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1

Role of C677T and A1298C MTHFR, A2756G MTR and -786 C/T eNOS Gene Polymorphisms in Atrial Fibrillation Susceptibility  

PubMed Central

Background Hyperhomocysteinemia has been suggested to play a role in the NonValvular Atrial Fibrillation (NVAF) pathogenesis. Polymorphisms in genes coding for homocysteine (Hcy) metabolism enzymes may be associated with hyperhomocysteinemia and NVAF. Methodologies 456 NVAF patients and 912 matched controls were genotyped by an electronic microchip technology for C677T and A1298C MTHFR, A2756G MTR, and -786C/T eNOS gene polymorphisms. Hcy was determined by an immunoassay method. Principal Findings The genotype distribution of the four polymorphisms as well as genotype combinations did not differ in patients and controls. Hcy was higher in patients than in controls (15.2, 95%CI 14.7–15.7 vs 11.3, 95%CI 11.0–11.6 µmol/L; p<0.0001). In both populations, a genotype-phenotype association (p<0.0001) between Hcy and C677T MTHFR polymorphism was observed; in controls a significant (p?=?0.029) association between tHcy and ?786C/T eNOS polymorphism was also observed. At the multivariate analysis the NVAF risk significantly increased in the upper quartiles of Hcy compared to the lowest: OR from 2.8 (1.68–4.54 95%CI) in Q2 to 12.9 (7.96–21.06 95%CI) in Q4. Conclusions Our data demonstrated the four polymorphisms, although able, at least in part, to affect Hcy, were not associated with an increased risk of NVAF per se or in combination. PMID:17551576

Giusti, Betti; Gori, Anna Maria; Marcucci, Rossella; Sestini, Ilaria; Saracini, Claudia; Sticchi, Elena; Gensini, Francesca; Fatini, Cinzia; Abbate, Rosanna; Gensini, Gian Franco

2007-01-01

2

Evaluation of the MTHFR A1298C variant in leukoaraiosis.  

PubMed

Vascular demyelinization of the white matter of the brain is referred to as leukoaraiosis (LA). This very frequent entity is associated with a cognitive decline, thereby resulting in a deteriorating quality of life. Besides poorly controlled hypertension and aging, its development is reported to be associated with an elevated serum homocysteine level. Although the methylenetetrahydrofolate reductase (MTHFR) C677T genetic variant is associated with an elevated serum homocysteine level, it has not been proved to be an independent risk factor for LA. The aim of the present study was to examine whether the MTHFR A1298C genetic variant, which is also believed to be unfavorable, is associated with the presence of LA. The clinical and genetic data on 198 LA patients and 235 neuroimaging alteration-free controls were analyzed. The presence of the A1298C or the 1298CC variant was calculated to be a risk factor for LA, as compared with the absence of both of them. The clustering of the heterozygous A1298C and C677T variants was proved to involve the risk of LA. Our results suggest that the MTHFR A1298C variant confers an independent genetic risk of LA, and this pathological role may be amplified by the MTHFR C677T variant. PMID:21845428

Szolnoki, Zoltan; Szaniszlo, Istvan; Szekeres, Marta; Hitri, Krisztina; Kondacs, Andras; Mandi, Yvette; Nedo, Erika; Somogyvari, Ferenc

2012-03-01

3

Cerebral sinovenous thrombosis associated with MTHFR A1298C mutation in the newborn: a case report.  

PubMed

Although cerebral sinovenous thrombosis (CSVT) is a rare condition in the neonatal period, high rates of morbidity and mortality necessitate the establishment of an early diagnosis. Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the folate cycle and mutations of MTHFR are associated with vascular disease. While the C677T common missense mutation is the most well-defined MTHFR polymorphism, another common missense mutation, A1298C also exists. There has been no reported case of CSVT associated with MTHFR A1298C mutation in the neonatal period. Herein, we report a neonate with CSVT who was found to have MTHFR A1298C homozygosity. PMID:22797907

Cizmeci, Mehmet Nevzat; Kanburoglu, Mehmet Kenan; Akelma, Ahmet Zulfikar; Donmez, Ahsen; Sonmez, Fatma Mujgan; Polat, Aziz; Kosehan, Dilek; Tatli, Mustafa Mansur

2013-02-01

4

Two cousins with neonatal stroke, PAI-1 4G variant and MTHFR A1298C mutation.  

PubMed

The authors describe 2 female cousins with neonatal stroke. One was heterozygous for the plasminogen activator inhibitor-1 4G variant and compound heterozygous for the A1298C and C677T methylenetetrahydrofolate reductase mutations. Her cousin was homozygous for the plasminogen activator inhibitor-1 4G variant and heterozygous for the methylenetetrahydrofolate reductase A1298C and factor V Leiden mutations. PMID:17641264

Golomb, Meredith R; Heiny, Mark; Garg, Bhuwan P

2007-06-01

5

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

PubMed Central

Objective 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. Methods We screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20–60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined. Results Prevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C=41%, C/T=47%, T/T=11%, A/A=66%, A/G=29%, G/G=4%). In the fluoxetine-treated subsample (n=49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response. Conclusion The C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples. PMID:22789065

Mischoulon, David; Lamon-Fava, Stefania; Selhub, Jacob; Katz, Judith; Papakostas, George I.; Iosifescu, Dan V.; Yeung, Albert S.; Dording, Christina M.; Farabaugh, Amy H.; Clain, Alisabet J.; Baer, Lee; Alpert, Jonathan E.; Nierenberg, Andrew A.; Fava, Maurizio

2014-01-01

6

Comparing Techniques for the Identification of the MTHFR A1298C Polymorphism  

PubMed Central

The restriction fragment length polymorphism (RFLP) technique with the MboII enzyme is used by a number of researchers as a methodology for the identification of the genetic polymorphism MTHFR A1298C. However, the reliability of this enzyme for genotyping this polymorphism has been questioned, since the silent polymorphism T1317C, located close to the polymorphic region A1298C on gene MTHFR, also has a recognition site for MboII. Thus, the fragments formed by the digestion of MboII present similar sizes, making it difficult to differentiate the allele MTHFR 1298A in the presence of the allele MTHFR 1317C. Hence, we investigated the A1298C polymorphism in a Brazilian population of renal transplant patients, using the RFLP technique with digestion by Mbo II and using sequencing, in order to examine the concordance between the two techniques. Our results showed an 8.6% difference in genotyping between RFLP and sequencing, but the statistical concordance test presented a kappa coefficient equal to 0.81 (CI 95% 0.74–88), which indicates a virtually perfect concordance, according to the criterion of Landis and Koch. Therefore, we concluded that the RFLP technique is concordant with automated sequencing in the detection of polymorphism A1298C under our laboratory conditions. PMID:19137091

de Alvarenga, Maria Paula Sanches; Pavarino-Bertelli, Érika Cristina; Goloni-Bertollo, Eny Maria

2008-01-01

7

Association of the A1298C polymorphism in MTHFR gene with ischemic stroke.  

PubMed

A meta-analysis was performed to assess the association between the methylenetetrahydrofolate reductase (MTHFR) A1298C genetic polymorphism and ischemic stroke. A comprehensive search was conducted to identify all case-control or cohort studies. The fixed or random effect pooled measure was selected based on the homogeneity between studies, as assessed by I(2). Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using Egger's linear regression test. Thirteen case-control studies corresponded to the inclusion criteria comprising 2133 patients and 2572 controls which were included in the present meta-analysis. After excluding articles that deviated from Hardy-Weinberg equilibrium in controls and the key contributors to between-study heterogeneity, significant associations between MTHFR A1298C genetic polymorphism and risk of ischemic stroke were observed in dominant (odds ratio [OR] 1.227, 95% confidence interval [CI] 1.062-1.416) and codominant (OR 1.138, 95% CI 1.007-1.286) inheritance models. Moreover, in the subgroup analysis based on region (Asia and Europe), significant associations were observed in most genetic models in Asia but not in Europe. This meta-analysis suggests that MTHFR A1298C genetic polymorphism is associated with increased risk of ischemic stroke, and the C allele may be an important risk factor for ischemic stroke. PMID:24128767

Kang, Shan; Wu, Yili; Liu, Lingling; Zhao, Xinxin; Zhang, Dongfeng

2014-02-01

8

Association of the MTHFR A1298C Variant with Unexplained Severe Male Infertility  

PubMed Central

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 consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR?=?3.372, 95% confidence interval CI?=?1.27–8.238; p?=?0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants. PMID:22457816

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

2012-01-01

9

Association of the MTHFR A1298C variant with unexplained severe male infertility.  

PubMed

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 consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR?=?3.372, 95% confidence interval CI?=?1.27-8.238; p?=?0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants. PMID:22457816

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

2012-01-01

10

MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer.  

PubMed

5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using data from an incident case-control study (1608 cases and 1972 controls) we investigated two polymorphisms in the MTHFR gene, C677T and A1298C, and their associations with risk of colon cancer. All of the combined genotypes were evaluated separately, and the 1298AA/677CC (wild-type/wild-type) group was considered the reference group. Among both men and women, the 677TT/1298AA (variant/wild-type) genotype was associated with a small reduction in risk [men: odds ratio (OR), 0.7, 95% confidence interval (CI), 0.5-1.0; women: OR, 0.8, 95% CI, 0.5-1.2]. However, the 677CC/1298CC (wild-type/variant) genotype was associated with a statistically significant lower risk among women (OR, 0.6; 95% CI, 0.4-0.9) but not men. When the polymorphisms were considered individually, for A1298C a significant risk reduction associated with the homozygous variant CC genotype was seen among women only (OR, 0.6; 95% CI, 0.5-0.9), and nonstatistically significant reduced risks were observed for the variant 677 TT genotypes among both men and women. Stratification by nutrient intakes showed inverse associations with higher intakes of folate, vitamin B(2), B(6), B(12), and methionine among women with the MTHFR 677CC/1298AA genotypes, but not those with 677TT/1298AA. We observed opposite risk trends for both MTHFR variants, depending on whether women used hormone-replacement therapy or not (P for interaction = <.01). In summary, this study supports recent findings that the MTHFR A1298C polymorphism may be a predictor of colon cancer risk and have functional relevance. The possible interaction with hormone-replacement therapy warrants additional investigation. PMID:14973104

Curtin, Karen; Bigler, Jeannette; Slattery, Martha L; Caan, Bette; Potter, John D; Ulrich, Cornelia M

2004-02-01

11

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

PubMed

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

Ucar, V B; Nami, B; Acar, H; K?l?nç, M

2015-02-01

12

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility  

PubMed Central

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

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

13

Association of methylenetetrahydrofolate reductase (A1298C and C677T) polymorphisms with retinal vein occlusion in Tunisian patients.  

PubMed

The role of two polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in the etiology of retinal vein occlusion (RVO) has not been adequately clarified. The aim of this study was to examine the prevalence of these polymorphisms among RVO Tunisian patients with and without systemic risk factors. Seventy-two patients with retinal vein occlusion (RVO) were studied. The control group included140 people matched for age, sex, and risk factors. Participants in the study were genotyped for the MTHFR C677T and A1298C polymorphisms. The genotyping was performed by PCR-RFLP. No significant differences were found in the frequencies of the three genotypes (AA, AC, CC) of the MTHFR A1298C polymorphism between RVO patients and healthy controls. However, the prevalence of the group of mutated genotypes (AC+CC) of the missense variant MTHFR A1298C was significantly different between patients and controls (16.67% vs. 6.42%, p=.01). Additionally, the frequency of the CT genotype as well as the group of combined mutated genotypes (CT+TT) for the C677T variant was significantly higher among RVO patients compared with controls (p<10(-3), p<10(-3)). This suggests an association between this polymorphism and RVO. Large study populations would be required to understand more completely the contribution of these markers in the risk of RVO. PMID:24440586

Mrad, Meriem; Wathek, Cheima; Saleh, Mekki Ben; Baatour, Makrem; Rannen, Riadh; Lamine, Khaled; Gabsi, Salem; Gritli, Nasreddine; Fekih-Mrissa, Najiba

2014-04-01

14

A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Previous studies revealed that a common mutation in MTHFR gene C677T is related to hyperhomocysteinemia and occlusive vascular pathology. In the current study, we determined the prevalence of a newly described mutation in the human MTHFR gene A1298C, and the already known C677T mutation, and related them to plasma total homocysteine and folate concentrations. We studied 377 Jewish subjects, including 190 men and 186 women aged 56.8 +/- 13 y (range 32-95 y). The frequency of the homozygotes for the A1298C and the C677T MTHFR mutations was common in the Jewish Israeli population (0.34 and 0.37, respectively). Subjects homozygous (TT) for the C677T mutation had significantly greater plasma total homocysteine concentrations (P < 0.01) than subjects without the mutation (CC). Homozygotes (CC) for the A1298C mutation did not have elevated plasma total homocysteine concentrations. Our study indicated that subjects with the 677CC/1298CC genotype had significantly lower concentrations (P < 0. 05) than those with a 677CC/1298AA genotype. Neither mutation (the A1298C and the C677T) was associated with established cardiovascular risk factors such as hypertension, elevated total cholesterol or body mass index. PMID:10460200

Friedman, G; Goldschmidt, N; Friedlander, Y; Ben-Yehuda, A; Selhub, J; Babaey, S; Mendel, M; Kidron, M; Bar-On, H

1999-09-01

15

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

PubMed

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

Rai, V

2014-11-01

16

Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease.  

PubMed

Elevation in homocysteine and methylenetetrahydrofolate reductase (MTHFR) gene variants, C677T and A1298C, have been linked with atherothrombosis. However their exact contribution to coronary artery disease (CAD) remains controversial. Moreover, data from Tunisian patients are scarse. We examined the association of MTHFR C677T and A1298C, and changes in plasma homocysteine in 352 Tunisian patients with angiographically-demonstrated CAD, and 390 age and gender-matched healthy subjects. Significantly higher frequency of 677T allele and homozygous 677T/T genotype were seen in patients vs. control subjects; the distribution of A1298C alleles and genotypes being comparable in the two groups. Specific MTHFR haplotypes comprising 677C/1298A (P < 0.001) and 677T/1298A (P < 0.001) were negatively and positively associated with CAD, respectively. Plasma homocysteine concentration was significantly higher in 677T/T genotype with respect to 677C/C and 677C/T genotypes in patients and controls, but homocysteine levels were generally comparable between both groups. Univariate analysis identified 677T/1298A (P = 0.033) haplotype to be positively associated with CAD, which remained significant by multivariate analysis after adjusting for a number of covariates (P = 0.038). MTHFR C677T, but not A1298C SNPs, is associated with CAD and with elevated homocysteine levels in a Tunisian population. The negative and positive association of the 1298A allele with CAD being indicative of a neutral (absent) effect of the A1298C SNP on disease pathogenesis. PMID:18204887

Ghazouani, Lakhdar; Abboud, Nesrine; Mtiraoui, Nabil; Zammiti, Walid; Addad, Faouzi; Amin, Haitham; Almawi, Wassim Y; Mahjoub, Touhami

2009-02-01

17

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

PubMed Central

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

Rai, V

2014-01-01

18

Multiloculated hydrocephalus of intrauterine-onset: a case report of an unexpected MTHFR A1298C positive test result.  

PubMed

Loculated hydrocephalus is a condition in which discrete fluid-filled compartments form in association with the ventricular system of the brain. Multiloculated hydrocephalus is a subgroup of this entity involving more than one segment of the ventricular system. Abnormal descent of the cerebellar components can cause multiloculated hydrocephalus due to various pathogenesis. However, studies report no more than 10% of correlation between cerebellar herniation and hydrocephalus. We report an infant with MTHFR A1298C homozygosity, who had hydrocephalus of intrauterine-onset. Alterations in the folate metabolism might lead to congenital hydrocephalus and there is growing data on the prothrombotic effects of MTHFR polymorphisms. To the best of our knowledge, there has been no reported case of MTHFR A1298C homozygosity and intrauterine-onset multiloculated hydrocephalus as a co-existence in the literature. PMID:24341140

Cizmeci, M N; Akelma, A Z; Kosehan, D; Kutukoglu, I; Sonmez, F M

2013-01-01

19

Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism in Iranian Women With Idiopathic Recurrent Pregnancy Losses  

PubMed Central

Background: Recurrent pregnancy loss (RPL) is a serious problem for pregnancy. There is evidence that vascular complications play a principal role in RPL. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Polymorphisms (C677T, A1298C) of MTHFR gene are associated with decreased MTHFR activity. Objectives: The aim of this study was to determine the association between MTHFR polymorphisms (C677T and A1298C) and recurrent pregnancy loss (RPL) in Iranian women. Materials and Methods: In this case-control study, blood samples were obtained from patients who had three or more consecutive pregnancy losses before the 22nd week of pregnancy (n = 204). The control group consisted of 116 age-matched women with at least one alive child and without any history of pregnancy loss or other gestational complications (n = 116). Following DNA extraction, samples were tested for MTHFR C677T and A1298C polymorphisms using the reverse hybridization method. Results: The prevalence of 677TT mutation was 8.8% (18/204) in the patient group and 8.6% (10/116) in the control group (P = 0.434). The prevalence of 1298CC mutation was 12.3 % (25/204) in the patient group and 8% (9/116) in the control group (P = 0.155). Investigation of the distributions of various genotypes of MTHFR C677T and A1298C did not indicate a significant difference between patients with RPL and healthy control subjects. Conclusions: The results suggest that MTHFR mutations might not be associated with RPL in the examined population. PMID:25237572

Yousefian, Elham; Kardi, Mohammad Taghi; Allahveisi, Azra

2014-01-01

20

MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in Brazilian women.  

PubMed

The aim of this study was to investigate the association between MTHFR gene polymorphisms and IVF outcomes in Brazilian women undergoing assisted reproduction treatment. A prospective study was conducted in the Human Reproduction Department at the ABC University School of Medicine and the Ideia Fertility Institute between December 2010 and April 2012. The patient population was 82 women undergoing assisted reproduction cycles. The MTHFR polymorphisms C677T and A1298C were evaluated and compared with laboratory results and pregnancy rates. The C677T variant was associated with proportions of mature (P=0.006) and immature (P=0.003) oocytes whereas the A1298C variant was associated with number of oocytes retrieved (P=0.044). The polymorphisms, whether alone or in combination, were not associated with normal fertilization, good-quality embryo or clinical pregnancy rates. This study suggests that the number and maturity of oocytes retrieved may be related to the MTHFR polymorphisms C677T and A1298C. It is believed that folate has a crucial function in human reproduction and that folate deficiency can compromise the function of the metabolic pathways it is involved in, leading to an accumulation of homocysteine. The gene MTHFR encodes the 5-MTHFR enzyme, which is involved in folate metabolism, and C677T/A1298C polymorphisms of this gene are related to decreased enzyme activity and consequent changes in homocysteine concentration. Folate deficiency and hyperhomocysteinaemia can also compromise fertility and lead to pregnancy complications by affecting the development of oocytes, preparation of endometrial receptivity, implantation of the embryo and pregnancy. In folliculogenesis, hyperhomocysteinaemia can activate apoptosis, leading to follicular atresia and affecting the maturity of oocytes and the quality of embryos cultured in vitro. This study was performed to investigate the association between MTHFR polymorphisms and IVF outcomes in women undergoing assisted reproduction treatment. PMID:24746944

D'Elia, Priscila Queiroz; dos Santos, Aline Amaro; Bianco, Bianca; Barbosa, Caio Parente; Christofolini, Denise Maria; Aoki, Tsutomu

2014-06-01

21

MTHFR C677T and A1298C polymorphisms are risk factors for Down's syndrome in Indian mothers.  

PubMed

Down's syndrome (DS), a chromosomal disorder due to trisomy 21, results mostly from nondisjunction in maternal meiosis. The present case-control study examined the association of genetic polymorphisms with predisposition to nondisjunction. Two common polymorphisms (SNPs), C677T and A1298C, in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene involved in folate metabolism, are known to lower the activity of this enzyme. Three hundred and fourteen mothers (with DS children and controls), mostly from the eastern states of India, were genotyped for the two above-mentioned SNPs. Significant association with both of these SNPs were detected, more specifically, in the mothers of DS children homozygous for the polymorphic alleles 677 T and 1298 C. The relative risk of T (C677T) and C (A1298C) homozygosity in mothers for DS-affected pregnancy was 7 (OR 7.67, 95% CI 1.67-35.08, P=0.003) and 4 (OR 4.40, 95% CI 1.45-13.26, P=0.008), respectively. Moreover, all 677TT mothers studied were less than 31 years of age, whereas no correlation with maternal age was observed for A1298C genotypes. Interestingly, all of the young 677TT mothers had either a first- or secondborn child with DS. Thus, this study reports that young Indian mothers with TT genotypes are genetically predisposed to nondisjunction due to abnormal folate metabolism. PMID:16489479

Rai, Amit Kumar; Singh, Satya; Mehta, Stuti; Kumar, Ashok; Pandey, L K; Raman, Rajiva

2006-01-01

22

Methylenetetrahydrofolate reductase gene C677T, A1298C polymorphisms and pre-eclampsia risk: a meta-analysis.  

PubMed

To determine whether methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are associated with pre-eclampsia susceptibility. Literature searches of the Pubmed, Embase, BIOSIS Previews and Web of Science were conducted to identify all eligible articles up to January 18th, 2013. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) of five genetic models were calculated by fixed-effects or random-effects model. Publication bias, subgroup analysis, meta-regression and sensitivity analysis were also performed. A number of 49 studies including 51 samples consisted of 18,009 subjects (6,238 patients and 11,771 controls) were finally included. MTHFR C677T allele (TT or CT) carriers were 1.12 times more likely to develop pre-eclampsia (95% CI 1.04-1.21) compared with 677CC homozygous individuals. Similar results were obtained under other genetic models. Restricted to severe pre-eclampsia, there was an increased risk for 677TT homozygotes compared with 677CC homozygotes (OR 1.43; 95% CI 1.12-1.83). Subgroup analysis revealed a significant positive association between the C677T polymorphism (TT or CT) and pre-eclampsia in Asians (OR 1.41; 95% CI 1.11-1.79) and white population (OR 1.14; 95% CI 1.03-1.25). Meta-regression showed that study population, blinded genotyping, matching of cases and controls were not substantial sources of heterogeneity. For the MTHFR A1298C, ORs for all genetic models yielded a null association. This meta-analysis suggests that the MTHFR 677T allele might be associated with increased pre-eclampsia risk in Asian and white ethnicity and the subgroup of severe pre-eclampsia, while no association is observed between the MTHFR A1298C polymorphism and pre-eclampsia. PMID:24898880

Li, Xing; Luo, Ya L; Zhang, Qiong H; Mao, Chen; Wang, Xi W; Liu, Shan; Chen, Qing

2014-08-01

23

Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: an examination of C677T and A1298C mutations.  

PubMed

Although rare in children, stroke is becoming increasingly recognized as an important cause of morbidity and mortality with an annual incidence of approximately 3 per 100,000 per year. While several studies have documented the underlying mechanisms and pathogenesis related to stroke in adults, including genetic and acquired prothrombotic conditions, the data available on similar conditions in children is limited. Evidence suggests that mutations in methylenetetrahydrofolate reductase (MTHFR) appear to be linked with hyperhomocysteinemia (HHC) and cerebral-thrombotic events in children. While the C677T common missense mutation is the best-characterized MTHFR polymorphism, another common missense mutation, A1298C also exists. A recent study of children demonstrated that the homozygous form of C677T polymorphism occurred two-times as often in those with stroke versus healthy controls. In our retrospective chart review of 33 children seen at Children's Hospital of Orange County from January 1, 2000 to September 30, 2003 with the diagnosis of stroke, we examined both the C677T and A1298C polymorphisms for occurrence and type. In the subset (n=21), which excluded those with a confounding disorder, we observed a significant increase in the frequency of A1298C and C677T homozygosity (0.25 [p=0.01] and 0.20 [p=0.100], respectively); expected rate: (0.06 and 0.08, respectively). Our observed rates of heterozygosity for both MTHFR mutations (0.35 and 0.40, respectively) were consistent with expected rates (0.28 and 0.38, respectively). In all subjects, homocysteine (HC) levels were normal. The results of our study suggest that mutations in MTHFR are associated with pediatric stroke. However, additional studies are required to confirm our findings and to determine if this relationship is causal. PMID:16282888

Rook, James L; Nugent, Diane J; Young, Guy

2005-11-01

24

Population distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C risk alleles for methotrexate toxicity in Israel.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a central regulatory enzyme in the folate pathway. Two non-synonymous single nucleotide polymorphisms in MTHFR, C677T (rs1801133) and A1298C (rs1801131) have been associated with reduced MTHFR enzyme activity. These polymorphisms, especially C677T, appear to be linked with methotrexate-related toxicity, particularly hepatotoxicity; thus, pretreatment identification of individuals carrying these polymorphisms may be of clinical relevance. The purpose of this study was to determine the frequency and distribution of MTHFR polymorphic variants, known to functionally impair MTHFR activity, in the highly heterogeneous Israeli population. MTHFR genotyping was carried out in the representatives of three major demographic groups in Israel by PCR-restriction fragment length polymorphism and high-resolution melting. The relative distribution of variant alleles 677T and 1298C was found to be similar in individuals of Jewish, Druze and Arab Moslem descent (p = 0.09). However, Ashkenazi Jews displayed a 1.9-fold higher frequency of variant 677T and a 1.8-fold lower frequency of variant 1298C compared to non-Ashkenazi Jews (p < 0.001). Distinct differences in the relative frequencies of both polymorphisms were also found between Ashkenazi Jews and Druze (p < 0.01 for C677T, p < 0.01 for A1298C) or Ashkenazi Jews and Arab Moslem (p < 0.01 for C677T, p < 0.05 for A1298C). These data underscore the importance of geographic genetic analysis for a better understanding of human pharmacotherapy and personalized medicine. PMID:22847291

Efrati, Edna; Elkin, Hela; Nahum, Sagi; Krivoy, Norberto

2013-04-01

25

Severe arterial thrombophilia associated with a homozygous MTHFR gene mutation (A1298C) in a young man with Klinefelter syndrome.  

PubMed

Klinefelter syndrome (KS) is the most common sex chromosome disorder in men. It may be associated with an increased risk for venous thrombosis and thromboembolism, which is partially explained by hypofibrinolysis due to androgen deficiency. Additional genetic or acquired thrombophilic states have been shown in KS patients complicated with venous thrombosis as isolated case reports. Arterial thrombotic events had not been previously reported in KS. In this study, a young man with KS who developed acute arterial thrombosis during testosterone replacement therapy is presented. He was homozygous for the A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. PMID:18160591

Ozbek, Mustafa; Oztürk, M Akif; Ureten, Kemal; Ceneli, Ozcan; Erdogan, Mehmet; Haznedaroglu, Ibrahim C

2008-07-01

26

Polymorphisms of MTHFR C677T and A1298C association with oral carcinoma risk: a meta-analysis.  

PubMed

Investigations regarding association of MTHFR polymorphisms with oral carcinoma risk have yielded inconclusive results. Thus, meta-analyses were performed. Results showed that no associations of C677T polymorphisms with oral carcinoma were observed for the overall data. In subgroup analyses by drinking status, homozygous TT alleles exhibited elevated oral cancer susceptibility in heavy drinkers. For A1298C polymorphism, CC alleles presented a possible preventive role for oral cancer. Collectively, results suggest that MTHFR 677TT polymorphism might be a low-penetrant risk factor for oral carcinoma only in heavy drinkers. Conversely, 1298CC alleles might play a preventive role for oral cancer. PMID:22536935

Zhuo, Xianlu; Ling, Junjun; Zhou, Yan; Zhao, Houyu; Song, Yufeng; Tan, Yinghui

2012-07-01

27

Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with male infertility: a meta-analysis.  

PubMed

Published data on the association between the methylenetetrahydrofolate reductase (MTHFR) gene A1298C (rs1801131) polymorphism and male infertility risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of seven case-control studies including 1633 cases and 1735 controls were selected to evaluate the possible association. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of the C1298 allele (C vs. A) was significantly associated with susceptibility to male infertility (OR = 1.12, 95% CI = 1.00-1.26). A subgroup analysis of the subjects showed that MTHFR 1298C was associated with significant increased risk of azoospermia in homozygote comparison (CC vs. AA) and recessive mode (CC vs. AA/AC) (OR = 1.66 for CC vs. AA genotype; OR = 1.67 for CC vs. AA/AC genotype). However, no statistically significant increased risk of oligoasthenoteratozoospermia was found in any of the genetic models. In conclusion, this meta-analysis supports that the MTHFR A1298C polymorphism is capable of causing male infertility susceptibility, especially azoospermia. PMID:22175540

Shen, Ouxi; Liu, Renping; Wu, Wei; Yu, Lugang; Wang, Xinru

2012-01-01

28

Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos.  

PubMed

The pathogenesis of spontaneous abortion is complex, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms are commonly associated with defects in folate dependent homocysteine metabolism and have been implicated as risk factors for recurrent embryo loss in early pregnancy. In the present study we have determined the prevalence of combined MTHFR C677T and A1298C polymorphisms in DNA samples from spontaneously aborted embryos (foetal death between sixth and twentieth week after conception) and adult controls using solid-phase minisequencing technique. There was a significant odds ratio of 14.2 (95% CI 1.78-113) in spontaneously aborted embryos comparing the prevalence of one or more 677T and 1298C alleles vs the wild type combined genotype (677CC/1298AA), indicating that the MTHFR polymorphisms may have a major impact on foetal survival. Combined 677CT/1298CC, 677TT/1298AC or 677TT/1298CC genotypes, which contain three or four mutant alleles, were not detected in any of the groups, suggesting complete linkage disequilibrium between the two polymorphisms. The present finding of high prevalence of mutated MTHFR genotypes in spontaneously aborted embryos emphasises the potential protective role of periconceptional folic acid supplementation. PMID:11938441

Zetterberg, Henrik; Regland, Björn; Palmér, Mona; Ricksten, Anne; Palmqvist, Lars; Rymo, Lars; Arvanitis, Demetrios A; Spandidos, Demetrios A; Blennow, Kaj

2002-02-01

29

Association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma susceptibility: evidence from a meta-analysis.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. A number of studies have examined the association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were contradictory. We searched available publications assessing the polymorphisms of MTHFR and NHL susceptibility from MEDLINE, EMBASE and CBM. Genotype-based mRNA expression analysis was performed using data from 270 individuals with three different ethnicities. Ultimately, a total of 7448 cases and 11146 controls from 25 studies were included for the C677T polymorphism, 6173 cases and 9725 controls from 19 studies for the A1298C polymorphism. Pooled results indicated that neither C677T nor A1298C polymorphism was associated with NHL susceptibility. However, C677T polymorphism showed a statistically significantly increased risk for Caucasians, but a decreased risk for Asians in the subgroup analysis by ethnicity. The same variants may confer increased susceptibility to develop follicular lymphoma (FL). Moreover, A1298C polymorphism was associated with increased NHL risk for Asians. This meta-analysis indicated that C677T polymorphism was associated with altered NHL susceptibility for Caucasians, Asians and FL. Increased NHL risk was also shown for A1298C among Asians. These findings warrant validation in large and well-designed prospective studies. PMID:25146845

He, Jing; Liao, Xiao-Yu; Zhu, Jin-Hong; Xue, Wen-Qiong; Shen, Guo-Ping; Huang, Shao-Yi; Chen, Wei; Jia, Wei-Hua

2014-01-01

30

The Frequency of A1298C and C677T Polymorphisms of the Methylentetrahydrofolate Gene in Turkish Patients with Rheumatoid Arthritis: Relationship with Methotrexate Toxicity  

PubMed Central

The C677T and A1298C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine the frequency of MTHFR C677 T and A1298C gene polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity. Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ±12.5 and 46.2 ± 13.4 years, were enrolled to the study. Demographic characteristics were obtained and MTX-related adverse effects were recorded in the patient group. The A1298C and C677T polymorphisms of the MTHFR gene were analyzed and the distribution of genotypes according side effects, were determined. The frequency of MTHFR C677T and A1298C polymorphisms were similar in the patient and control groups. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment, and MTX had been discontinued in 12 (18.8%) patients due to side effects and/or inefficacy. MTHFR C677T and A1298C gene polymorphisms were found to be similar in patients with and without MTX-related adverse events. In conclusion, A1298C and C677T polymorphisms in the MTHFR gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX toxicity in patients suffering from RA. PMID:22046205

Ta?ba?, Özgür; Borman, P?nar; Gürhan Karabulut, Halil; Tükün, Ajlan; Yorganc?o?lu, Rezan

2011-01-01

31

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

PubMed Central

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

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

32

Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298C mutations.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) mutations are commonly associated with hyperhomocysteinemia, and, through their defects in homocysteine metabolism, they have been implicated as risk factors for neural tube defects and unexplained, recurrent embryo losses in early pregnancy. Folate sufficiency is thought to play an integral role in the phenotypic expression of MTHFR mutations. Samples of neonatal cord blood (n=119) and fetal tissue (n=161) were analyzed for MTHFR C677T and A1298C mutations to determine whether certain MTHFR genotype combinations were associated with decreased in utero viability. Mutation analysis revealed that all possible MTHFR genotype combinations were represented in the fetal group, demonstrating that 677T and 1298C alleles could occur in both cis and trans configurations. Combined 677CT/1298CC and 677TT/1298CC genotypes, which contain three and four mutant alleles, respectively, were not observed in the neonatal group (P=.0402). This suggests decreased viability among fetuses carrying these mutations and a possible selection disadvantage among fetuses with increased numbers of mutant MTHFR alleles. This is the first report that describes the existence of human MTHFR 677CT/1298CC and 677TT/1298CC genotypes and demonstrates their potential role in compromised fetal viability. PMID:10958762

Isotalo, P A; Wells, G A; Donnelly, J G

2000-10-01

33

Neonatal and Fetal Methylenetetrahydrofolate Reductase Genetic Polymorphisms: An Examination of C677T and A1298C Mutations  

PubMed Central

Methylenetetrahydrofolate reductase (MTHFR) mutations are commonly associated with hyperhomocysteinemia, and, through their defects in homocysteine metabolism, they have been implicated as risk factors for neural tube defects and unexplained, recurrent embryo losses in early pregnancy. Folate sufficiency is thought to play an integral role in the phenotypic expression of MTHFR mutations. Samples of neonatal cord blood (n=119) and fetal tissue (n=161) were analyzed for MTHFR C677T and A1298C mutations to determine whether certain MTHFR genotype combinations were associated with decreased in utero viability. Mutation analysis revealed that all possible MTHFR genotype combinations were represented in the fetal group, demonstrating that 677T and 1298C alleles could occur in both cis and trans configurations. Combined 677CT/1298CC and 677TT/1298CC genotypes, which contain three and four mutant alleles, respectively, were not observed in the neonatal group (P=.0402). This suggests decreased viability among fetuses carrying these mutations and a possible selection disadvantage among fetuses with increased numbers of mutant MTHFR alleles. This is the first report that describes the existence of human MTHFR 677CT/1298CC and 677TT/1298CC genotypes and demonstrates their potential role in compromised fetal viability. PMID:10958762

Isotalo, Phillip A.; Wells, George A.; Donnelly, James G.

2000-01-01

34

Spectrum of MTHFR gene SNPs C677T and A1298C: a study among 23 population groups of India.  

PubMed

Elevated homocysteine is a risk factor for many complex disorders. The role of methylenetetrahydrofolate reductase (MTHFR) gene in methylation of homocysteine makes it one of the most important candidate genes for these disorders. Considering the heterogeneity in its distribution in world populations, we screened MTHFR C677T and A1298C single nucleotide polymorphisms in a total of 23 Indian caste, tribal and religious population groups from five geographical regions of India and belonging to four major linguistic groups. The frequencies of MTHFR 677T and 1298C alleles were found to be 10.08 and 20.66%, respectively. MTHFR homozygous genotype 677TT was absent in eight population groups and homozygous 1298CC was absent in two population groups. 677T allele was found to be highest among north Indian populations with Indo-European tongue and 1298C was high among Dravidian-speaking tribes of east India and south India. The less common mutant haplotype 677T-1298C was observed among seven population groups and overall the frequency of this haplotype was 0.008, which is similar to that of African populations. cis configuration of 677T and 1298C was 0.94%. However, we could not find any individual with four mutant alleles which supports the earlier observation that presence of more than two mutant alleles may decrease the viability of foetus and possibly be a selective disadvantage in the population. PMID:22147263

Saraswathy, Kallur Nava; Asghar, Mohammad; Samtani, Ratika; Murry, Benrithung; Mondal, Prakash Ranjan; Ghosh, Pradeep Kumar; Sachdeva, Mohinder Pal

2012-04-01

35

Effect of cystathionine beta-synthase variant 844ins68bp and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5-FU efficacy and doubling time.  

PubMed

The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling time of tumors with a variant C allele (AC or CC) in MTHFR-A1298C was significantly longer than that of tumors with a normal allele (AA) (P=0.0008). Twenty-nine cellular proliferation-related genes were associated with MTHFR-A1298C genotyping and with the doubling time. PMID:16307843

Sasaki, Shin; Watanabe, Toshiaki; Kobunai, Takashi; Nagawa, Hirokazu

2006-09-28

36

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

PubMed

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

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

2012-06-01

37

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene  

PubMed Central

Background: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. Objective: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. Design: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. Results: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. Conclusions: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis. PMID:15361376

Berkun, Y; Levartovsky, D; Rubinow, A; Orbach, H; Aamar, S; Grenader, T; Abou, A; Mevorach, D; Friedman, G; Ben-Yehuda, A

2004-01-01

38

Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses.  

PubMed

Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs 4.0%) genotypes was significantly higher in patients. While it was similar among patients and controls (P = 0.095), higher homocysteine was seen with the T/T (but not 1298A/C and 1298C/C) genotype among patients and controls compared with non-T/T carriers (P < 0.05), and in patients vs controls. Higher prevalence of MTHFR 677T/T was seen in late (P < 0.05) and early-late (P < 0.001) RPL, while higher prevalence of 1298C/C genotype was seen only in early-late RPL (P < 0.001), and the prevalence of double heterozygotes was statistically not significant between patients and controls (P = 0.10; odds ratio = 2.73). Logistic regression analysis showed that, after adjusting for all variables, homozygosity for MTHFR C677T was associated with late (P < 0.001), and combined early-late (P < 0.001), while homozygosity for A1298C was associated only with combined early-late (P = 0.026), as was secondary-level education, which was associated with early (P = 0.005), late (P = 0.026) and combined early-late (P = 0.004) abortions. Homozygosity for MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for RPLs, irrespectively of total homocysteine levels. PMID:16452733

Mtiraoui, N; Zammiti, W; Ghazouani, L; Braham, N Jmili; Saidi, S; Finan, R R; Almawi, W Y; Mahjoub, T

2006-02-01

39

Quantitative assessment of the associations between MTHFR C677T and A1298C polymorphisms and risk of fractures: a meta-analysis.  

PubMed

Many studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and risk of fractures, but the impact of MTHFR polymorphisms on fractures risk is unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between MTHFR C677T and A1298C polymorphisms and risk of fractures. We searched the PubMed, Embase and Wanfang databases for articles relating the association between MTHFR C677T and A1298C polymorphisms and risk of fractures in humans. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess the associations. Meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of any site fractures (for T vs. C, OR = 1.17, 95 % CI 1.03-1.32; for TT vs. CC, OR = 1. 31, 95 % CI 1.11-1.54; for TT vs. CT, OR = 1.22, 95 % CI 1.04-1.43; for TT vs. CT/CC, OR = 1.31, 95 % CI 1.13-1.51). Besides, MTHFR A1298C polymorphism was also associated with increased risk of any site fractures. Subgroup meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of vertebral fractures under three genetic contrast modes (for TT vs. CC, OR = 1.43, 95 % CI 1.05-1.95; for TT vs. CT, OR = 1.36, 95 % CI 1.01-1.85; for TT vs. CT/CC, OR = 1.50, 95 % CI 1.17-1.91), but there was no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures (all P values were more than 0.05). Thus, individuals with homozygote genotype TT of MTHFR C677T have obviously increased risk of vertebral fractures compared those with heterozygote genotype CT or homozygote genotype CC. There is no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures. PMID:23229495

Bai, Rui; Liu, Wanlin; Zhao, Aiqing; Zhao, Zhenqun; Jiang, Dianming

2013-03-01

40

Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population  

PubMed Central

Background The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL). Methods A case–control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility. Results No significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC?+?CC) was elevated by 1.1 times compared with the AA genotype [OR?=?2.100; 95% CI (1.149; 3.837); P?=?0.015]. Conclusions The MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population. PMID:24476575

2014-01-01

41

Association between MTHFR C677T and A1298C Polymorphisms and NSCL/P Risk in Asians: A Meta-Analysis  

PubMed Central

Objective Several studies have reported the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and nonsyndromic cleft lip with or without palate (NSCL/P) in Asian populations. However, findings have been conflicting. In order to investigate the association, a meta-analysis was performed. Methods We searched Pubmed, MedLine and EmBase database to selected eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using fixed effects model or random effects model to assess the association between MTHFR polymorphisms and NSCL/P in both Asian children and mothers. Results Finally, nine case-control studies were included. Overall, the MTHFR C677T polymorphism and NSCL/P showed pooled ORs (95%CI) of 1.41(1.23–1.61) in Asian children, and 1.70(1.19–2.42) in Asian mothers. Subgroup analyses by geographical locations further identified the association in Eastern Asian children, Western/Central Asian children and mothers, but not in Eastern Asian mothers. However, no significant relationship between MTHFR A1298C polymorphism and NSCL/P was found in this meta-analysis. Conclusions The MTHFR 677T allele was associated with an increased risk of NSCL/P in Asian populations. PMID:24658649

Zhao, Mengmeng; Ren, Yangwu; Shen, Li; Zhang, Yue; Zhou, Baosen

2014-01-01

42

Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia  

PubMed Central

The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n = 126) with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P = 0.0013); on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P < 0.0001). PMID:23198157

de Deus, Dayse Maria Vasconcelos; de Lima, Elker Lene Santos; Seabra Silva, Rafaela Maria; Leite, Edinalva Pereira; Cartaxo Muniz, Maria Tereza

2012-01-01

43

Mutations C677T and A1298C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease.  

