restricted Areas (RAs), and (3) development and application of procedures to assess impacts of aircraft emissions on visibility. Existing air quality models were considered to be inadequate for predicting ground-level concentrations of pollutants emitted by aircraft along MTRs; therefore, the Single-Aircraft Instantaneous Line Source (SAILS) and Multiple-Aircraft Instantaneous Line Source (MAILS) models were developed to estimate potential impacts along MTRs. Furthermore, a protocol was developed and then applied in the field to determine the degree of visibility impairment caused by aircraft engine exhaust plumes. 19 refs., 2 figs., 3 tabs.

  13. Genome-wide Association Scan for Childhood Caries Implicates Novel Genes

    PubMed Central

    Shaffer, J.R.; Wang, X.; Feingold, E.; Lee, M.; Begum, F.; Weeks, D.E.; Cuenco, K.T.; Barmada, M.M.; Wendell, S.K.; Crosslin, D.R.; Laurie, C.C.; Doheny, K.F.; Pugh, E.W.; Zhang, Q.; Feenstra, B.; Geller, F.; Boyd, H.A.; Zhang, H.; Melbye, M.; Murray, J.C.; Weyant, R.J.; Crout, R.; McNeil, D.W.; Levy, S.M.; Slayton, R.L.; Willing, M.C.; Broffitt, B.; Vieira, A.R.; Marazita, M.L.

    2011-01-01

    Dental caries is the most common chronic disease in children and a major public health concern due to its increasing incidence, serious health and social co-morbidities, and socio-demographic disparities in disease burden. We performed the first genome-wide association scan for dental caries to identify associated genetic loci and nominate candidate genes affecting tooth decay in 1305 US children ages 3-12 yrs. Affection status was defined as 1 or more primary teeth with evidence of decay based on intra-oral examination. No associations met strict criteria for genome-wide significance (p < 10E-7); however, several loci (ACTN2, MTR, and EDARADD, MPPED2, and LPO) with plausible biological roles in dental caries exhibited suggestive evidence for association. Analyses stratified by home fluoride level yielded additional suggestive loci, including TFIP11 in the low-fluoride group, and EPHA7 and ZMPSTE24 in the sufficient-fluoride group. Suggestive loci were tested but not significantly replicated in an independent sample (N = 1695, ages 2-7 yrs) after adjustment for multiple comparisons. This study reinforces the complexity of dental caries, suggesting that numerous loci, mostly having small effects, are involved in cariogenesis. Verification/replication of suggestive loci may highlight biological mechanisms and/or pathways leading to a fuller understanding of the genetic risks for dental caries. PMID:21940522

  14. Antimycobacterial and phototoxic evaluation of novel 6-fluoro/nitro-4-oxo-7-(sub)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid.

    PubMed

    Murugesan, Dinakaran; Palaniappan, Senthilkumar; Perumal, Yogeeswari; Arnab, China; Valakunja, Nagaraja; Sriram, Dharmarajan

    2008-04-01

    Several newer 6-fluoro/nitro-4-oxo-7-(sub)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids (10-11a-q) were synthesised from 3,4-difluoro aniline and 3-fluoro-4-nitro aniline by nine-step synthesis. The compounds were evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multidrug-resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) as well as being tested for their ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesised compounds, 7-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-6-nitro-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (11l) was found to be the most active compound in vitro, with minimum inhibitory concentrations (MICs) of 0.09 microM and <0.09 microM against MTB and MTR-TB, respectively. Compound 11l was found to be 4 times and >506 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in vivo animal model, 11l decreased the bacterial load in lung and spleen tissues by 30% and 42%, respectively, at a dose of 50 mg/kg body weight. PMID:18359434

  15. Quantitative analysis of cell surface membrane proteins using membrane-impermeable chemical probe coupled with 18O labeling

    PubMed Central

    Zhang, Haizhen; Brown, Roslyn N.; Qian, Wei-Jun; Monroe, Matthew E.; Purvine, Samuel O.; Moore, Ronald J.; Gritsenko, Marina A.; Shi, Liang; Romine, Margaret F; Fredrickson, James K.; Paša-Toli?, Ljiljana; Smith, Richard D.; Lipton, Mary S.

