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1

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

Microsoft Academic Search

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

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

2001-01-01

2

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

PubMed

We investigated the association between dietary intake of folate, vitamin B6, and the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotype with breast cancer. A matched case-control study was conducted, and 413 patients with newly diagnosed and histologically confirmed breast cancer and 436 controls were recruited. Folate intake, vitamin B6, and vitamin B12 levels were calculated, and the MTHFR C677T and A1298C and MTR A2756G polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Breast cancer cases were generally older, older at first live birth, and younger at menarche, had a higher body mass index, were smokers, had higher energy intake, and more first-degree relatives with breast cancer as well as more live births compared to controls. With respect to energy intake, we found that higher energy intake were more likely to increase the risk of breast cancer. The MTHFR 667TT genotype was associated with a moderately increased risk of breast cancer when compared with the CC genotype, and a significant odds ratio (OR; 95% confidence interval, CI) was found (OR = 1.70, 95%CI = 1.06-2.73). Individuals carrying T allele were associated with higher risk of breast cancer when compared with C allele (OR = 1.34, 95%CI = 1.06-1.70). We did not find a significant effect of the MTHFR A1298C and MTR A2756G on the risk of breast cancer. We did not find any association between folate intake and MTHFR C677T polymorphisms. In conclusion, we found that the MTHFR C667T polymorphism is associated with the risk of breast cancer, indicating that this genotype plays a role in breast cancer development. PMID:25366783

He, J M; Pu, Y D; Wu, Y J; Qin, R; Zhang, Q J; Sun, Y S; Zheng, W W; Chen, L P

2014-01-01

3

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and L-Dopa Treatment.  

PubMed

An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease. PMID:24532985

Rozycka, Agata; Jagodzinski, Pawel P; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

2013-12-01

4

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and L-Dopa Treatment  

PubMed Central

An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease. PMID:24532985

Rozycka, Agata; Jagodzinski, Pawel P.; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

2013-01-01

5

Association between dietary intake of folate, vitamin B6, B12 & MTHFR, MTR Genotype and breast cancer risk  

PubMed Central

Objective: we conducted a case-control study to investigate the association between dietary folate, vitamin B6 and vitamin B12 intake, MTHFR and MTR genotype, and breast cancer risk. Methods: Genotyping for MTHFR C677T and A1298C and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. The intake of folate, vitamin B6 and vitamin B12 were calculated by each food item from questionnaire. Results: Subjects with breast cancer tended to have more first-degree relatives (?2=30.77, P<0.001) and have high intake of folate (t=2.42, P=0.008) and Vitamin B6 (t=2.94, P=0.002). Compared to the reference group, women with MTHFR 677 TT genotype and T allele had a significantly increased risk of breast cancer, with ORs (95%CI) of 1.8(1.08-2.27) and 1.39(1.02-1.92), respectively. For those who had folate intake?450 ug/day, MTHFR 667TT genotype was associated with a higher risk of breast cancer (OR=2.45, 95% CI=1.09-5.82, P=0.02). Similarly, subjects with Vitamin B6 intake?0.84 mg/day and MTHFR 667T allele genotype was correlated with a marginally increased risk of breast cancer. A significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer (P for interaction was 0.025). Conclusion: This case-control study found a significant association between MTHFR C667T polymorphism, folate intake and vitamin B6 and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer. PMID:24639841

Weiwei, Zheng; Liping, Chen; Dequan, Li

2014-01-01

6

Prevalence of MTHFR gene polymorphisms (C677T and A1298C) among Tamilians  

Microsoft Academic Search

We have investigated the incidence of the C677T and A1298C methylene tetrahydrofolate reductase (MTHFR) gene single nucleotide polymorphisms (SNPs) in the South Indian Tamil Nadu population with a total number of 72 individuals. The MTHFR genotyping was performed using the polymerase chain reaction followed by restriction enzyme analysis. Homozygosity for the MTHFR A1298C SNP was detected in 15.3% (11\\/72) of

T. Angeline; Nirmala Jeyaraj; Selena Granito; Gregory J. Tsongalis

2004-01-01

7

Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility  

Microsoft Academic Search

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast\\u000a cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline,\\u000a PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between\\u000a the MTHFR A1298C polymorphism and breast

Li-Xin QiuJian; Jian Zhang; Wen-Hua Li; Qun-Ling Zhang; Hui Yu; Bi-Yun Wang; Lei-Ping Wang; Jia-Lei Wang; Hui-Jie Wang; Xiao-Jian Liu; Zhi-Guo Luo; Xiang-Hua Wu

2011-01-01

8

Further evidence that methylenetetrahydrofolate reductase A1298C polymorphism is a risk factor for schizophrenia  

Microsoft Academic Search

Previous work suggests that the methylenetetrahydrofolate reductase gene (MTHFR) functional polymorphism A1298C may be a risk factor for schizophrenia. In this study, the genetic association between the\\u000a MTHFR A1298C polymorphism and schizophrenia was investigated in 379 patients with schizophrenia and 380 age- and sex-matched controls\\u000a subjects. The results showed an association between the 1298C allele and the disorder (OR 1.39,

Chen ZhangBin; Bin Xie; Yasong Du; Wenhong Cheng; Yiru Fang; Shunying Yu

2010-01-01

9

Influence of maternal MTHFR A1298C polymorphism on the risk in offspring of schizophrenia  

Microsoft Academic Search

Several lines of evidence have suggested that two functional methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, C677T and A1298C, may be implicated in the etiology of schizophrenia. We examined these MTHFR polymorphisms in 111 families, composed of a patient and their parents, as well as 143 mothers of patients with schizophrenia and 235 age-matched mothers who had healthy children. The maternal MTHFR

Chen Zhang; Bin Xie; Yiru Fang; Wenhong Cheng; Yasong Du; Dongxiang Wang; Shunying Yu

2010-01-01

10

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

11

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

Microsoft Academic Search

Elevation in homocysteine and methylenetetrahydrofolate reductase (MTHFR) gene variants, C677T and A1298C, have been linked\\u000a with atherothrombosis. However their exact contribution to coronary artery disease (CAD) remains controversial. Moreover,\\u000a data from Tunisian patients are scarse. We examined the association of MTHFR C677T and A1298C, and changes in plasma homocysteine\\u000a in 352 Tunisian patients with angiographically-demonstrated CAD, and 390 age and

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

2009-01-01

12

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis.  

PubMed

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy (T2DN) risk is still unclear. This study was performed to evaluate if there is an association between the MTHFR A1298C gene polymorphism and T2DN risk using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library on 1 October 2013, and eligible studies were included and synthesized. Eight reports were recruited into this meta-analysis for the association of the MTHFR A1298C gene polymorphism with T2DN risk. The MTHFR A1298C C allele or CC genotype was shown to be not associated with T2DN risk (C allele: OR = 0.76, 95% CI: 0.43-1.34, p = 0.34; CC genotype: OR = 1.18, 95% CI: 0.63-2.22, p = 0.60). Interestingly, AA genotype was associated with the T2DN risk (OR = 0.68, 95% CI: 0.49-0.96, p = 0.03). In the sensitivity analysis according to the Hardy-Weinberg equilibrium (HWE), the results were consistent with those in non-sensitivity analysis. However, in the sensitivity analysis according to the control source from hospital, sample size of case (? 100), sample size of case (<100), the MTHFR A1298C gene polymorphism was not associated with T2DN risk. In conclusion, the MTHFR A1298C gene polymorphism was not associated with T2DN risk. However, additional studies are required to firmly establish a correlation between the MTHFR A1298C gene polymorphism and T2DN risk. PMID:24678913