PubMed

Mild hyperhomocysteinemia is associated with homozygosity for the thermolabile variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) and could increase the risk of venous thromboembolic disease (VTD). Recently, the second A1298C mutation of the MTHFR gene was described. The present study aimed to analyze both mutations of the MTHFR gene and plasma homocysteine levels in subjects with VTD. The study groups comprised 146 patients with VTD and 100 healthy subjects. There were no statistical differences in carrier frequency and allelic frequency for both A1298C and C677T mutations, nor were there any differences encountered between subjects with VTD and controls in either plasma homocysteine levels or according to C677T or A1298C genotypes of MTHFR. In our VTD patients and controls, neither MTHFR 677CT/1298CC nor MTHFR 677TT/1298CC combined genotypes were observed; double heterozygotes (A1298C/C677T) were represented only in 11% of VTD patients, and in 15% of the controls. In conclusion, the polymorphisms C677T and A1298C of MTHFR and fasting plasma homocysteine levels do not seem to be significant risk factors for venous thromboembolic disease. PMID:12138370

Domagala, T B; Adamek, L; Nizankowska, E; Sanak, M; Szczeklik, A

2002-07-01

44

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

PubMed Central

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

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

45

Cerebral venous sinus thrombosis presenting as transient ischemic attacks in a case with homozygous mutations of MTHFR A1298C and CG677T.  

PubMed

We report a case with recurrent, transient attacks of slurred speech, weakness, and numbness of the right half of the face and the right arm without seizure activity, accompanied by headache and double vision. Neurologic examination revealed bilateral papilledema and right abducens palsy. Brain magnetic resonance imaging revealed thrombosis of the dural venous sinuses and the cortical veins, with no evidence of parenchymal lesion. Homozygous mutations were found for methylenetetrahydrofolate reductase (MTHFR) A1298C and MTHFR CG677T. Anticoagulation with heparin and warfarin resulted in prompt cessation of the transient attacks, as well as the signs and symptoms of increased intracranial pressure. This report documents that, although rare, transient ischemic attacks can result from cerebral venous thrombosis. PMID:20833086

Yildiz, Ozlem Kayim; Cevik, Seyda; Cil, Gulsum; Oztoprak, Ibrahim; Bolayir, Ertugrul; Topaktas, Suat

2012-01-01

46

MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India  

PubMed Central

BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation. It stems predominantly from the failure of chromosome 21 to segregate normally during meiosis. Despite substantial research, the molecular mechanisms underlying non-disjunction leading to trisomy 21 are poorly understood. MATERIALS AND METHODS: Two common variants C677T and A1298C of the MTHFR gene were screened in 36 parents with DS children and 60 healthy couples from Tamil Nadu and Karnataka. The MTHFR genotypes were studied by RFLP analysis of PCR-amplified products and confirmed by sequencing. RESULTS: The CT genotype was seen in three each (8.3%) of case mothers and fathers. One case father showed TT genotype. All the control individuals exhibited the wild type CC genotype. A similar frequency for the uncommon allele C of the second polymorphism was recorded in case mothers (0.35) and fathers (0.37) in comparison with the control mothers (0.39) and fathers (0.37). CONCLUSION: This first report on MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south Indian population revealed that MTHFR 677CT polymorphism was associated with a risk for Down syndrome. PMID:20680153

Cyril, Cyrus; Rai, Padmalatha; Chandra, N.; Gopinath, P. M.; Satyamoorthy, K.

2009-01-01

47

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

PubMed Central

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

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

48

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

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

2014-01-01

49

MTHFR C677T and A1298C Genotypes and Haplotypes in Slovenian Couples with Unexplained Infertility Problems and in Embryonic Tissues from Spontaneous Abortions  

PubMed Central

The objective of this study was to analyze the methylenetetrahydrofolate reductases ( MTHFR s) C677T and A1298C genotype distributions in couples with unexplained fertility problems (UFP) and healthy controls, and to analyze the genotype and haplotype distribution in spontaneously aborted embryonic tissues (SAET) using allele specific polymerase chain reaction (PCR) in 200 probands with UFP, 353 samples of SAET and 222 healthy controls. The analysis revealed a significant overall representation of the 677T allele in male probands from couples with UFP ( p = 0.036). The combined genotype distribution for both MTHFR polymorphisms was also significantly altered (? 2 21.73, p <0.001) although female probands made no contribution (? 2 1.33, p = 0.72). The overall representation of the 677T allele was more pronounced in SAET (0.5 vs. 0.351 in controls, p <0.001) regardless of the karyotype status (aneuploidy vs. normal karyotype). In addition, the frequencies of the CA and CC haplotypes were significantly lower than in the control group ( p = 0.021 and p = 0.001, respectively), whereas the frequency of the TC haplotype was significantly higher than in controls ( p <0.0001). The presented findings indicate that only male probands contribute to the association of MTHFR mutations with fertility problems in grown adults and demonstrate a high prevalence of mutated MTHFR genotypes in SAET. PMID:24265582

Stangler Herodež, Š; Zagradišnik, B; Erjavec Škerget, A; Zagorac, A; Taka?, I; Vlaisavljevi?, V; Lokar, L; Kokalj Voka?, N

50

Methylenetetrahydrofolate reductase gene germ-line C677T and A1298C SNPs are associated with colorectal cancer risk in the Turkish population.  

PubMed

Colorectal cancer (CRC) is the third most common cause of death due to cancer in the worldwide and the incidence is also increasing in Turkey. Our present aim was to investigate any association between germ-line methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and CRC risk in Turkey. A total of 86 CRC cases and 212 control individuals of the same ethnicity were included in the current study. Peripheral blood-DNA samples were used for genotyping by StripAssay technique, based on the reverse- hybridization principle and real-time PCR methods. Results were compared in Pearson Chi-square and multiple logistic regression models. The MTHFR 677TT (homozygous) genotype was found in 20.9% and the T allele frequency 4.2-fold increased in CRC when compared with the control group.The second SNP MTHFR 1298CC (homozygous) genotype was found in 14.0% and the C allele frequency 1.4-fold elevated in the CRC group. The current data suggest strong associations between both SNPs of germ-line MTHFR 677 C>T and 1298 A>C genotypes and CRC susceptibility in the Turkish population. Now the results need to be confirmed with a larger sample size. PMID:25292054

Ozen, Filiz; Sen, Metin; Ozdemir, Ozturk

2014-01-01

51

MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients  

PubMed Central

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway. We aimed to test the hypothesis that C677T and A1298C variants of MTHFR predispose to microsatellite instable (MSI) colorectal cancer. We determined MTHFR genotypes in 175 sporadic colorectal cancer patients and a total of 231 normal controls in Shiraz, Southern Iran. Among the genotypes found in our samples, MTHFR CT and CT + TT were associated with increased risk for CRC incidence [odds ratio (OR) = 2.4, 95% confidence interval (95%CI) = 1.8–4.4; OR = 2.4, 95%CI = 1.6–3.6, respectively]. Double heterozygotes 677CT/1298AC and double homozygote 677TT/1298AA and 677CC/1298CC genotypes also showed a significantly increased risk of developing CRC compared with the wild-type 677CC/1298AA genotypes of the controls. Among the 151 tumors tested, 36 (23.8%) were MSI+. MSI was more common in proximal tumors (OR = 10.4; 95%CI = 3.9–27.8) and in smokers (OR = 2.9; 95%CI = 1.3–6.7). In a case–control comparison, the MTHFR 677CT + TT genotype was strongly associated with MSI (OR = 2.6; 95%CI = 1.3–5.3). Hypermethylation of mismatch repair genes was positively related with MSI incidence in these tumor series (P = 0.00). Our data suggest that the MTHFR 677CT + TT variant genotype may be a risk factor for MSI+ cancer. PMID:20193847

Naghibalhossaini, Fakhraddin; Mokarram, Pooneh; Khalili, Islam; Vasei, Mohammad; Hosseini, Seyed Vahid; Ashktorab, Hassan; Rasti, Mozhgan; Abdollahi, Kourosh

2013-01-01

52

MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway. We aimed to test the hypothesis that C677T and A1298C variants of MTHFR predispose to microsatellite instable (MSI) colorectal cancer. We determined MTHFR genotypes in 175 sporadic colorectal cancer patients and a total of 231 normal controls in Shiraz, Southern Iran. Among the genotypes found in our samples, MTHFR CT and CT+TT were associated with increased risk for CRC incidence [odds ratio (OR)=2.4, 95% confidence interval (95%CI)=1.8-4.4; OR=2.4, 95%CI=1.6-3.6, respectively]. Double heterozygotes 677CT/1298AC and double homozygote 677TT/1298AA and 677CC/1298CC genotypes also showed a significantly increased risk of developing CRC compared with the wild-type 677CC/1298AA genotypes of the controls. Among the 151 tumors tested, 36 (23.8%) were MSI+. MSI was more common in proximal tumors (OR=10.4; 95%CI=3.9-27.8) and in smokers (OR=2.9; 95%CI=1.3-6.7). In a case-control comparison, the MTHFR 677CT+TT genotype was strongly associated with MSI (OR=2.6; 95%CI=1.3-5.3). Hypermethylation of mismatch repair genes was positively related with MSI incidence in these tumor series (P=0.00). Our data suggest that the MTHFR 677CT+TT variant genotype may be a risk factor for MSI+ cancer. PMID:20193847

Naghibalhossaini, Fakhraddin; Mokarram, Pooneh; Khalili, Islam; Vasei, Mohammad; Hosseini, Seyed Vahid; Ashktorab, Hassan; Rasti, Mozhgan; Abdollahi, Kourosh

2010-03-01

53

Hyperhomocysteinemia and related genetic polymorphisms correlate with ulcerative colitis in Chinese Han population in Central China [corrected].  

PubMed

Increased levels of homocysteine are found systemically and in intestinal mucosa of patients with inflammatory bowel disease, and, specifically, in ulcerative colitis (UC). However, there are controversial reports regarding the factors contributing to increased levels of homocysteine in UC. Furthermore, little information is available regarding the relationship between hyperhomocysteinemia (HHcy), vitamin status, and genetic polymorphisms of homocysteine-related enzymes in these patients. This study examined four functional polymorphisms linked to homocysteine metabolism (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G), and evaluated plasma levels of homocysteine, folate, and vitamin B(12) in 310 consecutive patients with UC and 936 age- and sex-matched healthy controls from southeast China. The variant allele and genotypic frequencies in MTHFR A1298C, MTR A2756G and MTRR A66G genes were significantly higher in patients with UC compared to healthy controls. Further, HHcy and low levels of folate and vitamin B(12) were more frequent in patients with UC. The MTR 2756G allele, extent of the disease, and gender were the independent determinants of HHcy in these patients. These findings suggest that genetic and nutritional factors have a synergetic effect on HHcy in patients with UC. In conclusion, our data highlight a prevention strategy for moderation of HHcy and supplementation with folate and vitamine B(12) in patients with UC from Southeast China. PMID:21947961

Jiang, Yi; Xia, Xuanping; Wang, Wenxing; Lin, Limiao; Xu, Changlong; Cai, Zhenzai; Zheng, Bo; Pei, Jihua; Shen, Sujian; Xia, Bing

2012-01-01

54

Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men.  

PubMed

We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different ethnicity are required to confirm our findings. PMID:21046286

Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Shiva

2011-12-01

55

Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients.  

PubMed

Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase chain reaction-based restriction enzyme analysis was carried out to screen these mutations, and single-strand conformation analysis was established to identify variations using the primers selected for restriction enzyme analysis studies. As a result, a significant relationship was determined among FV Leiden, FII G20210A, and thrombosis. The FV Hong Kong mutation was observed in only 2 patients with pulmonary vein thrombosis who are FV Leiden/FV Hong Kong compound heterozygous for FV gene. MTHFR C677T and A1298C were equally distributed in the patient group compared with the control group. All named mutations were also identified with single-strand conformation analysis, but a new variant/polymorphism during studies was not found. Because some inherited abnormalities are associated with thromboembolic disorders, determining the mutations and gene-to-gene interactions in patients with thrombosis history has a great impact on diagnosis and treatment of these diseases. PMID:17911197

Dölek, Bilgen; Eraslan, Serpil; Ero?lu, Sevim; Kesim, Belgin Eroglu; Ulutin, Turgut; Yalçiner, Altan; Laleli, Yahya R; Gözükirmizi, Nermin

2007-10-01

56

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

57

Folate Levels and Polymorphisms in the Genes MTHFR, MTR, and TS in Colorectal Cancer  

PubMed Central

AIM The aim of the study was to explore and describe the effect of polymorphisms in folate-associated genes regarding the levels of different folate forms and their distribution in tumors and mucosa in patients with colorectal cancer. MATERIALS AND METHODS Tumor and mucosa tissues from 53 patients with colorectal cancer were analyzed. The concentrations of tetrahydrofolate (THF), 5-methylTHF, and 5,10-methyleneTHF were measured by liquid chromatography—mass spectrometry. Genotyping of polymorphisms in the folate-associated genes methylenetetrahydrofolate reductase (MTHFR, C677T), methionine synthase (MTR, A2756G), and thymidylate synthase (TS, 5?-TSER 28 bp tandem repeat and 3?-TSUTR 6 bp deletion/insertion), were done by real-time polymerase chain reaction. Folate levels and distributions were determined in the total patient cohort and after subgrouping by genotypes. RESULTS The total folate level, as well as the THF and 5,10-methyleneTHF levels, were significantly higher in the tumor compared with mucosa tissue (P = 0.030, 0.031, and 0.015, respectively). The individual variation in folate levels in both tumor and mucosa were larger than the variation found when the patients were subgrouped by the gene polymorphisms. No significant differences in the mean concentration of any folate in the mucosa or tumor tissue were found in relation to the analyzed polymorphisms. The percentage level of 5,10-methyleneTHF in tumors was highest in patients with the MTHFR 677 CC genotype, and lowest in patients with the TT genotype (P = 0.033). A significantly lower percentage level of the 5,10-methyleneTHF level was found in tumors of patients with the 5?-TSER 3R/3R genotype (P = 0.0031). CONCLUSION A significant difference was found between the percentage level of 5,10-methyleneTHF in tumor tissues in relation to the MTHFR C677T and 5?-TSER 28 bp repeat polymorphisms. However, no differences were found in the actual tissue folate levels, or in their distribution, in relation to the polymorphisms in the MTHFR, MTR, or TS genes. These findings could be of importance for further research in the field by explaining some of the difficulties of obtaining reproducible and uniform results when using a few selected polymorphisms as predictive markers. PMID:24596472

Taflin, Helena; Wettergren, Yvonne; Odin, Elisabeth; Carlsson, Göran; Derwinger, Kristoffer

2014-01-01

58

Impact of methionine synthase gene and methylenetetrahydrofolate reductase gene polymorphisms on the risk of sudden sensorineural hearing loss.  

PubMed

Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological disease of unknown etiology. In recent years, several inherited risk factors have been found in the pathogenesis of vascular diseases. In the present study, we determined whether specific polymorphism or the combination of polymorphisms in folate-dependent homocysteine metabolism genes can act as predisposing inherited vascular risk factors in the development of SSNHL. We conducted a prospective case-control study using DNA samples extracted from 81 patients diagnosed as suffering from SSNHL and 264 healthy control subjects. Three functional polymorphisms were analyzed by polymerase chain reaction amplification, restriction enzyme digestion, and DNA fragment separation by electrophoresis: methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms. The prevalence of the homozygous genotype of MTR 2756GG in the SSNHL patients (9%) was significantly higher than in the control group (4%) (p = 0.011). The allelic frequency of the G allele of the MTR A2756G polymorphism among SSNHL patients (12.5%) was also significantly higher than in the control group (5%) (p = 0.033). The prevalence of patients possessing two polymorphisms (31%) and three polymorphisms (17%) in the SSNHL group was significantly higher than in the control group (23 and 9%, respectively; p = 0.019). The frequency of patients with a very high rank risk (double homozygous) was significantly higher in the SSNHL group, MTHFR 677TT/MTR 2675GG--7%, than the frequency of patients in the control group, MTHFR 677TT/MTR 2675GG--3% (p = 0.030). Certain polymorphisms in genes encoding enzymes in the folate-dependent homocysteine metabolism are associated with SSNHL. In our case-control study, a significant association between MTR 2756GG genotype and SSNHL was found which may represent an inherited vascular risk factor in the pathogenesis of SSNHL. PMID:16778415

Gross, Menachem; Friedman, Gideon; Eliashar, Ron; Koren-Morag, Nira; Goldschmidt, Neta; Atta, Iman Abou; Ben-Yehuda, Arie

2006-01-01

59

Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review.  

PubMed

Epidemiologic and mechanistic evidence suggests that folate is involved in colorectal neoplasia. Some polymorphic genes involved in folate metabolism--methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), cystathionine beta-synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untranslated region)--have been investigated in colorectal neoplasia. For MTHFR C677T and A1298C, the variant allele is associated with reduced enzyme activity in vitro. For the other polymorphisms, functional data are limited and/or inconsistent. Genotype frequencies for all of the polymorphisms show marked ethnic and geographic variation. In most studies, MTHFR 677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are associated with moderately reduced colorectal cancer risk. In four of five genotype-diet interaction studies, 677TT subjects who had higher folate levels (or a "high-methyl diet") had the lowest cancer risk. In two studies, 677TT homozygote subjects with the highest alcohol intake had the highest cancer risk. Findings from six studies of MTHFR C677T and adenomatous polyps are inconsistent. There have been only one or two studies of the other polymorphisms; replication is needed. Overall, the roles of folate-pathway genes, folate, and related dietary factors in colorectal neoplasia are complex. Research priorities are suggested. PMID:14977639

Sharp, Linda; Little, Julian

2004-03-01

60

Levels of Key Enzymes of Methionine-Homocysteine Metabolism in Preeclampsia  

PubMed Central

Objective. To evaluate the role of key enzymes in the methionine-homocysteine metabolism (MHM) in the physiopathology of preeclampsia (PE). Methods. Plasma and placenta from pregnant women (32 controls and 16 PE patients) were analyzed after informed consent. Protein was quantified by western blot. RNA was obtained with RNA purification kit and was quantified by reverse transcritase followed by real-time PCR (RT-qPCR). Identification of the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and A2756G methionine synthase (MTR) SNP was performed using PCR followed by a high-resolution melting (HRM) analysis. S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) were measured in plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). The SNP association analysis was carried out using Fisher's exact test. Statistical analysis was performed using a Mann-Whitney test. Results. RNA expression of MTHFR and MTR was significantly higher in patients with PE as compared with controls. Protein, SAM, and SAH levels showed no significant difference between preeclamptic patients and controls. No statistical differences between controls and PE patients were observed with the different SNPs studied. Conclusion. The RNA expression of MTHFR and MTR is elevated in placentas of PE patients, highlighting a potential compensation mechanism of the methionine-homocysteine metabolism in the physiopathology of this disease. PMID:24024209

Pérez-Sepúlveda, Alejandra; España-Perrot, Pedro P.; Fernández B, Ximena; Ahumada, Verónica; Bustos, Vicente; Arraztoa, José Antonio; Dobierzewska, Aneta; Figueroa-Diesel, Horacio; Rice, Gregory E.; Illanes, Sebastián E.

2013-01-01

61

MTR plates modeling with MAIA  

SciTech Connect

MAIA is a thermo-mechanical code dedicated to the modeling of MTR fuel plates. The main physical phenomena modeled in the code are the cladding oxidation, the interaction between fuel and Al-matrix, the swelling due to fission products and the Al/fuel particles interaction. The creeping of the plate can be modeled in the mechanical calculation. MAIA has been validated on U-Mo dispersion fuel experiments such as IRIS 1 and 2 and FUTURE. The results are in rather good agreement with post-irradiation examinations. MAIA can also be used to calculate in-pile behavior of U{sub 3}Si{sub 2} plates as in the SHARE experiment irradiated in the SCK/Mol BR2 reactor. The main outputs given by MAIA throughout the irradiation are temperatures, cladding oxidation thickness, interaction thickness, volume fraction of meat constituents, swelling, displacements, strains and stresses. MAIA is originally a two-dimensional code but a three-dimensional version is currently under development. (author)

Marelle, V.; Dubois, S.; Ripert, M.; Noirot, J. [DEN/DEC, CEA Cadarache, 13108 St Paul Lez Durance (France); Lemoine, P. [DEN/DSOE, CEA Saclay, 91191 Gif sur Yvette (France)

2008-07-15

62

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

63

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

64

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

PubMed

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

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

2013-11-01

65

High-throughput multiplex single-nucleotide polymorphism (SNP) analysis in genes involved in methionine metabolism.  

PubMed

Hyperhomocysteinemia is a well-known independent marker factor for atherothrombotic diseases and may result from acquired and genetic influences. Several polymorphisms are suspected to be associated with hyperhomocysteinemia, but data are limited and inconsistent. High-throughput genotyping technologies, such as GenomeLab SNPStream, are now available. Moreover, an appropriate selection of SNPs to be analyzed could represent a strong resource to define the role of genetic risk factors. We developed a multiplex PCR-oligonucleotide extension approach by GenomeLab platform. We selected 72 SNPs based on their putative function and frequency in the candidate genes AHCY, BHMT, BHMT2, CBS, ENOSF1, FOLH1, MTHFD1, MTHFR, MTR, MTRR, NNMT, PON1, PON2, SLC19A1, SHMT1, TCN2, and TYMS. We were able to analyze 57 of the SNPs (79%). For MTHFR C677T and A1298C and MTR A2756G SNPs, we compared data obtained with an electronic microchip technology and found 99.2% concordance. We also performed a haplotype analysis. This approach could represent a useful tool to investigate the genotype-phenotype correlation and the association of these genes with hyperhomocysteinemia and correlated diseases. PMID:18427977

Giusti, Betti; Sestini, Ilaria; Saracini, Claudia; Sticchi, Elena; Bolli, Paola; Magi, Alberto; Gori, Anna Maria; Marcucci, Rossella; Gensini, Gian Franco; Abbate, Rosanna

2008-08-01

66

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

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

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

67

ETR AND MTR COMPLEXES IN CONTEXT. CAMERA FACING NORTHERLY. FROM ...  

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

ETR AND MTR COMPLEXES IN CONTEXT. CAMERA FACING NORTHERLY. FROM BOTTOM TO TOP: ETR COOLING TOWER, ELECTRICAL BUILDING AND LOW-BAY SECTION OF ETR BUILDING, HEAT EXCHANGER BUILDING (WITH U SHAPED YARD), COMPRESSOR BUILDING. MTR REACTOR SERVICES BUILDING IS ATTACHED TO SOUTH WALL OF MTR. WING A IS ATTACHED TO BALCONY FLOOR OF MTR. NEAR UPPER RIGHT CORNER OF VIEW IS MTR PROCESS WATER BUILDING. WING B IS AT FAR WEST END OF COMPLEX. NEAR MAIN GATE IS GAMMA FACILITY, WITH "COLD" BUILDINGS BEYOND: RAW WATER STORAGE TANKS, STEAM PLANT, MTR COOLING TOWER PUMP HOUSE AND COOLING TOWER. INL NEGATIVE NO. 56-4101. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

68

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

Code of Federal Regulations, 2013 CFR

...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...

2013-07-01

69

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

...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...

2014-07-01

70

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

Code of Federal Regulations, 2012 CFR

...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...

2012-07-01

71

Analysis of Structural MtrC Models Based on Homology with the Crystal Structure of MtrF  

SciTech Connect

The outer-membrane decahaem cytochrome MtrC is part of the transmembrane MtrCAB complex required for mineral respiration by Shewanella oneidensis. MtrC has significant sequence similarity to the paralogous decahaem cytochrome MtrF, which has been structurally solved through X-ray crystallography. This now allows for homology-based models of MtrC to be generated. The structure of these MtrC homology models contain ten bis-histidine-co-ordinated c-type haems arranged in a staggered cross through a four-domain structure. This model is consistent with current spectroscopic data and shows that the areas around haem 5 and haem 10, at the termini of an octahaem chain, are likely to have functions similar to those of the corresponding haems in MtrF. The electrostatic surfaces around haem 7, close to the ?-barrels, are different in MtrF and MtrC, indicating that these haems may have different potentials and interact with substrates differently.

Edwards, Marcus; Fredrickson, Jim K.; Zachara, John M.; Richardson, David; Clarke, Thomas A.

2012-12-01

72

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

73

Direct genotyping of single nucleotide polymorphisms in methyl metabolism genes using probe-free high-resolution melting analysis.  

PubMed

High-resolution melting (HRM) shows great promise for high-throughput, rapid genotyping of individual polymorphic loci. We have developed HRM assays for genotyping single nucleotide polymorphisms (SNP) in several key genes that are involved in methyl metabolism and may directly or indirectly affect the methylation status of the DNA. The SNPs are in the 5,10-methylenetetrahydrofolate reductase (MTHFR; C677T and A1298C), methionine synthetase (MTR; 5-methyltetrahydrofolate-homocysteine methyltransferase; A2756G), and DNA methyltransferase 3b (DNMT3b; C46359T and C31721T) loci. The choice of short amplicons led to greater melting temperature (Tm) differences between the two homozygous genotypes, which allowed accurate genotyping without the use of probes or spiking with control DNA. In the case of MTHFR, there is a second rarer SNP (rs4846051) close to the A1298C SNP that may result in inaccurate genotyping. We masked this second SNP by placing the primer over it and choosing a base at the polymorphic position that was equally mismatched to both alleles. The HRM assays were done on HRM capable real-time PCR machines rather than stand-alone HRM machines. Monitoring the amplification allows ready identification of samples that may give rise to aberrant melting curves because of PCR abnormalities. We show that samples amplifying markedly late can give rise to shifted melting curves without alteration of shapes and potentially lead to misclassification of genotypes. In conclusion, rapid and high-throughput SNP analysis can be done with probe-free HRM if sufficient attention is paid to amplicon design and quality control to omit aberrantly amplifying samples. PMID:18483346

Kristensen, Lasse S; Dobrovic, Alexander

2008-05-01

74

Polymorphisms in Methionine Synthase, Methionine Synthase Reductase and Serine Hydroxymethyltransferase, Folate and Alcohol Intake, and Colon Cancer Risk  

PubMed Central

Background/Aims We examined associations among folate and alcohol intake, SNPs in genes involved in one-carbon metabolism and colon cancer risk. Methods Colon cancer cases (294 African Americans and 349 whites) were frequency matched to population controls (437 African Americans and 611 whites) by age, race and sex from 33 North Carolina counties from 1996 to 2000. Folate and alcohol intakes were collected by dietary interview. Five SNPs were genotyped using DNA from whole blood: SHMT C1420T; MTRR A66G; MTR A2756G, and the previously-reported MTHFR C677T and MTHFR A1298C. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. Results An inverse association was observed for SHMT TT genotype as compared to CC genotype in whites (OR=0.6, 95%CI=0.4, 1.0), but not in African Americans. Inverse associations were observed for high folate intake in individuals carrying 0 or 1 variant allele [OR 0.2 (95%CI 0.06 – 0.8) for African Americans; OR 0.2 (95%CI 0.1– 0.6) for whites] compared to low folate intake. Modest interactions between these SNPs and alcohol or folate intakes were observed. Conclusions Our results are consistent with other findings and provide needed data on these associations among African Americans. PMID:19776626

Steck, Susan E.; Keku, Temitope; Butler, Lesley M.; Galanko, Joseph; Massa, Beri; Millikan, Robert C.; Sandler, Robert S.

2009-01-01

75

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

76

TOP OF MTR. CONTROL RODS AND GRID PLATE EMERGE FROM ...  

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

TOP OF MTR. CONTROL RODS AND GRID PLATE EMERGE FROM REACTOR TANK. INL NEGATIVE NO. 6206. R.G. Larsen, Photographer, 6/27/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

77

MTR MAIN FLOOR. MEN DEMONSTRATE INSERTION OF DUMMY PLUG INTO ...  

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

MTR MAIN FLOOR. MEN DEMONSTRATE INSERTION OF DUMMY PLUG INTO AN MTR BEAM HOLE. ONE MAN CHECKS RADIATION LEVEL AT THE END OF THE UNIVERSAL COFFIN, WHILE ANOTHER USES TOOL TO INSERT PLUG INTO HOLE THROUGH COFFIN. MEN WEAR "ANTI-C" (ANTI-CONTAMINATION) CLOTHING. INL NEGATIVE NO. 6198. R.G. Larsen, Photographer, 6/27/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

78

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

PubMed

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

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

2013-12-01

79

Biogenesis of Yeast Telomerase Depends on the Importin Mtr10  

PubMed Central

Telomerase is a ribonucleoprotein particle (RNP) involved in chromosome end replication, but its biogenesis is poorly understood. The RNA component of yeast telomerase (Tlc1) is synthesized as a polyadenylated precursor and then processed to a mature poly(A)? form. We report here that the karyopherin Mtr10p is required for the normal accumulation of mature Tlc1 and its proper localization to the nucleus. Neither TLC1 transcription nor the stability of poly(A)? Tlc1 is significantly affected in mtr10? cells. Tlc1 was mostly nuclear in a wild-type background, and this localization was not affected by mutations in other telomerase components. Strikingly, in the absence of Mtr10p, Tlc1 was found dispersed throughout the entire cell. Our results are compatible with two alternative models. First, Mtr10p may import a cytoplasmic complex containing Tlc1 and perhaps other components of telomerase, and shuttling of Tlc1 from the nucleus to the cytoplasm and back may be necessary for the biogenesis of telomerase (the “shuttling” model). Second, Mtr10p may be necessary for the nuclear import of some enzyme needed for the nuclear processing and maturation of Tlc1, and in the absence of this maturation, poly(A)+ Tlc1 is aberrantly exported to the cytoplasm (the “processing enzyme” model). PMID:12167699

Ferrezuelo, Francisco; Steiner, Barbara; Aldea, Martí; Futcher, Bruce

2002-01-01

80

Biogenesis of yeast telomerase depends on the importin mtr10.  

PubMed

Telomerase is a ribonucleoprotein particle (RNP) involved in chromosome end replication, but its biogenesis is poorly understood. The RNA component of yeast telomerase (Tlc1) is synthesized as a polyadenylated precursor and then processed to a mature poly(A)- form. We report here that the karyopherin Mtr10p is required for the normal accumulation of mature Tlc1 and its proper localization to the nucleus. Neither TLC1 transcription nor the stability of poly(A)- Tlc1 is significantly affected in mtr10delta cells. Tlc1 was mostly nuclear in a wild-type background, and this localization was not affected by mutations in other telomerase components. Strikingly, in the absence of Mtr10p, Tlc1 was found dispersed throughout the entire cell. Our results are compatible with two alternative models. First, Mtr10p may import a cytoplasmic complex containing Tlc1 and perhaps other components of telomerase, and shuttling of Tlc1 from the nucleus to the cytoplasm and back may be necessary for the biogenesis of telomerase (the "shuttling" model). Second, Mtr10p may be necessary for the nuclear import of some enzyme needed for the nuclear processing and maturation of Tlc1, and in the absence of this maturation, poly(A)+ Tlc1 is aberrantly exported to the cytoplasm (the "processing enzyme" model). PMID:12167699

Ferrezuelo, Francisco; Steiner, Barbara; Aldea, Martí; Futcher, Bruce

2002-09-01

81

MTR COMPRESSOR BUILDING, TRA651. RELATED AIR COMPRESSOR EQUIPMENT OUTSIDE BUILDING. ...  

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

MTR COMPRESSOR BUILDING, TRA-651. RELATED AIR COMPRESSOR EQUIPMENT OUTSIDE BUILDING. PIPE LEADS BELOW GRADE INTO MTR BUILDING. CAMERA FACING WEST, IE, EAST SIDE OF MTR BUILDING. INL NEGATIVE NO. 56-1265. Jack L. Larsen, Photographer, 4/20/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

82

CUTS FOR MTR EXCAVATION ILLUSTRATE SEDIMENTARY MANTLE OF SOIL AND ...  

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

CUTS FOR MTR EXCAVATION ILLUSTRATE SEDIMENTARY MANTLE OF SOIL AND GRAVEL OVERLAYING LAVA ROCK FIFTY FEET BELOW. SAGEBRUSH HAS BEEN SCOURED FROM REST OF SITE. CAMERA PROBABLY FACES SOUTHWEST. INL NEGATIVE NO. 67. Unknown Photographer, 6/4/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

83

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

84

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

85

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

86

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

87

Fission yeast mtr1p regulates interphase microtubule cortical dwell-time  

PubMed Central

ABSTRACT The microtubule cytoskeleton plays important roles in cell polarity, motility and division. Microtubules inherently undergo dynamic instability, stochastically switching between phases of growth and shrinkage. In cells, some microtubule-associated proteins (MAPs) and molecular motors can further modulate microtubule dynamics. We present here the fission yeast mtr1+, a new regulator of microtubule dynamics that appears to be not a MAP or a motor. mtr1-deletion (mtr1?) primarily results in longer microtubule dwell-time at the cell tip cortex, suggesting that mtr1p acts directly or indirectly as a destabilizer of microtubules. mtr1p is antagonistic to mal3p, the ortholog of mammalian EB1, which stabilizes microtubules. mal3? results in short microtubules, but can be partially rescued by mtr1?, as the double mutant mal3? mtr1? exhibits longer microtubules than mal3? single mutant. By sequence homology, mtr1p is predicted to be a component of the ribosomal quality control complex. Intriguingly, deletion of a predicted ribosomal gene, rps1801, also resulted in longer microtubule dwell-time similar to mtr1?. The double-mutant mal3? rps1801? also exhibits longer microtubules than mal3? single mutant alone. Our study suggests a possible involvement of mtr1p and the ribosome complex in modulating microtubule dynamics. PMID:24928430

Carlier-Grynkorn, Frédérique; Ji, Liang; Fraisier, Vincent; Lombard, Berangère; Dingli, Florent; Loew, Damarys; Paoletti, Anne; Ronot, Xavier; Tran, Phong T.

2014-01-01

88

The mtr locus is a two-gene operon required for transcription attenuation in the trp operon of Bacillus subtilis.  

PubMed Central

We have cloned and characterized the mtr operon of Bacillus subtilis. This operon encodes a presumed RNA-binding regulatory protein that is required for attenuation control of the trp operon. We have shown that the mtr operon consists of two structural genes, mtrA and mtrB, predicted to encode 22-kDa and 8-kDa polypeptides, respectively. MtrB shows homology with RegA, an RNA-binding regulatory protein of bacteriophage T4. The lesions in several mtr mutants were localized to mtrB or the putative mtr promoter. Several mtrB alleles were dominant to mtr+, suggesting that the regulatory factor is a multimeric protein. The in vivo action of the mtrA and mtrB gene products was analyzed in an E. coli strain containing a trpE-lacZ gene fusion under control of the B. subtilis trp promoter/attenuator region. Both MtrA and MtrB were necessary for regulation of beta-galactosidase production. Images PMID:2123343

Gollnick, P; Ishino, S; Kuroda, M I; Henner, D J; Yanofsky, C

1990-01-01

89

CONTROL CONSOLE FOR MTR FISSION PRODUCT MONITOR, USED TO DETECT ...  

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

CONTROL CONSOLE FOR MTR FISSION PRODUCT MONITOR, USED TO DETECT BREAKS IN CLADDING OF FUEL ELEMENTS. COUNT-RATE METER IN TOP PANEL INDICATES AMOUNT OF RADIOACTIVITY. LOWER PANELS SUPPLY POWER AND AMPLIFICATION OF SIGNALS GENERATED BY SCINTILLATION COUNTER/PHOTOMULTIPLIER TUBE COMBINATION IN RESPONSE TO RADIOACTIVITY IN A SAMPLE OF THE COOLING WATER. INL NEGATIVE NO. 56-771. Jack L. Anderson, Photographer, 3/15/1956. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

90

TOP OF MTR. MAN CLIMBS FRAME ON FOOT LADDER TO ...  

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

TOP OF MTR. MAN CLIMBS FRAME ON FOOT LADDER TO POSITION CRANE HOOK, WHICH WILL LIFT TOP PLUG FROM REACTOR AS A STEP IN REFUELING PROCEDURES. NOTE CRANE OPERATOR AT UPPER LEFT OF VIEW. ENTIRE APPARATUS, INCLUDING FRAME AND DRIVES FOR CONTROL RODS, WILL BE LIFTED. INL NEGATIVE NO. 6199. R.G. Larsen, Photographer, 6/22/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

91

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

92

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

93

Failed MTR Fuel Element Detect in a Sipping Tests  

SciTech Connect

This work describes sipping tests performed on Material Testing Reactor (MTR) fuel elements of the IEA-R1 research reactor, in order to find out which one failed in the core during a routine operation. Radioactive iodine isotopes {sup 131}I and {sup 133}I, employed as failure monitors, were detected in samples corresponding to the failed fuel element. The specific activity of each sample, as well as the average leaking rate, were measured for {sup 137}Cs. The nuclear fuels U{sub 3}O{sub 8} - Al dispersion and U - Al alloy were compared concerning their measured average leaking rates of {sup 137}Cs.

Zeituni, C.A.; Terremoto, L.A.A.; da Silva, J.E.R.

2004-10-06

94

Crystal Structure of the Open State of the Neisseria gonorrhoeae MtrE Outer Membrane Channel  

PubMed Central

Active efflux of antimicrobial agents is one of the most important strategies used by bacteria to defend against antimicrobial factors present in their environment. Mediating many cases of antibiotic resistance are transmembrane efflux pumps, composed of one or more proteins. The Neisseria gonorrhoeae MtrCDE tripartite multidrug efflux pump, belonging to the hydrophobic and amphiphilic efflux resistance-nodulation-cell division (HAE-RND) family, spans both the inner and outer membranes of N. gonorrhoeae and confers resistance to a variety of antibiotics and toxic compounds. We here describe the crystal structure of N. gonorrhoeae MtrE, the outer membrane component of the MtrCDE tripartite multidrug efflux system. This trimeric MtrE channel forms a vertical tunnel extending down contiguously from the outer membrane surface to the periplasmic end, indicating that our structure of MtrE depicts an open conformational state of this channel. PMID:24901251

Bolla, Jani Reddy; Kumar, Nitin; Radhakrishnan, Abhijith; Long, Feng; Delmar, Jared A.; Do, Sylvia V.; Rajashankar, Kanagalaghatta R.; Shafer, William M.; Yu, Edward W.

2014-01-01

95

Gamma-ray spectroscopy on irradiated MTR fuel elements  

NASA Astrophysics Data System (ADS)

The availability of burnup data is an important requirement in any systematic approach to the enhancement of safety, economics and performance of a nuclear research reactor. This work presents the theory and experimental techniques applied to determine, by means of nondestructive gamma-ray spectroscopy, the burnup of Material Testing Reactor (MTR) fuel elements irradiated in the IEA-R1 research reactor. Burnup measurements, based on analysis of spectra that result from collimation and detection of gamma-rays emitted in the decay of radioactive fission products, were performed at the reactor pool area. The measuring system consists of a high-purity germanium (HPGe) detector together with suitable fast electronics and an on-line microcomputer data acquisition module. In order to achieve absolute burnup values, the detection set (collimator tube+HPGe detector) was previously calibrated in efficiency. The obtained burnup values are compared with ones provided by reactor physics calculations, for three kinds of MTR fuel elements with different cooling times, initial enrichment grades and total number of fuel plates. Both values show good agreement within the experimental error limits.

Terremoto, L. A. A.; Zeituni, C. A.; Perrotta, J. A.; da Silva, J. E. R.

2000-08-01

96

Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis  

PubMed Central

Objectives: To establish whether magnetisation transfer ratio (MTR) histograms are sensitive to change in normal appearing grey matter (NAGM) in early relapsing-remitting multiple sclerosis (RRMS) in the absence of significant disability; and to assess whether grey or white matter MTR measures are associated with clinical measures of impairment in early RRMS Methods: 38 patients were studied (mean disease duration 1.9 years (range 0.5 to 3.7); median expanded disability status scale (EDSS) 1.5 (0 to 3)), along with 35 healthy controls. MTR was determined from proton density weighted images with and without MT presaturation. SPM99 was used to generate normal appearing white matter (NAWM) and NAGM segments of the MTR map, and partial voxels were minimised with a 10 pu threshold and voxel erosions. Mean MTR was calculated from the tissue segments. Atrophy measures were determined using a 3D fast spoiled gradient recall sequence from 37 patients and 17 controls. Results: Mean NAGM and NAWM MTR were both reduced in early RRMS (NAGM MTR: 31.9 pu in patients v 32.2 pu in controls; p<0.001; NAWM MTR: 37.9 v 38.3 pu, p = 0.001). Brain parenchymal fraction (BPF) correlated with NAGM MTR, but when BPF was included as a covariate NAGM MTR was still lower in the patients (p = 0.009). EDSS correlated with NAGM MTR (r = 0.446 p = 0.005). Conclusions: In early RRMS, grey matter MTR abnormality is apparent. The correlation with mild clinical impairment (in this essentially non-disabled cohort) suggests that NAGM MTR could be a clinically relevant surrogate marker in therapeutic trials. PMID:15201359

Davies, G; Ramio-Torrenta, L; Hadjiprocopis, A; Chard, D; Griffin, C; Rashid, W; Barker, G; Kapoor, R; Thompson, A; Miller, D

2004-01-01

97

ENGINEERING TEST REACTOR, TRA642. CONTEXTUAL VIEW ORIENTATING ETR TO MTR. ...  