    2010-01-01

    We report a mass spectrometry-based strategy for quantitative analysis of cell surface membrane proteome changes. The strategy includes enrichment of surface membrane proteins using a membrane-impermeable chemical probe followed by stable isotope 18O labeling and LC-MS analysis. We applied this strategy for enriching membrane proteins expressed by Shewanella oneidensis MR-1, a gram-negative bacterium with known metal-reduction capability via extracellular electron transfer between outer membrane proteins and extracellular electron receptors. LC/MS/MS analysis resulted in the identification of about 400 proteins with 79% of them being predicted to be membrane localized. Quantitative aspects of the membrane enrichment were shown by peptide level 16O and 18O labeling of proteins from wild-type and mutant cells (generated from deletion of a type II secretion protein, GspD) prior to LC-MS analysis. Using a chemical probe labeled pure protein as an internal standard for normalization, the quantitative data revealed reduced abundances in ?gspD mutant cells of many outer membrane proteins including the outer membrane c-cype cytochromes OmcA and MtrC, in agreement with previously investigation demonstrating that these proteins are substrates of the type II secretion system. PMID:20380418

  16. Global role for polyadenylation-assisted nuclear RNA degradation in posttranscriptional gene silencing.

    PubMed

    Wang, Shao-Win; Stevenson, Abigail L; Kearsey, Stephen E; Watt, Stephen; Bähler, Jürg

    2008-01-01

    Fission yeast Cid14, a component of the TRAMP (Cid14/Trf4-Air1-Mtr4 polyadenylation) complex, polyadenylates nuclear RNA and stimulates degradation by the exosome for RNA quality control. Here, we analyze patterns of global gene expression in cells lacking the Cid14 or the Dis3/Rpr44 subunit of the nuclear exosome. We found that transcripts from many genes induced during meiosis, including key regulators, accumulated in the absence of Cid14 or Dis3. Moreover, our data suggest that additional substrates include transcripts involved in heterochromatin assembly. Mutant cells lacking Cid14 and/or Dis3 accumulate transcripts corresponding to naturally silenced repeat elements within heterochromatic domains, reflecting defects in centromeric gene silencing and derepression of subtelomeric gene expression. We also uncover roles for Cid14 and Dis3 in maintaining the genomic integrity of ribosomal DNA. Our data indicate that polyadenylation-assisted nuclear RNA turnover functions in eliminating a variety of RNA targets to control diverse processes, such as heterochromatic gene silencing, meiotic differentiation, and maintenance of genomic integrity. PMID:18025105

  17. The Saccharomyces cerevisiae small GTPase, Gsp1p/Ran, is involved in 3' processing of 7S-to-5.8S rRNA and in degradation of the excised 5'-A0 fragment of 35S pre-rRNA, both of which are carried out by the exosome.

    PubMed

    Suzuki, N; Noguchi, E; Nakashima, N; Oki, M; Ohba, T; Tartakoff, A; Ohishi, M; Nishimoto, T

    2001-06-01

    Dis3p, a subunit of the exosome, interacts directly with Ran. To clarify the relationship between the exosome and the RanGTPase cycle, a series of temperature-sensitive Saccharomyces cerevisiae dis3 mutants were isolated and their 5.8S rRNA processing was compared with processing in strains with mutations in a S. cerevisiae Ran homologue, Gsp1p. In both dis3 and gsp1 mutants, 3' processing of 7S-to-5.8S rRNA was blocked at three identical sites in an allele-specific manner. In contrast, the 5' end of 5.8S rRNA was terminated normally in gsp1 and in dis3. Inhibition of 5.8S rRNA maturation in gsp1 was rescued by overexpression of nuclear exosome components Dis3p, Rrp4p, and Mtr4p, but not by a cytoplasmic exosome component, Ski2p. Furthermore, gsp1 and dis3 accumulated the 5'-A0 fragment of 35S pre-rRNA, which is also degraded by the exosome, and the level of 27S rRNA was reduced. Neither 5.8S rRNA intermediates nor 5'-A0 fragments were observed in mutants defective in the nucleocytoplasmic transport, indicating that Gsp1p regulates rRNA processing through Dis3p, independent of nucleocytoplasmic transport. PMID:11404326