Zhang, Jie; Xiao, Yan; Zhang, Xian-Wen; Gao, Zhi-Qing; Han, Jing-Hui

2014-07-01

13

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

14

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

Microsoft Academic Search

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

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

2002-01-01

15

C677T and A1298C Mutations in the MTHFR Gene and Survival in Colorectal Cancer  

Microsoft Academic Search

Background and aims: Our preliminary results laboratory have shown some association between C677T and A1298C MTHFR mutations and factors influencing survival in colorectal cancer. We studied the survival of patients with colorectal cancer depending on the initial Dukes- MAC stage of the disease at the time of diagnosis and the MTHFR mutation present. Methods: We randomly selected 69 patients with

Gelu Osian; Lucia Procopciuc; Liviu Vlad; Cornel Iancu; Teodora Mocan; Lucian Mocan

16

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

Microsoft Academic Search

Downs 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

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

2006-01-01

17

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

18

Methylenetetrahydrofolate reductase C677T and A1298C variants do not affect ongoing pregnancy rates following IVF  

Microsoft Academic Search

BACKGROUND: There is concern that IVF could compromise normal imprinting and methylation of DNA. Methyl- enetetrahydrofolate reductase (MTHFR) regulates the flow of folic acid-derived, one-carbon moieties for methylation and is critical to early embryonic development. Therefore, we hypothesized that common polymorphisms in MTHFR could associate with IVF outcome. METHODS: MTHFR C677T and A1298C polymorphism genotyping was per- formed on 374

A. T. Dobson; R. M. Davis; M. P. Rosen; S. Shen; P. F. Rinaudo; J. Chan; M. I. Cedars

2006-01-01

19

Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis.  

PubMed

Several independent studies have reported the role of the methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism in strokes, but the results are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed in the present study. In this meta-analysis, a total of 13 studies, including 1974 cases and 2660 controls, were selected to evaluate the possible association. Crude odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association in additive, dominant, and recessive models. The overall analysis showed that MTHFR A1298C was associated with a significant increase in the risk of stroke in the heterozygote comparison (AC vs AA: OR = 1.17; 95%CI = 1.03-1.34) and in the dominant model (AC/CC vs AA: OR = 1.22; 95%CI = 1.01-1.49). Stratified analysis showed a significantly strong association between the MTHFR A1298C polymorphism and stroke risk in Asian populations (OR = 1.32 for AC vs AA; OR = 1.94 for CC vs AA; OR = 1.37 for AC/CC vs AA; OR = 1.33 for C vs A allele), but not in Caucasian populations. Additionally, the MTHFR 1298C allele was found to be a risk factor for developing ischemic strokes. However, no statistically significant increased risk of hemorrhagic stroke was found in any of the genetic models. In conclusion, this meta-analysis supported that the MTHFR A1298C polymorphism could be capable of increasing stroke susceptibility in Asian, but not in Caucasian, populations. PMID:24391036

Lv, Q; Lu, J; Wu, W; Sun, H; Zhang, J

2013-01-01

20

Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and risk of hyperhomocysteinemia  

Microsoft Academic Search

Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate reductase (MTHFR) enzyme activity, owing to genetic\\u000a polymorphisms and\\/or inadequate folate intake. This study was aimed at investigating the prevalence of C677T and A1298C MTHFR\\u000a polymorphisms, and their impact on hyperhomocysteinemia in 95 epileptic patients and 98 controls. Double gradient-denaturing\\u000a gradient gel electrophoresis screening revealed that the frequency of T677 polymorphic allele was similar

D. Caccamo; S. Condello; G. Gorgone; G. Crisafulli; V. Belcastro; S. Gennaro; P. Striano; F. Pisani; R. Ientile

2004-01-01

21

A Common Mutation A1298C in Human Methylenetetrahydrofolate Reductase Gene: Association with Plasma Total Homocysteine and Folate Concentrations1  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocys- teine 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

Gideon Friedman; Netta Goldschmidt; Yechiel Friedlander; Arie Ben-Yehuda; Jacob Selhub; Sharona Babaey; Malka Mendel; Miriam Kidron; Hanoch Bar-On

22

Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects  

Microsoft Academic Search

Background: Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects (NTDs). Both C677T and A1298C MTHFR mutations are associated with NTDs, in some populations. Methods: The frequencies of the C677T and A1298C MTHFR mutations were determined in 25 children with NTDs, case mothers and 75 healthy individuals from

Andrea L. A Cunha; Mario H Hirata; Chong A Kim; Elvira M Guerra-Shinohara; Kymio Nonoyama; Rosario D. C Hirata

2002-01-01

23

Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: The A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal)  

Microsoft Academic Search

Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD), can result from nutritional deficiencies or genetic errors, including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms. The contribution of these polymorphisms in the development of CAD remains controversial. We analysed the impact of MTHFR C677T and A1298C on

Ana I. Freitas; Isabel Mendonça; Graça Guerra; Maria Brión; Roberto P. Reis; Angel Carracedo; António Brehm

2008-01-01

24

Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer  

Microsoft Academic Search

Authors report the results of four meta-analyses of studies that examined the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and head and neck cancer (nine studies, 2076 cases and 4834 controls for C677T; four studies, 1439 cases and 3941 controls for A1298C), and lung cancer (ten studies, 5274 cases and 7435 controls for C677T; seven studies, 5098 cases

Stefania Boccia; Paolo Boffetta; Paul Brennan; Gualtiero Ricciardi; Francesco Gianfagna; Keitaro Matsuo; Cornelia M. van Duijn; Rayjean J. Hung

2009-01-01

25

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

Microsoft Academic Search

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

N Mtiraoui; L Ghazouani; R R Finan; W Y Almawi; T Mahjoub

2006-01-01

26

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

27

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

PubMed Central

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

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

2014-01-01

28

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

29

The polymorphism of methylenetetrahydrofolate reductase C677T but not A1298C contributes to gastric cancer.  

PubMed

Increasing epidemiological studies have revealed the important role of methylenetetrahydrofolate reductase (MTHFR) in carcinogenesis. The association of MTHFR A1298C and MTHFR C677T polymorphisms with the risk for gastric cancer remains obscure due to inconsistent findings in independent studies among diverse ethnicities. A meta-analysis based on all available publications on this genetic association was performed. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the effect of MTHFR variants on gastric carcinogenesis. Totally, 25 eligible case-control studies were included into the meta-analysis according to the inclusion criteria. The MTHFR C677T polymorphism was demonstrated to significantly increase the susceptibility to gastric cancer (OR(T vs. C)?=?1.21, 95% CI 1.10-1.34; OR(TT vs. CC?)=?1.47, 95% CI 1.22-1.76; OR(TC vs. CC?)=?1.20, 95% CI 1.03-1.40; OR(TT + TC vs. CC)?=?1.27, 95% CI 1.10-1.47; OR(TT vs. CC + TC?)=?1.29, 95% CI 1.15-1.46), whereas no significant correlation was observed when assessing the MTHFR A1298C polymorphism (OR(C vs. A?)=?1.00, 95% CI 0.90-1.10; OR(CC vs. AA)?=?0.99, 95% CI 0.75-1.31; OR(CA vs. AA?)=?1.01, 95% CI 0.89-1.14; OR(CC + CA vs. AA)?=?1.00, 95% CI 0.89-1.13; OR(CC vs. AA + CA)?=?0.97, 95% CI 0.74-1.27). Subgroup analyses by ethnicity and source of controls further confirmed the findings in overall analysis. The meta-analysis suggests that the polymorphism of MTHFR C677T but not MTHFR A1298C confers a risk effect on the development of gastric cancer among Asians and Caucasians, which provides a new insight into the gastric cancer pathogenesis. PMID:23897558