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

ENGINEERING TEST REACTOR, TRA-642. CONTEXTUAL VIEW ORIENTATING ETR TO MTR. CAMERA IS ON ROOF OF MTR BUILDING AND FACES DUE SOUTH. MTR SERVICE BUILDING, TRA-635, IN LOWER RIGHT CORNER. STEEL FRAMES SHOW BUILDINGS TO BE ATTACHED TO ETR BUILDING. HIGH-BAY SECTION IN CENTER IS REACTOR BUILDING. TWO-STORY CONTROL ROOM AND OFFICE BUILDING, TRA-647, IS BETWEEN IT AND MTR SERVICE BUILDING. STRUCTURE TO THE LEFT (WITH NO FRAMING YET) IS COMPRESSOR BUILDING, TRA-643, AND BEYOND IT WILL BE HEAT EXCHANGER BUILDING, TRA-644, GREAT SOUTHERN BUTTE ON HORIZON. INL NEGATIVE NO. 56-2382. Jack L. Anderson, Photographer, 6/10/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

98

MTR, NORTH FACE. INL NEGATIVE NO. 10441. R.G. Larsen, Photographer, ...  

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

MTR, NORTH FACE. INL NEGATIVE NO. 10441. R.G. Larsen, Photographer, 4/20/1954 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

99

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

100

Mutational and gene expression analysis of mtrDEF, omcA and mtrCAB during arsenate and iron reduction in Shewanella sp. ANA-3.  

PubMed

Arsenate respiration and Fe(III) reduction are important processes that influence the fate and transport of arsenic in the environment. The goal of this study was to investigate the impact of arsenate on Fe(III) reduction using arsenate and Fe(III) reduction deficient mutants of Shewanella sp. strain ANA-3. Ferrihydrite reduction in the absence of arsenate was similar for an arsenate reduction mutant (arrA and arsC deletion strain of ANA-3) compared with wild-type ANA-3. However, the presence of arsenate adsorbed onto ferrihydrite impeded Fe(III) reduction for the arsenate reduction mutant but not in the wild-type. In an Fe(III) reduction mutant (mtrDEF, omcA, mtrCAB null mutant of ANA-3), arsenate was reduced similarly to wild-type ANA-3 indicating the Fe(III) reduction pathway is not required for ferrihydrite-associated arsenate reduction. Expression analysis of the mtr/omc gene cluster of ANA-3 showed that omcA and mtrCAB were expressed under soluble Fe(III), ferrihydrite and arsenate growth conditions and not in aerobically grown cells. Expression of arrA was greater with ferrihydrite pre-adsorbed with arsenate relative to ferrihydrite only. Lastly, arrA and mtrA were simultaneously induced in cells shifted to anaerobic conditions and exposed to soluble Fe(III) and arsenate. These observations suggest that, unlike Fe(III), arsenate can co-induce operons (arr and mtr) implicated in arsenic mobilization. PMID:20236164

Reyes, Carolina; Murphy, Julie N; Saltikov, Chad W

2010-07-01

101

The Mtr4 ratchet helix and arch domain both function to promote RNA unwinding  

PubMed Central

Mtr4 is a conserved Ski2-like RNA helicase and a subunit of the TRAMP complex that activates exosome-mediated 3?-5? turnover in nuclear RNA surveillance and processing pathways. Prominent features of the Mtr4 structure include a four-domain ring-like helicase core and a large arch domain that spans the core. The ‘ratchet helix’ is positioned to interact with RNA substrates as they move through the helicase. However, the contribution of the ratchet helix in Mtr4 activity is poorly understood. Here we show that strict conservation along the ratchet helix is particularly extensive for Ski2-like RNA helicases compared to related helicases. Mutation of residues along the ratchet helix alters in vitro activity in Mtr4 and TRAMP and causes slow growth phenotypes in vivo. We also identify a residue on the ratchet helix that influences Mtr4 affinity for polyadenylated substrates. Previous work indicated that deletion of the arch domain has minimal effect on Mtr4 unwinding activity. We now show that combining the arch deletion with ratchet helix mutations abolishes helicase activity and produces a lethal in vivo phenotype. These studies demonstrate that the ratchet helix modulates helicase activity and suggest that the arch domain plays a previously unrecognized role in unwinding substrates. PMID:25414331

Taylor, Lacy L.; Jackson, Ryan N.; Rexhepaj, Megi; King, Alejandra Klauer; Lott, Lindsey K.; van Hoof, Ambro; Johnson, Sean J.

2014-01-01

102

The Mtr4 ratchet helix and arch domain both function to promote RNA unwinding.  

PubMed

Mtr4 is a conserved Ski2-like RNA helicase and a subunit of the TRAMP complex that activates exosome-mediated 3'-5' turnover in nuclear RNA surveillance and processing pathways. Prominent features of the Mtr4 structure include a four-domain ring-like helicase core and a large arch domain that spans the core. The 'ratchet helix' is positioned to interact with RNA substrates as they move through the helicase. However, the contribution of the ratchet helix in Mtr4 activity is poorly understood. Here we show that strict conservation along the ratchet helix is particularly extensive for Ski2-like RNA helicases compared to related helicases. Mutation of residues along the ratchet helix alters in vitro activity in Mtr4 and TRAMP and causes slow growth phenotypes in vivo. We also identify a residue on the ratchet helix that influences Mtr4 affinity for polyadenylated substrates. Previous work indicated that deletion of the arch domain has minimal effect on Mtr4 unwinding activity. We now show that combining the arch deletion with ratchet helix mutations abolishes helicase activity and produces a lethal in vivo phenotype. These studies demonstrate that the ratchet helix modulates helicase activity and suggest that the arch domain plays a previously unrecognized role in unwinding substrates. PMID:25414331

Taylor, Lacy L; Jackson, Ryan N; Rexhepaj, Megi; King, Alejandra Klauer; Lott, Lindsey K; van Hoof, Ambro; Johnson, Sean J

2014-12-16

103

A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis  

PubMed Central

Introduction We determined the contribution of the methylene tetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C gene polymorphisms to the susceptibility to rheumatoid arthritis (RA). We also assessed whether these two MTHFR gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction, in a series of Spanish patients with RA. Methods Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo and Hospital San Carlos, Madrid, were studied. Patients and controls (n = 865) were genotyped using predesigned TaqMan SNP genotyping assays. Results No significant differences in allele or genotype frequencies for the MTHFR gene polymorphisms between RA patients and controls were found. Also, no association between the MTHFR 677 C>T polymorphism and CV events or endothelial dysfunction was observed. However, the MTHFR 1298 allele C frequency was increased in patients with CV events after 5 years (38.7% versus 30.3%; odds ratio = 1.45; 95% confidence interval = 1.00 to 2.10; P = 0.04) and 10 years (42.2% versus 31.0%; odds ratio = 1.62; 95% confidence interval = 1.08 to 2.43; P = 0.01) follow up. Moreover, patients carrying the MTHFR 1298 AC and CC genotypes had a significantly decreased flow-mediated endothelium-dependent vasodilatation (4.3 ± 3.9%) compared with those carrying the MTHFR 1298 AA genotype (6.5 ± 4.4%) (P = 0.005). Conclusions Our results show that the MTHFR 1298 A>C gene polymorphism confers an increased risk for subclinical atherosclerosis and CV events in patients with RA. PMID:20423475

2010-01-01

104

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

SciTech Connect

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.

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

2012-12-01

105

The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing  

SciTech Connect

The essential RNA helicase, Mtr4, performs a critical role in RNA processing and degradation as an activator of the nuclear exosome. The molecular basis for this vital function is not understood and detailed analysis is significantly limited by the lack of structural data. In this study, we present the crystal structure of Mtr4. The structure reveals a new arch-like domain that is specific to Mtr4 and Ski2 (the cytosolic homologue of Mtr4). In vivo and in vitro analyses demonstrate that the Mtr4 arch domain is required for proper 5.8S rRNA processing, and suggest that the arch functions independently of canonical helicase activity. In addition, extensive conservation along the face of the putative RNA exit site highlights a potential interface with the exosome. These studies provide a molecular framework for understanding fundamental aspects of helicase function in exosome activation, and more broadly define the molecular architecture of Ski2-like helicases.

Jackson, R.N.; Robinson, H.; Klauer, A. A.; Hintze, B. J.; van Hoof, A.; Johnson, S. J.

2010-07-01

106

MtrB from Bacillus subtilis binds specifically to trp leader RNA in a tryptophan-dependent manner.  

PubMed Central

MtrB regulates transcription attenuation of the Bacillus subtilis trp operon. We have shown that MtrB, either from B. subtilis or overexpressed in Escherichia coli, binds specifically to RNA from the leader region of the trp operon by a gel mobility-shift assay. This binding is tryptophan dependent. MtrB binds to a transcript terminated at the trp attenuator (-2 to +138) or a read-through transcript (-2 to +318). MtrB does not bind antisense trp leader RNA or single-stranded trp leader DNA. These results support the model in which attenuation is controlled by tryptophan-activated MtrB influencing the secondary structure of the leader region transcript to form a terminator structure. Images PMID:8419914

Otridge, J; Gollnick, P

1993-01-01

107

Role of Mex67-Mtr2 in the Nuclear Export of 40S Pre-Ribosomes  

PubMed Central

Nuclear export of mRNAs and pre-ribosomal subunits (pre40S and pre60S) is fundamental to all eukaryotes. While genetic approaches in budding yeast have identified bona fide export factors for mRNAs and pre60S subunits, little is known regarding nuclear export of pre40S subunits. The yeast heterodimeric transport receptor Mex67-Mtr2 (TAP-p15 in humans) binds mRNAs and pre60S subunits in the nucleus and facilitates their passage through the nuclear pore complex (NPC) into the cytoplasm by interacting with Phe-Gly (FG)-rich nucleoporins that line its transport channel. By exploiting a combination of genetic, cell-biological, and biochemical approaches, we uncovered an unanticipated role of Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes. We show that recruitment of Mex67-Mtr2 to pre40S subunits requires loops emanating from its NTF2-like domains and that the C-terminal FG-rich nucleoporin interacting UBA-like domain within Mex67 contributes to the transport of pre40S subunits to the cytoplasm. Remarkably, the same loops also recruit Mex67-Mtr2 to pre60S subunits and to the Nup84 complex, the respective interactions crucial for nuclear export of pre60S subunits and mRNAs. Thus Mex67-Mtr2 is a unique transport receptor that employs a common interaction surface to participate in the nuclear export of both pre-ribosomal subunits and mRNAs. Mex67-Mtr2 could engage a regulatory crosstalk among the three major export pathways for optimal cellular growth and proliferation. PMID:22956913

Occhipinti, Laura; Kemmler, Stefan; Panse, Vikram G.

2012-01-01

108

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

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

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

109

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

110

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

111

MTR WING, TRA604. A LABORATORY ROOM WITH ITS CABINETS AND ...  

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

MTR WING, TRA-604. A LABORATORY ROOM WITH ITS CABINETS AND SERVICE STRIP DOWN CENTER OF ROOM. CARD IN LEFT CORNER OF VIEW WAS INSERTED BY INL PHOTOGRAPHER TO COVER AN OBSOLETE SECURITY RESTRICTION PRINTED ON THE ORIGINAL NEGATIVE. INL NEGATIVE NO. 3817. Unknown Photographer, 11/28/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

112

MTR STACK, TRA71, DETAIL OF PUMICE BLOCK SERVICE BUILDING AT ...  

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

MTR STACK, TRA-71-, DETAIL OF PUMICE BLOCK SERVICE BUILDING AT BASE OF STACK. CAMERA FACING SOUTHEAST. INL NEGATIVE NO. HD52-1-2. Mike Crane, Photographer, 5/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

113

MTR WING A, TRA604, INTERIOR. MAIN FLOOR. VIEW DOWN CORRIDOR ...  

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

MTR WING A, TRA-604, INTERIOR. MAIN FLOOR. VIEW DOWN CORRIDOR 2 (BETWEEN ROOMS ON WEST WALL AND IN CENTER OF FLOOR). CAMERA FACING SOUTH. PUMICE BLOCK WALLS. INL NEGATIVE NO. HD46-12-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

114

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

115

MTR WING, TRA604. FIRST FLOOR PLAN. ENTRY LOBBY, MACHINE SHOP, ...  

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

MTR WING, TRA-604. FIRST FLOOR PLAN. ENTRY LOBBY, MACHINE SHOP, INSTRUMENT SHOP, COUNTING ROOM, HEALTH PHYSICS LAB, LABS AND OFFICES, STORAGE, SHIPPING AND RECEIVING. BLAW-KNOX 3150-4-2, 7/1950. INL INDEX NO. 053-604-00-099-100008, REV. 7. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

116

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

117

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

118

MTR, TRA603. INTERIOR SECTIONS, ELEVATIONS AND DETAILS. ARRANGEMENT OF CONTROL ...  

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

MTR, TRA-603. INTERIOR SECTIONS, ELEVATIONS AND DETAILS. ARRANGEMENT OF CONTROL ROOM, INSTRUMENT ROOM, FREIGHT AND PERSONNEL ELEVATORS. WEST BALCONY PLATFORM. CRANE GIRDER. BLAW-KNOX 3150-803-9, 7/1950. INL INDEX NO. 531-0603-00-098-100568, REV. 7. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

119

Kinetic Monte Carlo Simulations and Molecular Conductance Measurements of the Bacterial Decaheme Cytochrome MtrF  

SciTech Connect

Microorganisms overcome the considerable hurdle of respiring extracellular solid substrates by deploying large multiheme cytochrome complexes that form 20 nanometer conduits to traffic electrons through the periplasm and across the cellular outer membrane. Here we report the first kinetic Monte Carlo simulations and single-molecule scanning tunneling microscopy (STM) measurements of the Shewanella oneidensis MR-1 outer membrane decaheme cytochrome MtrF, which can perform the final electron transfer step from cells to minerals and microbial fuel cell anodes. We find that the calculated electron transport rate through MtrF is consistent with previously reported in vitro measurements of the Shewanella Mtr complex, as well as in vivo respiration rates on electrode surfaces assuming a reasonable (experimentally verified) coverage of cytochromes on the cell surface. The simulations also reveal a rich phase diagram in the overall electron occupation density of the hemes as a function of electron injection and ejection rates. Single molecule tunneling spectroscopy confirms MtrF's ability to mediate electron transport between an STM tip and an underlying Au(111) surface, but at rates higher than expected from previously calculated heme-heme electron transfer rates for solvated molecules.

Byun, H. S.; Pirbadian, S.; Nakano, Aiichiro; Shi, Liang; El-Naggar, Mohamed Y.

2014-09-05

120

MTR WING A, TRA604. SOUTH SIDE. CAMERA FACING NORTH. THIS ...  

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

MTR WING A, TRA-604. SOUTH SIDE. CAMERA FACING NORTH. THIS VIEW TYPIFIES TENDENCY FOR EXPANSIONS TO TAKE THE FORM OF PROJECTIONS AND INFILL USING AVAILABLE YARD SPACES. INL NEGATIVE NO. HD47-44-3. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

121

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

122

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

PubMed Central

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

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

2015-01-01

123

Domain Orientation in the Inactive Response Regulator Mycobacterium tuberculosis MtrA Provides a Barrier to Activation†‡  

PubMed Central

The structure of MtrA, an essential gene product for the human pathogen Mycobacterium tuberculosis, has been solved to a resolution of 2.1 Å. MtrA is a member of the OmpR/PhoB family of response regulators and represents the fourth family member for which a structure of the protein in its inactive state has been determined. As is true for all OmpR/PhoB family members, MtrA possesses an N-terminal regulatory domain and a C-terminal winged helix-turn-helix DNA-binding domain, with phosphorylation of the regulatory domain modulating the activity of the protein. In the inactive form of MtrA these two domains form an extensive interface that is composed of the ?4-?5-?5 face of the regulatory domain and the C-terminal end of the positioning helix, the trans-activation loop, and the recognition helix of the DNA-binding domain. This domain orientation suggests a mechanism of mutual inhibition by the two domains. Activation of MtrA would require a disruption of this interface to allow the ?4-?5-?5 face of the regulatory domain to form the inter-molecule interactions that are associated with the active state and to allow the recognition helix to interact with DNA. Furthermore, the interface appears to stabilize the inactive conformation of MtrA, potentially reducing the rate of phosphorylation of the N-terminal domain. This combination of effects may form a switch regulating the activity of MtrA. The domain orientation exhibited by MtrA also provides a rationale for the variation in linker length that is observed within the OmpR/PhoB family of response regulators. PMID:17511470

Friedland, Natalia; Mack, Timothy R.; Yu, Minmin; Hung, Li-Wei; Terwilliger, Thomas C.; Waldo, Geoffrey S.; Stock, Ann M.

2008-01-01

124

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

125

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

126

MTR WING A, TRA604, INTERIOR. BASEMENT. DETAIL OF A19 LAB ...  

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

MTR WING A, TRA-604, INTERIOR. BASEMENT. DETAIL OF A-19 LAB AREA ALONG SOUTH WALL. SIGN ON FLOOR DIRECTS WORKERS TO OBTAIN WHOLE BODY FRISK UPON LEAVING AREA. SIGN ON EQUIPMENT IN CENTER OF VIEW REQUESTS WORKERS TO "NOTIFY HEALTH PHYSICS BEFORE WORKING ON THIS SYSTEM." CAMERA FACING SOUTHWEST. INL NEGATIVE NO. HD46-13-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

127

Safety analysis of the reference research reactor MTR during reactivity insertion accident using the code MERSAT  

Microsoft Academic Search

The IAEA’s reference research reactor MTR-10MW has been modeled using the code MERSAT. The developed MERSAT model consists of detailed representation of primary and secondary loops including reactor pool, bypass, main pump, heat exchanger and reactor core with the corresponding neutronics and thermalhydraulic characteristics. Following the successful accomplishment of the steady state operation at nominal power of 10MW, reactivity insertion

A. Hainoun; N. Ghazi; B. Mansour Abdul-Moaiz

2010-01-01

128

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

SciTech Connect

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.

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

2012-07-01

129

A novel approach with "skeletonised MTR" measures tract-specific microstructural changes in early primary-progressive MS.  

PubMed

We combined tract-based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract-specific short-term changes in early primary-progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty-one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM "skeleton," which represents the tracts that are "common" to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co-registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a "skeletonised" MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow-up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal-appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract-specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross-subject and tract-specific changes in MTR. PMID:23616276

Bodini, Benedetta; Cercignani, Mara; Toosy, Ahmed; De Stefano, Nicola; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2014-02-01

130

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

SciTech Connect

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 Energias 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.

Sarta, Jose A. [Distrital University Francisco Jose de Caldas, Cr 7 40-53, Bogota D.C. (Colombia); Castiblanco, Luis A

2005-05-24

131

Investigation of Inter-Slice Magnetization Transfer Effects as a New Method for MTR Imaging of the Human Brain  

PubMed Central

We present a new method for magnetization transfer (MT) ratio imaging in the brain that requires no separate saturation pulse. Interslice MT effects that are inherent to multi-slice balanced steady-state free precession (bSSFP) imaging were controlled via an interslice delay time to generate MT-weighted (0 s delay) and reference images (5–8 s delay) for MT ratio (MTR) imaging of the brain. The effects of varying flip angle and phase encoding (PE) order were investigated experimentally in normal, healthy subjects. Values of up to ?50% and ?40% were observed for white and gray matter MTR. Centric PE showed larger MTR, higher SNR, and better contrast between white and gray matter than linear PE. Simulations of a two-pool model of MT agreed well with in vivo MTR values. Simulations were also used to investigate the effects of varying acquisition parameters, and the effects of varying flip angle, PE steps, and interslice delay are discussed. Lastly, we demonstrated reduced banding with a non-balanced SSFP-FID sequence and showed preliminary results of interslice MTR imaging of meningioma. PMID:25664938

Barker, Jeffrey W.; Han, Paul Kyu; Choi, Seung Hong; Bae, Kyongtae Ty; Park, Sung-Hong

2015-01-01

132

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

133

MTR WING, TRA604. ONE OF THE LABORATORY UNITS ALONG THE ...  

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

MTR WING, TRA-604. ONE OF THE LABORATORY UNITS ALONG THE SOUTH SIDE WALL. NOTE SINK, CABINET, TABLE, AND HOOD UNITS. DUCT ABOVE RECEIVES CONTAMINATED AIR AND SENDS IT TO FAN HOUSE AND STACK. NOTE PARTITION WALL BEHIND WORK UNITS. THE HEALTH PHYSICS LAB WAS SIMILARLY EQUIPPED. WINDOW AT LEFT EDGE OF VIEW. CARD IN LOWER RIGHT WAS INSERTED BY INL PHOTOGRAPHER TO COVER AN OBSOLETE SECURITY RESTRICTION PRINTED ON ORIGINAL NEGATIVE. INL NEGATIVE NO. 4225. Unknown Photographer, 2/13/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

134

AFM and Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) Studies on Formation of Air-Stable Supported Lipid Bilayers  

PubMed Central

Supported lipid bilayers (SLBs) were prepared by deposition of unilamellar vesicles on a silicon substrate. Atomic force microscopy (AFM) and a new Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) developed by us were used to trace the dynamic formation of lipid bilayers on the silicon surfaces. The evolution from deformation of vesicles to formation of bilayers can be distinguished clearly by AFM imaging. MTR-IR provided high quality infrared spectra of ultrathin lipid bilayers with high sensitivity and high signal to noise ratio (SNR). The structural and orientational changes during vesicle’s fusion were monitored with MTR-IR. MTR-IR shows superiority over other infrared approaches for ultrathin films on standard silicon wafers in view of its economy and high sensitivity. Both MTR-IR and AFM results were consistent with each other and they provided more information for understanding the self-assembling procedure of SLBs. PMID:19399256

Guo, Peng-Feng; Huang, Wen-Yi; Liu, Hong-Bo; Xiao, Shou-Jun

2009-01-01

135

Cloning, nucleotide sequence, and characterization of mtr, the structural gene for a tryptophan-specific permease of Escherichia coli K-12.  

PubMed Central

The mtr gene of Escherichia coli K-12 encodes an L-tryptophan-specific permease. This gene was originally identified through the isolation of mutations in the 69-min region of the chromosome, closely linked to argG. Cells with lesions in mtr display a phenotype of 5-methyltryptophan resistance. The mtr gene was cloned by using the mini-Mu system. The amino acid sequence of Mtr (414 codons), deduced by DNA sequence analysis, was found to be 33% identical to that of another single-component transport protein, the tyrosine-specific permease, TyrP. The hydropathy plots of the two permeases were similar. Possible operator sites for the tyrosine and tryptophan repressors are situated within the region of DNA that is likely to be the mtr promoter. PMID:1987112

Heatwole, V M; Somerville, R L

1991-01-01

136

Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: A meta-analysis.  

PubMed

Colorectal cancer (CRC) is one of the most common types of cancer worldwide and a leading cause of cancer-related mortality. This meta-analysis was conducted to determine the effect of methylenetetrahydrofolate reductase (MTHFR) mutants on the risk of CRC. A literature search was conducted on PubMed, Medline and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were collected based on rigorous criteria of inclusion. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by the fixed- or random-effects model. After all the studies were pooled, the OR of CRC for individuals carrying the MTHFR 677TT genotype, compared to the CC genotype, was 0.89 (95% CI: 0.82-0.97). When analyzed by ethnicity, Asians with the MTHFR 1298CC genotype exhibited a decreased risk of CRC (OR=0.69; 95% CI: 0.54-0.89). In a mixed population, a significantly reduced risk of CRC was observed among carriers of the 677TT (OR=0.86; 95% CI: 0.76-0.96) and the 1298CC (OR=0.82; 95% CI: 0.69-0.98) genotypes, compared to the wild-type homozygous genotype. In the subgroup of colon cancer, the OR of 677TT vs. CC+CT was 0.83 (95% CI: 0.72-0.96) and the OR of 1298CC vs. AA+AC was 0.81 (95% CI: 0.69-0.96). In the rectal cancer subgroup, the OR of 677TT vs. CC+CT was 0.86 (95% CI: 0.77-0.97). Therefore, this meta-analysis suggested that the MTHFR 677T and 1298C alleles were associated with a low risk of CRC. PMID:24649029

Zhao, Mengmeng; Li, Xuelian; Xing, Chengzhong; Zhou, Baosen

2013-09-01

137

Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: A meta-analysis  

PubMed Central

Colorectal cancer (CRC) is one of the most common types of cancer worldwide and a leading cause of cancer-related mortality. This meta-analysis was conducted to determine the effect of methylenetetrahydrofolate reductase (MTHFR) mutants on the risk of CRC. A literature search was conducted on PubMed, Medline and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were collected based on rigorous criteria of inclusion. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by the fixed- or random-effects model. After all the studies were pooled, the OR of CRC for individuals carrying the MTHFR 677TT genotype, compared to the CC genotype, was 0.89 (95% CI: 0.82–0.97). When analyzed by ethnicity, Asians with the MTHFR 1298CC genotype exhibited a decreased risk of CRC (OR=0.69; 95% CI: 0.54–0.89). In a mixed population, a significantly reduced risk of CRC was observed among carriers of the 677TT (OR=0.86; 95% CI: 0.76–0.96) and the 1298CC (OR=0.82; 95% CI: 0.69–0.98) genotypes, compared to the wild-type homozygous genotype. In the subgroup of colon cancer, the OR of 677TT vs. CC+CT was 0.83 (95% CI: 0.72–0.96) and the OR of 1298CC vs. AA+AC was 0.81 (95% CI: 0.69–0.96). In the rectal cancer subgroup, the OR of 677TT vs. CC+CT was 0.86 (95% CI: 0.77–0.97). Therefore, this meta-analysis suggested that the MTHFR 677T and 1298C alleles were associated with a low risk of CRC. PMID:24649029

ZHAO, MENGMENG; LI, XUELIAN; XING, CHENGZHONG; ZHOU, BAOSEN

2013-01-01

138

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

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.

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

139

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

SciTech Connect

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.

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

140

Amino Acid Residues in the a-Subunit C-Terminal Domain of Escherichia coli RNA Polymerase Involved in Activation of Transcription from the mtr Promoter  

Microsoft Academic Search

To examine the role of the amino acid residues (between positions 258 and 275 and positions 297 and 298) of the a-subunit of RNA polymerase in TyrR-mediated activation of the mtr promoter, we have carried out in vitro transcription experiments using a set of mutant RNA polymerases with a supercoiled mtr template. Decreases in factor-independent transcription in vitro by mutant

JI YANG; KATSUHIKO MURAKAMI; H. CAMAKARIS; NOBUYUKI FUJITA; AKIRA ISHIHAMA; A. J. PITTARD

1997-01-01

141

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

SciTech Connect

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.

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

142

A versatile interaction platform on the Mex67–Mtr2 receptor creates an overlap between mRNA and ribosome export  

PubMed Central

The transport receptor Mex67–Mtr2 functions in mRNA export, and also by a loop-confined surface on the heterodimer binds to and exports pre-60S particles. We show that Mex67–Mtr2 through the same surface that recruits pre-60S particles interacts with the Nup84 complex, a structural module of the nuclear pore complex devoid of Phe-Gly domains. In vitro, pre-60S particles and the Nup84 complex compete for an overlapping binding site on the loop-extended Mex67–Mtr2 surface. Chemical crosslinking identified Nup85 as the subunit in the Nup84 complex that directly binds to the Mex67 loop. Genetic studies revealed that this interaction is crucial for mRNA export. Notably, pre-60S subunit export impaired by mutating Mtr2 or the 60S adaptor Nmd3 could be partially restored by second-site mutation in Nup85 that caused dissociation of Mex67–Mtr2 from the Nup84 complex. Thus, the Mex67–Mtr2 export receptor employs a versatile binding platform on its surface that could create a crosstalk between mRNA and ribosome export pathways. PMID:18046452

Yao, Wei; Lutzmann, Malik; Hurt, Ed

2008-01-01

143

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

Microsoft Academic Search

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

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

2007-01-01

144

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

SciTech Connect

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.

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

2009-09-15

145

The RNA helicases AtMTR4 and HEN2 target specific subsets of nuclear transcripts for degradation by the nuclear exosome in Arabidopsis thaliana.  

PubMed

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

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

2014-08-01

146

Solution-based structural analysis of the decaheme cytochrome, MtrA, by small-angle X-ray scattering and analytical ultracentrifugation.  

PubMed

The potential exploitation of metal-reducing bacteria as a means for environmental cleanup or alternative fuel is an exciting prospect; however, the cellular processes that would allow for these applications need to be better understood. MtrA is a periplasmic decaheme c-type cytochrome from Shewanella oneidensis involved in the reduction of extracellular iron oxides and therefore is a critical element in Shewanella ability to engage in extracellular charge transfer. As a relatively small 333-residue protein, the heme content is surprisingly high. MtrA is believed to obtain electrons from the inner membrane-bound quinol oxidoreductase, CymA, and shuttle them across the outer membrane to MtrC, another decaheme cytochrome that directly interacts with insoluble metal oxides. How MtrA is able to perform this task is a question of interest. Here through the use of two solution-based techniques, small-angle X-ray scattering (SAXS) and analytical ultracentrifugation (AUC), we present the first structural analysis of MtrA. Our results establish that between 0.5 and 4 mg/mL, MtrA exists as a monomeric protein that is shaped like an extended molecular "wire" with a maximum protein dimension (D(max)) of 104 Å and a rod-like aspect ratio of 2.2 to 2.5. This study contributes to a greater understanding of how MtrA fulfills its role in the redox processes that must occur before electrons reach the outside of the cell. PMID:21838277

Firer-Sherwood, Mackenzie A; Ando, Nozomi; Drennan, Catherine L; Elliott, Sean J

2011-09-29

147

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

PubMed Central

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

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

148

Enhancement of the dissolution of albendazole from pellets using MTR technique  

PubMed Central

Albendazole (ABZ), a broad-spectrum anthelmintic agent, is poorly absorbed after oral administration due to its low aqueous solubility. The aim of this study was to improve albendazole dissolution rate by formulating avicel pellets loaded with 10% w/w drug using extrusion/spheronization technique. In addition the wet masses were characterized by mix torque rheometry (MTR) prior to pelletization process. Different additives (i.e., lactose, Tween 80 and low molecular weight chitosan) were formulated with avicel to enhance the dissolution rate of ABZ from the produced pellets. Moreover, mix torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The produced pellets were characterized for their ABZ content, particle size, particle shape, dissolution profile and thermal behaviors. The maximum consistencies (the peak torques) of the wet granules were obtained using 0.667–1.333 ml/g of water or water containing surfactant. Also, the produced pellets have size range from 1036 to 1246 ?m. The calculated drug RDR30 for 10%, 30% and 50% lactose concentrations were 1.08, 1.08 and 2.03, respectively, while that calculated for 10%, 30% and 50% w/w chitosan concentrations were 1.71, 3.62 and 3.62, respectively. The results revealed also that increasing the weight ratio of lactose and chitosan was accompanied by a significant reduction of the peak torque magnitude and this was accompanied by an enhanced ABZ dissolution rate. PMID:23960837

Ibrahim, Mohamed A.; Al-Anazi, Fars K.

2012-01-01

149

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

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

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

1995-04-01

150

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

PubMed

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 the MTHFR gene, A1298C, has also been described as a risk mutation. Furthermore, several studies have suggested that a defective methionine synthase ( MS) enzyme could be a critical defect in folate-related NTDs. An A-to-G transition at bp 2756 on the MS gene has also been reported. In this case-control study, we studied the frequencies of these two polymorphisms in 203 Italian probands with non-syndromic NTDs: 98 mothers, 67 fathers, and 210 control individuals. Although the A1298C polymorphism is common in the Italian population (0.25), the allelic frequency was significantly higher among NTD cases and their parents. Heterozygous patients and mothers have an odds ratio (OR) of 1.98 and 2.11, respectively. The risk associated with the 1298CC genotype was higher for cases (OR = 3.67), for fathers (OR = 3.28), and, above all, for mothers (OR = 6.23). The prevalence of the A2756G polymorphism of the MS gene was determined (0.15). No increased prevalence of the mutated G allele was found in NTD families. This study shows that the MTHFRA1298C polymorphism is a genetic determinant for NTD risk in Italy. No association between the MSA2756G and NTD susceptibility was found. PMID:12111380

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

2002-01-01

151

Characterization of Axial and Proximal Histidine Mutations of the Decaheme Cytochrome MtrA from Shewanella sp. Strain ANA-3 and Implications for the Electron Transport System  

PubMed Central

Extracellular respiration of solid-phase electron acceptors in some microorganisms requires a complex chain of multiheme c-type cytochromes that span the inner and outer membranes. In Shewanella species, MtrA, an ?35-kDa periplasmic decaheme c-type cytochrome, is an essential component for extracellular respiration of iron(III). The exact mechanism of electron transport has not yet been resolved, but the arrangement of the polypeptide chain may have a strong influence on the capability of the MtrA cytochrome to transport electrons. The iron hemes of MtrA are bound to its polypeptide chain via proximal (CXXCH) and distal histidine residues. In this study, we show the effects of mutating histidine residues of MtrA to arginine on protein expression and extracellular respiration using Shewanella sp. strain ANA-3 as a model organism. Individual mutations to six out of nine proximal histidines in CXXCH of MtrA led to decreased protein expression. However, distal histidine mutations resulted in various degrees of protein expression. In addition, the effects of histidine mutations on extracellular respiration were tested using ferrihydrite and current production in microbial fuel cells. These results show that proximal histidine mutants were unable to reduce ferrihydrite. Mutations to the distal histidine residues resulted in various degrees of ferrihydrite reduction. These findings indicate that mutations to the proximal histidine residues affect MtrA expression, leading to loss of extracellular respiration ability. In contrast, mutations to the distal histidine residues are less detrimental to protein expression, and extracellular respiration can proceed. PMID:22923588

Qian, Fang; Zhang, Alissa; Bondarev, Sergey; Welch, Angel; Thelen, Michael P.

2012-01-01

152

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

SciTech Connect

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. 

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

2007-07-31

153

Characterization of axial and proximal histidine mutations of the decaheme cytochrome MtrA from Shewanella sp. strain ANA-3 and implications for the electron transport system.  

PubMed

Extracellular respiration of solid-phase electron acceptors in some microorganisms requires a complex chain of multiheme c-type cytochromes that span the inner and outer membranes. In Shewanella species, MtrA, an ~35-kDa periplasmic decaheme c-type cytochrome, is an essential component for extracellular respiration of iron(III). The exact mechanism of electron transport has not yet been resolved, but the arrangement of the polypeptide chain may have a strong influence on the capability of the MtrA cytochrome to transport electrons. The iron hemes of MtrA are bound to its polypeptide chain via proximal (CXXCH) and distal histidine residues. In this study, we show the effects of mutating histidine residues of MtrA to arginine on protein expression and extracellular respiration using Shewanella sp. strain ANA-3 as a model organism. Individual mutations to six out of nine proximal histidines in CXXCH of MtrA led to decreased protein expression. However, distal histidine mutations resulted in various degrees of protein expression. In addition, the effects of histidine mutations on extracellular respiration were tested using ferrihydrite and current production in microbial fuel cells. These results show that proximal histidine mutants were unable to reduce ferrihydrite. Mutations to the distal histidine residues resulted in various degrees of ferrihydrite reduction. These findings indicate that mutations to the proximal histidine residues affect MtrA expression, leading to loss of extracellular respiration ability. In contrast, mutations to the distal histidine residues are less detrimental to protein expression, and extracellular respiration can proceed. PMID:22923588

Reyes, Carolina; Qian, Fang; Zhang, Alissa; Bondarev, Sergey; Welch, Angel; Thelen, Michael P; Saltikov, Chad W

2012-11-01

154

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

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.

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

155

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

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

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

2014-01-01

156

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

SciTech Connect

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.

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

157

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

Microsoft Academic Search

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

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

1998-01-01

158

Lack of Association Between MTHFR, MTR, MTRR, and TCN2 Genes and Nonsyndromic CL±P in a Chinese Population: Case-Control Study and Meta-Analysis.  

PubMed

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common congenital deformity, often associated with folate deficiency. The genes MTHFR, MTR, MTRR, and TCN2 play key roles in folate metabolism. The risk of NSCLP associated with particular variants in the folic acid pathway differs among ethnic groups. The goal of this study was to explore whether genetic variations in these four genes, as well as gene-gene interactions, are associated with NSCLP. We investigated 7 tagSNPs for MTHFR, 18 tagSNPs for MTR, 15 tagSNPs for MTRR, and 7 tagSNPs for TCN2 selected from HapMap data in a Chinese population. These single nucleotide polymorphisms (SNPs) were examined for associations with NSCLP in 204 patients and 226 controls. We then performed a meta-analysis of association between rs1801133 and NSCLP. There was a significant difference in the allele frequency and haplotype analysis of rs4077829 and rs10802565 in MTR between the NSCLP and control groups but not a significant difference after correction with 10,000 times permutations. The allele frequency, haplotype analysis, and gene-gene interactions of other SNPs did not show a significant difference. The meta-analysis results showed that no significant differences were found for allele comparison, heterozygote comparison, homozygote comparison, dominant model comparison, or recessive model comparison. The alterations of folate metabolism related to these polymorphisms are not involved in NSCLP in the Chinese population. PMID:25105440

Jiang, Chanyuan; Yin, Ningbei; Di Wu, Zhenmin Zhao; Wang, Yongqian; Li, Haidong; Song, Tao

2014-08-01

159

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

PubMed

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

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

2013-11-01

160

Kinetics of Reduction of Fe(III) Complexes by Outer Membrane Cytochromes MtrC and OmcA of Shewanella oneidensis MR-1  

SciTech Connect

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, we report the study of reduction kinetics of a series of Fe(III) complexes with citrate, NTA and EDTA by abiotically reduced MtrC and OmcA using a stopped-flow technique in combination with theoretical computation methods within the framework of the electron transfer theory of Marcus and speciation calculations based on the current thermodynamic database. Stopped-flow kinetic data showed that the reaction was very fast and appeared to proceed in two stages, a fast stage that completes in much less than a second and a slower stage afterwards. For a given complex, the reaction is faster by reduction with MtrC than OmcA, while for a given protein, the reaction completes in the decreasing order of Fe-EDTA > Fe-NTA > Fe-citrate. All the stopped-flow kinetic curves could be modeled by two parallel second-order bimolecular redox reactions with second-order rate constants ranging from 0.872 µM-1s-1 for the fast reaction between MtrC with Fe-EDTA complex to 0.012 µM-1s-1 for the slow reaction between OmcA and Fe-citrate complex. Speciation calculations indicated that at both metal:ligand ratios, 1:1.5 and 1:10, a single dominant ferric complex was responsible for the observed reaction for each ligand and, therefore, the observed dual-reaction pathways was attributed to the differences in the reduction behavior among various heme groups within each protein. The results of redox potential calculations with known thermodynamic data show only small differences on the scale of a few millivolts among the three complexes, suggested that the observed differences in reaction rate cannot be explained by the overall redox reaction free energy. In contrast, reorganization energies (?) calculated based on DFT-COSMO model are substantially different between the complexes, with a larger reorganization energy and therefore a larger activation energy associated with the citrate complex, and progressively smaller ones for the NTA and EDTA complexes. In combination with approximate electronic coupling terms, the theoretical results show good agreement with the observed trend and implicate the reorganization energy as the key factor in the kinetic reaction.

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

2008-11-01

161

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

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

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

162

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

PubMed

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

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

2014-12-01

163

Role of Outer Membrane C-Type Cytochromes MtrC and OmcA in Shewanella Oneidensis MR-1 Cell Production, Accumulation, and Detachment During Respiration on Hematite  

SciTech Connect

Solid phase iron oxides are considered to be important terminal electron acceptors for microbial respiration in many anoxic environments. Besides the knowledge that cells attach to and reduce these substrates, other aspects of surface-associated cell behavior and the related cell surface components that influence cell-mineral interactions are not well understood. In the present study, wild-type cells of the dissimilatory iron-reducing bacterium Shewanella oneidensis MR-1 formed thin biofilms one-to-two cell layers in thickness when respiring on natural specular hematite under flow conditions similar to those which exist in aquatic sediments and subsurface environments. The distribution of cells within the biofilm indicated that direct contact was not required for electron transfer from cells to the mineral surface. Detached biomass in the form of single cells represented >99% of the surface-associated wild-type cell production from respiration on hematite over the biofilm life cycle. A mutant deficient in the outer membrane c35 type cytochrome OmcA, while still able to respire and replicate on hematite, established a lower steady-state cell density on the mineral surface than that of the wild-type strain. A mutant deficient in MtrC, another outer membrane c-type cytochrome, and a mutant deficient in both cytochromes were unable to reduce sufficient amounts of hematite to support detectable growth on the mineral surface. When considered in the context of previous work, the results support a growing body of evidence that the relative importance of OmcA and MtrC to cell respiration and replication depends on the form of iron oxide available as terminal electron acceptor.

Mitchell, Andrew C.; Peterson, L.; Reardon, Catherine L.; Reed, Samantha B.; Culley, David E.; Romine, Margaret F.; Geesey, Gill G.

2012-07-01

164

MTR benchmark static calculations with MCNP5 code  

Microsoft Academic Search

With the sustained development in computer technology, the use of more powerful computational tools becomes mandatory. The challenge today is to revisit safety features of the existing nuclear research reactors using new generation of computer tools. The objective is to verify that the safety requirements still met and when necessary to introduce some amendments coming from the new attainments. In

Anis Bousbia-Salah; Hocine Benkharfia; Nateekoool Kriangchaiporn; Alessandro Petruzzi; Francesco D’Auria; Nidal Ghazi

2008-01-01

165

THE OPERATING CHARACTERISTICS OF THE MTR ON SPECIAL CORES  

Microsoft Academic Search

The operating characteristics of the Materials Testing Reactor with a ; 20% enriched uranium core and with a plutonium core have been compared with those ; of the standard 93% enriched uranium core. A series of reactor physics and ; engineering tests has been made on each core. This was followed by operation at ; 30 megawatts, the full design

D. E. deBoisblanc; R. S. Marsden

1958-01-01

166

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

PubMed

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

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

167

Neutronic analysis of the conversion of HEU to LEU fuel for a 5MW MTR core  

Microsoft Academic Search

In recent years, due to cessation of highly enriched uranium (HEU) fuel supply, practical steps have been taken to substitute HEU fuel in almost all research reactors by medium-enriched uranium or low-enriched uranium (LEU) fuels. In this study, a neutronic calculation of a 5-MW research reactor core fueled with HEU (93% ²³⁵U) is presented. In order to assess the performance

A. Pazirandeh; G. Bartsch

1987-01-01

168

Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility.  