  18. TRAMP complex enhances RNA degradation by the nuclear exosome component Rrp6.

    PubMed

    Callahan, Kevin P; Butler, J Scott

    2010-02-01

    The RNA-processing exosome contains ribonucleases that degrade aberrant RNAs in archael and eukaryotic cells. In Saccharomyces cerevisiae, the nuclear/nucleolar 3'-5' exoribonuclease Rrp6 distinguishes the nuclear exosome from the cytoplasmic exosome. In vivo, the TRAMP complex enhances the ability of the nuclear exosome to destroy some aberrant RNAs. Previous reports showed that purified TRAMP enhanced RNA degradation by the nuclear exosome in vitro. However, the exoribonucleolytic component(s) of the nuclear exosome enhanced by TRAMP remain unidentified. We show that TRAMP does not significantly enhance RNA degradation by purified exosomes lacking Rrp6 in vitro, suggesting that TRAMP activation experiments with nuclear exosome preparations reflect, in part, effects on the activity of Rrp6. Consistent with this, we show that incubation of purified TRAMP with recombinant Rrp6 results in a 10-fold enhancement of the rate of RNA degradation. This increased activity results from enhancement of the hydrolytic activity of Rrp6 because TRAMP cannot enhance the activity of an Rrp6 mutant lacking a key amino acid side chain in its active site. We observed no ATP or polyadenylation dependence for the enhancement of Rrp6 activity by TRAMP, suggesting that neither the poly(A) polymerase activity of Trf4 nor the helicase activity of Mtr4 plays a role in the enhancement. These findings identify TRAMP as an exosome-independent enhancer of Rrp6 activity. PMID:19955569

  19. Molecular Basis for Coordinating Transcription Termination with Noncoding RNA Degradation

    PubMed Central

    Tudek, Agnieszka; Porrua, Odil; Kabzinski, Tomasz; Lidschreiber, Michael; Kubicek, Karel; Fortova, Andrea; Lacroute, François; Vanacova, Stepanka; Cramer, Patrick; Stefl, Richard; Libri, Domenico

    2014-01-01

    Summary The Nrd1-Nab3-Sen1 (NNS) complex is essential for controlling pervasive transcription and generating sn/snoRNAs in S. cerevisiae. The NNS complex terminates transcription of noncoding RNA genes and promotes exosome-dependent processing/degradation of the released transcripts. The Trf4-Air2-Mtr4 (TRAMP) complex polyadenylates NNS target RNAs and favors their degradation. NNS-dependent termination and degradation are coupled, but the mechanism underlying this coupling remains enigmatic. Here we provide structural and functional evidence demonstrating that the same domain of Nrd1p interacts with RNA polymerase II and Trf4p in a mutually exclusive manner, thus defining two alternative forms of the NNS complex, one involved in termination and the other in degradation. We show that the Nrd1-Trf4 interaction is required for optimal exosome activity in vivo and for the stimulation of polyadenylation of NNS targets by TRAMP in vitro. We propose that transcription termination and RNA degradation are coordinated by switching between two alternative partners of the NNS complex. PMID:25066235

  20. The Hbs1-Dom34 protein complex functions in non-stop mRNA decay in mammalian cells.

    PubMed

    Saito, Syuhei; Hosoda, Nao; Hoshino, Shin-ichi

    2013-06-14

    In yeast, aberrant mRNAs lacking in-frame termination codons are recognized and degraded by the non-stop decay (NSD) pathway. The recognition of non-stop mRNAs involves a member of the eRF3 family of GTP-binding proteins, Ski7. Ski7 is thought to bind the ribosome stalled at the 3'-end of the mRNA poly(A) tail and recruit the exosome to degrade the aberrant message. However, Ski7 is not found in mammalian cells, and even the presence of the NSD mechanism itself has remained enigmatic. Here, we show that unstable non-stop mRNA is degraded in a translation-dependent manner in mammalian cells. The decay requires another eRF3 family member (Hbs1), its binding partner Dom34, and components of the exosome-Ski complex (Ski2/Mtr4 and Dis3). Hbs1-Dom34 binds to form a complex with the exosome-Ski complex. Also, the elimination of aberrant proteins produced from non-stop transcripts requires the RING finger protein listerin. These findings demonstrate that the NSD mechanism exists in mammalian cells and involves Hbs1, Dom34, and the exosome-Ski complex. PMID:23667253