Lv, Long; Wang, Ping; Sun, Beicheng; Chen, Gong

2014-01-01

30

Combined heterozygosity for methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C is associated with abruptio placentae but not with intrauterine growth restriction  

Microsoft Academic Search

Objective: This study was undertaken to investigate the involvement of MTHFR gene mutations C677T and A1298C implicated in vascular disease, in patients with abruptio placentae and intrauterine growth restriction (IUGR). Study Design: DNA was extracted from blood samples of 54 patients with placental vasculopathy (18 patients with abruptio placentae and 36 with IUGR) and 114 control patients and amplified by

Gabriël S. Gebhardt; Charlotte L. Scholtz; Renate Hillermann; Hein J. Odendaal

2001-01-01

31

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C  

Microsoft Academic Search

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both

Ali Sazci; Emel Ergul; Nese Tuncer; Gurler Akpinar; Ihsan Kara

2006-01-01

32

Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: Association is significant in men but not in women  

Microsoft Academic Search

Schizophrenia is a complex and common psychiatric disorder with a polygenic inheritance. In our previous report, we showed an association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and schizophrenia in patients from Bakirkoy in Istanbul, Turkey [Sazci, A., Ergul, E., Guzelhan, Y., Kaya, G., Kara, I., 2003. Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. Mol. Brain

Ali Sazci; Emel Ergul; Ismail Kucukali; Ihsan Kara; Guner Kaya

2005-01-01

33

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

Microsoft Academic Search

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,

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

2010-01-01

34

Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthritis treated with methotrexate: implication with elevation of transaminases  

Microsoft Academic Search

Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies

J P Mena; M Salazar-Páramo; L González-López; J I Gámez-Nava; L Sandoval-Ramirez; J D Sánchez; L E Figuera; F J Muñoz-Valle; M Vazquez del Mercado; I P Dávalos

2011-01-01

35

Genotypes of the C677T and A1298C polymorphisms of the MTHFR gene as a cause of human spontaneous embryo loss  

Microsoft Academic Search

BACKGROUND: Polymorphisms C677T and A1298C of the MTHFR gene have been implicated in fetal viability. In this study, we determined the allele and genotype frequencies of these polymorphisms in different populations, includ- ing spontaneous abortion (SA) fetal tissues, with the objective of evaluating their impact on fetal viability. METHODS: 342 samples of fetal tissues, selected from SA occurring during the

G. Callejon; A. Mayor-Olea; A. J. Jimenez; M. J. Gaitan; A. R. Palomares; F. Martinez; M. Ruiz; Armando Reyes-Engel

2007-01-01

36

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

37

MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients  

Microsoft Academic Search

Point mutations in methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia were implicated in the pathogenesis of diabetic nephropathy (DN) in many ethnic groups. This study addressed the association of C677T and A1298C single nucleotide polymorphisms (SNPs) of MTHFR gene with DN in Tunisian type 2 diabetes (T2DM) patients. Study subjects comprised 93 DN patients, 267 patients with normoalbuminuria, and 400 control subjects.

Nabil Mtiraoui; Intissar Ezzidi; Molka Chaieb; Hela Marmouche; Zied Aouni; Arbi Chaieb; Touhami Mahjoub; Martine Vaxillaire; Wassim Y. Almawi

2007-01-01

38

A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine\\/folate metabolism  

Microsoft Academic Search

5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine\\/methionine metabolism. The most-studied\\u000a C677T polymorphism in the MTHFR gene results in a thermolabile variant with reduced activity, and is associated with increased\\u000a levels of total plasma homocysteine, a risk factor for coronary artery disease. A new mutation in the MTHFR gene (A1298C)\\u000a has also been reported to lower enzyme activity.

S. Friso; D. Girelli; E. Trabetti; C. Stranieri; O. Olivieri; E. Tinazzi; N. Martinelli; G. Faccini; P. F. Pignatti; R. Corrocher

2002-01-01

39

Association of polymorphisms MTHFR C677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy  

Microsoft Academic Search

Background and aims  The enzyme MTHFR plays an important role in folate metabolism, and folate is implicated in carcinogenesis due to its role in DNA methylation,\\u000a repair, and synthesis. We analyze the relationship of MTHFR C677T and A1298C polymorphisms with biological, clinicopathological, genetic and epigenetic features of tumors, and the patient\\u000a outcome after treatment with 5-FU-based chemotherapy to determine the contribution

Antonia M. Fernández-Peralta; Lydia Daimiel; Nargisse Nejda; Daniel Iglesias; Vicente Medina Arana; Juan J. González-Aguilera

2010-01-01

40

Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B 12 levels and the extent of coronary artery disease  

Microsoft Academic Search

The question of whether mild hyperhomocysteinemia is a risk factor for coronary artery disease (CAD) has long been debated and is still unclear. We investigated whether there is a link between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms or plasma homocysteine and CAD. This is a case-control study that included 2,121 consecutive patients (cases) with angiographically proved CAD and

Klaus Kölling; Gjin Ndrepepa; Werner Koch; Siegmund Braun; Julinda Mehilli; Albert Schömig; Adnan Kastrati

2004-01-01

41

The common MTHFR C677T and A1298C variants are not associated with the risk of non-syndromic cleft lip\\/palate in northern Venezuela  

Microsoft Academic Search

Non-syndromic cleft lip with or without cleft palate (nsCL\\/P) is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL\\/P patients and, in

Mehmet A. Sözen; Marie M. Tolarova; Richard A. Spritz

2009-01-01

42

Meta and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: A Huge-GSEC review  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640

Stefania Boccia; Rayjean Hung; Gualtiero Ricciardi; Francesco Gianfagna; Matthias P. A. Ebert; Jing-Yuan Fang; Chang-Ming Gao; T. Götze; Francesco Graziano; M. Lacasaña-Navarro; Dongxin Lin; L. López-Carrillo; You-Lin Qiao; Hongbing Shen; Rachael Stolzenberg-Solomon; Toshiro Takezaki; Yu-Rong Weng; Fang Fang Zhang; P. Tikka-Kleemola; Paolo Boffetta; Emanuela Taioli

2008-01-01

43

MTHFR ( C677T and A1298C ) Polymorphisms and Risk of Sporadic Distal Colorectal Adenoma in the UK Flexible Sigmoidoscopy Screening Trial (United Kingdom)  

Microsoft Academic Search

Objective  The purpose of this study was to further evaluate the role of low activity MTHFR variants as well as to explore interactive effects between alcoholic drink consumption and MTHFR variants and risk of distal colorectal adenomatous polyps.\\u000a \\u000a \\u000a \\u000a Methods  We examined the relationship between MTHFR C677T and A1298C gene polymorphisms and risk of distal adenomas in one of the largest case control

Panagiota N. Mitrou; Mark A. Watson; Alexandre S. Loktionov; Christopher Cardwell; Marc J. Gunter; Wendy S. Atkin; Christopher P. Macklin; Tom Cecil; Timothy D. Bishop; John Primrose; Sheila A. Bingham

2006-01-01

44

Effects of the C677T and A1298C polymorphisms of the MTHFR gene on the genetic predisposition for diabetic nephropathy  

Microsoft Academic Search

Background. Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with low folic acid intake. A recently reported second common poly- morphism, A1298C, may increase homocysteine, but only in individuals carryingthe T677 allele. This study aimed to investigate the influence

Dariusz Moczulski; Hanna Fojcik; Ewa Zukowska-Szczechowska; Ilona Szydlowska; Wladyslaw Grzeszczak

2003-01-01

45

The Common Mutations C677T and A1298C in the Human Methylenetetrahydrofolate Reductase Gene Are Associated with Hyperhomocysteinemia and Cardiovascular Disease in Hemodialysis Patients  