PubMed

The aim of this study was to explore the relationship between 2 genetic polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), C677T and A1298C, and determine the long-term reproductive outcome in infertile men. This was a prospective study conducted in an andrology clinic. Men with a 1-year history of infertility were assessed for the MTHFR polymorphisms at a 5-year follow-up. We compared the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism between men who did and did not bear children during follow-up. Of the 215 men who were infertile at 1 year, 82 (38.1%) remained infertile and 133 (61.9%) achieved natural conception during the 5-year follow-up, with the highest rate in the first year (32.6%). The MTHFR 677TT genotype (homozygote) was associated with a substantially increased risk of infertility during follow-up [odds ratio (OR) = 10.242; 95% confidence interval (CI) = 1.257-83.464] relative to the MTHFR 677CC genotype (wild-type). Risk of infertility was not increased by the MTHFR A1298C polymorphism alone, but was increased by the combination of polymorphisms MTHFR C677T and MTHFR A1298C (OR = 11.818; 95%CI = 1.415-98.674). The homozygous MTHFR C677T genotype was a risk factor for male infertility during 5-year follow-up, whereas a correlation between MTHFR A1298C and infertility was not observed. The MTHFR C677T and MTHFR A1298C polymorphisms had additive effects on male infertility. PMID:24737513

Li, S-S; Li, J; Xiao, Z; Ren, A-G; Jin, L

2014-01-01

169

Association of deep venous thrombosis with prothrombotic gene polymorphism identified in lung cancer cases.  

PubMed

Venous thrombosis is a significant cause of morbidity and mortality in patients with malignancies. We aimed to investigate the association between prothrombotic gene polymorphisms detected in lung cancer cases and deep venous thrombosis (DVT). Totally 66 patients with an established diagnosis of lung cancer, of which 33 developed DVT, were enrolled. Multiplex PCR technique and reverse hybridization strip assay were performed on DNA extracted from peripheral blood, in order to analyze prothrombin G20210A, factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE), plasminogen activator inhibitor-1 (PAI-1), and glycoprotein IIIa (Gp IIIa) gene mutations. Among prothrombotic gene polymorphisms investigated in this study, the commonest ones were PAI-1 4G/5G (56% heterozygous, 39% homozygous) and ACE gene mutations (58% heterozygous, 17% homozygous). The presence of homozygous MTHFR A1298C mutation was significantly associated with DVT (P=0.020). Comparing the lung cancer patients with and without DVT, only MTHFR A1298C gene polymorphism differed significantly (P=0.040). We determined a higher rate of prothrombotic gene mutations in lung cancer patients who developed DVT. However, statistical significance was achieved only for MTHFR A1298C gene mutation. Therefore, nongenetic factors for disturbance of hemostatic metabolism should also be considered in lung cancer patients. PMID:21080081

Arslan, Sulhattin; Manduz, Sinasi; Epöztürk, Kür?at; Karahan, O?uz; Akkurt, Ibrahim

2011-04-01

170

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression. PMID:24338216

Khorshied, Mervat Mamdooh; Shaheen, Iman Abdel Mohsen; Abu Khalil, Reham E; Sheir, Rania Elsayed

2014-01-01

171

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...

172

The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing  

E-print Network

exosome. The molecular basis for this vital func- tion is not understood and detailed analysis with the exosome. These studies provide a mo- lecular framework for understanding fundamental aspects of helicase function in exosome activation, and more broadly define the molecular architecture of Ski2-like helicases

van Hoof, Ambro

173

Psychology 456: Social Psychology Summer 2012, 107 Esslinger Hall, M-TR 2:00 3:50  

E-print Network

Information Rosemary Bernstein, M.S (weeks 1&2) Office Hours: T/R 1-2 pm, 375 Straub Hall Contact info: reb@uoregon.edu Arielle Morganstern, M.S. (weeks 3&4) Office Hours: W 11am-1pm, 375 Straub Hall Contact info: ariellem

Lockery, Shawn

174

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

E-print Network

info: crystals@uoregon.edu Rosemary Bernstein, M.S. (weeks 2&3) Office Hours: T/R 2-3 pm, 302 Straub Hall Contact info: reb@uoregon.edu Course overview Welcome to Psychology 456! In the next four weeks

Lockery, Shawn

175

Program Guide for Basic Precision Machining 8754000 (IN48.052300) and Precision Machining MTR0470 (IN48.050300).  

ERIC Educational Resources Information Center

This competency-based program guide provides course content information and procedures for secondary schools, postsecondary vocational schools, and community colleges in Florida that conduct programs in basic precision machining and precision machining. The first section is on legal authority, which applies to all vocational education programs in…

University of South Florida, Tampa. Dept. of Adult and Vocational Education.

176

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies  

PubMed Central

Background 5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk. Methods Relevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity. Results C677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE?=?0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P?=?0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE?=?1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism. Conclusions The present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results. PMID:22943282

2012-01-01

177

The Importance of Homozygous Polymorphisms of Methylenetetrahydrofolate Reductase Gene in Romanian Patients with Idiopathic Venous Thromboembolism  

PubMed Central

Background: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have recently raised the interest as a possible thrombophilic factors. Aims: We aimed to assess the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic venous thromboembolism (VTE) in a Romanian population and the associated risk of VTE. Study Design: We performed a case-control transversal study including 90 patients diagnosed with VTE and 75 sex- and age-matched controls. Methods: MTHFR C677T and A1298C polymorphisms were detected using PCR-RFLP method. Results: The homozygous MTHFR 677TT genotype, present in 18.8% of patients with VTE versus 6.6% of controls, was significantly associated with VTE (p= 0.021, OR= 3.26, 95%CI (1.141–9.313)). The heterozygous MTHFR A1298C genotype, presenting the highest prevalence in the VTE group (34.4%) as well as in controls (37.3%), was not associated with VTE (p=0.7). No associations were found for heterozygous MTHFR C677T (with a frequency of 32.2% in VTE and 37.3% in controls, p=0.492), respective homozygous MTHFR A1298C genotype (with a frequency of 1.1% in VTE and 2.6% in controls, p=0.456). Conclusion: Among MTHFR polymorphisms, only homozygosity for MTHFR 677TT may be considered a risk factor for VTE; the MTHFR A1298C polymorphism is not significantly associated with an increased risk of VTE. PMID:25207100

Hotoleanu, Cristina; Trifa, Adrian; Popp, Radu; Fodor, Daniela

2013-01-01

178

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

PubMed

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

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

179

Tripartite efflux pumps: energy is required for dissociation, but not assembly or opening of the outer membrane channel of the pump  

PubMed Central

The MtrCDE multidrug pump, from Neisseria gonorrhoeae, is assembled from the inner and outer membrane proteins MtrD and MtrE, which are connected by the periplasmic membrane fusion protein MtrC. Although it is clear that MtrD delivers drugs to the channel of MtrE, it remains unclear how drug delivery and channel opening are connected. We used a vancomycin sensitivity assay to test for opening of the MtrE channel. Cells expressing MtrE or MtrE-E434K were insensitive to vancomycin; but became moderately and highly sensitive to vancomycin respectively, when coexpressed with MtrC, suggesting that the MtrE channel opening requires MtrC binding and is energy-independent. Cells expressing wild-type MtrD, in an MtrCE background, were vancomycin-insensitive, but moderately sensitive in an MtrCE-E434K background. The mutation of residues involved in proton translocation inactivated MtrD and abolished drug efflux, rendered both MtrE and MtrE-E434K vancomycin-insensitive; imply that the pump–component interactions are preserved, and that the complex is stable in the absence of proton flux, thus sealing the open end of MtrE. Following the energy-dependent dissociation of the tripartite complex, the MtrE channel is able to reseal, while MtrE-E434K is unable to do so, resulting in the vancomycin-sensitive phenotype. Thus, our findings suggest that opening of the OMP via interaction with the MFP is energy-independent, while both drug export and complex dissociation require active proton flux. PMID:23565750

Janganan, Thamarai K; Bavro, Vassiliy N; Zhang, Li; Borges-Walmsley, Maria Inês; Walmsley, Adrian R

2013-01-01

180

Methylenetetrahydrofolate reductase genotype association with the risk of follicular lymphoma.  

PubMed

The metabolism of folate is essential in DNA synthesis, and polymorphisms of genes involved in such metabolism have been implicated in many types of cancer. Among these, the methylene tetrahydrofolate reductase gene (MTHFR) encodes an enzyme that converts folate to a methyl donor used for DNA methylation. We studied the association between the different genotypes of the two most common MTHFR polymorphisms, C677T and A1298C, and the risk of follicular lymphoma (FL). For this purpose, 55 previously diagnosed FL patients and 170 normal control subjects were examined using polymerase chain reaction followed by restriction fragment length polymorphism. The frequency of the A1298C CC homozygous mutant genotype was significantly higher in patients with FL than in control subjects (OR = 3.51, 95% CI = 1.39-8.86, P = 0.008). No such association was found for the heterozygous A1298C AC genotype (OR = 1.08, 95% CI = 0.55-2.12, P = 0.83). On the other hand, no significant association was found for either the C677T CT heterozygous genotype (OR = 0.79, 95% CI = 0.42-1.51, P = 0.49) or the C677T TT homozygous mutant genotype (OR = 0.55, 95% CI = 0.12-2.65, P = 0.46). The present findings add to the very few reports suggesting a link between the A1298C CC homozygous MTHFR genotype and a higher risk of developing FL, and the first such in a Jordanian population. PMID:19963111

Ismail, Said I; Ababneh, Nida A; Khader, Yousef; Abu-Khader, Ahmad A; Awidi, Abdullah

2009-12-01

181

Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls  

PubMed Central

Background Several epidemiological studies have investigated the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with hypertension (H) or hypertension in pregnancy (HIP). However, the results were controversial. We therefore performed a comprehensive meta-analysis to provide empirical evidences on the associations. Methodologies The English and Chinese databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed in our study. Principal Findings A total of 114 studies with 15411 cases and 21970 controls were included, 111 studies with 15094 cases and 21633 controls for the C677T polymorphism and 21 with 2533 cases and 2976 controls for the A1298C polymorphism. Overall, the C677T polymorphism was significantly associated with H and HIP (H & HIP: OR?=?1.26, 95% CI?=?1.17–1.34; H: OR?=?1.36, 95% CI?=?1.20–1.53; HIP: OR?=?1.21, 95% CI?=?1.08–1.32). Stratified analysis by ethnicity revealed a significant association among East Asians and Caucasians, but not among Latinos, Black Africans, and Indians and Sri Lankans. In the stratified analyses according to source of controls, genotyping method, sample size and study quality, significant associations were observed in all the subgroups, with the exception of population based subgroup in H studies and large sample size and “others” genotyping method subgroups in HIP studies. For the A1298C polymorphism, no significant association was observed either in overall or subgroup analysis under all genetic models. Conclusions This meta-analysis suggests that the MTHFR C677T rather than A1298C polymorphism may be associated with H & HIP, especially among East Asians and Caucasians. PMID:24505291

Yang, Boyi; Fan, Shujun; Zhi, Xueyuan; Li, Yongfang; Liu, Yuyan; Wang, Da; He, Miao; Hou, Yongyong; Zheng, Quanmei; Sun, Guifan

2014-01-01

182

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

PubMed Central

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

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

2013-01-01

183

Methylenetetrahydrofolate reductase polymorphism C677T is a protective factor for pediatric acute lymphoblastic leukemia in the Chinese population: a meta-analysis.  

PubMed

Two polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, were hypothesized to decrease the risk of acute lymphoblastic leukemia (ALL). Studies examining the associations between these two polymorphisms and ALL susceptibility drew inconsistent results. To obtain a reliable conclusion in a Chinese population, we carried out a meta-analysis. In total, 11 studies on C677T polymorphism (1597 cases and 2295 controls) and 10 studies on A1298C polymorphism (1553 cases and 2224 controls) were included in the meta-analysis. We found a significant association between the 677T variant and reduced ALL risk in Chinese children (Dominant model: odds ratio [OR(FE)]=0.73, 95% confidence interval [CI]: 0.63-0.86, p<0.01). Heterogeneity between the studies in the children subgroup was weak and vanished after excluding one study deviating from HWE in the control group (p>0.1). In the adult subgroup, there was no significant association between the C677T variant and ALL risk (Dominant model: OR(RE)=0.88, 95% CI: 0.45-1.72, p=0.72). Significant heterogeneity was found in the adult subgroup in all the genetic model tests (p<0.1). The A1298C polymorphism had an effect on ALL risk neither in adults (Dominant model: OR(FE)=0.95, 95% CI: 0.71-1.27, p=0.72) nor in children (Dominant model: OR(FE)=1.02, 95% CI: 0.87-1.21, p=0.77). No significant heterogeneity between studies on A1298C polymorphism was found in the meta-analysis (p>0.1). The results showed that there was a protective effect of the MTHFR C677T variant on ALL risk in Chinese children. PMID:23061880

Wang, Haigang; Meng, Lujing; Zhao, Lixia; Wang, Jiali; Liu, Xinchun; Mi, Wenjie

2012-12-01

184

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

PubMed Central

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

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

2013-01-01

185

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

PubMed Central

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

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

2013-01-01

186

Influence of Nitrous Oxide Anesthesia, B-Vitamins, and MTHFR gene polymorphisms on Perioperative Cardiac Events: The Vitamins in Nitrous Oxide (VINO) Randomized Trial  

PubMed Central

Background Nitrous oxide causes an acute increase in plasma homocysteine that is more pronounced in patients with the MTHFR C677T or A1298C gene variant. In this randomized controlled trial we sought to determine if patients carrying the MTHFR C677T or A1298C variant had a higher risk for perioperative cardiac events after nitrous oxide anesthesia and if this risk could be mitigated by B-vitamins. Methods We randomized adult patients with cardiac risk factors undergoing noncardiac surgery to receive nitrous oxide plus intravenous B-vitamins before and after surgery or to nitrous oxide and placebo. Serial cardiac biomarkers and 12-lead electrocardiograms were obtained. The primary study endpoint was the incidence of myocardial injury, as defined by cardiac troponin I elevation within the first 72 hours after surgery. Results A total of 500 patients completed the trial. Patients who were homozygous for either MTHFR C677T or A1298C gene variant (n= 98; 19.6%) had no increased rate of postoperative cardiac troponin I elevation compared to wild-type and heterozygous patients (11.2% vs. 14.0%; relative risk 0.96, 95% CI 0.85 to 1.07, p=0.48). B-vitamins blunted the rise in homocysteine, but had no effect on cardiac troponin I elevation compared to patients receiving placebo (13.2% vs. 13.6%; relative risk 1.02, 95% CI 0.78 to 1.32, p=0.91). Conclusions Neither MTHFR C677T and A1298C gene variant nor acute homocysteine increase are associated with perioperative cardiac troponin elevation after nitrousoxide anesthesia. B-vitamins blunt nitrous oxide-induced homocysteine increase but have no effect on cardiac troponin elevation. PMID:23856660

Nagele, Peter; Brown, Frank; Francis, Amber; Scott, Mitchell G.; Gage, Brian F.; Miller, J. Philip

2013-01-01

187

MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: A meta-analysis of 3511 cases and 2762 controls.  

PubMed

Published data regarding the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and prostate cancer risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms and prostate cancer risk. Six studies including 3511 cases and 2762 controls described C677T genotypes, among which four articles totalling 838 cases and 1121 controls described A1298C genotypes, were involved in this meta-analysis. Overall meta-analysis indicated that the 677T allele was more likely to exert a protective effect on prostate cancer risk (OR=0.81, 95% CI: 0.68-0.98) with a recessive genetic model. No association was found for the 677CT genotype and the 677TT mutant homozygote with prostate cancer risk compared with 677CC, with OR=1.13 (95% CI: 0.88-1.45) and OR=0.85 (95% CI: 0.71-1.03), respectively. No evidence of an association of MTHFR A1298C polymorphism with prostate cancer was found. This meta-analysis supports that the C677T of the MTHFR gene is a low-penetrance susceptibility gene for prostate cancer, and might provide protective effects against prostate cancer risk. PMID:19223177

Bai, Jian-Ling; Zheng, Ming-Hua; Xia, Xian; Ter-Minassian, Monica; Chen, Yong-Ping; Chen, Feng

2009-05-01

188

Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR) polymorphisms on age at onset of Huntington disease  

PubMed Central

Background Huntington disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Recently, suggestive association has been reported between a single nucleotide polymorphism (SNP; rs1801131, also known as A1298C) in the methyltetrahydrofolate reductase (MTHFR) gene and AO of HD. 5,10-MTHFR is a key enzyme in the folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using part of a previously established study cohort plus additional patients and appropriate statistical methods, we reinvestigated two polymorphisms in the MTHFR gene, C677T and A1298C, as well as their association with AO in 167 HD patients. Results There was no statistically significant impact on AO for HD patients, neither of MTHFR SNPs nor of the combinations thereof. Conclusion Contrary to previously described evidence the A1298C polymorphism in the MTHFR gene does not appear to modulate AO of HD patients. PMID:16372906

Hansen, Wiebke; Saft, Carsten; Andrich, Jürgen; Müller, Thomas; Wieczorek, Stefan; Epplen, Jörg T; Arning, Larissa

2005-01-01

189

Association between MTHFR Polymorphisms and Acute Myeloid Leukemia Risk: A Meta-Analysis  

PubMed Central

Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and acute myeloid leukemia risk (AML) have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C) polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls) and 9 studies (1335 patients and 4295 controls) for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98–1.04; 95% CI, 0.86–0.92 to 1.09–1.25). Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis. PMID:24586405

Su, Yan; Lu, Ge-Ning; Wang, Ren-Sheng

2014-01-01

190

Reconstruction of Extracellular Respiratory Pathways for Iron(III) Reduction in Shewanella Oneidensis Strain MR-1  

PubMed Central

Shewanella oneidensis strain MR-1 is a facultative anaerobic bacterium capable of respiring a multitude of electron acceptors, many of which require the Mtr respiratory pathway. The core Mtr respiratory pathway includes a periplasmic c-type cytochrome (MtrA), an integral outer-membrane ?-barrel protein (MtrB), and an outer-membrane-anchored c-type cytochrome (MtrC). Together, these components facilitate transfer of electrons from the c-type cytochrome CymA in the cytoplasmic membrane to electron acceptors at and beyond the outer-membrane. The genes encoding these core proteins have paralogs in the S. oneidensis genome (mtrB and mtrA each have four while mtrC has three) and some of the paralogs of mtrC and mtrA are able to form functional Mtr complexes. We demonstrate that of the additional three mtrB paralogs found in the S. oneidensis genome, only MtrE can replace MtrB to form a functional respiratory pathway to soluble iron(III) citrate. We also evaluate which mtrC/mtrA paralog pairs (a total of 12 combinations) are able to form functional complexes with endogenous levels of mtrB paralog expression. Finally, we reconstruct all possible functional Mtr complexes and test them in a S. oneidensis mutant strain where all paralogs have been eliminated from the genome. We find that each combination tested with the exception of MtrA/MtrE/OmcA is able to reduce iron(III) citrate at a level significantly above background. The results presented here have implications toward the evolution of anaerobic extracellular respiration in Shewanella and for future studies looking to increase the rates of substrate reduction for water treatment, bioremediation, or electricity production. PMID:22363330

Coursolle, Dan; Gralnick, Jeffrey A.

2012-01-01

191

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

SciTech Connect

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.

K. Winterholler

2007-01-30

192

(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

reaction contained ,10 pmol of hsp70 50 RNA, ,2 pmol of dSpt6­ exosome complex (2 ml of dSpt6FH or mock is linked to the nuclear exosome. Nature 413, 538­542 (2001). 7. Butler, J. S. The yin and yang of the exosome. Trends Cell Biol. 12, 90­96 (2002). 8. Bousquet-Antonelli, C., Presutti, C. & Tollervey, D

Cai, Long

193

33 CFR 154.1016 - Facility classification by COTP.  

Code of Federal Regulations, 2010 CFR

...Facility classification by COTP. (a) The COTP may upgrade the classification of: (1) An MTR facility not specified in § 154.1015...The COTP may downgrade, the classification of: (1) An MTR facility specified in §...

2010-07-01

194

Genetic polymorphisms influence runners' responses to the dietary ingestion of antioxidant supplementation based on pequi oil (Caryocar brasiliense Camb.): a before-after study.  

PubMed

Genes have been implicated in the levels of oxidative stress, lipids, CVD risk, immune reactivity, and performance. Pequi oil (Caryocar brasiliense) has shown anti-inflammatory and hypotensive effects, besides reducing exercise-induced DNA, tissue damages, and anisocytosis. Given that diet can interact with the human genome to influence health and disease, and because genetic variability can influence response to diet, we aim to investigate the influence of 12 gene polymorphisms on inflammatory markers, postprandial lipids, arterial pressure, and plasma lipid peroxidation of runners (N = 125), before and after 14 days of 400 mg pequi-oil supplementation, after races under closely comparable conditions. Arterial pressure was checked before races; blood samples were taken immediately after racing to perform leukogram and plateletgram, Tbars assay, lipid, and CRP dosages and genotyping. CAT, GST-M1/T1, CRP-G1059C, and MTHFR-C677T polymorphisms influenced post-pequi-oil responses in leukogram; Hp and MTHFR-C677T, in plateletgram; Hp, ACE, GSTT1, and MTHFR-A1298C, in lipid profile; MTHFR-A1298C, in C-reactive protein (CRP) levels; and Hp and MnSOD, in Tbars assay. Differences between ACE genotypes in leukogram and total cholesterol disappeared after pequi, and the same occurred for Hp and MnSOD in Tbars assay and for MTHFR-A1298C with CRP levels. Because genetic inheritance is one of the factors that drive atherosclerosis-related lipid abnormalities, results can contribute to a greater understanding of the influence of genetic polymorphisms in situations that push up free radicals. Knowledge is also expanded on how antioxidant supplementation affects an individual's genes and how athletic genetic makeup can affect the way a person responds to antioxidant supplements. PMID:21484158

Miranda-Vilela, Ana Luisa; Lordelo, Graciana Souza; Akimoto, Arthur Kenji; Alves, Penha Cristina Zaidan; Pereira, Luiz Carlos da Silva; Klautau-Guimarães, Maria de Nazaré; Grisolia, Cesar Koppe

2011-11-01

195

Infants' MTHFR polymorphisms and nonsyndromic orofacial clefts susceptibility: a meta-analysis based on 17 case-control studies.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, is thought to be involved in the development of nonsyndromic orofacial clefts (NSOC). However, conflicting results have been achieved when evaluating the associations between infants' MTHFR C677T and A1298C polymorphisms and the risk of NSOC. To obtain more precise estimations of these associations, a meta-analysis recruiting 17 case-control studies was performed. Among Asians we found that CT heterozygote, TT homozygote, and CT/TT of infants' MTHFR C677T variant could contribute to elevated risks of NSOC, compared with CC wild-type homozygote (OR=1.741, 95% CI=1.043-2.907 for CT vs. CC, OR=2.311, 95% CI=1.313-4.041 for TT vs. CC, and OR=1.740, 95% CI=1.051-2.882 for CT/TT vs. CC, respectively). Similar effect was also observed on MTHFR 677T T allele, when using C allele as a reference in Asians (OR=1.420, 95% CI=1.191-1.693, for T allele vs. C allele). Furthermore, in stratified analysis by types of disease, CT/CC was suggested to confer decreased susceptibility to CL/P under recessive genetic model (OR=0.854, 95% CI=0.730-1.000). For MTHFR A1298C, the MTHFR 1298C allele in the case group of Caucasians was significantly lower than that in the control group, suggesting a protective effect against NSOC in Caucasian populations (OR=0.711, 95% CI=0.641-0.790, for C allele vs. A allele). In conclusion, the meta-analysis provided confirmative evidences that infants' MTHFR C677T and A1298C polymorphisms were involved in the development of NSOC. PMID:22847888

Pan, Yongchu; Zhang, Weibing; Ma, Junqing; Du, Yifei; Li, Dandan; Cai, Qi; Jiang, Hongbing; Wang, Meilin; Zhang, Zhengdong; Wang, Lin

2012-09-01

196

5,10-Methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic leukemia risk: a meta-analysis.  

PubMed

There is evidence supporting a role for 5-10 methylenetetrahydrofolate reductase (MTHFR) gene variants in acute lymphoblastic leukemia (ALL). To provide a more robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a meta-analysis to reevaluate the association between the two most commonly studied MTHFR polymorphisms (C677T and A1298C) and ALL risk. All case-control studies investigating an association between the C677T or A1298C polymorphisms and risk of ALL were included. We applied both fixed-effects and random-effects models to combine odds ratio (OR) and 95% confidence intervals (95% CI). Q-statistic was used to evaluate the homogeneity and both Egger and Begg-Mazumdar tests were used to assess publication bias. The meta-analysis of the C677T polymorphism and risk of childhood ALL included 13 studies with a total of 4,894 individuals. Under a fixed-effects model, the TT genotype failed to be associated with a statistically significant reduction of childhood ALL risk (TT versus CT + CC: OR, 0.88; 95% CI, 0.73-1.06; P = 0.18). However, individuals homozygous for the 677T allele exhibited a 2.2-fold decrease in risk of adult ALL (TT versus CT + CC: OR, 0.45; 95% CI, 0.26-0.77; P = 0.004). In both cases, no evidence of heterogeneity was observed. No association between the A1298C variant and susceptibility to both adult and childhood ALL was disclosed. Our findings support the proposal that the common genetic C677T polymorphism in the MTHFR contributes to the risk of adult ALL, but not to the childhood ALL susceptibility. PMID:17035405

Pereira, Tiago Veiga; Rudnicki, Martina; Pereira, Alexandre Costa; Pombo-de-Oliveira, Maria S; Franco, Rendrik França

2006-10-01

197

Methylenetetrahydrofolate reductase gene polymorphisms in 13 Chinese ethnic populations.  

PubMed

It has been shown that the polymorphisms of Methylenetetrahydrofolate reductase (MTHFR) gene are associated with susceptibility to several disorders including hyperhomocysteinemia, vascular disease, birth defect, and certain cancers, and exhibit great diversities among various populations. The aim of this study was to investigate the prevalence of two common non-synonymous single nucleotide polymorphisms (i.e., C677T and A1298C) at MTHFR gene in 13 Chinese populations. A total of 1015 healthy individuals from 13 populations distributed widely from north to south in China were studied. DNA samples were isolated from peripheral blood samples and genotyped using polymerase chain reaction-restriction fragment length polymorphism. For C677T polymorphism, the frequency in Chinese of CC homozygous was 42.4%; CT heterozygous was 49.8%; and TT homozygous was 7.9%. For A1298C, AA homozygous was 39.2%; AC heterozygous was 38.6%; and CC homozygous was 22.2%. The allelic frequency of 677T and 1298C was 32.8 and 41.5%, respectively, and each allele frequency had significant variance in 13 Chinese populations. The frequency of the 677T allele among southern populations was 30.7% compared to 38.0% among northeastern and 30.5% among northwestern populations. The difference was statistically significant (p < 0.01). The frequency of 1298C mutation in southerns was 58.9% whereas in northeasterns it was 24.0% and 37.6% in northwesterns. This was also statistically significant (p < 0.01). The MTHFR C677T and A1298C sites were in linkage disequilibrium in the Chinese population revealed by our data. PMID:18098118

Mao, Renfang; Fan, Yihui; Chen, Feng; Sun, Donglin; Bai, Jing; Fu, Songbin

2008-04-01

198

Correlation of methylenetetrahydrofolate reductase polymorphisms with homocysteine metabolism in healthy Lebanese adults.  

PubMed

Hyperhomocysteinemia is associated with several vascular and teratogenic conditions. Determinants of total homocysteine concentrations include genetic and nutritional factors. This study assesses the relation between homocysteine concentrations and MTHFR gene polymorphisms at two common alleles (C677T (rs1801133) and A1298C (rs1801131)) as well as other predictors of homocysteine (folate, vitamin B(12), body mass index (BMI), age, and gender) in a group of healthy Lebanese: 109 males and 124 females aged 17-55years. We used serum for the determination of homocysteine, folate and vitamin B(12) levels and blood drawn in EDTA tubes for molecular analysis of MTHFR polymorphisms. Hyperhomocysteinemia was present in 59/233 (25.3%) of the subjects, with male/female ratio of 1.95. Multivariable regression analysis showed that homocysteine levels were negatively related to folate and vitamin B(12) and positively related to male gender and C677T homozygosity; but not A1298C polymorphism, BMI or age. The prevalence of wild, heterozygous, and homozygous C677T genotypes was 45.0%, 43.3% and 11.6%, respectively; with a carrier frequency of 54.9% and allelic frequency of 33.3%. The A1298C genotypic prevalence was 39.5%, 30.9%, and 29.6% respectively; with a carrier frequency of 60.5% and allelic frequency of 45.1%. C677T/A1289C compound heterozygosity was present in 47/233 (20.2%) of volunteers. In this first pilot study, gender, folate, vitamin B(12) and C677T mutational status could explain around 32% of homocysteine variations. Future larger studies are recommended to investigate other predictors of homocysteine variation and combine them with markers explored in this and other studies, in order to evaluate their impact on vascular and/or congenital diseases. PMID:22652272

Mahfouz, Rami A; Cortas, Najwa K; Charafeddine, Khalil M; Abdul Khalik, Rabab N; Sarieddine, Doja S; Kadi, Raneem H; Daher, Rose T

2012-08-10

199

Pharmacogenetic polymorphisms contributing to toxicity induced by methotrexate in the southern Spanish population with rheumatoid arthritis.  

PubMed

Abstract Rheumatoid arthritis (RA) is a common illness of global significance for public health. Methotrexate (MTX) is the most broadly used disease-modifying antirheumatic drug for the treatment of RA, but it displays marked person-to-person variation in its propensity for toxicity. Several studies have suggested that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC1) G80A, and ABCB1 C3435T, could be related to methotrexate toxicity. This prospective study examined the different frequencies of MTHFR, RFC1, and ABCB1 pharmacogenetic variations between patients who have RA and those without RA. We also sought to assess the association between these polymorphisms and MTX toxicity. Four single-nucleotide polymorphisms (SNPs) were genotyped: C677T and A1298C from MTHFR, G80A from RFC1, and C3435T from ABCB1. The efficacy and toxicity of MTX were evaluated through clinical follow-up during 1 year of treatment. RA patients showed a higher frequency of the T allele at MTHFR C677T than patients without RA (p=0.049). There was a significant association between the presence of both the T allele at MTHFR C677T (p=0.006), and the C allele at ABCB1 C3435T (p=0.046), with toxicity development after 12 months of MTX treatment. However, there was no correlation between MTX toxicity and either the A allele at MTHFR A1298C or the G allele at RFC1 A80G. These data suggest that the presence of the MTHFR C677T and ABCB1 C3435T SNPs contribute to MTX toxicity in patients with RA. These observations contribute to a rapidly-growing knowledge base on the pharmacogenetics of RA and personalized medicine. PMID:23095111

Plaza-Plaza, José Cristian; Aguilera, Margarita; Cañadas-Garre, Marisa; Chemello, Clarice; González-Utrilla, Alfonso; Faus Dader, María José; Calleja, Miguel Angel

2012-11-01

200

MTHFR/p53 polymorphisms as genetic factors for cervical intraepithelial neoplasia and cervical cancer in HPV-infected Mexican women.  

PubMed

We performed a case-control association study to evaluate the association between common polymorphisms in MTHFR (C677T and A1298C) and the Arg72Pro polymorphism in the p53 gene and the risk for cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC) in Mexican HPV-infected women. We included 131 women with diagnosis of CIN grade I-II and 78 with CIN III or ICC; as controls we also included 274 women with normal Pap smear and negative HPV test. Genotyping for MTHFR and p53 polymorphisms was performed by PCR-RFPLs. HPV was tested by Hybrid Capture II. Odds ratios and 95% confidence intervals were estimated. Genotype frequencies for the 3 studied polymorphisms were distributed according to the Hardy-Weinberg equilibrium. The A1298C-MTHFR polymorphism showed significant differences for the heterozygous AC genotype and the C allele, whereas the AA genotype and A allele resulted to be genetic risk factors for CIN or ICC (p<0.03). The Arg72Pro-p53 polymorphism showed for the genotypes Arg/Pro and Pro/Pro, and for the Pro allele, a significant association only to the risk for CIN (p<0.03). The MTHFR/p53 interaction showed that the genotype combinations AA/ArgArg and AA/ArgPro were associated, respectively, to the risk of ICC and CIN (p<0.05). This study suggests that the A1298C-MTHFR polymorphism contributes to the genetic risk for both CIN and ICC, whereas the Arg72Pro-p53 polymorphism only contributes to the risk for CIN. The MTHFR/p53 genetic combinations AA/ArgArg and AA/ArgPro are associated genetic risk factors for ICC and CIN in Mexican HPV-infected women. PMID:24474455

González-Herrera, Lizbeth; Rodríguez-Morales, Patricia; Gonza Lez-Losa, María Del Refugio; Pérez-Mendoza, Gerardo; Canul-Canché, Jaqueline; Rosado-López, Iván; Cetina, Thelma Canto de

2014-01-01

201

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

PubMed Central

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

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

2011-01-01

202

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

Microsoft Academic Search

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

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

2008-01-01

203

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 Central

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

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

2014-01-01

204

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

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

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

2014-11-01

205

Bilateral transverse sinus thrombosis secondary to a homozygous C677T MTHFR gene mutation.  

PubMed

We describe the case of a previously healthy young man who presented with headache, diplopia, nausea, vomiting, and bilateral papilledema. Magnetic resonance venography of the brain revealed thrombosis of the right transverse sinus. Blood tests showed elevated homocysteine levels, and coagulation studies revealed a homozygous C677T mutation and a heterozygous A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. The patient had no other etiology for venous thrombosis. We recommend screening patients who present with sinus thrombosis for MTHFR gene mutations. PMID:18666857

Kanaan, Ziad M; Mahfouz, Rami; Taher, Ali; Sawaya, Raja A

2008-09-01

206

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population  

PubMed Central

Background Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk. Methods We evaluated the role of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Results The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P < 0.01) while the A1298C polymorphism was not associated with lung cancer risk. The minor alleles of both polymorphisms behaved in a recessive fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking). Conclusions The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the MTHFR polymorphisms in lung cancer development. PMID:22024018

2011-01-01

207

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

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.

Winterholler, K.

2007-01-31

208

Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis.  

PubMed

Previous studies examining the possible role of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis was therefore designed to get a more reliable assessment. A total of 38 articles were identified through a search of electronic databases, up to 27 February 2014. Odds ratios (ORs) with 95 % confidence interval (CIs) were calculated using random effects models. Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95 % CI: 1.18-1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95 % CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR = 1.13, 95 % CI: 1.03-1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR polymorphism is associated with SZ and BPD among Asian, African populations, but not the white. PMID:24938371

Hu, Cai-Yun; Qian, Zhen-Zhong; Gong, Feng-Feng; Lu, Shan-Shan; Feng, Fang; Wu, Yi-Le; Yang, Hui-Yun; Sun, Ye-Huan

2015-02-01

209

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

PubMed

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

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

2014-02-15

210

Metabolic and genetic risk factors for migraine in children.  

PubMed

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 mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/- 2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation. PMID:16686913

Bottini, F; Celle, M E; Calevo, M G; Amato, S; Minniti, G; Montaldi, L; Di Pasquale, D; Cerone, R; Veneselli, E; Molinari, A C

2006-06-01

211

The methylenetetrahydrofolate reductase C677T polymorphism influences risk of esophageal cancer in Chinese.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism. This study with 381 esophageal cancer patients and 432 healthy controls was conducted to examine the association of MTHFR C677T and A1298C polymorphisms with susceptibility to esophageal cancer (EC) in a Chinese population. Compared with the CC genotype of MTHFR C677T, subjects carrying homozygote TT and variant genotypes (CT+TT) demonstrated reduced risk of EC with adjusted ORs (95% CI) of 0.44 (0.28-0.71) and 0.57 (0.37-0.88), respectively. However, no association was found between the MTHFR A1298C polymorphism and the risk of EC. Comparing to haplotype CA, haplotypes TA and TC could reduce the susceptibility to EC with adjusted ORs (95% CI) of 0.61(0.47-0.79) and 0.06 (0.01-0.43), respectively. In conclusion, the present study suggested that the MTHFR C677T polymorphism can markedly influence the risk of EC in Chinese. PMID:23803097

Qu, Hong-Hong; Cui, Li-Hong; Wang, Ke; Wang, Peng; Song, Chun-Hua; Wang, Kai-Juan; Zhang, Jian-Ying; Dai, Li-Ping

2013-01-01

212

Methylenetetrahydrofolate reductase gene polymorphisms and skin cancer risk: a meta-analysis.  

PubMed

We sought to determine whether the methylenetetrahydrofolate reductase (MTHFR) A1298C and C677T polymorphisms are associated with increased skin cancer risk. We performed literature searches of the PubMed, BIOSIS Previews, and Web of Science databases to identify eligible articles published through September 15, 2013. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Publication bias and subgroup analyses were also performed. Eight articles, which consisted of 10,066 subjects (2,672 patients and 7,394 controls), were included in the meta-analysis. Homozygous MTHFR 1298C individuals were 1.29 times more likely to develop skin cancer (95% CI, 1.04-1.61) compared with A1298C allele (AA or AC) carriers. There was an increased risk for C allele homozygotes compared with the 1,298 AA+AC carriers (OR, 1.45; 95% CI, 1.08-1.96) when restricted to basal cell carcinomas (BCC). The 1298C homozygote carriers increased the odds of BCC by 1.47 times (95% CI, 1.07-2.01) compared with those who were 1298A homozygote carriers. ORs for all genetic models yielded a null association. The data obtained from this meta-analysis suggest that the MTHFR 1298C allele is associated with increased skin cancer risk, particularly BCC; however, no association was observed between the MTHFR C677T polymorphism and skin cancer. PMID:25306137

Deng, Feng; Gao, Ying; L V, Ju-Hong; Gao, Jian-Min

2014-01-01

213

DNA methylation and sensitivity to antimetabolites in cancer cell lines.  

PubMed

The prediction of the cellular direction of metabolic pathways toward either DNA synthesis or DNA methylation is crucial for determining the susceptibility of cancers to anti-metabolites such as fluorouracil (5-FU). We genotyped the methylenetetrahydrofolate reductase (MTHFR) gene in NCI-60 cancer cell lines, and identified the methylation status of 24 tumor suppressor genes using methylation-specific multiplex ligation-dependent probe amplification. The susceptibility of the cancer cell lines to seven antimetabolites was then determined. Cells homozygous for CC at MTHFR-A1298C were significantly more sensitive to cyclocytidine, cytarabine (AraC) and floxuridine than those with AA or AC (p=0.0215, p=0.0166, and p=0.0323, respectively), and carried more methylated tumor suppressor genes (p=0.0313). Among the 12 tumor suppressor genes which were methylated in >25% of cancer cell lines, the methylation status of TIMP3, APC and IGSF4 significantly correlated with sensitivity to pyrimidine synthesis inhibitors. In particular, cells with methylated TIMP3 had reduced mRNA levels and were significantly more sensitive to aphidicolin-glycinate, AraC and 5-FU than cells with unmethylated TIMP3. We speculate that MTHFR-A1298C homozygous CC might direct the methylation rather than the synthesis of DNA, and result in the methylation of several tumor suppressor genes such as TIMP3. These genes could be useful biological markers for predicting the efficacy of antimetabolites. PMID:18202788

Sasaki, Shin; Kobunai, Takashi; Kitayama, Joji; Nagawa, Hirokazu

2008-02-01

214

Etiopathogenesis of Sheehan's Syndrome: Roles of Coagulation Factors and TNF-Alpha  

PubMed Central

Sheehan's Syndrome (SS) is defined as pituitary hormone deficiency due to ischemic infarction of the pituitary gland as a result of massive postpartum uterine hemorrhage. Herein, we aimed to investigate the roles of Factor II (G20210A), Factor V (G1691A), MTHFR (C677T and A1298C), PAI-1 4G/5G, and TNF-? (?308??G > A) gene polymorphisms in the etiopathogenesis of SS. Venous blood samples were obtained from 53 cases with SS and 43 healthy women. Standard methods were used to extract the genomic DNAs. Factor II (G20210A), Factor V (G1691A), and MTHFR (C677T and A1298C) polymorphisms were identified by real-time PCR. PAI-1 4G/5G and TNF-? (?308??G > A) gene polymorphisms were detected with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. According to statistical analysis, none of the polymorphisms were found to be significantly higher in the SS group compared to the control group. Hence, we suggest that genetic factors other than Factor II, Factor V, MTHFR, PAI-1, and TNF-? gene polymorphisms should be researched in the etiopathogenesis of SS. PMID:24891849

Bayram, Fahri; Tascioglu, Nazife; Simsek, Yasin; Dundar, Munis

2014-01-01

215

Association of C677T transition of the human methylenetetrahydrofolate reductase (MTHFR) gene with male infertility.  

PubMed

The human methylenetetrahydrofolate reductase (MTHFR) gene encodes one of the key enzymes in folate metabolism. This gene is located on chromosome 1 (1p36.3), which has 12 exons. The aim of the present study was to investigate the possible association of the two (C677T and A1298C) polymorphisms of this gene with male infertility. In a case-control study, 250 blood samples were collected from IVF centres in Sari and Babol (Iran): 118 samples were from oligospermic men and 132 were from controls. Two single nucleotide polymorphisms of the MTHFR genotype were detected using polymerase chain reaction-restriction fragment length polymorphism. There was no association found between the A1298C variant and male infertility. However, carriers of the 677T allele (CT and TT genotypes) were at a higher risk of infertility than individuals with other genotypes (odds ratio 1.84; 95% confidence interval 1.11-3.04; P=0.0174). Structural analysis of human MTHFR flavoprotein showed that C677T transition played an important role in the change in affinity of the MTHFR-Flavin adenine dinucleotide binding site. Based on our results, we suggest that C677T transition in MTHFR may increase the risk of male infertility, and detection of the C677T polymorphism biomarker may be helpful in the screening of idiopathic male infertility. PMID:25412139

Karimian, Mohammad; Colagar, Abasalt Hosseinzadeh

2014-11-21

216

[Association between methylene-tetrahydrofolate reductase gene polymorphisms and chronic myeloid leukemia].  

PubMed

Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolism. Few studies were reported about its relationship with chronic myeloid leukemia (CML). We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T and MTHFR A1298C in Algerians CML patients. Using TaqMan(®) allelic discrimination assay, we investigate MTHFR C677T and A1298C polymorphism distribution in 90 cases of CML and 100 healthy subjects. The frequencies of 677T alleles and genotypes 677TT and 677CT were significantly higher in cases than in control (P?=?1E-6; OR?=?6.77 [4.22-10.86]) and (P?=?1E-6; OR?=?10.38 [4.56-23.6]) respectively. Also, the frequencies of 1298C alleles and genotypes 1298CC and 1298AC were higher in cases (P?=?9 E-6; OR?=?2.65 [1.71-4.10]) and (P?=?0.008; OR?=?2.22 [1.21-4.06]) respectively. We report also the higher significance of the haplotype 677T/1298A and 677T/1298C in cases (P?=?0.007; OR?=?2.57 [1.26-5.24]) and (P?=?5 E-6, OR?=?6.91 [2.7646-17.2899]) respectively. Our results demonstrate that 677T and 1298C alleles are both associated with an increased risk of CML in Algeria. PMID:25036376

Dorgham, Samia; Aberkane, Meriem; Boughrara, Wefa; Antar Soltan, Badra; Mehalhal, Nemra; Touhami, Hadj; Sidimansour, Noureddine; Merad Boudia, Nadia; Louhibi, Lotfi; Boudjema, Abdallah

2014-09-01

217

Genetic Background of Nontraumatic Osteonecrosis of the Femoral Head in the Korean Population  

PubMed Central

Major thrombophilic mutations have been identified as risk factors for nontraumatic osteonecrosis of the femoral head (ONFH) in Caucasians. We asked whether the genetic background of patients with ONFH in the Korean population was similar. We analyzed factor V G1691A mutation (factor V Leiden), prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in 71 patients (53 men, 18 women) with ONFH. We classified these patients as 51 alcohol-induced, 18 idiopathic, one steroid-induced, and one dysbaric. We recruited 200 normal control subjects (128 men, 72 women). We used multiplex PCR/restriction fragment length polymorphism for each genotyping. We observed neither factor V Leiden nor prothrombin G20210A mutation. Although methylenetetrahydrofolate reductase A1298C genotypes were not associated with osteonecrosis, methylenetetrahydrofolate reductase C677T variant genotypes increased the risk of ONFH compared with 677CC. Odds ratios of 677CT and 677CT+TT were 2.00 (95% confidence interval, 1.05–3.81) and 1.96 (95% confidence interval, 1.07–3.59), respectively, compared with 677CC. Our data suggest methylenetetrahydrofolate reductase C677T polymorphism plays a role in the pathogenesis of osteonecrosis in the Korean population. It also implies the genetic risk profile of ONFH may differ among ethnic populations. Level of Evidence: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18350352

Chang, Jun-Dong; Lee, Sang-Soo; Yoo, Je-Hyun; Lee, Kyu Man

2008-01-01

218

Associations between Intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans  

PubMed Central

Prostate cancer (PC) is the second leading cause of cancer death in men. Recent reports suggest that excess of nutrients involved in the one-carbon metabolism pathway increases PC risk; however, empirical data are lacking. Veteran American men (272 controls and 144 PC cases) who attended the Durham Veteran American Medical Center between 2004–2009 were enrolled into a case-control study. Intake of folate, vitamin B12, B6, and methionine were measured using a food frequency questionnaire. Regression models were used to evaluate the association among one-carbon cycle nutrients, MTHFR genetic variants, and prostate cancer. Higher dietary methionine intake was associated with PC risk (OR = 2.1; 95%CI 1.1–3.9) The risk was most pronounced in men with Gleason sum <7 (OR = 2.75; 95%CI 1.32– 5.73). The association of higher methionine intake and PC risk was only apparent in men who carried at least one MTHFR A1298C allele (OR = 6.7; 95%CI = 1.6–27.8), compared to MTHFR A1298A noncarrier men (OR = 0.9; 95%CI = 0.24–3.92) (p-interaction = 0.045). There was no evidence for associations between B vitamins (folate, B12, and B6) and PC risk. Our results suggest that carrying the MTHFR A1298C variants modifies the association between high methionine intake and PC risk. Larger studies are required to validate these findings. PMID:22927849

Vidal, Adriana C.; Grant, Delores J.; Williams, Christina D.; Masko, Elizabeth; Allott, Emma H.; Shuler, Kathryn; McPhail, Megan; Gaines, Alexis; Calloway, Elizabeth; Gerber, Leah; Chi, Jen-Tsan; Freedland, Stephen J.; Hoyo, Cathrine

2012-01-01

219

MTHFR 677CC/1298CC genotypes are highly associated with chronic myelogenous leukemia: a case-control study in Korea.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in acute lymphoblastic leukemia (ALL). We evaluated the C677T and A1298C polymorphisms using the TaqMan allelic discrimination assay in various malignancies. The study population included 115 subjects with chronic myelogenous leukemia (CML), 200 with acute myelogenous leukemia (AML), 196 with multiple myeloma (MM) and 434 healthy control subjects. The frequency of 1298CC was statistically significantly higher in subjects with CML than that of the controls (OR=5.12, 95% CI: 1.75-14.9, P-value=.003). Of note, the frequencies of 677CC/1298CC genotype were statistically significantly higher in subjects with CML, AML and MM than that of the controls (OR=8.8, 3.5, 3.83, P-value=.002, 0.036, 0.023, respectively). Our results demonstrate that the MTHFR 1298CC homozygote variant is strongly associated with an increased risk of CML, while MTHFR C677T does not significantly affect the risk of CML. Moreover, we demonstrated that MTHFR 677CC and 1298CC genotype might have combined effect on risk of CML, AML and MM and it is inferred that the A1298C may play a different role in carcinogenesis, depending on the types of organs involved, the types of disease entities and the genotype of C677T. PMID:17156840

Moon, Hee Won; Kim, Tae Young; Oh, Bo Ra; Min, Hyun Chung; Cho, Han Ik; Bang, Soo Mee; Lee, Jae Hoon; Yoon, Sung Soo; Lee, Dong Soon

2007-09-01

220

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

PubMed Central

The mineral-respiring bacterium Shewanella oneidensis uses a protein complex, MtrCAB, composed of two decaheme cytochromes, MtrC and MtrA, brought together inside a transmembrane porin, MtrB, to transport electrons across the outer membrane to a variety of mineral-based electron acceptors. A proteoliposome system containing a pool of internalized electron carriers was 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, the established in vivo orientation, electron transfer from the interior electron carrier pool through MtrCAB to solid-phase Fe(III) oxides was demonstrated. The rates were 103 times higher than those reported for reduction of goethite, hematite, and lepidocrocite by S. oneidensis, and the order of the reaction rates was consistent with those observed in S. oneidensis cultures. In contrast, established rates for single turnover reactions between purified MtrC and Fe(III) oxides were 103 times lower. By providing a continuous flow of electrons, the proteoliposome experiments demonstrate that conduction through MtrCAB directly to Fe(III) oxides is sufficient to support in vivo, anaerobic, solid-phase iron respiration. PMID:23538304

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

2013-01-01

221

Characterization of an electron conduit between bacteria and the extracellular environment  

SciTech Connect

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

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

222

[Right atrial thrombus: a rare presentation of plasminogen activator inhibitor deficiency].  

PubMed

Free-floating right atrial thrombi are rare but associated with high mortality. Although advances in echocardiography have improved diagnosis, their management is still the subject of debate. A 24-year-old woman with a history of smoking, obesity and oral contraceptive use presented to the emergency department with dyspnea, cough and hemoptysis. Transthoracic echocardiography revealed a large free-floating cardiac mass occupying the right atrial chamber and restricting tricuspid valve opening. In view of recurrent pulmonary embolism, she was referred for cardiac surgery and the cardiac mass was excised. Anatomopathological analysis revealed an organized and calcified thrombus. Genetic study showed her to be homozygous for the 4G/4G allelic variant of plasminogen activator inhibitor-1 and heterozygous for the allelic variant A1298C of 5,10-methylenetetrahydrofolate reductase. PMID:22230099

Cordeiro Piçarra, Bruno; Santos, Ana Rita; Dionísio, Pedro; Vasconcelos, João; Banazol, Nuno; Lourenço, Sílvia; Caetano, Fátima; Jara, António

2012-02-01

223

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

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

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

2014-03-01

224

MTHFR polymorphisms' influence on outcome and toxicity in acute lymphoblastic leukemia patients.  

PubMed

Recently the influence of polymorphisms of different genes involved in metabolism of chemoterapic agents have been studied especially in childhood acute lymphoblastic leukemia (ALL). We evaluated the influence of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms on time to relapse and survival and on methotrexate (MTX) toxicity in 82 ALL adult patients. Relapse free survival and event free survival between homozygous wild-type and variant patients in both polymorphisms were not significantly different. However, we observed an association between 677TT variant and survival in a subset of ALL patients homogenously treated with MTX-based maintenance (p=0.02). In the same subgroup we confirmed the role of 677TT variant on toxicity during MTX treatment (p=0.003). PMID:17512587

Chiusolo, Patrizia; Reddiconto, Giovanni; Farina, Giuliana; Mannocci, Alice; Fiorini, Alessia; Palladino, Mariangela; La Torre, Giuseppe; Fianchi, Luana; Sorà, Federica; Laurenti, Luca; Leone, Giuseppe; Sica, Simona

2007-12-01

225

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

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

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

2014-01-01

226

Methylenetetrahydrofolate reductase (MTHFR) genetic variation and major depressive disorder prognosis: A five-year prospective cohort study of primary care attendees.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) genetic variation has been associated with the diagnosis of major depressive disorder (MDD) but no study to date has examined the effect MTHFR variation has on MDD prognosis. We sought to examine the prospective effects of two common MTHFR variants (C677T and A1298C) as well as seven haplotype-tagging single nucleotide polymorphisms (htSNPs) on MDD prognosis over a 5-year (60-month) period. Participants were 147 depressed primary care attendees enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) prospective cohort study. Prognosis of MDD was measured using three methods: (1) DSM-IV criteria, (2) Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9), and (3) Center for Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria for MDD was assessed using the Composite International Diagnostic Interview at baseline and 24, 36, 48, and 60 months post-baseline; whereas, PHQ-9 and CESD measures were employed at baseline and 12, 24, 36, 48, and 60 months post-baseline. Repeated measures analysis of variance showed that PHQ-9 symptom severity trajectories differed by C677T genotype (F?=?3.34, df?=?2,144, P?=?0.038), with 677CC genotype showing the most severe symptom severity course over the 60 months of observation. Neither the A1298C polymorphism nor any of the htSNPs were associated with MDD prognosis regardless of measure used. Our results suggest that the MTHFR C677T polymorphism may serve as a marker for MDD prognosis pending independent replication. PMID:24123968

Bousman, Chad A; Potiriadis, Maria; Everall, Ian P; Gunn, Jane M

2014-01-01

227

Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one-carbon metabolism for DNA synthesis and methylation, both are implicated in carcinogenesis. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate cancer-predisposing factor. To evaluate the C677T and A1298C functional polymorphisms in the MTHFR gene and their associations with breast cancer risk, as well as the potential modifying effect by plasma folate status on the MTHFR-associated risk, a hospital-based case-control study was conducted on a Taiwanese population consisting of 146 histologically confirmed incident breast cancer cases and their 285 age-matched controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping and RIA was used to measure the plasma folate. Statistical evaluations were performed using logistic regression analysis. The plasma folate level was inversely associated with breast cancer risk with an adjusted odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.26-1.05] observed among women who were in the highest plasma folate tertile. The MTHFR 677T and 1298C variant alleles were associated with decreased risk for breast cancer [adjusted ORs were 0.81 (95% CI: 0.54-1.21) and 0.57 (95% CI: 0.36-0.89) for 677CT + TT genotypes and 1298AC + CC genotypes, respectively]. Furthermore, compound heterozygote and homozygote variants (677CT + TT and 1298AC + CC) had greater reduced risk (adjusted OR: 0.11, 95% CI: 0.03-0.43) among women with lower plasma folate levels. These results provide support for the important role of folate metabolism in breast tumorigenesis. Further mechanistic studies are warranted to investigate how MTHFR combined genotypes exert their effect on cancer susceptibility. PMID:16777985

Chou, Yu-Ching; Wu, Mei-Hsuan; Yu, Jyh-Cherng; Lee, Meei-Shyuan; Yang, Tsan; Shih, Hsiu-Lan; Wu, Tsai-Yi; Sun, Chien-An

2006-11-01

228

Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR)?= 1.42, 95% confidence interval (CI): 1.09-1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09-2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08-3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12-2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02-2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56-0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism. PMID:23653228

Pu, Danhua; Shen, Yiping; Wu, Jie

2013-10-01

229

Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review.  

PubMed

The authors performed a meta-analysis of studies examining the association between polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, including MTHFR C677T and A1298C, and common psychiatric disorders, including unipolar depression, anxiety disorders, bipolar disorder, and schizophrenia. The primary comparison was between homozygote variants and the wild type for MTHFR C677T and A1298C. For unipolar depression and the MTHFR C677T polymorphism, the fixed-effects odds ratio for homozygote variants (TT) versus the wild type (CC) was 1.36 (95% confidence interval (CI): 1.11, 1.67), with no residual between-study heterogeneity (I(2) = 0%)--based on 1,280 cases and 10,429 controls. For schizophrenia and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.44 (95% CI: 1.21, 1.70), with low heterogeneity (I(2) = 42%)--based on 2,762 cases and 3,363 controls. For bipolar disorder and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.82 (95% CI: 1.22, 2.70), with low heterogeneity (I(2) = 42%)-based on 550 cases and 1,098 controls. These results were robust to various sensitively analyses. This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention. PMID:17074966

Gilbody, Simon; Lewis, Sarah; Lightfoot, Tracy

2007-01-01

230

MTHFR polymorphic variant C677T is associated to vascular complications in sickle-cell disease.  

PubMed

Vaso-occlusion is a determinant for most signs and symptoms of sickle-cell anemia (SCA). The mechanisms involved in the pathogenesis of vascular complications in SCA remain unclear. It is known that genetic polymorphisms associated with thrombophilia may be potential modifiers of clinical features of SCA. The genetic polymorphisms C677T and A1298C relating to the enzyme methylenetetrahydrofolate reductase (MTHFR), a clotting Factor V Leiden mutation (1691G?A substitution of Factor V Leiden), and the mutant prothrombin 20210A allele were analyzed in this study. The aim was to find possible correlations with vascular complications and thrombophilia markers in a group of SCA patients in Pernambuco, Brazil. The study included 277 SCA patients, divided into two groups: one consisting of 177 nonconsanguineous SCA patients who presented vascular manifestations of stroke, avascular necrosis, leg ulcers, priapism, and acute chest syndrome (group 1); and the other consisting of 100 SCA patients without any reported vascular complication (group 2). Molecular tests were done using either polymerase chain reaction (PCR) restriction fragment length polymorphism or allele-specific PCR techniques. Comparisons between the groups were made using the ?(2) test. The 677 CT and TT genotypes showed a significant risk of vascular complications (p=0.015). No significant associations between the groups were found when samples were analyzed for the MTHFR A1298C allele (p=0.913), Factor V G1691 (p=0.555), or prothrombin G20210A mutation (p=1.000). The polymorphism MTHFR C677T seemed to be possibly predictive for the development of some vascular complications in SCA patients among this population. PMID:22924497

Hatzlhofer, Betânia L D; Bezerra, Marcos André C; Santos, Magnun N N; Albuquerque, Dulcinéia M; Freitas, Elizabete M; Costa, Fernando F; Araújo, Aderson S; Muniz, Maria Tereza C

2012-09-01

231

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

PubMed

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 (ORTvsC =1.20; 95 % CI?=?1.13-1.28) and MTRR A66G polymorphism (ORGvsA?=?1.21; 95 % CI?=?0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (ORCvsA?=?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 (ORTvsC?=?1.43; 95 % CI: 1.05-1.94), European (ORTvsC?=?1.13; 95 % CI: 1.04-1.24) and American (ORTvsC?=?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

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

2015-02-01

232

Meta-analysis of Methylenetetrahydrofolate reductase maternal gene in Down syndrome: increased susceptibility in women carriers of the MTHFR 677T allele.  

PubMed

Because a number of data studies include some controversial results about Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Down syndrome (DS), we performed a meta-analysis to determine a more precise estimation of this association. Studies were searched on PubMed, EMBASE and Lilacs-Scielo, up to April 2013, and they were eligible if they included case mothers (DSM) that have gave birth to children with DS, and controls mothers (CM) that have gave birth to healthy children without chromosomal abnormality, syndrome or malformation. The combined odds ratio with 95% confidence intervals was calculated by fixed or random effects models to assess the strength of associations. Potential sources of heterogeneity between studies were evaluated using Q test and the I(2). Publication bias was estimated using Begg's test and Egger's linear regression test. Sensitivity analyses were performed by using allelic, dominant, recessive and codominant genetic models, Hardy-Weinberg equilibrium (HWE) and ethnicity. Twenty-two studies with 2,223 DSM and 2,807 CM were included for MTHFR C677T and 15 studies with 1,601 DSM and 1,849 CM were included for MTHFR A1298C. Overall analysis suggests an association of the MTHFR C677T polymorphism with maternal risk for DS. Moreover, no association between the MTHFR A1298C polymorphism and maternal risk for DS was found. There is also evidence of higher heterogeneity, with I(2) test values ranging from 8 to 89%. No evidence of publication bias was found. Taken together, our meta-analysis implied that the T allele carriers might carry an increased maternal risk for DS. PMID:24913031

Victorino, D B; Godoy, M F; Goloni-Bertollo, E M; Pavarino, E C

2014-08-01

233

Genetic polymorphisms of methylenetetrahydrofolate reductase and promoter methylation of MGMT and FHIT genes in diffuse large B cell lymphoma risk in Middle East.  

PubMed

Diffuse large B cell lymphoma (DLBCL) is one of the most common non-Hodgkin's lymphoma types. Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one carbon metabolism of deoxyribonucleic acid (DNA) synthesis and methylation; both are implicated in carcinogenesis of many types of cancer including lymphoma. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate as a cancer-predisposing factor. The O6 methylguanine DNA methyltransferase (MGMT) and fragile histidine triad (FHIT) genes are transcriptionally silenced by promoter hypermethylation in DLBCL. These genetic differences are highly race specific and have never been screened in the Saudi DLBCL patients. We conducted a hospital-based case-control study including 160 DLBCL cases and 511 Saudi control samples analyzing the MTHFR C677T and A1298C functional polymorphisms by the restriction fragment length polymorphism method and their association with MGMT and FHIT genes promoter hypermethylation. Our data demonstrated that Saudi individuals carrying MTHFR genotype 1298CC (p < 0.001) and the 1298C allele (p = 0.012) had 4.23 and 1.73-fold higher risk of developing DLBCL, respectively. Additionally, combined genotype CCCC (MTHFR 677CC + MTHFR 1298CC) was associated with 3.489-fold, and CTCC (MTHFR 677 CT + 1298CC) was related to 9.515-fold higher risk, compared with full MTHFR enzyme activity. No significant association between MTHFR variant genotypes and methylation of MGMT and FHIT genes were observed. Our findings suggested that polymorphisms of MTHFR enzyme genes might be associated with the individual susceptibility to develop DLBCL. Additionally, the results indicated that MTHFR variants were not related to MGMT or FHIT hypermethylation in DLBCL. PMID:17712558

Siraj, Abdul K; Ibrahim, Muna; Al-Rasheed, Maha; Bu, Rong; Bavi, Prashant; Jehan, Zeenath; Abubaker, Jehad; Murad, Walid; Al-Dayel, Fouad; Ezzat, Adnan; El-Solh, Hassan; Uddin, Shahab; Al-Kuraya, Khawla

2007-12-01

234

Molecular cloning, pharmacological characterization, and histochemical distribution of frog vasotocin and mesotocin receptors  

Microsoft Academic Search

The neurohypophysial nonapeptides vasotocin (VT) and mesotocin (MT) are the amphibian counterparts of arginine vasopressin (AVP) and oxytocin (OT). We have here reported the cloning and functional characterization of the receptors for vasotocin (VTR) and mesotocin (MTR) in two species of frog, Rana catesbeiana and Rana esculenta. The frog VTR and MTR cDNAs encode proteins of 419 and 384 amino

S Acharjee; J-L Do-Rego; D Y Oh; R S Ahn; K Lee; D G Bai; H Vaudry; H B Kwon; J Y Seong

2004-01-01

235

Export of detritus and invertebrate from headwater streams: linking mountaintop removal and valley fill coal mining to downstream receiving waters  

EPA Science Inventory

Mountaintop removal and valley fill (MTR/VF) coal mining has resulted in large scale alteration of the topography, reduced forest productivity, and burial of headwater streams in the U.S. Central Appalachians. Although MTR/VF coal mining has occurred for several decades and the ...

236

Central Learning Centre Tsimshatsui East Ocean  

E-print Network

#12;* Date* Central Learning Centre Tsimshatsui East Ocean Learning Centre Tseung Kwan O Station Exit J3 or Admiralty MTR Station Exit B) 981 D1 Tsimshatsui East Ocean Learning Centre Basement 1, East Ocean Centre, 98 Granville Road, Tsim Sha Tsui (Hung Hom MTR Station Exit D1) C15M17M 17 Tseung

Huang, Jianwei

237

Ultrasonic Characterization of the Upper Trapezius Muscle in Patients with Chronic Neck Pain  

PubMed Central

Myofascial trigger points (MTrPs) are palpable, tender nodules in taut bands of skeletal muscle that are painful on compression. MTrPs are characteristic findings in myofascial pain syndrome (MPS). The role of MTrPs in the pathophysiology of MPS is unknown. Localization, diagnosis, and clinical outcome measures of painful MTrPs can be improved by objectively characterizing and quantitatively measuring their properties. The goal of this study was to evaluate whether ultrasound imaging and elastography can differentiate symptomatic (active) MTrPs from normal muscle. Patients with chronic (>3 months) neck pain with spontaneously painful, palpable (i.e., active) MTrPs and healthy volunteers without spontaneous pain (having palpably normal muscle tissue) were recruited for this study. The upper trapezius muscles in all subjects were imaged, and the echotexture was analyzed using entropy filtering of B-mode images. Vibration elastography was performed by vibrating the muscle externally at 100 Hz. Color Doppler variance imaging was used to quantify the regions of color deficit exhibiting low vibration amplitude. The imaging measures were compared against the clinical findings of a standardized physical exam. We found that sites with active MTrPs (n = 14) have significantly lower entropy (p < 0.05) and significantly larger nonvibrating regions (p < 0.05) during vibration elastography compared with normal, uninvolved muscle (n = 15). A combination of both entropy analysis and vibration elastography yielded 69% sensitivity and 81% specificity in discriminating active MTrPs from normal muscle. These results suggest that active MTrPs have more homogeneous texture and heterogeneous stiffness when compared with normal, unaffected muscle. Our methods enabled us to improve the imaging contrast between suspected MTrPs and surrounding muscle. Our results indicate that in subjects with chronic neck pain and active MTrPs, the abnormalities are not confined to discrete isolated nodules but instead affect the milieu of the muscle surrounding palpable MTrPs. With further refinement, ultrasound imaging can be a promising objective method for characterizing soft tissue abnormalities associated with active MTrPs and elucidating the role of MTrPs in the pathophysiology of MPS. PMID:23493615

Turo, Diego; Otto, Paul; Shah, Jay P.; Heimur, Juliana; Gebreab, Tadesse; Zaazhoa, Maryam; Armstrong, Katherine; Gerber, Lynn H.; Sikdar, Siddhartha

2015-01-01

238

Multiple Sclerosis Normal-Appearing White Matter: Pathology-Imaging Correlations  

PubMed Central

Objective To determine the pathologic basis of subtle abnormalities in magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) parameters observed in normal-appearing white matter (NAWM) in multiple sclerosis (MS) brains. Methods Brain tissues were obtained through a rapid post-mortem protocol that included in situ MRI. Four types of MRI-defined regions of interest (ROIs) were analyzed: (1) Regions that were abnormal on all images (“T2T1MTR lesions”); (2) NAWM regions with slightly-abnormal MTR located close to white matter lesions (“sa-WM Close”); (3) NAWM regions with slightly-abnormal MTR located far from lesions (“sa-WM Far”); and (4) NAWM regions with normal MTR (“NAWM”). Immunohistochemical analysis for each ROI comprised immunostaining for myelin, axonal markers, activated microglia/macrophages, astrocytes, plasma proteins and blood vessels. Results Forty-eight ROIs from four secondary progressive MS brains were analyzed. Sa-WM Close ROIs were associated with significantly more axonal swellings. There were more enlarged MHCII(+) microglia and macrophages detected in sa-WM Far, sa-WM Close, and T2T1MTR lesions than in NAWM. Across all ROIs, MTR and DTI measures were moderately correlated with myelin density, axonal area and axonal counts. Excluding T2T1MTR lesions from analysis revealed that MTR and DTI measures in non-lesional WM were correlated with activated microglia, but not with axonal or myelin integrity. Interpretation The pathologic substrates for MRI abnormalities in NAWM vary based on distance from focal WM lesions. Close to WM lesions, axonal pathology and microglial activation may explain subtle MRI changes. Distant from lesions, microglial activation associated with proximity to cortical lesions might underlie MRI abnormalities. PMID:22162059

Moll, Natalia M.; Rietsch, Anna M.; Thomas, Smitha; Ransohoff, Amy J.; Lee, Jar-Chi; Fox, Robert; Chang, Ansi; Ransohoff, Richard M.; Fisher, Elizabeth

2011-01-01

239

PTRM Class 2008 Inefficient mRNA/mRNP reactions are challenged by  

E-print Network

, Mft1p, Tho2p, Thp1p) TRAMP (Trf4p, Air2p, Mtr4p) DAPI stains DNA Rrp6p: exosome component exonuclease, Mtr4p) Rrp47p: exosome component interacts with Rrp6p TET-Off #12;6 The entire TRAMP complex operates in mRNA surveillance THO (Hpr1p, Mft1p, Tho2p, Thp1p) TRAMP (Trf4p, Air2p, Mtr4p) Rrp47p: exosome

Bedwell, David M.

240

Importance of Multidrug Efflux Pumps in the Antimicrobial Resistance Property of Clinical Multidrug-Resistant Isolates of Neisseria gonorrhoeae  

PubMed Central

The contribution of drug efflux pumps in clinical isolates of Neisseria gonorrhoeae that express extensively drug-resistant or multidrug-resistant phenotypes has heretofore not been examined. Accordingly, we assessed the effect on antimicrobial resistance of loss of the three gonococcal efflux pumps associated with a known capacity to export antimicrobials (MtrC-MtrD-MtrE, MacA-MacB, and NorM) in such clinical isolates. We report that the MIC of several antimicrobials, including seven previously and currently recommended for treatment was significantly impacted. PMID:24733458

Golparian, Daniel; Shafer, William M.; Ohnishi, Makoto

2014-01-01

241

Estimating benthic secondary production from aquatic insect emergence in streams affected by mountaintop removal coal mining, West Virginia USA  

EPA Science Inventory

Mountaintop removal and valley fill (MTR/VF) coal mining recountours the Appalachian landscape, buries headwater stream channels, and degrades downstream water quality. The goal of this study was to compare benthic community production estimates, based on seasonal insect emergen...

242

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

SciTech Connect

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.

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

2012-02-15

243

Sediment and epilithon metabolism and hydrolytic activity in streams affected by mountaintop removal coal mining, West Virginia, U.S.A.  

EPA Science Inventory

Mountaintop removal and valley filling (MTR/VF) is a method of coal mining used in the Central Appalachians. Despite regulations requiring that potential mpacts to stream function be considered in determining compensatory mitigation associated with permitted fill activities, asse...

244

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

SciTech Connect

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.

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

2007-01-01

245

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

Microsoft Academic Search

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-

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

2008-01-01

246

The Shortest Telomere, Not Average Telomere Length, Is Critical for Cell Viability and Chromosome Stability  

Microsoft Academic Search

Loss of telomere function can induce cell cycle arrest and apoptosis. To investigate the processes that trigger cellular responses to telomere dysfunction, we crossed mTR?\\/? G6 mice that have short telomeres with mice heterozygous for telomerase (mTR+\\/?) that have long telomeres. The phenotype of the telomerase null offspring was similar to that of the late generation parent, although only half

Michael T Hemann; Margaret A Strong; Ling-Yang Hao; Carol W Greider

2001-01-01

247

Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA  

Microsoft Academic Search

To examine the role of telomerase in normal and neoplastic growth, the telomerase RNA component (mTR) was deleted from the mouse germline. mTR?\\/? mice lacked detectable telomerase activity yet were viable for the six generations analyzed. Telomerase-deficient cells could be immortalized in culture, transformed by viral oncogenes, and generated tumors in nude mice following transformation. Telomeres were shown to shorten

Maria A. Blasco; Han-Woong Lee; M. Prakash Hande; Enrique Samper; Peter M. Lansdorp; Ronald A. DePinho; Carol W. Greider

1997-01-01

248

ETR COMPLEX. CAMERA FACING SOUTH. FROM BOTTOM OF VIEW TO ...  

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

ETR COMPLEX. CAMERA FACING SOUTH. FROM BOTTOM OF VIEW TO TOP: MTR, MTR SERVICE BUILDING, ETR CRITICAL FACILITY, ETR CONTROL BUILDING (ATTACHED TO ETR), ETR BUILDING (HIGH-BAY), COMPRESSOR BUILDING (ATTACHED AT LEFT OF ETR), HEAT EXCHANGER BUILDING (JUST BEYOND COMPRESSOR BUILDING), COOLING TOWER PUMP HOUSE, COOLING TOWER. OTHER BUILDINGS ARE CONTRACTORS' CONSTRUCTION BUILDINGS. INL NEGATIVE NO. 56-4105. Unknown Photographer, ca. 1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

249

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

NASA Astrophysics Data System (ADS)

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 the International Space Station (MTR Phase 2A). It consists of a human phantom, a Base Structure and a Carbon fibre container - simulating the astronaut‘s space suit. The phantom itself is made up of 33 slices composed of natural bones, embedded in tissue equivalent plastic of different density for tissue and lung. The Phantom slices are equipped with channels and cut-outs to allow the accommodation of active and passive dosemeters, temperature and pressure sensors. Over 4800 passive detectors (thermoluminescence detectors (TLDs) and plastic nuclear track detectors) constitute the radiation experiments which are beside inside the phantom also located on top the head of the phantom, in front of the belly and around the body as part of a Poncho and a Hood. In its 1st exposure phase (MTR 1: 2004 - 2005) MTR measured the depth dose distribution of an astronaut performing an EVA - mounted outside the Zvezda Module. In its 2nd exposure phase the phantom was positioned inside the ISS to monitor the radiation environment and measure the depth dose distribution in dependence on the inside shielding configurations. The majority of the TLDs provided for the determination of the depth dose distribution was provided by IFJ-PAN, ATI and DLR. Data of "combined" depth dose distribution of the three different groups will be shown for the MTR-1 exposure (outside the ISS) and the MTR-2A (inside the ISS). The discussion will focus on the difference in depth dose as well as skin dose distribution based on the different shielding thickness provided by the two experimental phases.

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

250

Rate 16\\/17 maximum transition run (3;11) code on an EEPRML channel with an error-correcting postprocessor  

Microsoft Academic Search

A rate 16\\/17 maximum transition run (MTR) (3;11) code on an EEPRML channel with a postprocessor (turbo-EEPRML) has been developed. The postprocessor compensates for the degradation in performance due to noise correlation. The proposed method has high performance and simple circuitry. Simulation results showed that the rate 16\\/17 MTR (3;11) code on a turbo-EEPRML channel has a performance gain of

Takushi Nishiya; Kyoko Tsukano; Tatsuya Hirai; Seiichi Mita; Takashi Nara

1999-01-01

251

REACTOR SERVICE BUILDING, TRA635, INTERIOR. CAMERA FACES NORTHWEST TOWARDS INTERIOR ...  

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

REACTOR SERVICE BUILDING, TRA-635, INTERIOR. CAMERA FACES NORTHWEST TOWARDS INTERIOR WALL ENCLOSING STORAGE AND OFFICE SPACE ALONG THE WEST SIDE. AT RIGHT EDGE IS DOOR TO MTR BUILDING. FROM RIGHT TO LEFT, SPACE WAS PLANNED FOR A LOCKER ROOM, MTR ISSUE ROOM, AND STORAGE AREAS AND RELATED OFFICES. NOTE SECOND "MEZZANINE" FLOOR ABOVE. INL NEGATIVE NO. 10227. Unknown Photographer, 3/23/1954 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

252

Development of a Proteoliposome Model to Probe Transmembrane Electron-Transfer Reactions  

SciTech Connect

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 has been developed that contains methyl viologen (MV) as an internalised electron acceptor and valinomycin (V) as a membrane associated cation exchanger. These proteoliposomes can be used as a model system to investigate MtrCAB function.

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

2012-12-01

253

PRELIMINARY EVALUATION OF THE 20% ENRICHED URANIUM CORE FOR THE MATERIALS TESTING REACTOR  

Microsoft Academic Search

In November, 1957 the MTR was successfully operated on 20% enriched fuel ;\\u000a for 646 Mwd, of which 550 were at the original MTR design power of 30 Mw. This ;\\u000a power level was selected before the experiment on the basis of heat transfer ;\\u000a limitations imposed by the use of a uniform fuel distribution. The plate spacing ;\\u000a of

D. R. deBoisblanc; R. S. Marsden

1958-01-01

254

Early structural changes in individuals at risk of familial Alzheimer’s disease: a volumetry and magnetization transfer MR imaging study  

Microsoft Academic Search

Presenilin 1 (PS1) mutation carriers provide the opportunity to asses early features of neurodegeneration in familial Alzheimer’s\\u000a disease (AD). Gray matter (GM) regional volume loss and decrease of magnetization transfer ratio (MTR) consistent with microstructural\\u000a changes have been reported in sporadic AD. We performed a regional volumetric and MTR analysis in carriers of PS1 mutations.\\u000a Six non-demented mutated PS1 carriers

A. Ginestroni; M. Battaglini; R. Della Nave; M. Moretti; C. Tessa; M. Giannelli; P. Caffarra; B. Nacmias; V. Bessi; S. Sorbi; L. Bracco; N. De Stefano; M. Mascalchi

2009-01-01

255

Genetic Mediators of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia  

PubMed Central

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive problems, with significant interindividual variability in outcome. This study examined genetic polymorphisms associated with variability in neurocognitive outcome. Patients and Methods Neurocognitive outcomes were evaluated at the end of therapy in 243 survivors treated on an institutional protocol featuring risk-adapted chemotherapy without prophylactic cranial irradiation. Polymorphisms in genes related to pharmacokinetics or pharmacodynamics of antileukemic agents, drug metabolism, oxidative stress, and attention problems in noncancer populations were examined as predictors of outcome, using multiple general linear models and controlling for age at diagnosis, sex, race, and treatment intensity. Results Compared with national norms, the cohort demonstrated significantly higher rates of problems on direct assessment of sustained attention (P = .01) and on parent ratings of attention problems (P = .02). Children with the A2756G polymorphism in methionine synthase (MS) were more likely to demonstrate deficits in attentiveness (P = .03) and response speed (P = .02), whereas those with various polymorphisms in glutathione S-transferase demonstrated increased performance variability (P = .01) and reduced attentiveness (P = .003). Polymorphisms in monoamine oxidase (T1460CA) were associated with increased attention variability (P = .03). Parent-reported attention problems were more common in children with the Cys112Arg polymorphism in apoliopoprotein E4 (P = .01). Conclusion These results are consistent with our previous report of association between attention problems and MS in an independent cohort of long-term survivors of childhood ALL treated with chemotherapy only. The results also raise the possibility of an impact from genetic predispositions related to oxidative stress and CNS integrity. PMID:23650422

Krull, Kevin R.; Bhojwani, Deepa; Conklin, Heather M.; Pei, Deqing; Cheng, Cheng; Reddick, Wilburn E.; Sandlund, John T.; Pui, Ching-Hon

2013-01-01

256

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

PubMed Central

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

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

2014-01-01

257

Measurement of photon flux with a miniature gas ionization chamber in a Material Testing Reactor  

NASA Astrophysics Data System (ADS)

Nuclear heating measurements in Material Testing Reactors (MTR) are crucial for the design of the experimental devices and the prediction of the temperature of the hosted samples. Nuclear heating in MTR materials (except fuel) is mainly due to the energy deposition by the photon flux. Therefore, the photon flux is a key input parameter for the computer codes which simulate nuclear heating and temperature reached by samples/devices under irradiation. In the Jules Horowitz MTR under construction at the CEA Cadarache, the maximal expected nuclear heating levels will be about 15 to 18 W g-1 and it will be necessary to assess this parameter with the best accuracy. An experiment was performed at the OSIRIS reactor to combine neutron flux, photon flux and nuclear heating measurements to improve the knowledge of the nuclear heating in MTR. There are few appropriate sensors for selective measurement of the photon flux in MTR even if studies and developments are ongoing. An experiment, called CARMEN-1, was conducted at the OSIRIS MTR and we used in particular a gas ionization chamber based on miniature fission chamber design to measure the photon flux. In this paper, we detail Monte-Carlo simulations to analyze the photon fluxes with ionization chamber measurements and we compare the photon flux calculations to the nuclear heating measurements. These results show a good accordance between photon flux measurements and nuclear heating measurement and allow improving the knowledge of these parameters.

Fourmentel, D.; Filliatre, P.; Villard, J. F.; Lyoussi, A.; Reynard-Carette, C.; Carcreff, H.

2013-10-01

258

Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis  

PubMed Central

OBJECTIVES—To assess (a) whether the changes in the normal appearing brain tissue (NABT), as revealed by magnetisation transfer (MT) histogram analysis, correlates with cognitive dysfunction in patients with multiple sclerosis and (b) the relative contribution of these changes by comparison with that of multiple sclerosis lesions visible on conventional MRI.?METHODS—Dual echo, T1 weighted and MT scans of the brain were obtained in 12 patients with multiple sclerosis with cognitive impairment and in seven without cognitive impairment. Lesion loads were assessed from T2 and T1 weighted scans. To create MT histograms of the NABT, multiple sclerosis lesion outlines from dual echo scans were superimposed automatically and nulled out from the coregistered and scalp stripped MTR maps. Average lesion MT ratio (MTR) and brain size were also measured.?RESULTS—T2 and T1 lesion loads were significantly higher and the average lesion MTR and brain size were significantly lower in the group of cognitively impaired patients. Patients with cognitive deficits also had significantly lower average MTR and peak location of the NABT histogram. Logistic regression analysis showed that 68% of the total variance was explained by average NABT-MTR alone. A multivariable regression model showed that NABT-MTR was the only factor that significantly correlated with cognitive impairment in these patients (p=0.001).?CONCLUSIONS—The extent of abnormalities which go undetected when using conventional MRI is relevant in determining cognitive impairment in multiple sclerosis.?? PMID:10644780

Filippi, M; Tortorella, C; Rovaris, M; Bozzali, M; Possa, F; Sormani, M; Iannucci, G; Comi, G

2000-01-01

259

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

SciTech Connect

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.

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

260

A Cajal body-independent pathway for telomerase trafficking in mice  

SciTech Connect

The intranuclear trafficking of human telomerase involves a dynamic interplay between multiple nuclear sites, most notably Cajal bodies and telomeres. Cajal bodies are proposed to serve as sites of telomerase maturation, storage, and assembly, as well as to function in the cell cycle-regulated delivery of telomerase to telomeres in human cells. Here, we find that telomerase RNA does not localize to Cajal bodies in mouse cells, and instead resides in separate nuclear foci throughout much of the cell cycle. However, as in humans, mouse telomerase RNA (mTR) localizes to subsets of telomeres specifically during S phase. The localization of mTR to telomeres in mouse cells does not require coilin-containing Cajal bodies, as mTR is found at telomeres at similar frequencies in cells from wild-type and coilin knockout mice. At the same time, we find that human TR localizes to Cajal bodies (as well as telomeres) in mouse cells, indicating that the distinct trafficking of mTR is attributable to an intrinsic property of the RNA (rather than a difference in the mouse cell environment such as the properties of mouse Cajal bodies). We also find that during S phase, mTR foci coalesce into short chains, with at least one of the conjoined mTR foci co-localizing with a telomere. These findings point to a novel, Cajal body-independent pathway for telomerase biogenesis and trafficking in mice.