Microsoft Academic Search

Background: Plasma total homocysteine (tHcy) level might be an important risk factor for the development of cardiovascular disease (CVD) in dialysis patients. While both renal failure and mutations of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene may result in hyperhomocysteinemia and CVD, the distinct roles of the thermolabile MTHFR mutation at nucleotide C677T and the more recently described mutation at nucleotide A1298C

Y. S. Haviv; V. Shpichinetsky; N. Goldschmidt; I. Abou Atta; A. Ben-Yehuda; G. Friedman

2002-01-01

46

MTHFR gene C677T and A1298C polymorphisms and homocysteine levels in primary open angle and primary closed angle glaucoma  

Microsoft Academic Search

PURPOSE: To investigate the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genotypes and plasma concentrations of total homocysteine (tHcy) in Pakistani patients with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG). METHODS: This was a prospective case-control study. A total of 295 patients (173 POAG, 122 PCAG) and 143 age- and sex-matched controls were subdivided into two ethnic

Shazia Micheal; Raheel Qamar; Farah Akhtar; Muhammad Imran Khan; Wajid Ali Khan; Asifa Ahmed

2009-01-01

47

Association of the C677T and A1298C polymorphisms in the 5,10 methylenetetrahydrofolate reductase gene in patients with migraine risk  

Microsoft Academic Search

Although controversial, diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose to migraine in Turkish people. In a case-control study, we determined the prevalence of two common MTHFR polymorphisms,C677T and A1298C, in 102 migraine patients (23 migraine with aura, 70 migraine without aura and nine with tension-type headache) and compared it to that of

Ihsan Kara; Ali Sazci; Emel Ergul; Guner Kaya; Gamze Kilic

2003-01-01

48

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus  

Microsoft Academic Search

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.

Mehrali Rahimi; Ali Hasanvand; Zohreh Rahimi; Asad Vaisi-Raygani; Hadi Mozafari; Mansour Rezaei; Javad Zargooshi; Farid Najafi; Ebrahim Shakiba

2010-01-01

49

Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis.  

PubMed

The aim of this study was to explore whether the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) play a role in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). MEDLINE and EMBASE database searches and subsequent manual searches were utilized to identify articles in which C677T and A1298C MTHFR polymorphisms were evaluated in RA patients taking MTX. A meta-analysis was conducted to identify associations between MTHFR polymorphisms and MTX toxicity. Twelve studies comprising a total of 2,288 RA patients were included in our meta-analysis. Meta-analysis revealed an association between the overall toxicity of MTX and the MTHFR 677TT genotype (odds ratio [OR]?=?1.615, 95 % confidence interval [CI]?=?1.185-2.200, p?=?0.002). Stratification by ethnicity indicated an association between the MTHFR 677TT genotype and the overall toxicity of MTX in East Asians (OR?=?1.583, 95 % CI?=?1.075-2.331, p?=?0.020). The toxicity of MTX also was found to be associated with the TT genotype in patients taking folate (OR?=?1.893, 95 % CI?=?1.283-2.793, p?=?0.001). Stratification by toxicity type indicated an association between the MTHFR 677TT genotype and any adverse effects (OR?=?1.716, 95 % CI?=?1.127-2.612, p?=?0.012). Meta-analysis stratified by toxicity type indicated an association between the MTHFR 1298CC genotype and any adverse effects (OR?=?0.501, 95 % CI?=?0.284-0.886, p?=?0.017). The results of our meta-analysis suggest that the MTHFR C677T and A1298C polymorphisms are associated with MTX toxicity in RA patients. PMID:24794492

Song, Gwan Gyu; Bae, Sang-Cheol; Lee, Young Ho

2014-12-01

50

Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis  

Microsoft Academic Search

Association studies on the MTHFR polymorphisms (C677T and A1298C) in colorectal cancer (CRC) and colorectal adenoma have shown conflicting results. We performed\\u000a a meta-analysis to better assess the purported associations. Overall, the 677T allele (10,131 patients and 15,362 controls)\\u000a showed a small but significant protective effect against CRC compared to the 677C allele [P=0.0003, odds ratio (OR)=0.93; 95% confidence interval

Yan Huang; Shizhong Han; Yao Li; Yumin Mao; Yi Xie

2007-01-01

51

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

52

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

53

MTHFR gene C677T and A1298C polymorphisms and homocysteine levels in primary open angle and primary closed angle glaucoma  

PubMed Central

Purpose To investigate the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genotypes and plasma concentrations of total homocysteine (tHcy) in Pakistani patients with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG). Methods This was a prospective case-control study. A total of 295 patients (173 POAG, 122 PCAG) and 143 age- and sex-matched controls were subdivided into two ethnic groups, Punjabis (Punjab province, central Pakistan) and Pathans (North-West Frontier Province, northern Pakistan). Genotypes of the MTHFR C677T and A1298C polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). An enzyme-linked immunosorbent assay was used to determine the total serum homocysteine (tHcy) levels. Associations were determined by logistic regression analysis. Results Frequency distributions of genotypes and combined genotypes as well as homocysteine levels were obtained. The overall distribution of the C677T genotype was found to be significantly associated with PCAG (CC 69%, CT 21%, TT 10%; p=0.001, ?2=12.6), but not with POAG (CC 71%, CT 28%, TT 1%; p=0.98, ?2=0.02) as compared to the controls (CC 71%, CT 29%, TT 1%). The Pathan cohorts revealed no association with the disease; however, the Punjabis demonstrated a significant association with PCAG (CC 75%, CT 11%, TT 13%; p<0.001, ?2=17.2). PCAG in the Punjabi subjects was also significantly associated with the A1298C polymorphism (AA 43%, AC 54%, CC 3%; p<0.001, ?2=33.9) as compared to the controls. Combined genotype data showed no association with POAG; however, a significant association with all combined genotypes was observed in the overall PCAG subjects (p<0.05, ?2=20.1). This difference was particularly apparent in the TTAA and TTAC combinations that were completely absent in the control groups (p<0.05. ?2=49.6). Mean serum tHcy levels were found to be significantly increased in the POAG (15.2±1.28 µmol/l, p<0.001) and PCAG (20.8±4.8 µmol/l) groups as compared to the controls (10.0±0.97 µmol/l). The tHcy levels in the TT and AC genotype were significantly elevated in the PCAG group (67±12.39 µmol/l, p<0.001; 23±5.94 µmol/l, p=0.027) as compared to the controls. Conclusion The TT and AC genotypes of MTHFR C677T and A1298C polymorphisms and the combined genotype TTAC were associated with PCAG in Punjabi subjects of Pakistani origin and correlated with the high serum tHcy levels seen in these patients. PMID:19936026

Micheal, Shazia; Qamar, Raheel; Akhtar, Farah; Khan, Muhammad Imran; Khan, Wajid Ali

2009-01-01

54

Ethnic variation of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase (MTHFR) gene in southwestern Mexico.  