Tomlinson, Rebecca L.; Li, Jian; Culp, Bradley R.; Terns, Rebecca M., E-mail: rterns@bmb.uga.edu; Terns, Michael P., E-mail: mterns@bmb.uga.edu

2010-10-15

261

Understanding the Vascular Environment of Myofascial Trigger Points using Ultrasonic Imaging and Computational Modeling  

PubMed Central

Myofascial pain syndrome (MPS) is a common, yet poorly understood, acute and chronic pain condition. MPS is characterized by local and referred pain associated with hyperirritable nodules known as myofascial trigger points (MTrPs) that are stiff, localized spots of exquisite tenderness in a palpable taut band of skeletal muscle. Recently, our research group has developed new ultrasound imaging methods to visualize and characterize MTrPs and their surrounding soft tissue. The goal of this paper was to quantitatively analyze Doppler velocity waveforms in blood vessels in the neighborhood of MTrPs to characterize their vascular environment. A lumped parameter compartment model was then used to understand the physiological origin of the flow velocity waveforms. 16 patients with acute neck pain were recruited for the study and the blood vessels in the upper trapezius muscle in the neighborhood of palpable MTrPs were imaged using Doppler ultrasound. Preliminary findings show that symptomatic MTrPs have significantly higher peak systolic velocities and negative diastolic velocities compared to latent MTrPs and normal muscle sites. Using compartment modeling, we show that a constricted vascular bed and an enlarged vascular volume could explain the observed flow waveforms with retrograde diastolic flow. PMID:21096064

Sikdar, Siddhartha; Ortiz, Robin; Gebreab, Tadesse; Gerber, Lynn H.; Shah, Jay P.

2012-01-01

262

Probable Mechanisms of Needling Therapies for Myofascial Pain Control  

PubMed Central

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

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

2012-01-01

263

Thrombotic genetic risk factors and warfarin pharmacogenetic variants in São Miguel's healthy population (Azores)  

PubMed Central

Background The Azorean population presents the highest standardized mortality rate for cardiovascular diseases (CVD) when compared to mainland Portugal and other populations. Since thrombosis is a common cause of CVD, we assessed four polymorphisms in three thrombotic risk genes – F5 (G1691A), F2 (G20210A) and MTHFR (C677T, A1298C), in 469 healthy blood donors from São Miguel Island (Azores). We also analysed the CYP2C9 (C430T, A1075C) and VKORC1 (G1639A) variants in fifty-eight individuals with predisposition to thrombosis (possessing at least one variation in F5 or F2 genes and one in MTHFR) to evaluate their warfarin drug response genetic profiles. Results Among the 469 individuals, the data showed that thrombotic risk allele frequencies – 1691A (4.9%), 20210A (1.8%), 677T (41.7%) and 1298C (24.8%) – were similar to other Caucasians, but significantly different from mainland Portuguese (?2, p < 0.001). The combined analysis of these variants identified twenty-two different genetic profiles (genotype order: F5, F2, MTHFR C677T and A1298C). Complete homozygosity for all wild-type alleles (GG GG CC AA) was present in 11.7%, being GG GG CT AA (22.4%) the most frequent profile. The results also demonstrated that 12.4% (58 out of 469) of São Miguel islanders have increased genetic predisposition to thrombosis. Subsequently, we evaluated these individuals for their warfarin response genetic profiles. The data showed that seven out of fifty-eight individuals are poor metabolizers (two with CYP2C9*2/*2 and five with CYP2C9*2/*3 genotypes). VKORC1 polymorphism analysis identified twelve individuals (20.7%) with AA genotype, who probably will require lower doses of warfarin. The joint analysis of CYP2C9 and VKORC1 revealed that 79.3% (46 out of 58) of the individuals carry at least one polymorphism in these genes. Within these, twenty-five individuals (43.1%) need intermediate and/or low doses of warfarin, if treatment is started. Conclusion The present study demonstrated, for the first time, that São Miguel, and possibly the Azores population, shows significant differences on allele frequencies of thrombotic risk factors when compared to mainland Portugal. This research constitutes a primary approach for future studies on CVD, as well as for the implementation of warfarin dosing protocols using the patient's genotypic information. PMID:19538716

Branco, Claudia C; Pereirinha, Tânia; Cabral, Rita; Pacheco, Paula R; Mota-Vieira, Luisa

2009-01-01

264

Magnetic resonance imaging, magnetisation transfer imaging, and diffusion weighted imaging correlates of optic nerve, brain, and cervical cord damage in Leber's hereditary optic neuropathy  

PubMed Central

OBJECTIVES—Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to bilateral loss of central vision and severe optic nerve atrophy. A subtype of LHON presents additional clinical and MRI aspects indistinguishable from those of multiple sclerosis (MS) (LHON-MS). In patients with LHON or LHON-MS, an assessment was made of (a) the severity of optic nerve damage, using MRI and magnetisation transfer imaging (MTI), and (b) the presence and extent of macroscopic and microscopic pathology in the brain and cervical cord, using MRI and MT ratio (MTR) and mean diffusivity (&Dmacr;) histogram analysis.?METHODS—Ten patients with LHON, four with LHON-MS, and 20 age and sex matched healthy controls were studied. For the optic nerve and the brain, dual-echo turbo spin echo (TSE), T1 weighted spin echo, and MT images were obtained. For the brain, fast fluid attenuated inversion recovery (fast FLAIR) and diffusion weighted images were also obtained. For the cervical cord, fast short tau inversion recovery (STIR) and MT images were obtained. The volume and the average MTR value of both the optic nerves were measured. MTR and &Dmacr; histograms of the normal appearing brain tissue (NABT) and MTR histograms of the whole cervical cord tissue were created.?RESULTS—The mean values of optic nerve volumes and MTR were significantly lower in patients with LHON than in healthy controls. Mean NABT-MTR histogram peak height was significantly lower in patients with LHON than in controls, whereas no significant difference was found for any of the cervical cord MTR histogram derived measures. Average diffusivity (&Dmacr;) was higher in patients with LHON than in controls. Optic nerve volume and MTR value and mean NABT-MTR were lower in patients with LHON-MS than in those with LHON.?CONCLUSIONS—The severity of optic nerve pathology in LHON is measurable in vivo using MRI and MTI. MTR and &Dmacr; histogram analysis suggests that microscopic brain damage occurs in LHON and that it is more severe in the MS-like form of the disease.?? PMID:11254765

Inglese, M; Rovaris, M; Bianchi, S; Mantia, L; Mancardi, G; Ghezzi, A; Montagna, P; Salvi, F; Filippi, M

2001-01-01

265

Systemic thrombolysis with the use of tenecteplase for segmental acute renal in-farction potentially associated with multiple thrombophilic gene polymorphisms  

PubMed Central

Background/aim: The potential association of acute renal infarction with multiple thrombophilic gene polymorphisms and the experience of treatment with tenecteplase are described for the first time in the international literature. Description of the case: The case of a 50-year old male with segmental acute renal infarction potentially associated with multiple thrombophilic gene polymorphisms is presented. He was thrombolysed with a single intravenous bolus of tenecteplase in a weight-adjusted dose (0.53mg/Kg bodyweight). Within 30 minutes after drug administration, the patient’s symptoms were completely relieved. Patient’s clinical course was uneventful with an acceptable renal function outcome eight weeks post-treatment. The following gene polymorphisms were identified: G455A (b-fibrinogen); C677T; A1298C (methylenetetrahydropholate reductase); T196C (platelet glycoprotein IIIa); 4G/5G (plasminogen activator inhibitor-1). Conclusion: Tenecteplase is a safe and simple to use thrombolytic, with favourable pharmacokinetic profile, which might be useful if administered early, especially when local thrombolysis is impossible or unavailable and therefore warrants further investigation in clinical trials. Hippokratia 2014; 18 (1): 67-70. PMID:25125956

Chondros, K; Karpathakis, N; Tsetis, D; Sofras, F; Mamoulakis, C

2014-01-01

266

MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders  

PubMed Central

Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%), but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism. PMID:25431675

Oztop, Didem Behice; Ozkul, Yusuf

2014-01-01

267

Risk factors for perinatal arterial stroke: a study of 60 mother-child pairs.  

PubMed

The objective of the present study was to examine demographic, historical, and prothrombotic risk factors in infants with perinatal arterial stroke and their mothers. Risk factors were evaluated in 60 mother-child pairs with perinatal arterial stroke. Prothrombotic factors analyzed included the DNA mutations factor V Leiden, prothrombin 20210, MTHFR C677T and A1298C; serum activity levels for protein C, protein S, and antithrombin III; serum levels of lipoprotein(a); and, in the mothers, antiphospholipid antibodies. Boys predominated, 36:24. There were four twin sets. Sixty percent were term and 22% were post-date. Ten were large for gestational age. Five mothers had abdominal trauma. Nine mothers (15%) had preeclampsia. Emergency caesarean section was performed in 17 cases (28%). Eight placental exams revealed seven with abnormalities. Seizures were the presenting sign in 70%, and 30% presented with early handedness or cerebral palsy. Prothrombotic risk factors were found in 28 of 51 mothers (55%) and 30 of 60 children (50%). Forty-one pairs (68%) had at least one abnormality in mother, child, or both. Long-term sequelae included cerebral palsy (40 of 51; 78%), cognitive impairment (35 of 51; 68%), seizures (23 of 51; 45%), and microcephaly (26 of 51; 51%). Perinatal arterial stroke is the result of multifactorial, synergistic fetal and maternal factors among which the prothrombotic factors, both fetal and maternal, appear significant. PMID:17675024

Curry, Cynthia J; Bhullar, Sundeep; Holmes, Jon; Delozier, C Dawn; Roeder, Elizabeth R; Hutchison, H Terry

2007-08-01

268

Thrombophilias and Pregnancy Complications: A Case-Control Study  

PubMed Central

Inherited thrombophilia is believed to be a multiple gene disease with more than one defect. We wanted to determine the association between single thrombophilic patterns and a variety of pregnancy diseases. 301 pregnant women were recruited for the present case-control study and were divided into two groups: A group (176 controls) and B group (125 cases). Patients belonging to the B group had one of the following: severe preeclampsia, HELLP syndrome, gestational hypertension, fetal growth restriction (FGR), intrauterine death, abruptio placentae, placenta previa, disseminated intravascular coagulopathy (DIC) and preterm labour. To detect MTHFR A1298C, MTHFR C677T, Factor V Leiden, PAI-1, Mutant Prothrombin G20210A, an inverse hybridization technology was used. Plasma homocysteine, Antithrombin III and protein levels S were determined. A modified functional activated protein C resistance was assayed. MTHFR C677T and hyperhomocysteinemia were more numerous than other thrombophilias. Deficiency in AT III was significantly linked with preeclampsia (Pearson Index and p value: 0.131 and 0.022, respectively) and disseminated intravascular coagulopathy (Pearson Index and p value: 0.138 and 0.016 respectively). Activated Protein C resistance was related to abruptio placentae (Pearson Index and p value: 0.159 and 0.005 respectively). Apart from the linkage between AT III deficiency and the occurrence of preeclampsia and disseminated intravascular coagulopathy, we obtained findings in contrast to some literature. In our case series, no association of preeclampsia with Factor V Leiden or with prothrombin gene mutation was found. PMID:23675040

Giovanni, Larciprete; Antonio, Angelucci Piero; Danilo, Celleno; Stefano, Gioia; Therese, Deaibess; Elisabetta, Romanini Maria; Letizia, Brienza; Elio, Cirese; Domenico, Arduini

2007-01-01

269

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

PubMed Central

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

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

2012-01-01

270

Association Between MTHFR Polymorphisms and Congenital Heart Disease: A Meta-analysis based on 9,329 cases and 15,076 controls  

PubMed Central

The aim of our study was to evaluate the association between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and the risk for congenital heart disease (CHD). Electronic literature databases were searched to identify eligible studies published before Jun, 2014. The association was assessed by the odds ratio (OR) with a 95% confidence interval (CI). The publication bias was explored using Begg's test. Sensitivity analysis was performed to evaluate the stability of the crude results. A total of 35 studies were included in this meta-analysis. For the MTHFR C677T polymorphism, we detected significant association in all genetic models for Asian children and the maternal population. Significant association was also detected in T vs. C for a Caucasian paediatric population (OR = 1.163, 95% CI: 1.008–1.342) and in both T vs. C (OR = 1.125, 95% CI: 1.043–1.214) and the dominant model (OR = 1.216, 95% CI:b1.096–1.348) for a Caucasian maternal population. For the MTHFR A1298C polymorphism, the association was detected in CC vs. AC for the Caucasian paediatric population (OR = 1.484, 95% CI: 1.035–2.128). Our results support the MTHFR -677T allele as a susceptibility factor for CHD in the Asian maternal population and the -1298C allele as a risk factor in the Caucasian paediatric population. PMID:25472587

Xuan, Chao; Li, Hui; Zhao, Jin-Xia; Wang, Hong-Wei; Wang, Yi; Ning, Chun-Ping; Liu, Zhen; Zhang, Bei-Bei; He, Guo-Wei; Lun, Li-Min

2014-01-01

271

MTHFR Gene Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Adults and Children: A Case Control Study in India.  

PubMed

Genetic polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. The role of MTHFR polymorphism in the development of pediatric acute lymphoblastic leukemia (ALL) has been extensively studied among north Indians in various settings, yet its association with acute leukemias remains unresolved. To evaluate the relationship between functional MTHFR polymorphisms, C677T and A1298C and possible effect on risk of ALL in adults and children in North Indian population by comparing them with healthy controls. DNA was isolated from peripheral blood of 184 ALL patients (33 adults, 151 children) and 155 controls and analyzed by a PCR-restriction fragment length polymorphism assay. The frequency of MTHFR 677CT and 1298 AC genotypes were significantly lower among adult ALL cases when compared to the controls. We found a 1.74-fold reduced risk of ALL in individuals with 1298AC polymorphic variant and a 9.17-fold decreased risk of adult ALL. However, no statistically significant difference was evident between the above polymorphisms and susceptibility to ALL in children. Polymorphisms in the MTHFR gene possibly modulate risk of ALL in north Indian adults but not in children, although larger studies are needed. PMID:25435717

Sazawal, Sudha; Chaubey, Rekha; Kaur, Pawandeep; Chikkara, Sunita; Kumar, Bijender; Bakshi, Sameer; Arya, L S; Raina, Vinod; Das Gupta, Alakananda; Saxena, Renu

2014-12-01

272

Influence of methylenetetrahydrofolate reductase gene polymorphisms on the outcome of pediatric patients with non-Hodgkin lymphoma treated with high-dose methotrexate.  

PubMed

High-dose methotrexate (MTX) is a key component of most treatment protocols for childhood and adolescent non-Hodgkin lymphoma (NHL). Recent studies have suggested that the toxicity of antifolate drugs, such as MTX, is affected by inherited single nucleotide polymorphisms (SNPs) in folate metabolizing genes. The aim of our study was to investigate the potential influence of the C677T and A1298C genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene on the clinical toxicity and efficacy of MTX in pediatric patients with NHL (n = 95) treated with therapeutic protocols Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) LNH-97 and EURO LB-02. We demonstrated that patients with the 677T genotype had an approximately six-fold greater risk of developing hematological toxicity compared with wild-type carriers, especially in the 1 g/m(2) treatment group (p = 0.01). Moreover, we identified a correlation between the risk of relapse and the T genotype: T carriers had reduced disease-free survival compared with wild-type patients (67% vs. 100%). Our data suggest a pharmacogenetic influence on the adverse effects of high-dose MTX in the 1 g/m(2) treatment group. PMID:23488607

D'Angelo, Velia; Ramaglia, Maria; Iannotta, Adriana; Francese, Matteo; Pota, Elvira; Affinita, Maria Carmen; Pecoraro, Giulia; Indolfi, Cristiana; Di Martino, Martina; Di Pinto, Daniela; Buffardi, Salvatore; Poggi, Vincenzo; Indolfi, Paolo; Casale, Fiorina

2013-12-01

273

Lower incidence of nonsyndromic cleft lip with or without cleft palate in females: is homocysteine a factor?  

PubMed

In India, as in other parts of the world, nonsyndromic cleft lip with or without cleft palate (NSCL +/- P) is a highly prevalent birth defect, its incidence in males being twice that in females. A case-control association study has been carried out with respect to homocysteine level and MTHFR C677T, A1298C and SLC19A1 (RFC1) G80A genotypes from an eastern Indian cohort to investigate whether Hcy and other Hcy-pathway genes also contribute to the risk level. While MTHFR 677T and SLC19A1 80G are individually and cumulatively risk factors, SLC19A1 80A appears to be protective against MTHFR 677T risk allele. Elevated Hcy associates with NSCL +/- P both in case mothers and cases. Significantly, this difference shows a gender bias: the level of elevation of Hcy in female cases is distinctly higher than in males, and more case females are hyperhomocyteinemic than the case males. It implies that compared with the males, higher level of Hcy is needed for NSCL +/- P to manifest in the females. We consider this as one of the possible factors why the incidence of this disorder in females is much lower than in males. PMID:23385809

Kumari, Priyanka; Ali, Akhtar; Sukla, Krishna K; Singh, Subodh K; Raman, Rajiva

2013-03-01

274

Dietary intake of folate and co-factors in folate metabolism, MTHFR polymorphisms, and reduced rectal cancer  

PubMed Central

Little is known about the contribution of polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and the folate metabolism pathway in rectal cancer alone. Data were from participants in a case-control study conducted in Northern California and Utah (751 cases and 979 controls). We examined independent associations and interactions of folate, B vitamins, methionine, alcohol, and MTHFR polymorphisms (MTHFR C677T and A1298C) with rectal cancer. Dietary folate intake was associated with a reduction in rectal cancer OR 0.66, 95% CI 0.48-0.92 (>475 mcg day compared to < = 322 mcg) as was a combination of nutrient intakes contributing to higher methyl donor status (OR 0.79, 95% CI 0.66-0.95). Risk was reduced among women with the 677 TT genotype (OR 0.54, 95% CI 0.30-0.9), but not men (OR 1.11, 95% CI 0.70-1.76) and with the 1298 CC genotype in combined gender analysis (OR 0.67, 95% CI 0.46-0.98). These data are consistent with a protective effect of increasing dietary folate against rectal cancer and suggest a protective role of the MTHFR 677 TT genotype in women and 1298 CC in men and women. Folate intake, low methyl donor status, and MTHFR polymorphisms may play independent roles in the etiology of rectal cancer. PMID:17245555

Murtaugh, Maureen A.; Curtin, Karen; Sweeney, Carol; Wolff, Roger K.; Holubkov, Richard; Slattery, Martha L.; Caan, Bette J.

2008-01-01

275

Methylenetetrahydrofolate reductase gene mutations as risk factors for sudden hearing loss.  

PubMed

Sudden hearing loss (SHL) can be caused by vascular disorders favoring impaired cochlear perfusion. Several inherited prothrombotic risk factors have been considered in the pathogenesis of vascular impairment, and the possible role of genetic alterations has recently been suggested. Methylenetetrahydrofolate reductase (MTHFR) gene mutations at nucleotides 677 and 1298 cause reduced MTHFR enzyme activity, which leads to increased homocysteine and reduced serum folate levels that are known to be involved in vascular impairment. We studied the relationship between SHL and MTHFR C677T and A1298C gene polymorphisms in 67 patients with SHL and 134 controls. Wild-type MTHFR CC677/AA1298 was significantly more frequent in the controls (P = .05), and gene mutations were significantly more frequent in the patients (P = .001; P = .001 for trend). Fifty-three patients (79.1%) and 56 controls (41.8%) (P = .012) had a double mutation (homozygosis 677TT or 1298CC; compound heterozygosis for both polymorphisms). Homocysteine levels were significantly higher and serum folate levels significantly lower in the patients than in the controls (P < .0001). These data suggest that MTHFR gene polymorphisms may be involved in the pathogenesis of SHL. PMID:16275406

Capaccio, Pasquale; Ottaviani, Francesco; Cuccarini, Valeria; Ambrosetti, Umberto; Fagnani, Enrico; Bottero, Alessandro; Cenzuales, Salvatore; Cesana, Bruno Mario; Pignataro, Lorenzo

2005-01-01

276

A Possible Genetic Link between MTHFR Genotype and Smoking Behavior  

PubMed Central

Background Hyperhomocysteinemia is an independent risk factor for stroke and other vascular events. The variant methylenetetrahydrofolate reductase (MTHFR) C677T is associated with elevated homocysteine levels, cardiovascular disease and stroke, which supports a causal relationship between hyperhomocysteinemia and vascular disease. However, MTHFR variants have also been reported to be associated with smoking behavior, which could be an important confounder. Methodology/Principal Findings We analyzed the MTHFR variants C677T and A1298C in two independent samples of 525 and 535 individuals, respectively. 21% of the non-smokers, but only 12% of the smokers were homozygous carriers of both MTHFR wildtype alleles, i.e. 677CC and 1298AA (Chi2?=?15.8; p<0.001; binary regression). Plasma homocysteine levels were higher in smokers (13.9±4.1 µmol/L) than in non-smokers (12.6±4.0 µmol/L; F?=?11.4; p?=?0.001; ANOVA). Smoking MTHFR 677TT individuals had the highest plasma homocysteine levels (16.2±5.2 µmol/L), non-smoking 677CC individuals had the lowest (12.2±13.6 µmol/L). Conclusions/Significance In our study samples, MTHFR variants and smoking behaviour were associated with homocysteine plasma levels. In addition, the MTHFR variants were associated with smoking behaviour. Such an association may be a relevant confounder between MTHFR variants, homocysteine plasma levels and vascular diseases. PMID:23285280

Linnebank, Michael; Moskau, Susanna; Semmler, Alexander; Hoefgen, Barbara; Bopp, Gisela; Kallweit, Ulf; Maier, Wolfgang; Schütz, Christian G.; Wüllner, Ullrich

2012-01-01

277

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

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

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

278

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

PubMed Central

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

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

2013-01-01

279

Magnetization Transfer Ratio Relates to Cognitive Impairment in Normal Elderly  

PubMed Central

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

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

280

Magnetization transfer imaging of acute black holes in patients on glatiramer acetate.  

PubMed

The aim of this study was to determine evolution of T1 unenhanced hypointense lesions (acute or chronic black holes (ABHs, CBHs)) by measuring their magnetization transfer ratio (MTR) changes over 12 months. 40 glatiramer acetate (GA)-naive patients with relapsing-remitting MS who presented with 1 or more contrast-enhancing lesions (CELs) at baseline underwent 1.5-T MRI at baseline and after 12 months. Lesions were classified into 4 patterns based on differences in lesion isointensity or hypointensity over 12 months. Of 115 CELs detected at baseline, 64, after 12 months, followed pattern A (isointense-isointense), 6 pattern B (isointense-hypointense), 33 pattern C (hypointense-isointense), and 12 pattern D (hypointense-hypointense). MTR significantly increased for all unenhanced T1 hypointense lesions (p = 0.02). Highest MTR increases were observed for patterns C (ABHs +18.2 %, p less than 0.001) and D (CBHs +34.2 %, p = 0.023), but significant improvement was also detected for pattern A (+1.4 %, p = 0.046); no significant MTR changes were found for pattern B. GA treatment significantly recovered MTR in ABHs and CBHs, possibly indicating a greater potential for remyelination. PMID:22201970

Zivadinov, Robert; Hussein, Sara; Bergsland, Niels; Minagar, Alireza; Dwyer, Michael G

2012-01-01

281

Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery  

NASA Astrophysics Data System (ADS)

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.

Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.

2000-02-01

282

Links between dwarf and classical novae, and implications for the space densities and evolution of cataclysmic binaries  

SciTech Connect

The effects of mass and angular momentum losses during a nova eruption are investigated by simulation in the context of a new nova evolution model. It is argued that surveys for cataclysmic variables (CVs) are very incomplete and that the local space density of CVs could well be 0.0001/cu pc. It is shown that the competing effets of mass and angular momentum loss usually increase the separation of a red and white dwarf during a nova eruption. The reasons why old novae remain bright for about a century after eruption and why they reduce the mass transfer rate (MTR) and eventually go into a state of hibernation for a thousand to a million years, eventually reviving as dwarf novae or novalike variables, are discussed. The results of these simulations are used to demonstrate the consistency of variable MTR in resolving the MTR discrepancy. 43 references.

Shara, M.M.; Livio, M.; Moffat, A.F.J.; Orio, M.

1986-12-01

283

Fluence-dependent effects of low-level laser therapy in myofascial trigger spots on modulation of biochemicals associated with pain in a rabbit model.  

PubMed

Evidence strongly supports that low-level laser therapy (LLLT) is an effective physical modality for the treatment of pain associated with myofascial trigger points (MTrP). However, the effect of laser fluence (energy intensity in J/cm(2)) on biochemical regulation related to pain is unclear. To better understand the biochemical mechanisms modulated by high- and low-fluence LLLT at myofascial trigger spots (MTrSs; similar to human MTrPs) in skeletal muscles of rabbits, the levels of ?-endorphin (?-ep), substance P (SP), tumor necrosis factor-? (TNF-?), and cyclooxygenase-2 (COX-2) were investigated in this study. New Zealand rabbits (2.5-3.0 kg in weight) were used in this study. High-fluence LLLT (27 J/cm(2)), low-fluence LLLT (4.5 J/cm(2)), or sham operations were applied on MTrSs of biceps femoris of rabbits for five sessions (one session per day). Effects of LLLT at two different fluences on biceps femoris, dorsal root ganglion (DRG), and serum were determined by ?-ep, SP, TNF-?, and COX-2 immunoassays. LLLT irradiation with fluences of 4.5 and 27 J/cm(2) at MTrSs can significantly reduce SP level in DRG. LLLT with lower fluence of 4.5 J/cm(2) exerted lower levels of TNF-? and COX-2 expression in laser-treated muscle, but LLLT with higher fluence of 27 J/cm(2) elevated the levels of ?-ep in serum, DRG, and muscle. This study demonstrated fluence-dependent biochemical effects of LLLT in an animal model on management of myofascial pain. The findings can contribute to the development of dosage guideline for LLLT for treating MTrP-induced pain. PMID:25190639

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

2015-01-01

284

Mechanical pain sensitivity of deep tissues in children - possible development of myofascial trigger points in children  

PubMed Central

Background It is still unclear when latent myofascial trigger points (MTrPs) develop during early life. This study is designed to investigate the mechanical pain sensitivity of deep tissues in children in order to see the possible timing of the development of latent MTrPs and attachment trigger points (A-TrPs) in school children. Methods Five hundreds and five healthy school children (age 4- 11 years) were investigated. A pressure algometer was used to measure the pressure pain threshold (PPT) at three different sites in the brachioradialis muscle: the lateral epicondyle at elbow (site A, assumed to be the A-TrP site), the mid-point of the muscle belly (site B, assumed to be the MTrP site), and the muscle-tendon junction as a control site (site C). Results The results showed that, for all children in this study, the mean PPT values was significantly lower (p < 0.05) at the assumed A-TrP site (site A) than at the other two sites, and was significantly lower (p < 0.05) at the assumed MTrP site (site B) than at the control site (site C). These findings are consistent if the data is analyzed for different genders, different dominant sides, and different activity levels. Conclusions It is concluded that a child had increased sensitivity at the tendon attachment site and the muscle belly (endplate zone) after age of 4 years. Therefore, it is likely that a child may develop an A-Trp and a latent MTrP at the brachioradialis muscle after the age of 4 years. The changes in sensitivity, or the development for these trigger points, may not be related to the activity level of children aged 7-11 years. Further investigation is still required to indentify the exact timing of the initial occurrence of a-Trps and latent MTrPs. PMID:22316064

2012-01-01

285

Possible dynamically gated conductance along heme wires in bacterial multiheme cytochromes.  

PubMed

The staggered cross decaheme configuration of electron transfer cofactors in the outer-membrane cytochrome MtrF serves as a prototype for conformationally gated multiheme electron transport. Derived from the bacterium Shewanella oneidensis, the staggered cross configuration reveals intersecting c-type octaheme and tetraheme "wires" containing thermodynamic "hills" and "valleys" (Proc. Natl. Acad. Sci. U. S. A. 2014, 11, 611-616), suggesting that the protein structure may include a dynamical mechanism for conductance and pathway switching depending on enzymatic functional need. Here, we applied classical molecular and statistical mechanics calculations of large-amplitude protein dynamics in MtrF, to address its potential to modulate pathway conductance, including assessment of the effect of the total charge state. Explicit solvent molecular dynamics simulations of fully oxidized and fully reduced MtrF showed that the slowest mode of collective decaheme motion is 90% similar between the oxidized and reduced states and consists primarily of interheme separation with minor rotational contributions. The frequency of this motion is 1.7 × 10(7) s(-1), both for fully oxidized and fully reduced MtrF, slower than the downhill electron transfer rates between stacked heme pairs at the octaheme termini and faster than the electron transfer rates between parallel hemes in the tetraheme chain. This implies that MtrF uses slow conformational fluctuations to modulate electron flow along the octaheme pathway, apparently for the purpose of increasing the residence time of electrons on lowest potential hemes 4 and 9. This apparent gating mechanism should increase the success rate of electron transfer from MtrF to low potential environmental acceptors via these two solvent-exposed hemes. PMID:24975678

Smith, Dayle M A; Rosso, Kevin M

2014-07-24

286

Age independently affects myelin integrity as detected by magnetization transfer magnetic resonance imaging in multiple sclerosis  

PubMed Central

Background Multiple sclerosis (MS) is a heterogeneous disorder with a progressive course that is difficult to predict on a case-by-case basis. Natural history studies of MS have demonstrated that age influences clinical progression independent of disease duration. Objective To determine whether age would be associated with greater CNS injury as detected by magnetization transfer MRI. Materials and methods Forty MS patients were recruited from out-patient clinics into two groups stratified by age but with similar clinical disease duration as well as thirteen controls age-matched to the older MS group. Images were segmented by automated programs and blinded readers into normal appearing white matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1 weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as well as MTR histogram skew and kurtosis were calculated for each region. Results All MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS subjects and controls, as expected and previously reported by several studies, but not between MS groups. However, MTR measures in the WML did significantly differ between the MS groups, in spite of no significant differences in lesion counts and volumes. Conclusions Despite matching for clinical disease duration and recording no significant WML volume difference, we demonstrated strong MTR differences in WMLs between younger and older MS patients. These data suggest that aging-related processes modify the tissue response to inflammatory injury and its clinical outcome correlates in MS. PMID:24936415

Newbould, R.D.; Nicholas, R.; Thomas, C.L.; Quest, R.; Lee, J.S.Z.; Honeyfield, L.; Colasanti, A.; Malik, O.; Mattoscio, M.; Matthews, P.M.; Sormani, M.P.; Waldman, A.D.; Muraro, P.A.

2014-01-01

287

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

288

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

289

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

290

Solar spectropolarimetry with THEMIS  

NASA Astrophysics Data System (ADS)

We report spectropolarimetric observations with THEMIS telescope multi-lines operating mode (MTR) during the last campaigns. We demonstrate the very favorable performances of THEMIS for investigations of the magnetic field and we report also observations devoted to the measurement of the scattering polarization. In that case, the signals are weak and are not “a priori" included in the THEMIS objectives but results show that THEMIS is a suitable instrument not only for strong field at high spatial resolution but also for weak signal at high polarimetric sensitivity. We describe briefly the multi-line spectropolarimetry mode (MTR) available at the franco-italian solar telescope THEMIS.

Molodij, G.; Rayrole, J.

291

ETR CRITICAL FACILITY, TRA654. CONTEXTUAL VIEW. CAMERA ON ROOF OF ...  

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

ETR CRITICAL FACILITY, TRA-654. CONTEXTUAL VIEW. CAMERA ON ROOF OF MTR BUILDING AND FACING SOUTH. ETR AND ITS COOLANT BUILDING AT UPPER PART OF VIEW. ETR COOLING TOWER NEAR TOP EDGE OF VIEW. EXCAVATION AT CENTER IS FOR ETR CF. CENTER OF WHICH WILL CONTAIN POOL FOR REACTOR. NOTE CHOPPER TUBE PROCEEDING FROM MTR IN LOWER LEFT OF VIEW, DIAGONAL TOWARD LEFT. INL NEGATIVE NO. 56-4227. Jack L. Anderson, Photographer, 12/18/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

292

Specific and common genes implicated across major mental disorders: A review of meta-analysis studies.  

PubMed

Major efforts have been directed at family-based association and case-control studies to identify the involvement of candidate genes in the major disorders of mental health. What remains unknown is whether candidate genes are associated with multiple disorders via pleiotropic mechanisms, and/or if other genes are specific to susceptibility for individual disorders. Here we undertook a review of genes that have been identified in prior meta-analyses examining specific genes and specific mental disorders that have core disruptions to emotional and cognitive function and contribute most to burden of illness- major depressive disorder (MDD), anxiety disorders (AD, including panic disorder and obsessive compulsive disorder), schizophrenia (SZ) and bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD). A literature review was conducted up to end-March 2013 which included a total of 1519 meta-analyses across 157 studies reporting multiple genes implicated in one or more of the five disorders studied. A total of 134 genes (206 variants) were identified as significantly associated risk variants for MDD, AD, ADHD, SZ or BD. Null genetic effects were also reported for 195 genes (426 variants). 13 genetic variants were shared in common between two or more disorders (APOE e4, ACE Ins/Del, BDNF Val66Met, COMT Val158Met, DAOA G72/G30 rs3918342, DAT1 40-bp, DRD4 48-bp, SLC6A4 5-HTTLPR, HTR1A C1019G, MTHR C677T, MTHR A1298C, SLC6A4 VNTR and TPH1 218A/C) demonstrating evidence for pleiotrophy. Another 12 meta-analyses of GWAS studies of the same disorders were identified, with no overlap in genetic variants reported. This review highlights the progress that is being made in identifying shared and unique genetic mechanisms that contribute to the risk of developing several major psychiatric disorders, and identifies further steps for progress. PMID:25287955

Gatt, Justine M; Burton, Karen L O; Williams, Leanne M; Schofield, Peter R

2015-01-01

293

Genetic Variability in the MTHFR gene and colorectal cancer risk using the Colorectal Cancer Family Registry  

PubMed Central

Background The MTHFR C677T TT genotype is associated with a 15%–18% reduction in colorectal cancer (CRC) risk but it is not clear if other variants of the gene are associated with CRC risk. Methods We used a tagSNP approach to comprehensively evaluate associations between variation in the MTHFR gene and CRC risk using a large family-based case control study of 1,750 population-based and 245 clinic-based families from the Colon Cancer Family Registry (CCFR).We assessed 22 TagSNPs, selected based on pairwise r2>95%, using Haploview Tagger and genotyped on the Illumina GoldenGate or Sequenom platforms. The association between SNPs and colorectal cancer was assessed using log additive, co-dominant, and recessive models. Results From studying the population-based families, the C677T (rs1801133) and A1298C (rs1801131) polymorphisms were associated with a decreased CRC risk overall (OR=0.81, 95% CI=0.63–1.04 and OR=0.82, 95% CI=0.64–1.07, respectively). The 677 TT genotype was associated with a decreased risk of microsatellite stable/microsatellite low tumors (OR=0.69, 95% CI=0.49–0.97) and an increased risk of microsatellite high tumors (OR= 2.22, 95% CI=0.91–5.43) (interaction p-value = 0.01), as well as an increased risk of proximal cancers and a decreased risk of distal and rectal cancers (interaction p-value = 0.02). No other SNP was associated with risk overall or within subgroups. Conclusion The 677 TT and 1298 CC genotypes may each be associated with a decrease in CRC risk. We observed little evidence of additional genetic variability in the MTHFR gene relevant to CRC risk. PMID:20056627

Levine, A. Joan; Figueiredo, Jane C.; Lee, Won; Poynter, Jenny N.; Conti, David; Duggan, David J; Campbell, Peter T.; Newcomb, Polly; Martinez, Maria Elena; Hopper, John L.; Le Marchand, Loic; Baron, John A.; Limburg, Paul J.; Ulrich, Cornelia M; Haile, Robert W

2009-01-01

294

Quantitative assessment of the association between MTHFR rs1801131 polymorphism and risk of liver cancer.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folate metabolism which plays a key role in cell metabolism. MTHFR rs1801131 (A1298C) polymorphism can decrease in vitro MTHFR enzyme activity and has been hypothesized to be associated with liver cancer risk. This study aimed to quantify the strength of the association between MTHFR rs1801131 polymorphism and liver cancer risk by performing a meta-analysis. We searched the PubMed and Wanfang databases for studies relating on the association between MTHFR rs1801131 polymorphism and risk of liver cancer. Seven studies with 2,030 cases of liver cancer and 3,096 controls were finally included into the meta-analysis. Meta-analysis of a total of seven studies showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer (for CC versus AA: odds ratio (OR)?=?0.65, 95% confidence interval (CI) 0.47-0.89, P?=?0.007; for CC versus AA?+?AC: OR?=?0.65, 95% CI 0.48-0.89, P?=?0.006). Subgroup by race showed that the homozygote genotype CC of MTHFR rs1801131 polymorphism was significantly associated with decreased risk of liver cancer in Asians (CC versus AA: OR?=?0.64, 95% CI 0.46-0.90, P?=?0.010; for CC versus AA?+ AC: OR?=?0.63, 95% CI 0.45-0.88, P?=?0.007). However, the association in Caucasians was still unclear owing to the limited data available now. Thus, Asian individuals with the homozygote genotype CC of MTHFR rs1801131 polymorphism are significantly associated with decreased risk of liver cancer. The association in Caucasians needs further studies. PMID:24014085

Liang, Tie-Jun; Liu, Hui; Zhao, Xiao-Qian; Tan, Yan-Rong; Jing, Kai; Qin, Cheng-Yong

2014-01-01

295

Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and age of onset in schizophrenia.  

PubMed

Different lines of evidence indicate that methylenetetrahydrofolate reductase (MTHFR) functional gene polymorphisms, causative in aberrant folate-homocysteine metabolism, are associated with increased vulnerability to several heritable developmental disorders. Opposing views are expressed considering the possible association between MTHFR and susceptibility for schizophrenia. In order to evaluate if age of onset could explain some of this discrepancy we investigated the relationship between two functional MTHFR gene polymorphisms and age at onset in this disorder. Scandinavian patients (n = 820) diagnosed with schizophrenia, schizoaffective disorder, and schizophreniform disorder were investigated. Two functional MTHFR single nucleotide polymorphisms (SNPs; rs1801131 and rs1801133) were genotyped and the effect of MTHFR polymorphisms on the age of onset was examined with survival analysis. In an attempt to replicate the findings from the Scandinavian sample, the association between rs1801133 and age at onset was also analyzed in Chinese high-risk families, with two or more affected siblings (n = 243). Among the Scandinavian patients the functional MTHFR SNP rs1801133 (C677T) significantly affected age at onset of schizophrenia in a dose-dependent manner (P = 0.0015), with lower age of onset with increasing numbers of the mutant T-allele. There was no evidence of rs1801131 (A1298C) affecting age of onset in schizophrenia. Within the Chinese high-risk families carriers of the MTHFR 677T allele showed earlier age at onset than siblings being homozygous for the wild-type allele (P = 0.008). The MTHFR C677T polymorphism may play a role as a modifying factor for age of onset in schizophrenia. PMID:19746410

Vares, Maria; Saetre, Peter; Deng, Hong; Cai, Guiqing; Liu, Xiehe; Hansen, Thomas; Rasmussen, Henrik B; Werge, Thomas; Melle, Ingrid; Djurovic, Srdjan; Andreassen, Ole A; Agartz, Ingrid; Hall, Håkan; Terenius, Lars; Jönsson, Erik G

2010-03-01

296

Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis.  

PubMed

The aim was to investigate different genotypes and haplotypes of methylenetetrahydrofolate reductase (MTHFR-677, -1298) and plasma concentration of total homocysteine (tHcy) in Macedonian patients with occlusive artery disease (OAD) and deep venous thrombosis (DVT). Investigated groups consists of 80 healthy, 74 patients with OAD, and 63 patients with DVT. Plasma tHcy was measured with Microplate Enzyme Immunoassay. Identification of MTHFR genotypes and haplotypes was done with CVD StripAssay. The probability level (P-value) was evaluated by the Student's t-test. Plasma concentration of tHcy in CC and CT genotypes of MTHFR C677T was significantly increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy in AC genotype of MTHFR A1298C was increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal:heterozygote (CC:AC), heterozygote:normal (CT:AA), and heterozygote:heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote:heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT. PMID:18800176

Spiroski, Igor; Kedev, Sashko; Antov, Slobodan; Arsov, Todor; Krstevska, Marija; Dzhekova-Stojkova, Sloboda; Bosilkova, Gordana; Kostovska, Stojanka; Trajkov, Dejan; Petlichkovski, Aleksandar; Strezova, Ana; Efinska-Mladenovska, Olivija; Spiroski, Mirko

2008-01-01

297

Genetic polymorphism of MTHFR G1793A in Chinese populations.  