PubMed

In this study, we examined the distribution of genotype and allele frequencies of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase gene (MTHFR) in two ethnic groups in the State of Guerrero, Mexico, which were compared with those of the Mestizo population of the region. A comparative study was conducted on 455 women from two ethnic groups and a group of Mestizo women of the State of Guerrero, Mexico: 135 Nahuas, 124 Mixtecas, and 196 Mestizas. Genotyping of both polymorphisms were performed by using polymerase chain reaction-restriction fragment length polymorphism methods. We found that the 677TT genotype was more frequent in Nahua and Mixteca women compared to Mestiza women (P = 0.008), and the most prevalent genotype in both ethnic groups was the 1298AA genotype (P < 0.001). We also compared the 677T allele frequency obtained from the groups studied with the frequencies reported in other ethnic groups of Mexico (Huichol, Tarahumara, and Purepecha). There were significant differences between the three ethnic groups compared to Nahuas (Huicholes, P = 0.004; Tarahumaras, P < 0.001; Purepechas, P = 0.042). Our results indicated significant differences in the frequencies of the C677T and A1298C polymorphisms between the two ethnic groups and the Mestizo population of the State of Guerrero. In addition, we found strong differences with other ethnic groups in Mexico. These results could be useful for future studies investigating diseases related to folate metabolism, and could help the government to design specific nutrition programs for different ethnic groups. PMID:25299110

Antonio-Véjar, V; Del Moral-Hernández, O; Alarcón-Romero, L C; Flores-Alfaro, E; Leyva-Vázquez, M A; Hernández-Sotelo, D; Illades-Aguiar, B

2014-01-01

55

The Association between Two Common Mutations C677T and A1298C in Human Methylenetetrahydrofolate Reductase Gene and the Risk for Diabetic Nephropathy in Type II Diabetic Patients1  

Microsoft Academic Search

Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be associated with a predisposition to developing diabetic nephropathy (DN) in specific populations. The frequency of two MTHFR mutations, a recently described mutation in the human MTHFR gene A1298C and C677T, whose association with DN is already known, was determined in an Israeli Jewish population with type 2 diabetes

Vlad Shpichinetsky; Itamar Raz; Yechiel Friedlander; Neta Goldschmidt; Isaiah D. Wexler; Arie Ben-Yehuda; Gideon Friedman

56

5,10-Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms: genotype frequency and association with homocysteine and folate levels in middle-southern Italian adults.  

PubMed

Two genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) can influence the plasma homocysteine (Hcy) levels, especially in the presence of an inadequate folate status. The aim of this study was to evaluate the frequencies of C677T and of A1298C MTHFR polymorphisms and their correlation with Hcy and serum folate concentrations in a population of blood donors living in a region of middle-southern Italy (the Molise Region). One hundred ninety seven blood donors were studied for total plasma Hcy, serum folate and C677T and A1298C MTHFR genotypes. The frequency of C677T genotypes was 20.8% (CC), 49.8% (CT) and 29.4% (TT); for the A1298C genotypes: 48.7% (AA), 43.7% (AC) and 7.6% (CC). Hcy and serum folate concentrations were significantly different among genotypes of the C677T polymorphism (CC versus CT versus TT: <0.0001 both for Hcy and folate), with Hcy values increasing, and serum folate decreasing, from CC to TT subjects. Regarding to A1298C polymorphism, the difference among genotypes (AA versus AC versus CC; p: 0.026 for Hcy and 0.014 for serum folate), showed an opposite trend for both parameters, with Hcy higher in the wild-type and lower in the homozygotes and serum folate higher in CC than in AA subjects. In conclusion, we found a high frequency of MTHFR allele associated with high level of Hcy and low levels of folate in an Italian southern population. PMID:24277487

Zappacosta, Bruno; Graziano, Mirella; Persichilli, Silvia; Di Castelnuovo, Augusto; Mastroiacovo, Pierpaolo; Iacoviello, Licia

2014-01-01

57

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

58

Association between C677T and A1298C MTHFR gene polymorphism and nonsyndromic orofacial clefts in the Turkish population: a case-parent study.  

PubMed

Two common MTHFR gene polymorphisms (C677T and A1298C) have been implicated in the etiology of nonsyndromic cleft lip/palate (nsCL/P). To investigate the genotype association among nsCL/P in the Turkish population, 56 case-parent trios were recruited into the study. Genotype frequencies were compared to two groups of controls from the same population. A total of 46 case-parent trios were included in transmission disequilibrium test (TDT) analysis. The mothers of the study group had a higher frequency of 677TT genotype, with a three-fold increased risk of having nsCL/P offspring (odds ratio [OR]: 3.14, p=0.03). The combined 677CT/1298AC genotype was also common among these mothers (28%), but it did not reach statistical significance (OR: 2.27, p=0.07). TDT analysis for (C677T) T allele transmission did not reveal a significant association. In conclusion, mothers carrying 677TT genotype or with 677CT/1298AC combined genotype have increased risk of having nsCL/P offspring; therefore, higher periconceptional folic acid supplementation should be advised for decreasing the recurrence risk. PMID:23692788

Semiç-Jusufagiç, Aida; Bircan, R?fat; Çelebiler, Özhan; Erdim, Melike; Akarsu, Nurten; Elçio?lu, Nursel H

2012-01-01

59

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

60

Polymorphism C776G in the transcobalamin II gene and homocysteine, folate and vitamin B 12 concentrations. Association with MTHFR C677T and A1298C and MTRR A66G polymorphisms in healthy children  

Microsoft Academic Search

One of the etiologies of hyperhomocysteinemia is decreased vitamin B12. Genetic variation in the transcobalamin II gene, the transporter of vitamin B12 to the cells, may produce altered homocysteine levels. We determined transcobalamin II C776G polymorphism, homocysteine, folate and vitamin B12 levels and analyzed the interactive effect with the methylenetetrahydrofolate reductase C677T and A1298C and methionine synthase reductase A66G polymorphisms

Ana C. M. Aléssio; Nelci F. Höehr; Lúcia H. Siqueira; Sérgio P. Bydlowski; Joyce M. Annichino-Bizzacchi

2007-01-01

61

Molecular Analysis of Factor V Leiden, Factor V Hong Kong, Factor II G20210A, Methylenetetrahydrofolate Reductase C677T, and A1298C Mutations Related to Turkish Thrombosis Patients  

Microsoft Academic Search

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

Bilgen Dölek; Serpil Eraslan; Sevim Ero?lu; Belgin Eroglu Kesim; Turgut Ulutin; Altan Yalç?ner; Yahya R. Laleli; Nermin Gözükirm?z?

2007-01-01

62

C677T and A1298C Polymorphisms of the Methylenetetrahydrofolate Reductase Gene: Incidence and Effect of Combined Genotypes on Plasma Fasting and Post-Methionine Load Homocysteine in Vascular Disease  

Microsoft Academic Search

Background: Moderately increased plasma concentra- tions of total homocysteine (tHcy) have been shown to be an important risk factor for vascular diseases. Two common polymorphisms of the methylenetetrahydro- folate reductase (MTHFR) gene, the thermolabile C677T and a more recently reported A1298C polymorphism, may contribute to hyperhomocysteinemia. Methods: Using PCR and restriction fragment length polymorphism analysis, we studied the prevalence of

Naomi Q. Hanson; Omer Aras; Feng Yang; Michael Y. Tsai

63

MTR OFFICE WINGS AT WEST SIDE OF MTR HIGH BAY ...  

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

MTR OFFICE WINGS AT WEST SIDE OF MTR HIGH BAY REACTOR BUILDING. CONTEXTUAL VIEW. CAMERA FACING NORTHEAST. FROM LEFT TO RIGHT, TRA-652 (OFFICE WING), TRA-661 (SOUTH WING EXTENSION), SECOND/THIRD FLOOR (BALCONIES) OF MTR-603, MTR HIGH-BAY. AT RIGHT EDGE OF VIEW IS REACTOR SERVICES BUILDING (TRA-635). INL NEGATIVE NO. HD46-44-1. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

64

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, Goran; Derwinger, Kristoffer

2014-01-01

65

Stromelysin-1 5A\\/6A and eNOS T-786C Polymorphisms, MTHFR C677T and A1298C Mutations, and Cigarette-Cannabis Smoking: A Pilot, Hypothesis-Generating Study of Gene-Environment Pathophysiological Associations With Buerger’s Disease  

Microsoft Academic Search

Buerger’s disease (BD) etiologies are poorly understood. Beyond smoking cessation, medical-surgical treatments have limited success. We hypothesized that mutations associated with arterial vasospasm (stromelysin-1 5A\\/6A, eNOS T-786C) and C677T-A1298C methylene tetrahydrofolate reductase (MTHFR) interacted with cigarette-cannabis smoking, reducing vasodilatory nitric oxide (NO), promoting arterial spasm-thrombosis. Of 21 smoking BD patients (14 men [2 siblings], 7 women; 20 white, 1 African-American),

Charles J. Glueck; Mofiz Haque; Magdalena Winarska; Swapna Dharashivkar; Robert N. Fontaine; Binghua Zhu; Ping Wang

2006-01-01

66

Reduced folate carrier-1 G80a gene polymorphism is associated with neuroblastoma's development.  

PubMed

Neuroblastoma is a malignant embryonal tumor of neural crest cells that give rise to the sympathetic nervous system, responsible for 10-70% of all cases of childhood cancer. Because of its early appearance, it has been suggested that risk factors active in the prenatal can be associated with the pathogenesis of neuroblastoma. The aim of this study was to investigate whether the genetic polymorphisms MTHFR C677T and A1298C, MTR A2756G, TYMS 2R/3R and SLC19A1 G80A, involved in folate metabolism, increase the risk of neuroblastoma in Brazilian children. This study comprised 31 Brazilian children (0-14 years old) diagnosed with neuroblastoma compared with 92 controls. Investigation of polymorphisms MTHFR C677T, MTR A2756G and SLC19A1 A80G was performed using PCR-RFLP, the TYMS 2R/3R using PCR and MTHFR A1298C using AS-PCR. The SLC19A1 A80A genotype was significantly associated with the development of neuroblastoma, compared with the control group (Williams G-Test = 0.0286; OR = 5.1667; 95% CI = 1.4481-18.4338; p = 0.0175). When analyzed together, the 80AG+AA genotypes showed a trend toward association (OR = 3.3033; 95% CI = 1.0586-10.3080; p = 0.0563). Our results suggest that individuals carriers of genotype AA for the SLC19A1 gene present risk for the development of neuroblastoma and possibly have difficulty in absorption of folic acid by the cells, and this may adversely affect the metabolism of folate causing genomic instability and promoting the development of cancer. This is the first retrospective/prospective study to examine the relationship between polymorphisms of folate pathway genes and risk of neuroblastoma. PMID:24771227

de Miranda, Dyego O; Barros, Jemima E X S; Vieira, Maria Madalena S; Lima, Elker L S; Moraes, Vera L L; da Silva, Helker A; Garcia, Helder L B O; Lima, Cássia A; Gomes, Adriana V; Santos, Neide; Muniz, Maria T C

2014-08-01

67

Detection of Thrombophilic Mutations Related to Spontaneous Abortions by a Multiplex SNaPshot Method  

PubMed Central

Spontaneous abortion is a significant clinical problem of different etiologies. Certain thrombophilia gene mutations have been associated with an increased risk of spontaneous abortion. Also, mutations in folate-related genes can lead to abnormal chromosomal segregation during meiosis which is the most common cause of spontaneous abortion. We have developed a multiplex single-base extension reaction assay that allows simultaneous analysis of 10 different mutations in thrombophilia- and folate-related genes (Factor V Leiden G1691A, Factor V H1299R, Factor II G20210A, Factor XIII V34L, PAI-I -675 4G/5G, FGB -455G/A, MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G). Using this method we have studied 232 women who had a spontaneous abortion and 209 of their male partners. Prevalence of Factor II G20210A and Factor V H1299R mutations was significantly higher in the women than in their male partners (2.4% and 0.7%, respectively [p=0.0499] for the Factor II mutation and 9.3% and 5.7%, respectively [p=0.0485] for the Factor V mutation). The prevalence of MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G mutations did not differ between the studied groups. In conclusion, we have developed a rapid, simple, reliable, and inexpensive multiplex SNaPshot method for determination of 10 thrombophilic mutations that may result in spontaneous abortions. PMID:22023244

Madjunkova, Svetlana; Volk, Marija; Peterlin, Borut

2012-01-01

68

Evaluation of GenoFlow Thrombophilia Array Test Kit in Its Detection of Mutations in Factor V Leiden (G1691A), Prothrombin G20210A, MTHFR C677T and A1298C in Blood Samples from 113 Turkish Female Patients.  

PubMed

Thrombophilia is a heritable blood disease characterized by an increased tendency to form abnormal blood clots that can block blood vessels. In obstetrics and gynecology, it has been shown by a number of reports that a proportion of recurrent miscarriages involve thrombophilia-related mutations, in particular, Factor V G1691A, prothrombin G20210A, and MTHFR C677T and A1298C. In this study, we examined the frequency of these four mutations in 113 female Turkish patients who had prior complications in pregnancy, using the DiagCor GenoFlow Thrombophilia Array Test kit. Heterozygous MTHFR C677T and A1298C mutations were detected in 46% of the patients, and among these patients, 60% of them carried double heterozygous mutations. In contrast, the heterozygous Factor V G1691A and prothrombin G20210A were detected only in a smaller number of patients, respectively, 13% and 3%. The GenoFlow kit demonstrated 100% concordance with results from Sanger sequencing, which can be translated into sensitivity and specificity both at 100% within this series of patients. PMID:25153695

Aytekin, Ebru; Ergun, Sezen Guntekin; Ergun, Mehmet Ali; Percin, Ferda E

2014-11-01

69

Stromelysin-1 5A/6A and eNOS T-786C polymorphisms, MTHFR C677T and A1298C mutations, and cigarette-cannabis smoking: a pilot, hypothesis-generating study of gene-environment pathophysiological associations with Buerger's disease.  

PubMed

Buerger's disease (BD) etiologies are poorly understood. Beyond smoking cessation, medical-surgical treatments have limited success. We hypothesized that mutations associated with arterial vasospasm (stromelysin-1 5A/6A, eNOS T-786C) and C677T-A1298C methylene tetrahydrofolate reductase (MTHFR) interacted with cigarette-cannabis smoking, reducing vasodilatory nitric oxide (NO), promoting arterial spasm-thrombosis. Of 21 smoking BD patients (14 men [2 siblings], 7 women; 20 white, 1 African-American), compared to 21 age-gender-race matched healthy controls, 5A/6A stromelysin- 1 homozygosity was present in 7 of 21 (33%) BD cases versus 5 of 21 (24%) controls (risk ratio 1.4; 95% confidence interval [CI] 0.5-3.7), and eNOS T-786C homozygosity was present in 3 of 21 (14%) BD cases versus 1 of 21 (5%) controls (risk ratio 3.0; 95% CI 0.3-26.6). C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in 7 of 21 cases (33%) versus 11 of 21 controls (52%) (risk ratio 0.6; 95% CI 0.3-1.3). In 18 patients who stopped and 3 who continued smoking, all stromelysin-1 5A/6A and/or eNOS heterozygotes-homozygotes, superficial phlebitis, lower limb gangrenous ulcers, and intractable ischemic rest pain with arterial occlusion progressed despite conventional medical therapy, threatening amputation. In 15 patients, to increase vasodilatory NO via endothelial NO synthase, l-arginine (15 g/day) was given, along with folic acid (5 mg), vitamin B6 (100 mg), and B12 (2000 mg/day) to optimize homocysteine metabolism and reduce asymmetric dimethylarginine, a NO synthase inhibitor. Unexpectedly quickly and strikingly, within 8 weeks to 8 months receiving l-arginine-folic acid, 11 of 15 treated patients improved with uniform pain reduction, ulcer healing, and in 5, full recovery of previously absent peripheral pulses. In smokers homo/heterozygous for stromelysin-1 5A/6A and eNOS T-786C mutations, we speculate that the development and severity of BD are related to a gene-environment vasospastic interaction with reduced NO-mediated vasodilatation. Increasing NO production by l-arginine while optimizing homocysteine metabolism by folic acid-B6-B12 may have therapeutic benefit. Further blinded, placebo-controlled studies are needed to determine whether our observations can be generalized to larger BD cohorts. PMID:17000887

Glueck, Charles J; Haque, Mofiz; Winarska, Magdalena; Dharashivkar, Swapna; Fontaine, Robert N; Zhu, Binghua; Wang, Ping

2006-10-01

70

MTR BUILDING, TRA603. WEST SIDE OF MTR SECOND/THIRD FLOOR AND ...  