PubMed

5,10-methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism. A novel polymorphic site in MTHFR (G1793A) could influence the homocysteine levels and was first described in 2002. Investigations revealed that this allele was associated with susceptibility to several cancers, but its distribution around the world was not adequate. To study the prevalence of the mutant frequency in Chinese populations, 923 healthy individuals from 13 Chinese populations distributing widely from north to south were collected. DNA samples were isolated from peripheral blood samples and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), with the digestion of restriction endonuclease BsrBI. Of the 923 individuals, 82.1% were GG homozygous, 17.2% were GA heterozygous and 0.7% were AA homozygous. The frequency of the MTHFR 1793A allele in all tested individuals was 9.3%, which was slightly lower than indicated by HapMap (10%, Beiing Han, 45 samples). The frequencies of A allele were generally higher in southern China than that in northern China, and the frequencies had significant variance in 13 Chinese populations (X2 = 26.315, P = 0.010). Summarizing of the MTHFR G1793A allele polymorphism, including control groups in the case-control studies, we found only 20 normal peoples with AA homozygous (7 Chineses, 1 Caucasian, 2 Java Indonesias, 2 non-Hispanic whites, 6 Irish women, 2 Indians). The Java Indonesias and Ashkenzai Jevish had the highest (26.6%) and the lowest (1.3%) 1793A frequency, respectively. Together with our previous data, the MTHFR G1793A polymorphism was in linkage disequilibrium with both C677T and A1298C polymorphism sites in Chinese population, but not as strong as presented by HapMap. PMID:18409008

Mao, Renfang; Fan, Yihui; Chen, Feng; Fu, Songbin

2008-01-01

298

Multiple cerebral sinus thromboses complicating meningococcal meningitis: a pediatric case report  

PubMed Central

Background Cerebral venous sinus thrombosis (CVT) is a rare and potentially life-threatening condition in the pediatric population. The clinical presentation is frequently nonspecific; thus diagnosis is often delayed or missed. Case presentation A previously healthy 8 month-old boy was diagnosed with meningococcal meningitis. At hospital admission, an urgent non contrast-enhanced computed tomography (CT) of the head and neck was performed with normal results. Ceftriaxone was promptly started and the clinical condition of the patient improved. However, on the 7th day of hospitalization, the child suddenly manifested irritability and lethargy. An urgent contrast-enhanced CT of the head and neck was immediately performed, revealing thrombosis of the superior sagittal, transverse and rectus sinuses. A thrombophilic evaluation was performed, revealing hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) variants (C677T and A1298C). Conclusions The causes of CVT may be categorized into three main groups: hypercoagulable states, conditions causing blood flow disturbances, and all causes of inflammation or infection. In this case report, we observed more than one risk factor that predisposed the patient to CVT. Consequently, even if a causative factor is detected, a thrombophilic blood evaluation should be performed. In fact, in case of a prothrombotic condition, the patient’s family should be advised that prompt administration of anticoagulant is necessary in the event of situations that could lead to thrombosis. Finally, CVT may be considered a possible complication of infection even when recent imaging results are normal. A prompt CVT diagnosis is required to obtain a good outcome. Delayed diagnosis is mainly due to the rarity of the disease and physicians’ unawareness of this type of complication. PMID:24923843

2014-01-01

299

[Study of the genetic markers of thrombosis in hypertensive patients of the native population in the Republic of Mordovia].  

PubMed

The genetic markers (encoding factor of blood coagulation, the PAI-1 gene, the prothrombin gene, the GP IIb/IIIa gene, and the MTHFR gene) of thrombosis were studied in the Mordovians and Russians with essential hypertension (EH), who were residents of the Republic of Mordovia. One hundred and forty patients with TH and 90 healthy individuals of three nationalities, such as Russian, Moksha-Mordovian, and Erzya-Mordovian, were examined. Along with the routine clinical and instrumental studies, alleles of polymorphic markers were identified by the polymerase chain reaction (PCR). The polymorphic markers of the Arg 506 Gln gene, encoding factor V of blood coagulation, 4G5G of the PAI-1 gene, the G 20210 A prothrombin gene, the GP IIb/IIIa gene, and the A 1298 C MTHFR gene were also studied. The data were statistically analyzed using a package of the programs: Statistica for Windows 6.0 (Stat Soft), SPSS (version 14.0), and MS Excel XP (Microsoft). The authors used a chi-2 (chi-square) test was used to compare the incidence of genotypes and alleles in the patient groups. Hypertensive and normotensive persons were found to have no significant differences in the distribution of genotypes (encoding factor of blood coagulation, the PAI-1 gene, the prothrombin gene, and the GP IIb/IIIa gene) with regard to ethnicity in the Russian, and Moksha-Mordovian, and Erzya-Mordovian groups). Meanwhile, there was a significant preponderance of MTHFR gene mutation with the unfavorable genotype for Moksha-Mordovian patients with EH. The findings suggest that drug therapy for preventing venous thrombosis in patients with EH should be adjusted in relation to ethnicity. PMID:19824427

Postnov, A Iu; Goncharova, L N; Khasanova, Z B; Birliukova, D V; Konovalova, N V; Timoshkina, E I; Semenova, S V; Snegovsko?, V A; Kuzovenkova, O N

2009-01-01

300

Relationship of MTHFR gene polymorphisms with renal and cardiac disease  

PubMed Central

AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255

Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

2015-01-01

301

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

PubMed Central

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 large prospective studies: the Nurses’ Health Study, the Health Professionals Follow-up Study, and the Physicians’ Health Study. A total of 602 incident cases were identified and individually matched to controls who provided blood specimens. We used conditional logistic regression to calculate the relative risk (RR) and 95% confidence interval (95% CI) and then pooled the estimates using a random effects model. We found a lower risk of colorectal cancer among participants with low plasma folate levels: compared with the lowest quartile, RRs (95% CIs) for each successively higher quartile of plasma folate levels were 1.55 (1.14–2.11), 1.37 (1.00–1.88), and 1.47 (1.07–2.01; P for trend = 0.10). For the MTHFR polymorphisms, RRs (95% CIs) were 0.62 (0.44–0.90) for the 677TT vs. CC/CT and 0.68 (0.31–1.51) for the 1298CC vs. AC/AA, and these lower risk genotypes were associated with lower circulating plasma folate levels. When we partitioned the variation in plasma folate levels, variation due to folate intake was not positively associated with colorectal cancer risk. We found that low plasma folate levels were associated with lower risk of colorectal cancer. The reasons underlying a lower risk of colorectal cancer with low plasma folate levels require elucidation because plasma folate levels can reflect dietary intake, genetic influences, and other factors. PMID:22367721

Lee, Jung Eun; Wei, Esther K.; Fuchs, Charles S.; Hunter, David J.; Lee, I-Min; Selhub, Jacob; Stampfer, Meir J.; Willett, Walter C.; Ma, Jing; Giovannucci, Edward

2013-01-01

302

The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk.  

PubMed

This study aimed to determine the relation between methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism and lung cancer risk and the frequency of this polymorphism. The study involved 64 lung cancer patients (the study group) with definitive diagnosis and 61 noncancerous subjects (the control group). MTHFR C677T and A1298C mutation analysis was made using DNA isolated from peripheric blood and multiplex PCR and reverse hybridization strip test. Eighty-four percent of the patients were male. The age, gender, and history of alcohol use of the patients and control group were statistically similar. While MTHFR 677T and 677C allele frequency was 0.33 and 0.67 in the patients respectively, it was 0.29 and 0.71 in the control group. The frequencies of MTHFR 1298C and 1298A were 0.33 and 0.67 in the patients, and it was 0.31 and 0.69 in the control group respectively. When MTHFR 677TT and 677CT genotypes were compared with 677CC genotype, lung cancer risk was 2.4 times higher in the 677TT genotype. When MTHFR 1298AC and 1298CC genotypes were compared with 1298AA genotype, lung cancer risk was 1.5 times higher in 1298CC genotype. According to the results, allele frequency of homozygote T and C was high in lung cancer patients. It was 3.05 and 1.29 times higher in smokers than in non-smokers, and 3.05 and 1.64 times higher in males than in females; 3.0 and 2.44 times higher in those with non-small cell lung cancer than in those with small-cell lung cancer. PMID:20532637

Arslan, Sulhattin; Karadayi, Sule; Yildirim, Malik Ejder; Ozdemir, Ozturk; Akkurt, Ibrahim

2011-02-01

303

Biochemistry www.BioTechniques.com/rd1BioTechniques Rapid Dispatches doi: 10.2144/000113864  

E-print Network

,theNEXTcomplex,and the nuclear cap binding complex (CBC). The eukaryotic exosome complex has been shown to play a central. Commensurate with its diverse activities, the exosome varies in compo- sition along with cellular localization as hMTR4, has recently been shown to target the exosome for the specific degra- Improved methodology

Chait, Brian T.

304

EMERGING TECHNOLOGY BULLETIN: VOLATILE ORGANIC COMPOUND REMOVAL FROM AIR STREAMS BY MEMBRANES SEPARATION MEMBRANE TECHNOLOGY AND RESEARCH, INC.  

EPA Science Inventory

This membrane separation technology developed by Membrane Technology and Research (MTR), Incorporated, is designed to remove volatile organic compounds (VOCs) from contaminated air streams. In the process, organic vapor-laden air contacts one side of a membrane that is permeable ...

305

Structural and Functional Characteristics of Natural and Constructed Channels Draining a Reclaimed Mountaintop Removal and Valley Fill Coal Mine  

EPA Science Inventory

Mountaintop removal and valley fill (MTR/VF) coal mining has altered the landscape of the Central Appalachian region in the USA. Among the changes are large-scale topographic recontouring, burial of headwater streams, and degradation of downstream water quality. The goals of our ...

306

EFFECT OF RADIATION ON CORROSION OF STRUCTURAL MATERIALS BY MOLTEN FLUORIDES  

Microsoft Academic Search

A survey of the experimental methods used in testing the radiation ; stability of molten salts and their corrosion properties is presented. The ; effects of irradiation on the corrosion of Inconel exposed to fluoride fuel ; mixtures and on the physical and chemical stability of the fuel mixtures were ; investigated by irradiating in the MTR capsules filled with

G. W. Keilholtz; J. G. Morgan; W. E. Browning

1959-01-01

307

PLUG STORAGE BUILDING, TRA611, AWAITS SHIELDING SOIL TO BE PLACED ...  

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

PLUG STORAGE BUILDING, TRA-611, AWAITS SHIELDING SOIL TO BE PLACED OVER PLUG STORAGE TUBES. WING WALLS WILL SUPPORT EARTH FILL. MTR, PROCESS WATER BUILDING, AND WORKING RESERVOIR IN VIEW BEYOND PLUG STORAGE. CAMERA FACES NORTHEAST. INL NEGATIVE NO. 2949. Unknown Photographer, 7/30/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

308

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

PubMed Central

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

2012-01-01

309

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

310

33 CFR 154.1055 - Exercises.  

Code of Federal Regulations, 2011 CFR

...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...

2011-07-01

311

33 CFR 154.1055 - Exercises.  

Code of Federal Regulations, 2010 CFR

...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...

2010-07-01

312

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

PubMed Central

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

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

2012-01-01

313

HOT CELL BUILDING, TRA632. ELEVATIONS FOR SOUTH, NORTH AND WEST ...  

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

HOT CELL BUILDING, TRA-632. ELEVATIONS FOR SOUTH, NORTH AND WEST SIDES OF 1958 EXTENSION. H.K. FERGUSON CO. 895-MTR-ETR-632-A3, 12/1958. INL INDEX NO. 531-0632-00-279-101926, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

314

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

315

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

316

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

317

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

318

Transcriptional Analysis of Shewanella oneidensis MR-1 with an Electrode Compared to Fe(III)Citrate or Oxygen  

E-print Network

because of its versatile metabolic capabilities, especially with regard to respiration with extracellular electron acceptors. The physiological activity of S. oneidensis to respire at electrodes is of great to be involved in electrode respiration, such as the entire mtr operon. We also formulate hypotheses on other

Angenent, Lars T.

319

Single-cell imaging and spectroscopic analyses of Cr(VI) reduction on the surface of bacterial cells.  

PubMed

We investigate the 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, highly soluble Cr(VI) can be efficiently reduced to less toxic, nonsoluble Cr(2)O(3) nanoparticles by MR-1. Cr(2)O(3) 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 Cr(2)O(3) 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 MR-1 is wild type > single mutant ?mtrC or mutant ?omcA > double mutant (?omcA-?mtrC). Moreover, our results also suggest that direct microbial Cr(VI) reduction and Fe(II) (hematite)-mediated Cr(VI) reduction mechanisms may coexist in the reduction processes. PMID:23249294

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

2013-01-22

320

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

PubMed Central

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

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

321

GAMMA FACILITY, TRA641. PIPING LAYOUT FOR DEMINERALIZED WATER, DRAINS, SUMP. ...  

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

GAMMA FACILITY, TRA-641. PIPING LAYOUT FOR DEMINERALIZED WATER, DRAINS, SUMP. PICTORIAL VIEW OF CANAL AND LOCATION OF INPUTS AND DRAINS. IDAHO OPERATIONS OFFICE MTR-641-IDO-15P, 10/1954. INL INDEX NO. 531-0641-00-396-110615, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

322

Decommissioning of the Austrian 10 MW Research Reactor, Results and Lessons learned Paper  

Microsoft Academic Search

After the decision to shut down the 10 MW ASTRA-MTR Research Reactor was reached in May 1998, the possible options and required phases for decommissioning and removal of the radioactive components were evaluated in a decommissioning study. To support the decisions at each phase, an estimate of the activity inventory in the various parts of the reactor and the waste

G. Hillebrand; F. Meyer

2008-01-01

323

High bit rate mass data storage device  

NASA Technical Reports Server (NTRS)

The HDDR-II mass data storage system consists of a Leach MTR 7114 recorder reproducer, a wire wrapped, integrated circuit flat plane and necessary power supplies for the flat plane. These units, with interconnecting cables and control panel are enclosed in a common housing mounted on casters. The electronics used in the HDDR-II double density decoding and encoding techniques are described.

1973-01-01

324

HOT CELL BUILDING, TRA632. ELEVATIONS. PUMICE BLOCK WALLS. BLOWER AND ...  

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

HOT CELL BUILDING, TRA-632. ELEVATIONS. PUMICE BLOCK WALLS. BLOWER AND FILTER LOFT PLATFORM AND LADDER ON EAST SIDE. IDAHO OPERATIONS OFFICE MTR-632-IDO-4, 11/1952. INL INDEX NO. 531-0632-00-396-110563, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

325

ARMF, TRA660. NORTH, WEST AND EAST ELEVATIONS. PUMICE BLOCK WALLS. ...  

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

ARMF, TRA-660. NORTH, WEST AND EAST ELEVATIONS. PUMICE BLOCK WALLS. VERTICAL LIFT DOOR IN WEST WALL. WINDOWS AND LOUVERS WERE LATER COVERED. H.K. FERGUSON 8956 MTR-ETR-660-53, 9/1959. INL INDEX NO. 531-0660-00-279-101994, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

326

COMPRESSOR BUILDING, TRA626. ELEVATIONS. WINDOWS. WALL SECTIONS. PUMICE BLOCK BUILDING ...  

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

COMPRESSOR BUILDING, TRA-626. ELEVATIONS. WINDOWS. WALL SECTIONS. PUMICE BLOCK BUILDING HOUSED COMPRESSORS FOR AIRCRAFT NUCLEAR PROPULSION EXPERIMENTS. MTR-626-IDO-2S, 3/1952. INL INDEX NO. 531-0626-00-396-110535, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

327

CONTROL HOUSE, TRA620. MASONS ERECT PUMICE BLOCK WALLS. BUILDING WILL ...  

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

CONTROL HOUSE, TRA-620. MASONS ERECT PUMICE BLOCK WALLS. BUILDING WILL CONTROL ACCESS TO MTR AND OTHER "HOT" AND CLASSIFIED AREAS. INL NEGATIVE NO. 577. Unknown Photographer, 9/11/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

328

The EMBO Journal Vol.18 No.19 pp.53995410, 1999 Functions of the exosome in rRNA, snoRNA and  

E-print Network

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

Chanfreau, Guillaume

329

Safety analysis of the IAEA reference research reactor during loss of flow accident using the code MERSAT  

Microsoft Academic Search

Using the thermal hydraulic code MERSAT detailed model including primary and secondary loop was developed for the IAEA's reference research reactor MTR 10MW. The developed model enables the simulation of expected neutronic and thermal hydraulic phenomena during normal operation, reactivity and loss of flow accidents.Two different loss of flow accident (LOFA) have been simulated using slow and fast decrease time

A. Hainoun; N. Ghazi; B. Mansour Abdul-Moaiz

2010-01-01

330

Solvability of a stationary nonlinear Black-Scholes equation under conditions on the potential  

NASA Astrophysics Data System (ADS)

In this work, we study a nonlinear problem suggested by the Black-Scholes model for option pricing with stochastic volatility, namely, {mtr>1/2?2S2?2f/?S2+1/2?2V2?2f/??2+??2VS?2f/?S??-1/2??2V?f/??+rS?f/?S = r?(f)in ?,mtr>>f(S,?) = h(S,?),on ??mtr>| where the variables S and ? are respectively the asset value and the market volatility ([1], [2]). In [1], an analogous nonlinear problem has been investigated with a nonlinearity ? of the following type ?(f) = g(f)f. It has been used an iterative procedure under the hypothesis that g(f)f is nondecreasing, applying upper and lower solutions. The function g was assumed to be C2 and this regularity was used in computations in the proofs. We consider a Hölder continuous nonlinearity ?(f) and, assuming certain conditions on the potential ? of ?, we prove the existence of a positive solution. The method of the proof, which is based on the construction of upper and lower solutions, obtained as solutions of an auxiliary initial value problem, also yields information on the localization of f.

Fabião, Fátima; do Rosário Grossinho, Maria; Simões, Onofre

2009-05-01

331

ETR HEAT EXCHANGER BUILDING, TRA644. FLOOR PLAN AND SECTIONS. PUMP ...  

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

ETR HEAT EXCHANGER BUILDING, TRA-644. FLOOR PLAN AND SECTIONS. PUMP CUBICLES WITH PUMP MOTORS OUTSIDE CUBICLES. HEAT EXCHANGER EQUIPMENT. COOLANT PIPE TUNNEL ENTERS FROM REACTOR BUILDING. KAISER ETR-5582-MTR-644-A-3, 2/1956. INL INDEX NO. 532-0644-00-486-101294, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

332

ETR HEAT EXCHANGER BUILDING, TRA644. EAST SIDE. CAMERA FACING WEST. ...  

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

ETR HEAT EXCHANGER BUILDING, TRA-644. EAST SIDE. CAMERA FACING WEST. NOTE COURSE OF PIPE FROM GROUND AND FOLLOWING ROOF OF BUILDING. MTR BUILDING IN BACKGROUND AT RIGHT EDGE OF VIEW. INL NEGATIVE NO. HD46-36-3. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

333

PROCESS WATER BUILDING, TRA605. CAMERA LOOKING EAST AND TO WEST ...  

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

PROCESS WATER BUILDING, TRA-605. CAMERA LOOKING EAST AND TO WEST WALL NOW ENCLOSING FLASH EVAPORATORS. PIPES IN FOREGROUND WILL CARRY DEMINERALIZED COOLING WATER TO AND FROM THE MTR. INL NEGATIVE NO. 2937. Unknown Photographer, 7/30/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

334

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...

335

HOT CELL BUILDING, TRA632. SECTION DETAILS OF SHIELD CONCRETE, OPERATING ...  

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

HOT CELL BUILDING, TRA-632. SECTION DETAILS OF SHIELD CONCRETE, OPERATING WINDOWS, CHARGING HOLES. IDAHO OPERATIONS OFFICE MTR-632-IDO-5, 11/1950. INL INDEX NO. 531-0632-60-396-110564, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

336

Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis  

Microsoft Academic Search

Hyperammonemia is a universal finding after gastrointestinal hemorrhage in cirrhosis. We administered an oral amino acid solution mimicking the hemoglobin molecule to examine neuropsychological changes, brain glutamine levels, and brain magnetization transfer ratio (MTR). Forty-eight metabolically stable patients with cirrhosis and no evidence of “overt” hepatic encephalopathy (HE) were randomized to receive 75 g of amino acid solution or placebo;

Sherzad Balata; Steven W. M. Olde Damink; Karen Ferguson; Ian Marshall; Peter C. Hayes; Nicolaas E. P. Deutz; Roger Williams; Joanna Wardlaw; Rajiv Jalan

2003-01-01

337

ETR, TRA642. EASTWEST SECTION, LOOKING NORTH. CONTROL ROOM SECTION. FREIGHT ...  

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

ETR, TRA-642. EAST-WEST SECTION, LOOKING NORTH. CONTROL ROOM SECTION. FREIGHT ELEVATOR. KAISER ETR-5528-MTR-642-A-10, 11/1955. INL INDEX NO. 532-0642-00-486-100918, REV. 7. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

338

Hydrolytic activity and metabolism of sediment and epilithon in streams draining mountaintop removal coal mining, West Virginia, U.S.A.  

EPA Science Inventory

Mountaintop removal and valley filling (MTR/VF) is a method of coal mining used in the Central Appalachians. Regulations require that potential impacts to stream functions must be considered when determining the compensatory mitigation necessary for replacing aquatic resources un...

339

QUANTITATIVE MR IMAGING OF TWO-POOL MAGNETIZATION TRANSFER MODEL PARAMETERS IN MYELIN MUTANT SHAKING PUP  

PubMed Central

Magnetization transfer (MT) imaging quantitatively assesses cerebral white matter disease through its sensitivity to macromolecule-bound protons including those associated with myelin proteins and lipid bilayers. However, traditional MT contrast measured by the MT ratio (MTR) lacks pathologic specificity as demyelination, axon loss, inflammation and edema all impact MTR, directly and/or indirectly through multiple covariances among imaging parameters (particularly MTR with T1) and tissue features (e.g. axon loss with demyelination). In this study, more complex modeling of MT phenomena (“quantitative” MT or qMT) was applied to a less complex disease model (the myelin mutant shaking [sh] pup, featuring hypomyelination but neither inflammation nor axon loss) in order to eliminate the covariances on both sides of the MR-pathology “equation” and characterize these important relationships free from the usual confounds. qMT measurements were acquired longitudinally in 6 sh pups and 5 age-matched controls ranging from 3 to 16 months of age and compared with histology. The qMT parameter, bound pool fraction (f), was the most distinctive between diseased and control animals; both f and longitudinal relaxation rate R1 tracked myelination with normal aging, whereas MTR did not—presumably owing to counterbalancing MT and R1 effects. qMT imaging provides a more accurate and potentially more specific non-invasive tissue characterization. PMID:22664569

Samsonov, Alexey; Alexander, Andrew L.; Mossahebi, Pouria; Wu, Yu-Chien; Duncan, Ian D.; Field, Aaron S.

2012-01-01

340

Criticality safety of the ET-RR-1 new spent fuel storage pool  

Microsoft Academic Search

A new ET-RR-1 spent fuel storage pool is now under construction on the reactor site at Inshass. In addition, the pool is designed to accommodate spent fuel of MTR type as well. Criticality safety of this pool for the different fuel types has been evaluated as a function of U235 loading. The effect of fuel element separation (rows and columns)

E. Massoud; O. H. Sallam; E. Amin

2001-01-01

341

The Russian image of future war  

Microsoft Academic Search

Like its Soviet predecessor, the Russian military perceives the concept of a military?technical revolution (MTR) as the nucleus of future warfare. Emerging technologies are radically changing military capabilities and altering the character of warfare. The main efforts in future armed combat will be concentrated on the vertical or aerospace coordinate, and efforts on the ground will have a supporting role.

Mary C. Fitzgerald

1994-01-01

342

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

Microsoft Academic Search

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

Rizwan Ahmed; Aslam; Nasir Ahmad

2005-01-01

343

PLUG STORAGE BUILDING, TRA611, AS IT LOOKED WITH EARTHEN SHIELD ...  

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

PLUG STORAGE BUILDING, TRA-611, AS IT LOOKED WITH EARTHEN SHIELD COVERING STORAGE TUBES. MTR WING, TRA-604, AT RIGHT OF VIEW. CAMERA FACES NORTHWEST. INL NEGATIVE NO. 3177. Unknown Photographer, 8/29/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

344

Regulation of RNA processing and transport by a nuclear guanine nucleotide release protein and members of the Ras superfamily.  

PubMed Central

The RCC1 gene of mammals encodes a guanine nucleotide release protein (GNRP). RCC1 and a homolog in Saccharomyces cerevisiae (MTR1/PRP20/SRM1) have previously been implicated in control of mRNA metabolism and export from the nucleus. We here demonstrate that a temperature-sensitive fission yeast mutant which has a mutation in a homologous gene, and two of three additional (mtr1/prp20/srm1) mutants accumulate nuclear poly(A)+ RNA at 37 degrees C. In S.cerevisiae, maturation of rRNA and tRNA is also inhibited at 37 degrees C. Nevertheless, studies with the corresponding BHK-21 cell mutant indicate that protein import into the nucleus continues. MTR1 homologs regulate RNA processing at a point which is distinct from their regulation of chromosome condensation since: (i) poly(A)+ RNA accumulation in the fission yeast mutant precedes chromosome condensation, and (ii) unlike chromosome condensation, accumulation of nuclear poly(A)+ RNA does not require p34cdc28 kinase activation or protein synthesis. Moreover, experiments involving inhibition of DNA synthesis indicate that the S.cerevisiae homolog does not govern cell cycle checkpoint control. Since RCC1p acts as GNRP for Ran, a small nuclear GTPase of the ras superfamily, we have identified two homologs of Ran in S.cerevisiae (CNR1 and CNR2). Only CNR1 is essential, but both code for proteins extremely similar to Ran and can suppress mtr1 mutations in allele-specific fashion. Thus, MTR1 and its homologs appear to act as GNRPs for a family of conserved GTPases in controlling RNA metabolism and transport. Their role in governing checkpoint control appears to be restricted to higher eukaryotes. Images PMID:7687541

Kadowaki, T; Goldfarb, D; Spitz, L M; Tartakoff, A M; Ohno, M

1993-01-01

345

Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis  

PubMed Central

OBJECTIVE—To assess the feasibility of a new technique based on diffusion anisotropy to segment white and grey matter of the brain. To use this technique to measure the mean diffusivity (&Dmacr;) and magnetisation transfer ratio (MTR) of normal appearing white matter (NAWM) and grey matter (NAGM) from patients with multiple sclerosis.?METHODS—Dual echo turbo spin echo, MT, and diffusion weighted scans of the brain were obtained from 30 patients with multiple sclerosis and 18 sex and age matched healthy controls. After image coregistration and removal of T2 visible lesions, white and grey matter were segmented from 10 supratentorial slices using diffusion anisotropy thresholds. Histograms of the average MTR and &Dmacr; were created for normal white and grey matter of controls and NAWM and NAGM of patients with multiple sclerosis.?RESULTS—All the MTR histogram derived metrics of the NAWM from patients with multiple sclerosis were significantly lower than those of white matter from controls. The peak height of the &Dmacr; histogram of NAWM from patients with multiple sclerosis was also significantly different from that of normal white matter. The average MTR, the peak location of the MTR histogram, and peak height of the &Dmacr; histogram of the NAGM of patients with multiple sclerosis were significantly lower than the corresponding quantities of grey matter from controls.?CONCLUSIONS—A technique was developed for segmenting white and grey matter with the potential for improving the understanding of the pathophysiology of many neurological conditions. Its application to the study of multiple sclerosis confirms the presence of a diffuse tissue damage in the NAWM of these patients and suggests that subtle changes also occur in the NAGM.?? PMID:11181851

Cercignani, M; Bozzali, M; Iannucci, G; Comi, G; Filippi, M

2001-01-01

346

Magnetization transfer histograms in clinically isolated syndromes suggestive of multiple sclerosis.  

PubMed

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 32 years) a mean of 19 weeks (SD 3.8, range 12-33 weeks) after symptom onset with a clinically isolated syndrome and in 50 healthy controls (34 women, 16 men, median age 32.5 years). SPM99 software was used to generate segmented NAWM and NAGM MTR maps. The volumes of T2 lesions, white matter and grey matter were calculated. Eighty-one patients were followed up clinically and with conventional MRI after 3 years (n = 61) or until they developed multiple sclerosis if this occurred sooner (n = 20). Multiple regression analysis was used to investigate differences between patients and controls with age, gender and volume measures as covariates to control for potential confounding effects. The MTR histograms for both NAWM and NAGM showed a reduction in the mean (NAWM, 38.14 versus 38.33, P = 0.001; NAGM 32.29 versus 32.50, P = 0.009; units in pu) and peak location, with a left shift in the histogram. Mean NAWM and NAGM MTR were also reduced in the patients who developed clinically definite multiple sclerosis and multiple sclerosis according to the McDonald criteria but not in the 24 patients with normal T2-weighted brain magnetic resonance imaging (MRI). MTR abnormalities occur in the NAWM and NAGM at the earliest clinical stages of multiple sclerosis. PMID:16219673

Fernando, K T M; Tozer, D J; Miszkiel, K A; Gordon, R M; Swanton, J K; Dalton, C M; Barker, G J; Plant, G T; Thompson, A J; Miller, D H

2005-12-01

347

The crystal structure of S. cerevisiae Ski2, a DExH helicase associated with the cytoplasmic functions of the exosome  

PubMed Central

Ski2 is a cytoplasmic RNA helicase that functions together with the exosome in the turnover and quality control of mRNAs. Ski2 is conserved in eukaryotes and is related to the helicase Mtr4, a cofactor of the nuclear exosome involved in the processing and quality control of a variety of structured RNAs. We have determined the 2.4 Å resolution crystal structure of the 113 kDa helicase region of Saccharomyces cerevisiae Ski2. The structure shows that Ski2 has an overall architecture similar to that of Mtr4, with a core DExH region and an extended insertion domain. The insertion is not required for the formation of the Ski2–Ski3–Ski8 complex, but is instead an RNA-binding domain. While this is reminiscent of the Mtr4 insertion, there are specific structural and biochemical differences between the two helicases. The insertion of yeast Mtr4 consists of a ?-barrel domain that is flexibly attached to a helical stalk, contains a KOW signature motif, and binds in vitro-transcribed tRNAiMet, but not single-stranded RNA. The ?-barrel domain of yeast Ski2 does not contain a KOW motif and is tightly packed against the helical stalk, forming a single structural unit maintained by a zinc-binding site. Biochemically, the Ski2 insertion has broad substrate specificity, binding both single-stranded and double-stranded RNAs. We speculate that the Ski2 and Mtr4 insertion domains have evolved with different properties tailored to the type of transcripts that are the substrates of the cytoplasmic and nuclear exosome. PMID:22114319

Halbach, Felix; Rode, Michaela; Conti, Elena

2012-01-01

348

Quantitative evaluation in combination with nonquantitative evaluation in early patellar cartilage osteoarthritis at 3.0 T  

PubMed Central

Purpose To evaluate quantitative T1 and T2 relaxation times and magnetization transfer ratios (MTRs) in the early diagnosis of patellar cartilage osteoarthritis (OA) and to quantify and possibly refine the current Kellgren-Lawrence score criteria. Materials and methods A total of 92 cases of knee joints with 40 normal volunteers and 30 patients with OA were prospectively evaluated. The knee joints with OA were divided into mild and moderate groups according to the Kellgren-Lawrence score criteria. The discriminative analysis method was used to analyze the accuracy of the original grouped cases correctly classified by age, sex, T1 relaxation times, T2 relaxation times, and MTR values. Linear regression analysis was used between T1 relaxation time, T2 relaxation time, and MTR values. Results The mean T1 relaxation times decreased with the severity of OA, and a significant difference was only found between the normal and moderate OA groups (P<0.05). The mean T2 relaxation times increased, and significant differences were found between the normal and mild OA groups and the normal and moderate OA groups (P<0.001). The MTR values were 35.8%±4.2%, 36.1%±3.2%, and 35.4%±3.8%, respectively. There were no significant differences between the normal and OA groups. In addition, T1 relaxation times were positively correlated with MTR values (P<0.01). A discriminative analysis using a synthesis of all the influential factors indicated a high accuracy rate (93.9%) for the correct classification of the original grouped cases. Conclusion Quantitative T1 and T2 relaxation times were useful in the diagnosis of early OA; T2 relaxation times were more relatively sensitive. The functional usefulness of MTR values may be limited. T1 relaxation times positively correlated with MTR values. Multiple quantitative parameters, combined with some relative nonquantitative clinical parameters and Kellgren-Lawrence scores, may be useful in the early stage of OA and provide better information for clinical treatment and follow-up. PMID:25075182

Zuo, Houdong; Yao, Weiwu; Qu, Nan; Yang, Shixun; Wang, Jianhua; Cui, Xiaojiang

2014-01-01

349

Comparing Hydrologic Response Times Between a Forested and Mountaintop Mined Catchment  

NASA Astrophysics Data System (ADS)

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.

Miller, A. J.; Zegre, N.

2012-12-01

350

A Systematic Comparison Between Subjects with No Pain and Pain Associated with Active Myofascial Trigger Points  

PubMed Central

Objective To determine whether standard evaluations of pain distinguish subjects with no pain from those with myofascial pain syndromes (MPS) and active trigger points (MTrPs); and to assess whether self-reports of mood, function and health-related quality of life differ between these groups. Design Prospective, descriptive study. Setting University Patients Adults with and without neck pain Methods We evaluated adults with MPS and active (painful) MTrPs and those without pain. Subjects in the “Active” (‘A’) group had at least one active MTrP with spontaneous pain which was persistent, lasted more than 3 months and had characteristic pain on palpation. Subjects in the “No pain” (‘Np’) group had no spontaneous pain. However, some had discomfort on MTrP palpation (latent MTrP) while others in the Np group had no discomfort on palpation of nodules or had no nodules. Outcome Measures Each participant underwent range of motion (ROM) measurement, 10-point manual muscle test, and manual and algometric palpation. The latter determined the pain/pressure threshold using an algometer of 4 pre-determined anatomical sites along the upper trapezius. Participants rated pain using a verbal analogue scale (0–10); completed the Brief Pain Inventory and Oswestry Disability Scale (ODS), which included a sleep sub-scale; Short Form 36(SF36) and the Profile of Mood States (POMS). Results here were 24 in the ‘A’ group (mean 36 yrs, 16 women) and 26 in the ‘Np’ group (mean 26 yrs, 12 women). Subjects in group ‘A’ differed from ‘Np’ in number of latent MTrPs (p=.0062); asymmetrical cervical ROM (p=.01 side bending and p=.002 rotation); in all pain reports (p<.0001); algometry (p<.03); POMS (p<.038); SF36 (p<.01) and ODS (p<.0001). Conclusion A systematic musculoskeletal evaluation of people with MPS reliably distinguishes them from subjects with no pain. The two groups are significantly different in their physical findings and self-reports of pain, sleep disturbance, disability, health status and mood. These findings support the view that a “local” pain syndrome has significant associations with mood, health-related quality of life and function.. PMID:23810811

Gerber, Lynn H.; Sikdar, Siddhartha; Armstrong, Katee; Diao, Guoqing; Heimur, Juliana; Kopecky, John; Turo, Diego; Otto, Paul; Gebreab, Tadesse; Shah, Jay

2013-01-01

351

Mammographic texture resemblance generalizes as an independent risk factor for breast cancer  

PubMed Central

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

2014-01-01

352

Exploring the biochemistry at the extracellular redox frontier of bacterial mineral Fe(III) respiration  

SciTech Connect

Many species of the bacterial Shewanella genus are notable for their ability to respire in anoxic environments utilizing insoluble minerals of Fe(III) and Mn(IV) as extracellular electron acceptors. In Shewanella oneidensis, the process is dependent on the decahaem electron-transport proteins that lie at the extracellular face of the outer membrane where they can contact the insoluble mineral substrates. These extracellular proteins are charged with electrons provided by an inter-membrane electron-transfer pathway that links the extracellular face of the outer membrane with the inner cytoplasmic membrane and thereby intracellular electron sources. In the present paper, we consider the common structural features of two of these outermembrane decahaem cytochromes, MtrC and MtrF, and bring this together with biochemical, spectroscopic and voltammetric data to identify common and distinct properties of these prototypical members of different clades of the outer-membrane decahaem cytochrome superfamily.

Richardson, David J.; Edwards, Marcus; White, Gaye F.; Baiden, Nanakow; Hartshorne, Robert S.; Fredrickson, Jim K.; Shi, Liang; Zachara, John M.; Gates, Andrew J.; Butt, Julea N.; Clarke, Thomas

2012-06-01

353

Magnetization transfer magnetic resonance of human atherosclerotic plaques ex vivo detects areas of high protein density  

PubMed Central

Background Proteins are major plaque components, and their degradation is related to the plaque instability. We sought to assess the feasibility of magnetization transfer (MT) magnetic resonance (MR) for identifying fibrin and collagen in carotid atherosclerotic plaques ex vivo. Methods Human carotid artery specimens (n = 34) were obtained after resection from patients undergoing endarterectomy. MR was completed within 12 hr after surgery on an 11.7T MR microscope prior to fixation. Two sets of T1W spoiled gradient echo images were acquired with and without the application of a saturation pulse set to 10 kHz off resonance. The magnetization transfer ratio (MTR) was calculated, and the degree of MT contrast was correlated with histology. Results MT with appropriate calibration clearly detected regions with high protein density, which showed a higher MTR (thick fibers (collagen type I) (54 ± 8%)) compared to regions with a low amount of protein including lipid (46 ± 8%) (p = 0.05), thin fibers (collagen type III) (11 ± 6%) (p = 0.03), and calcification (6.8 ± 4%) (p = 0.02). Intraplaque hemorrhage (IPH) with different protein density demonstrated different MT effects. Old (rich in protein debris) and recent IPH (rich in fibrin) had a much higher MTR 69 ± 6% and 55 ± 9%, respectively, compared to fresh IPH (rich in intact red blood cells)(9 ± 3%). Conclusions MT MR enhances plaque tissue contrast and identifies the protein-rich regions of carotid artery specimens. The additional information from MTR of IPH may provide important insight into the role of IPH on plaque stability, evolution, and the risk for future ischemic events. PMID:22107813

2011-01-01

354

Glacial geomorphology of terrestrial-terminating fast flow lobes/ice stream margins in the southwest Laurentide Ice Sheet  

NASA Astrophysics Data System (ADS)

Glacial geomorphological mapping of southern Alberta, Canada, reveals landform assemblages that are diagnostic of terrestrial-terminating ice streams/fast flowing outlet glaciers with lobate snouts. Spatial variability in features that comprise the landform assemblages reflects changes in (a) palaeo-ice stream activity (switch on/off); and (b) snout basal thermal regimes associated with climate sensitive, steady state flow. Palaeo-ice stream tracks reveal distinct inset sequences of fan-shaped flowsets indicative of receding lobate ice stream margins. Former ice lobe margins are demarcated by (a) major, often glacially overridden transverse moraine ridges, commonly comprising glacitectonically thrust bedrock; and (b) minor, closely spaced recessional push moraines and hummocky moraine arcs. Details of these landform types are well exhibited around the former southern margins of the Central Alberta Ice Stream, where larger scale, more intensive mapping identifies a complex glacial geomorphology comprising minor transverse ridges (MTR types 1-3), hummocky terrain (HT types 1-3), flutings, and meltwater channels/spillways. The MTR type 1 constitute the summit corrugation patterns of glacitectonic thrust moraines or major transverse ridges and have been glacially overrun and moderately streamlined. The MTR type 2 sequences are recessional push moraines similar to those developing at modern active temperate glacier snouts. The MTR type 3 document moraine construction by incremental stagnation because they occur in association with hummocky terrain. The close association of hummocky terrain with push moraine assemblages indicates that they are the products of supraglacial controlled deposition on a polythermal ice sheet margin, where the HT type 3 hummocks represent former ice-walled lake plains. The ice sheet marginal thermal regime switches indicated by the spatially variable landform assemblages in southern Alberta are consistent with palaeoglaciological reconstructions proposed for other ice stream/fast flow lobes of the southern Laurentide Ice Sheet, where alternate cold, polythermal, and temperate marginal conditions associated with climate sensitive, steady state flow sequentially gave way to more dynamic streaming and surging activity.

Evans, David J. A.; Young, Nathaniel J. P.; Ó Cofaigh, Colm

2014-01-01

355

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

356

Fibre optics for metrology in nuclear research reactors applications to dimensional measurements  

Microsoft Academic Search

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 Fibre 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, is

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

2009-01-01

357

DESIGN AND OPERATION OF THE ORR  

Microsoft Academic Search

The ORNL Researeh Reactor is a general purpose, high flux, research tool ; designed to meet the needs fer thermal neutron fluxes of 10¹⁴n\\/cm²-; sec. The physical arrangement combines the high flux of aa MTR-type reactor with ; some of the ease of access exemplified by pool-type reactors. The result is a ; long narrow pool of water with the

T. E. Cole; J. A. Cox

1958-01-01

358

Opening of ATP-sensitive potassium channels causes generation of free radicals in vascular smooth muscle cells  

Microsoft Academic Search

.   Recent evidence suggests that opening of mitochondrial KATP channels in cardiac muscle triggers the preconditioning phenomenon through free radical production. The present study tested\\u000a the effects of KATP channel openers in a vascular smooth muscle cell model using the fluorescent probe MitoTracker (MTR) Red™ for detection of\\u000a reactive oxygen species (ROS). Rat aortic smooth muscle cells (A7r5) were incubated

Maike Krenz; Olaf Oldenburg; Holly Wimpee; Michael V. Cohen; Keith D. Garlid; Stuart D. Critz; James M. Downey; Joseph N. Benoit

2002-01-01

359

ETR, TRA642 AND TRA647. FLOOR PLANS FOR FIRST AND SECOND ...  

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

ETR, TRA-642 AND TRA-647. FLOOR PLANS FOR FIRST AND SECOND FLOORS OF THE OFFICE AND CONTROL BUILDING ALONG THE NORTH WALL OF THE ETR BUILDING. HEALTH PHYSICS, OPERATIONS, AND CONTROL ROOM. AIRLOCK DOOR. OFFICES. STAIRWAY LOCATIONS. KAISER ETR-5528-MTR-642-A-3, 10/1955. INL INDEX NO. 532-0642-00-100911, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

360

HEALTH AND SAFETY BUILDING, TRA667. SOUTH AND WEST ELEVATIONS. FLOOR ...  

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

HEALTH AND SAFETY BUILDING, TRA-667. SOUTH AND WEST ELEVATIONS. FLOOR PLAN AND ROOM DESIGNATIONS. NOTE PAIR OF ENTRY DOORS IN WEST ELEVATION FOR MEN AND WOMEN. CONCRETE T-BEAMS. F.C. TORKELSON CO. 842-MTR-667-A1, 1/1963. INL INDEX NO. 531-0667-00-851-151143, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

361

ETR, TRA642. EASTWEST SECTION, LOOKING NORTH. PATH OF COOLING WATER ...  