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

MTR BUILDING, TRA-603. WEST SIDE OF MTR SECOND/THIRD FLOOR AND HIGH-BAY REACTOR FLOOR (WITH STAIRWAY FROM ROOF). CAMERA FACING EAST FROM ROOF OF TRA-604. INL NEGATIVE NO. HD46-42-3. Mike Crane, Photographer, April 2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

71

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

72

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

73

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

74

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

75

MTR BUILDING, TRA603. DETAILED VIEW OF NORTHWEST CORNERS OF MTR ...  

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

MTR BUILDING, TRA-603. DETAILED VIEW OF NORTHWEST CORNERS OF MTR HIGH-BAY AND SECOND/THIRD STORY SECTIONS. NOTE SHAPE OF PANEL ABOVE WINDOW OVER "TRA-603" BUILDING NUMBERS. THIS IS A "STANDARD PANEL." INL NEGATIVE NUMBER HD46-42-2. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

76

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

Code of Federal Regulations, 2010 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...

2010-07-01

77

MATERIALS TESTING REACTOR (MTR) BUILDING, TRA603. CONTEXTUAL VIEW OF MTR ...  

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

MATERIALS TESTING REACTOR (MTR) BUILDING, TRA-603. CONTEXTUAL VIEW OF MTR BUILDING SHOWING NORTH SIDES OF THE HIGH-BAY REACTOR BUILDING, ITS SECOND/THIRD FLOOR BALCONY LEVEL, AND THE ATTACHED ONE-STORY OFFICE/LABORATORY BUILDING, TRA-604. CAMERA FACING SOUTHEAST. VERTICAL CONCRETE-SHROUDED BEAMS SUPPORT PRECAST CONCRETE PANELS. CONCRETE PROJECTION FORMED AS A BUNKER AT LEFT OF VIEW IS TRA-657, PLUG STORAGE BUILDING. INL NEGATIVE NO. HD46-42-1. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

78

Mycobacterium tuberculosis MtrB Sensor Kinase Interactions with FtsI and Wag31 Proteins Reveal a Role for MtrB Distinct from That Regulating MtrA Activities.  

PubMed

The septal association of Mycobacterium tuberculosis MtrB, the kinase partner of the MtrAB two-component signal transduction system, is necessary for the optimal expression of the MtrA regulon targets, including ripA, fbpB, and ftsI, which are involved in cell division and cell wall synthesis. Here, we show that MtrB, irrespective of its phosphorylation status, interacts with Wag31, whereas only phosphorylation-competent MtrB interacts with FtsI. We provide evidence that FtsI depletion compromises the MtrB septal assembly and MtrA regulon expression; likewise, the absence of MtrB compromises FtsI localization and, possibly, FtsI activity. We conclude from these results that FtsI and MtrB are codependent for their activities and that FtsI functions as a positive modulator of MtrB activation and MtrA regulon expression. In contrast to FtsI, Wag31 depletion does not affect MtrB septal assembly and MtrA regulon expression, whereas the loss of MtrB increased Wag31 localization and the levels of PknA/PknB (PknA/B) serine-threonine protein kinase-mediated Wag31 phosphorylation. Interestingly, we found that FtsI decreased levels of phosphorylated Wag31 (Wag31?P) and that MtrB interacted with PknA/B. Overall, our results indicate that MtrB interactions with FtsI, Wag31, and PknA/B are required for its optimal localization, MtrA regulon expression, and phosphorylation of Wag31. Our results emphasize a new role for MtrB in cell division and cell wall synthesis distinct from that regulating the MtrA phosphorylation activities. PMID:25225272

Plocinska, Renata; Martinez, Luis; Gorla, Purushotham; Pandeeti, Emmanuel; Sarva, Krishna; Blaszczyk, Ewelina; Dziadek, Jaroslaw; Madiraju, Murty V; Rajagopalan, Malini

2014-12-01

79

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

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

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

80

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

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

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

81

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

82

MtrR modulates rpoH expression and levels of antimicrobial resistance in Neisseria gonorrhoeae.  

PubMed

The MtrR transcriptional-regulatory protein is known to repress transcription of the mtrCDE operon, which encodes a multidrug efflux pump possessed by Neisseria gonorrhoeae that is important in the ability of gonococci to resist certain hydrophobic antibiotics, detergents, dyes, and host-derived antimicrobials. In order to determine whether MtrR can exert regulatory action on other gonococcal genes, we performed a whole-genome microarray analysis using total RNA extracted from actively growing broth cultures of isogenic MtrR-positive and MtrR-negative gonococci. We determined that, at a minimum, 69 genes are directly or indirectly subject to MtrR control, with 47 being MtrR repressed and 22 being MtrR activated. rpoH, which encodes the general stress response sigma factor RpoH (sigma 32), was found by DNA-binding studies to be directly repressed by MtrR, as it was found to bind to a DNA sequence upstream of rpoH that included sites within the rpoH promoter. MtrR also repressed the expression of certain RpoH-regulated genes, but this regulation was likely indirect and a reflection of MtrR control of rpoH expression. Inducible expression of MtrR was found to repress rpoH expression and to increase gonococcal susceptibility to hydrogen peroxide (H(2)O(2)) and an antibiotic (erythromycin) recognized by the MtrC-MtrD-MtrE efflux pump system. We propose that, apart from its ability to control the expression of the mtrCDE-encoded efflux pump operon and, as a consequence, levels of gonococcal resistance to host antimicrobials (e.g., antimicrobial peptides) recognized by the efflux pump, the ability of MtrR to regulate the expression levels of rpoH and RpoH-regulated genes also modulates levels of gonococcal susceptibility to H(2)O(2). PMID:18978065

Folster, Jason P; Johnson, Paul J T; Jackson, Lydgia; Dhulipali, Vijaya; Dyer, David W; Shafer, William M

2009-01-01

83

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

84

Automation Negotiation System Based on Web in MTR Construction  

Microsoft Academic Search

This paper analyzes problems of low efficient information negotiation in MTR construction among different participants. An automation negotiation system scheme based on Web is proposed. Also, concession strategies and negotiation utility assessment mechanism are built to make sure all the participants in construction can auto-negotiate with each other through the system. Its maneuverability is validated by a calculating case analysis.

Zhou Ying; Ding Lie-Yun

2009-01-01

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

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

87

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

88

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

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

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

89

MTR MAIN FLOOR. NEUTRON TUNNEL (SPANNED BY STILELIKE STEPS) PROJECTS ...  