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

ETR, TRA-642. EAST-WEST SECTION, LOOKING NORTH. PATH OF COOLING WATER PIPE TUNNEL. WORKING AND STORAGE CANAL. SUB-PILE ROOM. CONTROL ROD ACCESS ROOM. FLOOR NAMES. (THIS WAS A CONCEPT DRAWING.) KAISER ETR-5528-MTR-642-A-5, 11/1955. INL INDEX NO. 532-0642-00-486-100913. REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

362

EAST FACE OF REACTOR BASE. COMING TOWARD CAMERA IS EXCAVATION ...  

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

EAST FACE OF REACTOR BASE. COMING TOWARD CAMERA IS EXCAVATION FOR MTR CANAL. CAISSONS FLANK EACH SIDE. COUNTERFORT (SUPPORT PERPENDICULAR TO WHAT WILL BE THE LONG WALL OF THE CANAL) RESTS ATOP LEFT CAISSON. IN LOWER PART OF VIEW, DRILLERS PREPARE TRENCHES FOR SUPPORT BEAMS THAT WILL LIE BENEATH CANAL FLOOR. INL NEGATIVE NO. 739. Unknown Photographer, 10/6/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

363

Electron flow in multiheme bacterial cytochromes is a balancing act between heme electronic interaction and redox potentials  

PubMed Central

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

Breuer, Marian; Rosso, Kevin M.; Blumberger, Jochen

2014-01-01

364

LOW-PRESSURE MEMBRANE CONTACTORS FOR CARBON DIOXIDE CAPTURE  

SciTech Connect

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.

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

365

Electron Flow in Multiheme Bacterial Cytochromes is a Balancing Act Between Heme Electronic Interaction and Redox Potentials  

SciTech Connect

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 multi-heme c-type cytochromes to arrange heme cofactors into wires that cooperatively span the cellular envelope, transmitting electrons along distances greater than 100 Angstroms. 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 effciently, remains a mystery so far inaccessible to experiment. To shed light on this critical topic, we carried out extensive computer simulations to calculate Marcus theory quantities for electron transfer along the ten heme cofactors in the recently crystallized outer membrane cytochrome MtrF. The combination of electronic coupling matrix elements with free energy calculations of heme redox potentials and reorganization energies for heme-to-heme electron transfer allows the step-wise and overall electron transfer rate to be estimated and understood in terms of structural and dynamical characteristics of the protein. 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 MtrCAB protein complex. Intriguingly, this flux must navigate thermodynamically uphill steps past low potential hemes. 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 suggests that the protein evolved to harbor low potential hemes, presumably necessary for reduction of certain soluble substrates, without slowing down electron ow. These findings are particularly profound in light of the apparently well conserved staggered cross heme wire structural motif in functionally related outer-membrane proteins.

Breuer, Marian; Rosso, Kevin M.; Blumberger, Jochen

2014-01-14

366

HOT CELL BUILDING, TRA632. FLOOR PLAN OF EXPANSION SHOWS LOCATION ...  

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

HOT CELL BUILDING, TRA-632. FLOOR PLAN OF EXPANSION SHOWS LOCATION OF NEW CELLS, "HEAVY" CELL AT WEST END, "LIGHT" CELLS AT EAST. MOCK-UP AND STORAGE AREAS IN SOUTH HALF OF FLOOR. H.K. FERGUSON 895-MTR-ETR-632-A1, 12/1958. INL INDEX NO. 531-0632-00-279-101924, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

367

Involvement of gene polymorphisms of the folate pathway enzymes in gene expression and anticancer drug sensitivity using the NCI60 panel as a model  

Microsoft Academic Search

Folate, a vitamin of the B group involved in one-carbon group metabolism, plays an important role in DNA synthesis and methylation. Several polymorphisms in the genes involved in folate uptake and biotransformations have been shown to be associated to the risk of cancer and to anticancer drug response. We studied common polymorphisms in MTHFR (N5,10-methylene-tetrahydrofolate reductase), MTHFD1 (N5,10-methylene-tetrahydrofolate dehydrogenase), MTR

Virginie Charasson; Dominique Hillaire-Buys; Isabelle Solassol; Armelle Laurand-Quancard; Frédéric Pinguet; Valérie Le Morvan; Jacques Robert

2009-01-01

368

Nondestructive burnup measurements by gamma-ray spectroscopy on spent fuel elements of the RP10 research reactor  

Microsoft Academic Search

Gamma-ray spectroscopy is an important nondestructive method for the qualification of irradiated nuclear fuels. Regarding research reactors, the main parameter required in the scope of such qualification is the average burnup of spent fuel elements. This work describes the measurement, using nondestructive gamma-ray spectroscopy, of the average burnup attained by Material Testing Reactor (MTR) fuel elements irradiated in the RP-10

Mariano Vela Mora; Alberto Gallardo Padilla; José Luis Castro Palomino; Luís Antônio Albiac Terremoto

2011-01-01

369

Analysis of a research reactor under anticipated transients without scram events using the RELAP5/MOD3.2 computer program  

E-print Network

. . . 54 III Primary Loop Parameters: Comparison of Research Reactor With a Typical PWR. IV Summary of the Results of the Simulated Transients. . . 57 93 ACRONYMS AAEC ANL Australian Atomic Energy Commission Argonne National Laboratory ANSTO... Australian Nuclear Science and Technology Organization (Formerly AAEC) ATWS CCA CHF DBA ECCS HIFAR HIZAPP HFIR IAEA INEL LOCA LUT MTR MLUT NTD ORNL PWR Anticipated Transients Without Scram Coarse Control Arm Critical Heat Flux Design...

Hari, Sridhar

2012-06-07

370

MATERIALS TESTING REACTOR IRRADIATION OF THORIUM  

Microsoft Academic Search

Various methods of irradiating Th in the MTR for production of U²³³; have been considered. The effects on reactor operation and experimental ; facilities have also been investigated. Production would come chiefly from Th ; placed in the reactor core shim-rod (shim-safety rod) positions and\\/or the Be ; reflector. The graphite reflector is not attractive for Th irradiation. The ;

Leyse

1951-01-01

371

ETR, TRA642. BASEMENT FLOOR PLAN. PART PLAN TO CONTROLROD ROOM ...  

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

ETR, TRA-642. BASEMENT FLOOR PLAN. PART PLAN TO CONTROL-ROD ROOM BELOW BASEMENT. CONTAMINATED AIR DUCT. STAIRWAYS ON EAST CORNERS AND EAST OF REACTOR TO CONTROL ROD ROOM. SPIRAL STAIR IN SOUTHWEST CORNER. GENERAL OPEN WORK SPACE. KAISER ETR-5528-MTR-642-A-6, 12/1955. INL INDEX NO. 532-0642-00-486-100914, REV. 7. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

372

Experimental analysis of sapphire contact probes for Nd-YAG laser angioplasty.  

PubMed

Laser angioplasty may offer percutaneous recanalization of occluded vessels where conventional guidewire and balloon techniques fail. Metal laser thermal angioplasty probes may, however, cause excessive thermal damage due to high tip temperatures (greater than 400.C). Therefore, contact probes made from artificial sapphire crystal designed for general laser surgery are currently being evaluated for use in laser angioplasty with continuous wave Nd-YAG energy. The sapphire modifies the laser energy in various ways, and this paper examines the physical characteristics of five types of rounded sapphire probe (SMTR, MTR, MTRL, OS, LT) and how these properties are affected by clinical usage. The laser beam profile emitted by these probes demonstrates a focal spot 1-2 mm in front of the tip. However, the forward transmission of Nd-YAG energy through the sapphires varied (SMTR, 85%; MTR, 83%; MTRL, 75%; OS, 54%; LT, 69%). Probe heating occurs owing to energy absorption within the sapphire. The surface temperature of the sapphires was measured in air by infrared thermography and the hottest region within the probes localized by an isothermographic technique. At energy settings used clinically (20 J, 10 watts for 2 s) the SMTR, MTR, and MTRL probes exhibited higher temperature rises (94-112.C) than the OS and LT probes (30.C), and heating was localized to the front surface of the former probes. Peak sapphire temperatures remained lower than those of metal probes even at higher energies. After clinical use, the MTR probe demonstrated reduced transmission, beam defocusing, and increased heating, due to surface pitting. Thus, recanalization with sapphire probes occurs by a combination of photothermal and contact thermal effects that are localized to the probe tip and may reduce the degree of thermal injury associated with metal probes. Understanding these basic properties is important to the application and development of contact probes for laser recanalization. PMID:2142867

Ashley, S; Brooks, S G; Gehani, A A; Kester, R C; Rees, M R

1990-06-01

373

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

374

RECOVERY OF Np²³⁷ BY THE NEPTEX SOLVENT-EXTRACTION PROCESS  

Microsoft Academic Search

Flowsheets are presented for the solvent extraction recovery of uranium ;\\u000a and Np²³⁷ from special highly irradiated MTR fuel elements and from ;\\u000a nonvolatile fluoride residues from the Oak Ridge Gaseous Diffusion Plant. In ;\\u000a both cases the material containing the neptunium and uranium is dissolved and ;\\u000a digested to inactivate emulsion-forming impurities, the neptunium and uranium are ;\\u000a extracted

J. R. Flanary; J. H. Goode; R. G. Mansfield; R. P. Wischow

1957-01-01

375

Conversion and Evaluation of the University of Massachusetts Lowell Research Reactor From High-Enriched To Low-Enriched Uranium Fuel  

Microsoft Academic Search

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

Leo M. Bobek

2003-01-01

376

Burnup studies of spent fuels of varying types and enrichment  

Microsoft Academic Search

This paper describes the results of fuel burnup measurements, made over a period of several years on discharged fuel from nuclear power plant and research reactor. The measured and calculated burnup of different spent fuel types, viz.: Natural uranium CANDU fuel bundles; 10.5% enriched booster rods; 20% enriched MTR fuel elements have been presented. High-resolution gamma spectrometry, using 137Cs and

S. A. Ansari; M. Asif; T. Rashid; K. G. Qasim

2007-01-01

377

Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism.  

PubMed

The hypothesis underlying this study is that variations in genes involved in methionine metabolism may contribute to genetic susceptibility for early-onset ischaemic stroke. We investigated 58 polymorphisms in AHCY, BHMT, BHMT2, CBS, ENOSF1, FOLH1, MTHFD1, MTHFR, MTR, MTRR, NNMT, PON1, PON2, SLC19A1, SHMT1, TCN2, TYMS genes on genomic DNA from 501 young patients who survived ischaemic stroke and 1,211 sex and age comparable controls. Genotype distribution was significantly different between patients and controls for the following SNPs: rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, rs202680 FOLH1, rs2274976 MTHFR, rs1979277 SHMT1, rs20721958 TCN2. On multiple logistic regression analysis adjusted for traditional risk factors, rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, and rs202680 FOLH1 remained independent risk factors for stroke. After haplotype reconstruction, generalised linear model analyses adjusted for traditional risk factors and using the FDR multiple testing correction showed significant associations between ischaemic stroke and BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes. This study identifies significant genetic associations between premature ischaemic stroke and haplotypes in BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS genes involved in methionine metabolism. PMID:20458436

Giusti, Betti; Saracini, Claudia; Bolli, Paola; Magi, Alberto; Martinelli, Ida; Peyvandi, Flora; Rasura, Maurizia; Volpe, Massimo; Lotta, Luca A; Rubattu, Speranza; Mannucci, Pier Mannuccio; Abbate, Rosanna

2010-08-01

378

Altered white matter connectivity in never-medicated patients with schizophrenia.  

PubMed

Numerous diffusion tensor imaging (DTI) studies have implicated white matter brain tissue abnormalities in schizophrenia. However, the vast majority of these studies included patient populations that use antipsychotic medication. Previous research showed that medication intake can affect brain morphology and the question therefore arises to what extent the reported white matter aberrations can be attributed to the disease rather than to the use of medication. In this study we included 16 medication-naïve patients with schizophrenia and compared them to 23 healthy controls to exclude antipsychotic medication use as a confounding factor. For each subject DTI scans and magnetization transfer imaging (MTI) scans were acquired. A new tract-based analysis was used that combines fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer ratio (MTR) to examine group differences in 12 major white matter fiber bundles. Significant group differences in combined FA, MD, MTR values were found for the right uncinate fasciculus and the left arcuate fasciculus. Additional analysis revealed that the largest part of both tracts showed an increase in MTR in combination with an increase in MD for patients with schizophrenia. We interpret these group-related differences as disease-related axonal or glial aberrations that cannot be attributed to antipsychotic medication use. PMID:22461372

Mandl, René C W; Rais, Monica; van Baal, Gertrudis Caroline M; van Haren, Neeltje E M; Cahn, Wiepke; Kahn, René S; Hulshoff Pol, Hilleke E

2013-09-01

379

Noise properties of motion-compensated tomographic image reconstruction methods  

PubMed Central

Motion-compensated image reconstruction (MCIR) methods incorporate motion models to improve image quality in the presence of motion. MCIR methods differ in terms of how they use motion information and they have been well-studied separately. However, there have been less theoretical comparisions of different MCIR methods. This paper compares the theoretical noise properties of three popular MCIR methods assuming known nonrigid motion. We show the relationship among three MCIR methods - motion-compensated temporal regularization (MTR), the parametric motion model (PMM), and post-reconstruction motion correction (PMC) - for penalized weighted least square cases. These analyses show that PMM and MTR are matrix-weighted sums of all registered image frames, while PMC is a scalar-weighted sum. We further investigate the noise properties of MCIR methods with Poisson models and quadratic regularizers by deriving accurate and fast variance prediction formulas using an “analytical approach”. These theoretical noise analyses show that the variances of PMM and MTR are lower than or comparable to the variance of PMC due to the statistical weighting. These analyses also facilitate comparisons of the noise properties of different MCIR methods, including the effects of different quadratic regularizers, the influence of the motion through its Jacobian determinant, and the effect of assuming that total activity is preserved. 2D PET simulations demonstrate the theoretical results. PMID:22759442

Chun, Se Young; Fessler, Jeffrey A.

2012-01-01

380

Enrichment of functional redox reactive proteins and identification by mass spectrometry results in several terminal Fe(III)-reducing candidate proteins in Shewanella oneidensis MR-1.  

PubMed

Identification of the proteins directly involved in microbial metal-reduction is important to understanding the biochemistry involved in heavy metal-reduction/immobilization and the ultimate cleanup of DOE contaminated sites. Although previous strategies for the identification of these proteins have traditionally required laborious protein purification/characterization of metal-reducing capability, activity is often lost before the final purification step, thus creating a significant knowledge gap. In the current study, subcellular fractions of Shewanella oneidensis MR-1 were enriched for Fe(III)-NTA reducing proteins in a single step using several orthogonal column matrices. The protein content of eluted fractions that demonstrated activity was determined by ultra-high pressure liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A comparison of the proteins identified from active fractions in all separations produced 30 proteins that may act as the terminal electron-accepting protein for Fe(III)-reduction. These include MtrA, MtrB, MtrC and OmcA as well as a number of other proteins not previously associated with Fe(III)-reduction. This is the first report of such an approach where the laborious procedures for protein purification are not required for identification of metal-reducing proteins. Such work provides the basis for a similar approach with other cultured organisms as well as analysis of sediment and groundwater samples from biostimulation efforts at contaminated sites. PMID:17137661

Elias, Dwayne A; Yang, Feng; Mottaz, Heather M; Beliaev, Alexander S; Lipton, Mary S

2007-02-01

381

Understanding the role of multiheme cytochromes in iron(III) reduction and arsenic mobilization by Shewanella sp. ANA-3  

NASA Astrophysics Data System (ADS)

The reduction of Fe (III) to Fe (II) and of arsenate (As (V)) to arsenite (As (III)) by Fe (III) reducing and As (V) respiring prokaryotes such as the bacterium Shewanella sp. ANA-3 may contribute to arsenic mobilization in aquifers contaminated with arsenic, specifically in places such as Bangladesh. Under oxic conditions As (V) predominates and is often adsorbed onto mineral surfaces such as amorphous ferrihydrite. However, under anoxic conditions As (III) predominates, sorbs to fewer minerals, and has a greater hydrologic mobility compared to As (V). The genetic mechanism underlying arsenic release from subsurface material most likely involves a combination of respiratory gene clusters (e.g. mtr/omc and arr). In this study, we are investigating the genetic pathways underlying arsenic mobilization. We have generated various mutations in the mtr/omc gene cluster, which encodes several outermembrane decaheme c-type cytochromes. Deletions in one mtr/omc gene did not eliminate iron reduction. However, strains carrying multiple gene deletions were greatly impaired in iron reduction abilities. Work is currently underway to generate combinations of iron reduction and arsenate reduction single and double mutants that will be used to investigate microbial mobilization of arsenic in flow-through columns containing As (V)-HFO coated sand. This work will address the importance of arsenate reduction and iron reduction in the mobilization of arsenic.

Reyes, C.; Duenas, R.; Saltikov, C.

2006-12-01

382

Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI - Correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH  

PubMed Central

Amide proton transfer (APT) MRI is sensitive to ischemic tissue acidosis and has been increasingly used as a research tool to investigate disrupted tissue metabolism during acute stroke. However, magnetization transfer asymmetry (MTRasym) analysis is often used for calculating APT contrast, which only provides pH-weighted images. In addition to pH- dependent APT contrast, in vivo MTRasym is subject to a baseline shift (?MTR?asym) attributable to the slightly asymmetric magnetization transfer (MT) effect. Additionally, APT contrast approximately scales with T1 relaxation time. Tissue relaxation time may also affect the experimentally obtainable APT contrast via saturation efficiency and RF spillover effects. In this study, we acquired perfusion, diffusion, relaxation and pH-weighted APT MRI data, and spectroscopy (MRS) in an animal model of acute ischemic stroke. We modeled in vivo MTRasym as a superposition of pH-dependent APT contrast and a baseline shift ?MTR?asym (i.e., MTRasym=APTR(pH) + ?MTR?asym), and quantified tissue pH. We found pH of the contralateral normal tissue to be 7.03 ± 0.05 and the ipsilateral ischemic tissue pH was 6.44 ± 0.24, which correlated with tissue perfusion and diffusion rates. In summary, our study established an endogenous and quantitative pH imaging technique for improved characterization of ischemic tissue acidification and metabolism disruption. PMID:22178815

Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S

2011-01-01

383

Arx1 Is a Nuclear Export Receptor for the 60S Ribosomal Subunit in Yeast  

PubMed Central

We previously showed that nuclear export of the large (60S) ribosomal subunit relies on Nmd3 in a Crm1-dependent manner. Recently the general mRNA export factor, the Mtr2/Mex67 heterodimer, was shown to act as an export receptor in parallel with Crm1. These observations raise the possibility that nuclear export of the 60S subunit in Saccharomyces cerevisiae requires multiple export receptors. Here, we show that the previously characterized 60S subunit biogenesis factor, Arx1, also acts as an export receptor for the 60S subunit. We found that deletion of ARX1 was synthetic lethal with nmd3 and mtr2 mutants and was synthetic sick with several nucleoporin mutants. Deletion of ARX1 led to accumulation of pre-60S particles in the nucleus that were enriched for Nmd3, Crm1, Mex67, and Mtr2, suggesting that in the absence of Arx1, 60S export is impaired even though the subunit is loaded with export receptors. Finally, Arx1 interacted with several nucleoporins in yeast two-hybrid as well as in vitro assays. These results show that Arx1 can directly bridge the interaction between the pre-60S particle and the NPC and thus is a third export receptor for the 60S subunit in yeast. PMID:18077551

Hung, Nai-Jung; Lo, Kai-Yin; Patel, Samir S.; Helmke, Kara

2008-01-01

384

The Crystal Structure of the Extracellular 11-heme Cytochrome UndA Reveals a Conserved 10-heme Motif and Defined Binding Site for Soluble Iron Chelates.  

SciTech Connect

Members of the genus Shewanella translocate deca- or undeca-heme cytochromes to the external cell surface thus enabling respiration using extracellular minerals and polynuclear Fe(III) chelates. The high resolution structure of the first undeca-heme outer membrane cytochrome, UndA, reveals a crossed heme chain with four potential electron ingress/egress sites arranged within four domains. Sequence and structural alignment of UndA and the deca-heme MtrF reveals the extra heme of UndA is inserted between MtrF hemes 6 and 7. The remaining UndA hemes can be superposed over the heme chain of the decaheme MtrF, suggesting that a ten heme core is conserved between outer membrane cytochromes. The UndA structure is the first outer membrane cytochrome to be crystallographically resolved in complex with substrates, an Fe(III)-nitrilotriacetate dimer or an Fe(III)-citrate trimer. The structural resolution of these UndA-Fe(III)-chelate complexes provides a rationale for previous kinetic measurements on UndA and other outer membrane cytochromes.

Edwards, Marcus; Hall, Andrea; Shi, Liang; Fredrickson, Jim K.; Zachara, John M.; Butt, Julea N.; Richardson, David; Clarke, Thomas A.

2012-07-03

385

A phase I open-label study of the safety, tolerability, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab for relapsed or refractory metastatic colorectal cancer.  

PubMed

Background Pazopanib is a multi-targeted tyrosine kinase inhibitor shown to be clinically active in the treatment of various cancer types. This study aimed to evaluate the maximum tolerated regimen (MTR), safety, and pharmacokinetics of pazopanib in combination with irinotecan and cetuximab in adult patients with relapsed or refractory metastatic colorectal cancer (mCRC). Patients and methods This was a Phase I, 3?+?3 design, open-label, dose-escalation study (NCT0050943; VEG108925) conducted in sequential cohorts to determine the MTR of pazopanib and irinotecan administered with cetuximab. Twenty-five patients received treatment in three dosing cohorts and were evaluated for safety and tolerability of the combination and pharmacokinetics of individual drugs. Results The MTR was determined to be 400 mg pazopanib per day orally in combination with 150 mg/m(2) irinotecan biweekly and 250 mg/m(2) cetuximab weekly by infusion. Neutropenia was the main dose-limiting toxicity. Pharmacokinetic results suggested that the overall systemic exposure to SN-38, the active metabolite of irinotecan, was affected by pazopanib to a greater extent than was the systemic exposure to irinotecan itself. Conclusions This study provided evidence for the manageable safety profile and feasibility of using the novel triplet combination of pazopanib, irinotecan, and cetuximab in patients with refractory mCRC. Further large-scale Phase II studies are warranted. PMID:25248752

Bennouna, Jaafar; Deslandres, Marion; Senellart, Helene; de Labareyre, Cecile; Ruiz-Soto, Rodrigo; Wixon, Claire; Botbyl, Jeff; Suttle, A Benjamin; Delord, Jean-Pierre

2015-02-01

386

A dynamic C-terminal segment in the Mycobacterium tuberculosis Mn/Fe R2lox protein can adopt a helical structure with possible functional consequences.  

PubMed

Mycobacterium tuberculosis R2-like ligand-binding oxidase (MtR2lox) belongs to a recently discovered group of proteins that are homologous to the ribonucleotide reductase R2 proteins. MtR2lox carries a heterodinuclear Mn/Fe cofactor and, unlike R2 proteins, a large ligand-binding cavity. A unique tyrosine-valine cross link is also found in the vicinity of the active site. To date, all known structures of R2 and R2lox proteins show a disordered C-terminal segment. Here, we present two new crystal forms of MtR2lox, revealing an ordered helical C-terminal. The ability of alternating between an ordered and disordered state agrees well with bioinformatic analysis of the protein sequence. Interestingly, ordering of the C-terminal helix shields a large positively charged patch on the protein surface, potentially used for interaction with other cellular components. We hypothesize that the dynamic C-terminal segment may be involved in control of protein function in vivo. PMID:22976985

Andersson, Charlotta S; Berthold, Catrine L; Högbom, Martin

2012-09-01

387

Ski2-like RNA helicase structures  

PubMed Central

Ski2-like RNA helicases are large multidomain proteins involved in a variety of RNA processing and degradation events. Recent structures of Mtr4, Ski2 and Brr2 provide our first view of these intricate helicases. Here we review these structures, which reveal a conserved ring-like architecture that extends beyond the canonical RecA domains to include a winged helix and ratchet domain. Comparison of apo- and RNA-bound Mtr4 structures suggests a role for the winged helix domain as a molecular hub that coordinates RNA interacting events throughout the helicase. Unique accessory domains provide expanded diversity and functionality to each Ski2-like family member. A common theme is the integration of Ski2-like RNA helicases into larger protein assemblies. We describe the central role of Mtr4 and Ski2 in formation of complexes that activate RNA decay by the eukaryotic exosome. The current structures provide clues into what promises to be a fascinating view of these dynamic assemblies. PMID:22995828

Johnson, Sean J.; Jackson, Ryan N.

2013-01-01

388

Field Demonstration of a Membrane Process to Separate Nitrogen from Natural Gas  

SciTech Connect

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.

Kaaeid Lokhandwala

2007-03-31

389

Interrater Reliability of Palpation of Myofascial Trigger Points in Three Shoulder Muscles  

PubMed Central

This observational study included both asymptomatic subjects (n=8) and patients with unilateral or bilateral shoulder pain (n=32). Patient diagnoses provided by the referring medical physicians included subacromial impingement, rotator cuff disease, tendonitis, tendinopathy, and chronic subdeltoid-subacromial bursitis. Three raters bilaterally palpated the infraspinatus, the anterior deltoid, and the biceps brachii muscles for clinical characteristics of a total of 12 myofascial trigger points (MTrPs) as described by Simons et al. The raters were blinded to whether the shoulder of the subject was painful. In this study, the most reliable features of trigger points were the referred pain sensation and the jump sign. Percentage of pair-wise agreement (PA) was ? 70% (range 63–93%) in all but 3 instances for the referred pain sensation. For the jump sign, PA was ? 70% (range 67–77%) in 21 instances. Finding a nodule in a taut band (PA = 45–90%) and eliciting a local twitch response (PA = 33–100%) were shown to be least reliable. The best agreement about the presence or absence of MTrPs was found for the infraspinatus muscle (PA = 69–80%). This study provides preliminary evidence that MTrP palpation is a reliable and, therefore, potentially useful diagnostic tool in the diagnosis of myofascial pain in patients with non-traumatic shoulder pain. PMID:19066669

Bron, Carel; Franssen, Jo; Wensing, Michel; Oostendorp, Rob A.B.

2007-01-01

390

Low frequency of mutated methylenetetrahydrofolate reductase 677C-->T and 1298A-->C genetics single nucleotide polymorphisms (SNPs) in Sub-Saharan populations.  

PubMed

5,10-Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are two of the key enzymes in the folate/vitamin B12-dependent remethylation of homocysteine to methionine. The frequencies of MTHFR single nucleotide polymorphisms (SNPs), 677C-->T, 1298A-->C, 1317T-->C and of MTR, 2756A-->G, have been widely studied in Caucasians, but they have never been reported simultaneously in a large population from Sub-Saharan Africa. Presently, we report the prevalence of these SNPs and their relationship to homocysteine in 240 subjects recruited in West Africa. The frequencies of the mutant genotypes 677TT (0.8%) and 1298CC (2%) were lower than that usually observed in Caucasians, while the frequency of the mutant 1317CC was higher (16%). We formed a systematic association of the mutated MTHFR 677C-->T SNP with a 1298A/1317T common haplotype. The MTHFR mutant genotype 677TT was associated with an intermediate hyperhomocysteinemia (92.4 +/- 6.0 micromol/l) higher than that described in Caucasians. The 2756A-->G SNP in the MTR was similarly distributed in Africans compared to Caucasians. In conclusion, the MTHFR 677TTor 1298CC genotypes are much rarer in Africans than in Caucasians. The 677TT low frequency may be related to the high effect of this mutation on homocysteine metabolism in the environmental conditions of this African region. PMID:12964809

Adjalla, Charles E; Amouzou, Emile K; Sanni, Ambaliou; Abdelmouttaleb, Idrissia; Chabi, Nicodème W; Namour, Fares; Soussou, Batoma; Guéant, Jean-Louis

2003-08-01

391

MTHFR C677T genotype as a risk factor for epilepsy including post-traumatic epilepsy in a representative military cohort.  

PubMed

The well-studied C677T variant in the methylenetetrahydrofolate reductase (MTHFR) enzyme is a biologically plausible genetic risk factor for seizures or epilepsy. First, plasma/serum levels of homocysteine, a pro-convulsant, are moderately elevated in individuals with the homozygote TT genotype. Furthermore, the TT genotype has been previously linked with migraine with aura-a comorbid condition-and with alcohol withdrawal seizures. Finally, several small studies have suggested that the TT genotype may be overrepresented in epilepsy patients. In this study, we consider whether the MTHFR C677T or A1298C variants are associated with risk of epilepsy including post-traumatic epilepsy (PTE) in a representative military cohort. Study subjects were selected from the cohort of military personnel on active duty during the years 2003 through 2007 who had archived serum samples at the DoD Serum Repository, essentially all active duty personnel during this time frame. We randomly selected 800 epilepsy patients and 800 matched controls based on ICD-9-CM diagnostic codes. We were able to isolate sufficient genetic material from the archived sera to genotype approximately 85% of our study subjects. The odds of epilepsy were increased in subjects with the TT versus CC genotype (crude OR=1.52 [1.04-2.22], p=0.031; adjusted OR=1.57 [1.07-2.32], p=0.023). In our sensitivity analysis, risk was most evident for patients with repeated rather than single medical encounters for epilepsy (crude OR=1.85 [1.14-2.97], p=0.011, adjusted OR=1.95 [1.19-3.19], p=0.008), and particularly for PTE (crude OR=3.14 [1.41-6.99], p=0.005; adjusted OR=2.55 [1.12-5.80], p=0.026). Our early results suggest a role for the common MTHFR C677T variant as a predisposing factors for epilepsy including PTE. Further exploration of baseline homocysteine and folate levels as predictors of seizure risk following traumatic brain injury is warranted. PMID:21787169

Scher, Ann I; Wu, Holly; Tsao, Jack W; Blom, Henk J; Feit, Preethy; Nevin, Remington L; Schwab, Karen A

2011-09-01

392

HAMLET -Human Model MATROSHKA for Radiation Exposure Determination of Astronauts -Current status and results  

NASA Astrophysics Data System (ADS)

The exploration of space as seen in specific projects from the European Space Agency (ESA) acts as groundwork for human long duration space missions. One of the main constraints for long duration human missions is radiation. The radiation load on astronauts and cosmonauts in space (as for the ISS) is a factor of 100 higher than the natural radiation on Earth and will further increase should humans travel to Mars. In preparation for long duration space missions it is important to evaluate the impact of space radiation in order to secure the safety of the astronauts and minimize their radiation risks. To determine the radiation risk on humans one has to measure the radiation doses to radiosensitive organs within the human body. One way to approach this is the ESA facility MATROSHKA (MTR), under the scientific and project lead of DLR. It is dedicated to determining the radiation load on astronauts within and outside the International Space Station (ISS), and was launched in January 2004. MTR is currently preparing for its fourth experimental phase inside the Japanese Experimental Module (JEM) in summer 2010. MTR, which mimics a human head and torso, is an anthropomorphic phantom containing over 6000 radiation detectors to determine the depth dose and organ dose distribution in the body. It is the largest international research initiative ever performed in the field of space dosimetry and combines the expertise of leading research institutions around the world, thereby generating a huge pool of data of potentially immense value for research. Aiming at optimal scientific exploitation, the FP7 project HAMLET aims to process and compile the data acquired individually by the participating laboratories of the MATROSHKA experiment. Based on experimental input from the MATROSHKA experiment phases as well as on radiation transport calculations, a three-dimensional model for the distribution of radiation dose in an astronaut's body will be built up. The scientific achievements contribute essentially to radiation risk estimations for future interplanetary space exploration by humans, putting them on a solid experimental and theoretical basis. The talk will give an overview of the current status of the MATROSHKA data evaluation and results and comparisons of the first three MTR experimental phases (MTR-1, 2A and 2B). The HAMLET project is funded by the European Commission under the EUs Seventh Frame-work Programme (FP7) under Project Nr: 218817 and coordinated by the German Aerospace Center (DLR) http://www-fp7-hamlet.eu

Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Burmeister, Soenke; Labrenz, Johannes; Hager, Luke; Palfalvi, Jozsef K.; Hajek, Michael; Puchalska, Monika; Sihver, Lembit

393

A study on the interactions of the MSL and the movement of amphydromic points and their impact on the mean tidal range in the North Sea  

NASA Astrophysics Data System (ADS)

According to IPCC (2007), the global average sea level rise projections are significant to the end of the century. Even the current time series analyses of the North Sea show, that there have been significant changes in the tidal regime starting from 1955 to 1960. While one can observe an appreciable increase in the mean tidal high water (MHW) from then on, the mean tidal low water (MLW) behaves contrary; as difference between the MHW and the MLW, the mean tidal range (MTR) in the German Bight rises (JENSEN and MUDERSBACH 2007). The reason for this behaviour is not as yet clarified entirely, but there have been many theoretical approaches ascribing the changes in the MTR either to anthropogenic or natural processes. The changes in the MTR can not only be observed in the German Bight, but also along the British east coast. However the MTR along the British coast shows a small decrease being the largest in the area of Aberdeen and reduces in northern and southern direction respectively reverses in the most southern part of England. According to JEVREJEVA et al. (2006) there is a significant change in the sea level of the north-eastern Atlantic starting at the same time as mentioned above, which is characterized by an uncommon increase. A tidal wave is influenced by the coriolis force which causes a deflection in the currents towards the right side of the direction of the motion in the northern hemisphere. In wide and at the end closed channels - what the North Sea may be considered as - the reflection of the tidal wave away from the boundary results in two waves travelling in the opposite directions. The resulting waves are oscillating around a time dependent position which is called an amphidromic point; in this position, the waves amplitude respectively the tidal range is zero. In the North Sea there are two amphidromic systems and a third incomplete amphidromic system. In the North Sea the average tidal range is between 0 to 8 metres. With an increasing distance from this position, the amplitude of the tidal wave and thereby the MTR rises. If the reflected wave within the basin is weaker than the in going tidal wave, the resulting centre of rotation in the northern hemisphere is shifted towards the left side of the running in (PUGH 1987). That is what one can also observe in the North Sea. Due to the proportionally more dissipated energy in the shallower shelf of the German Bight in relations to the steeper shelf of the British coast, there is an eastwards displacement of the amphidromic points. In consequence of the above mentioned sea level rise, the relative amount of energy being absorbed in the shallower shelf is considerably larger than in already steeper shelf regions. Additionally, anthropogenic interventions influence the topography along coastlines. As a result, the overall time dependent positions of the amphidromic points in the German Bight could have moved westwards. On basis of the measured MSL rise, the data of German and British gauges so far are indicating a long term shifting of the amphidromic points and a correlation with changes in the MTR. Recollecting the future MSL rise, the changes in the MTR could intensify and as FÜHRBÖTER and JENSEN (1985) pointed out, have impacts on the morphology, ecology but also the safety in coastal regions and estuaries.

Jensen, Juergen; Arns, Arne

2010-05-01

394

PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION  

SciTech Connect

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.

J.G. Wijmans; J.O. Stull

2001-11-07

395

Intranasal insulin delivery and therapy 1 Abbreviations: ?-CD, ?-cyclodextrin; ?-CD, ?-cyclodextrin; ?-CD, ?-cyclodextrin; AUC, area under the plasma\\/serum concentration versus time curve; C max, maximum or peak plasma\\/serum concentration; C min, minimum plasma\\/serum concentration; DDPC, didecanoyl- L-?-phosphatidylcholine; DM-?-CD, dimethyl-?-cyclodextrin; EDTA, ethylenediaminetetraacetic acid; FITC, fluorescein isothiocyanate; HLB, hydrophile–lipophile balance; hGH, human growth hormone; HP-?-CD, hydroxy-propyl-?-cyclodextrin; HPC, hydroxypropylcellulose; HSA, human serum albumin; Hyaff 11, hyaluronic acid ester; IDDM, insulin-dependent diabetes mellitus; Ig, immunoglobulin; Laureth-9, polyoxyethylene-9-lauryl ether; LPC, lysophosphatidylcholine; LPG, lysophosphatidylglycerol; MCC, microcrystalline cellulose; MTR, mucociliary transport rate; NIDDM, non-insulin-dependent diabetes mellitus; PC, phosphatidylcholine; RAMEB, randomly methylated ?-cyclodextrin; SDC, sodium deoxycholate; SG  

Microsoft Academic Search

Intranasal insulin delivery has been widely investigated as an alternative to subcutaneous injection for the treatment of diabetes. The pharmacokinetic profile of intranasal insulin is similar to that obtained by intravenous injection and, in contrast to subcutaneous insulin delivery, bears close resemblance to the `pulsatile' pattern of endogenous insulin secretion during meal-times. The literature suggests that intranasal insulin therapy has

Michael Hinchcliffe; Lisbeth Illum

1999-01-01

396

White matter hyperintensities and normal-appearing white matter integrity in the aging brain.  

PubMed

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) m(2)s(-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

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

2015-02-01

397

Multi-modal MRI of mild traumatic brain injury  

PubMed Central

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

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

398

Testing of a Transport Cask for Research Reactor Spent Fuel - 13003  

SciTech Connect

Since the beginning of the last decade three Latin American countries that operate research reactors - Argentina, Brazil and Chile - have been joining efforts to improve the regional capability in the management of spent fuel elements from the TRIGA and MTR reactors operated in the region. A main drive in this initiative, sponsored by the International Atomic Energy Agency, is the fact that no definite solution regarding the back end of the research reactor fuel cycle has been taken by any of the participating country. However, any long-term solution - either disposition in a repository or storage away from reactor - will involve at some stage the transportation of the spent fuel through public roads. Therefore, a licensed cask that provides adequate shielding, assurance of subcriticality, and conformance to internationally accepted safety, security and safeguards regimes is considered a strategic part of any future solution to be adopted at a regional level. As a step in this direction, a packaging for the transport of irradiated fuel for MTR and TRIGA research reactors was designed by the tri-national team and a half-scale model equipped with the MTR version of the internal basket was constructed in Argentina and Brazil and tested in Brazil. Three test campaigns have been carried out so far, covering both normal conditions of transportation and hypothetical accident conditions. After failing the tests in the first two test series, the specimen successfully underwent the last test sequence. A second specimen, incorporating the structural improvements in view of the previous tests results, will be tested in the near future. Numerical simulations of the free drop and thermal tests are being carried out in parallel, in order to validate the computational modeling that is going to be used as a support for the package certification. (authors)

Mourao, Rogerio P.; Leite da Silva, Luiz [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte (Brazil)] [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte (Brazil); Miranda, Carlos A.; Mattar Neto, Miguel [Instituto de Pesquisas Energeticas e Nucleares, Sao Paulo (Brazil)] [Instituto de Pesquisas Energeticas e Nucleares, Sao Paulo (Brazil); Quintana, Jose F.A.; Saliba, Roberto O. [Comision Nacional de Energia Atomica, Bariloche (Argentina)] [Comision Nacional de Energia Atomica, Bariloche (Argentina); Novara, Oscar E. [Comision Nacional de Energia Atomica, Buenos Aires (Argentina)] [Comision Nacional de Energia Atomica, Buenos Aires (Argentina)

2013-07-01

399

Adiposity is associated with structural properties of the adolescent brain.  

PubMed

Obesity, a major risk factor for cardiometabolic disease, is associated with variations in a number of structural properties in the adult brain, as assessed with magnetic resonance imaging (MRI). In this study, we investigated the cross-sectional relationship between visceral fat (VF), total body fat (TBF) and three MRI parameters in the brains of typically developing adolescents: (i) T1-weighted (T1W) signal intensity; (ii) T1W signal contrast between white matter (WM) and gray matter (GM); and (iii) magnetization transfer ratio (MTR). In a community-based sample of 970 adolescents (12-18 years old, 466 males), VF was quantified using MRI, and total body fat was measured using a multifrequency bioimpedance. T1W images of the brain were used to determine signal intensity in lobar GM and WM, as well as WM:GM signal contrast. A magnetization transfer (MT) sequence of MT(ON) and MT(OFF) was used to obtain MTR in GM and WM. We found that both larger volumes of VF and more TBF were independently associated with higher signal intensity in WM and higher WM:GM signal contrast, as well as higher MTR in both GM and WM. These relationships were independent of a number of potential confounders, including age, sex, puberty stage, household income and height. Our results suggest that both visceral fat and fat deposited elsewhere in the body are associated independently with structural properties of the adolescent brain. We speculate that these relationships suggest the presence of adiposity-related variations in phospholipid composition of brain lipids. PMID:25255944

Schwartz, Deborah H; Dickie, Erin; Pangelinan, Melissa M; Leonard, Gabriel; Perron, Michel; Pike, G Bruce; Richer, Louis; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomáš

2014-12-01

400

Effect of cropland management and slope position on soil organic carbon pool at the North Appalachian Experimental Watersheds  

SciTech Connect

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).

Hao, Yueli; Lal, Rattan; Owens, Lloyd; Izaurralde, R Cesar C.; Post, W M.; Hothem, Daniel

2002-12-01

401

c-Type Cytochrome-Dependent Formation of U(IV) Nanoparticles by Shewanella oneidensis  

SciTech Connect

Modern approaches for bioremediation of radionuclide contaminated environments are based on the ability of microorganisms to effectively catalyze changes in the oxidation states of metals that in turn influence their solubility. Although microbial metal reduction has been identified as an effective means for immobilizing highly-soluble uranium(VI) complexes in situ, the biomolecular mechanisms of U(VI) reduction are not well understood. Here, we show that c-type cytochromes of a dissimilatory metal reducing bacterium, Shewanella oneidensis MR-1 are essential for the reduction of U(VI) and formation of extracelluar UO2 nanoparticles.