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

MTR MAIN FLOOR. NEUTRON TUNNEL (SPANNED BY STILE-LIKE STEPS) PROJECTS FROM THE SOUTHEAST CORNER OF THE MTR TOWARD SOUTHEAST CORNER OF BUILDING, WHERE SHIELDING BLOCKS BEGIN TO SURROUND THE TUNNEL AS IT NEARS DETECTING INSTRUMENTS NEAR THE BUILDING WALL. GEAR RELATED TO CRYSTAL NEUTRON SPECTROMETER IS IN FOREGROUND SURROUNDED BY SHIELDING. DATA CONSOLES ARE AT MID-LEVEL OF EAST FACE. OTHER WORK PROCEEDS ON TOP OF AND ELSEWHERE AROUND REACTOR. NOTE TOOLS HANGING AGAINST SOUTHEAST CORNER, USED TO CHANGE FUEL ELEMENTS AND OTHER REACTOR ITEMS DURING REFUELING CYCLES. INL NEGATIVE NO. 10439. Unknown Photographer, 4/20/1954 - 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

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

92

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

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

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

93

MTR, TRA603. BASEMENT DECONTAMINATION ROOM DETAILS. WALLS OF SOLID CONCRETE ...  

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

MTR, TRA-603. BASEMENT DECONTAMINATION ROOM DETAILS. WALLS OF SOLID CONCRETE MASONRY. STAINLESS STEEL WORK BENCH, FLOOR COVING AND DRAINS. "WARM" FLOOR DRAIN. OVERHEAD SHOWER WITH CHAIN PULL. IDO MTR-603-IDO-4, 12/1952. INL INDEX NO. 531-0603-00-396-110468, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

94

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

95

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

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

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

96

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

97

Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population  

Microsoft Academic Search

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

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

2005-01-01

98

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

Microsoft Academic Search

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

Rogelio Palomino-Morales; Carlos Gonzalez-Juanatey; Tomas R Vazquez-Rodriguez; Luis Rodriguez; Jose A Miranda-Filloy; Benjamin Fernandez-Gutierrez; Javier Llorca; Javier Martin; Miguel A Gonzalez-Gay

2010-01-01

99

Polymorphism of cytosolic serine hydroxymethyltransferase, estrogen and breast cancer risk among Chinese women in Taiwan  

Microsoft Academic Search

Cytosolic serine hydroxymethyltransferase (cSHMT) is key to intersection of folate-metabolic pathway, participating in the pyrimidine synthesis for DNA repair. Based on the\\u000a hypothesis that variants of the cSHMT\\u000a C1420T together with methionine synthase (MS A2756G) and 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) are associated with breast cancer, we performed a multigenic case–control study of the effects to breast cancer risk

Chun-Wen Cheng; Jyh-Cherng Yu; Chiun-Sheng Huang; Jia-Ching Shieh; Yi-Ping Fu; Hsiao-Wei Wang; Pei-Ei Wu; Chen-Yang Shen

2008-01-01

100

CONTEXTUAL AERIAL VIEW OF "COLD" NORTH HALF OF MTR COMPLEX. ...  

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

CONTEXTUAL AERIAL VIEW OF "COLD" NORTH HALF OF MTR COMPLEX. CAMERA FACING EASTERLY. FOREGROUND CORNER CONTAINS OIL STORAGE TANKS. WATER TANKS AND WELL HOUSES ARE BEYOND THEM TO THE LEFT. LARGE LIGHT-COLORED BUILDING IN CENTER OF VIEW IS STEAM PLANT. DEMINERALIZER AND WATER STORAGE TANK ARE BEYOND. SIX-CELL COOLING TOWER AND ITS PUMP HOUSE ARE ABOVE IT IN VIEW. SERVICE BUILDINGS INCLUDING CANTEEN ARE ON NORTH SIDE OF ROAD. "EXCLUSION" AREA IS BEYOND ROAD. COMPARE LOCATION OF EXCLUSION-AREA GATE WITH PHOTO ID-33-G-202. INL NEGATIVE NO. 3608. Unknown Photographer, 10/30/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

101

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

102

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

103

MTR and In-vivo 1H-MRS studies on mouse brain with parkinson's disease  

NASA Astrophysics Data System (ADS)

The aim of this study was to investigate whether the changes in the magnetization transfer ratio (MTR) histogram are related to specific characteristics of Parkinson's disease (PD) and to investigate whether the MTR histogram parameters are associated with neurochemical dysfunction by performing in vivo proton magnetic resonance spectroscopy (1H-MRS). MTR and in vivo 1H-MRS studies were performed on control mice (n = 10) and 1-methyl-1,2,3,6-tetrahydropyridine intoxicated mice (n = 10). All the MTR and in vivo 1H-MRS experiments were performed on a 9.4 T MRI/MRS system (Bruker Biospin, Germany) using a standard head coil. The protondensity fast spin echo (FSE) images and the T2-weighted spin echo (SE) images were acquired with no gap. Outer volume suppression (OVS), combined with the ultra-short echo-time stimulated echo acquisition mode (STEAM), was used for the localized in-vivo 1H-MRS. The quantitative analysis of metabolites was performed from the 1H spectra obtained in vivo on the striatum (ST) by using jMRUI (Lyon, France). The peak height of the MTR histograms in the PD model group was significantly lower than that in the control group (p < 0.05). The midbrain MTR values for volume were lower in the PD group than the control group(p < 0.05). The complex peak (Glx: glutamine+glutamate+ GABA)/creatine (Cr) ratio of the right ST in the PD group was significantly increased as compared to that of the control group. The present study revealed that the peak height of the MTR histogram was significantly decreased in the ST and substantia nigra, and a significant increase in the Gl x /Cr ratio was found in the ST of the PD group, as compared with that of the control group. These findings could reflect the early phase of neuronal dysfunction of neurotransmitters.

Yoon, Moon-Hyun; Kim, Hyeon-Jin; Chung, Jin-Yeung; Doo, Ah-Reum; Park, Hi-Joon; Kim, Seung-Nam; Choe, Bo-Young

2012-12-01

104

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

105

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

106

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

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

MTR WING A, TRA-604, INTERIOR. MAIN FLOOR. DETAIL VIEW INSIDE LABORATORY 110. CAMERA FACING SOUTH. INL NEGATIVE NO. HD46-12-3. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

107

MTR WING A, TRA604, INTERIOR. MAIN FLOOR, DETAIL OF LABORATORY ...  

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

MTR WING A, TRA-604, INTERIOR. MAIN FLOOR, DETAIL OF LABORATORY 123. CAMERA LOOKING NORTHEAST. INL NEGATIVE NO. HD46-12-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

108

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

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

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

109

MTR WING, TRA604. DETAILS OF LABORATORIES ALONG SOUTH WALL: TABLES, ...  

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

MTR WING, TRA-604. DETAILS OF LABORATORIES ALONG SOUTH WALL: TABLES, FUME HOODS, DESKS. BLAW-KNOX 3150-404-4, 7/1950. INL INDEX NO. 531-0604-00-098-100084, REV. 8. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

110

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

111

MTR BLOWER AND FAN HOUSE, TRA610. ELEVATION OF STACK ON ...  

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

MTR BLOWER AND FAN HOUSE, TRA-610. ELEVATION OF STACK ON WEST SIDE OF FAN HOUSE. BLAW-KNOX 3150-10-2, 6/1950. INL INDEX NO. 531-0610-00-098-100021, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

112

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

113

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

114

MTR WING, TRA604. PRECAST CONCRETE PANELS AND DIMENSIONS FOR PANELS ...  

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

MTR WING, TRA-604. PRECAST CONCRETE PANELS AND DIMENSIONS FOR PANELS K THROUGH Q. BLAW-KNOX 3150-804-21, SHEET #2, 11/1950. INL INDEX NO. 531-0604-62-098-100645, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

115

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. CONTEXTUAL VIEW OF SOUTHWEST ...  

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

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. CONTEXTUAL VIEW OF SOUTHWEST CORNER OF REACTOR. WEST FACE IS TOWARD LEFT OF VIEW. CAMERA FACING NORTHEAST. INL NEGATIVE NO. HD46-2-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

116

REACTOR SERVICES BUILDING, TRA635. EAST SIDE. CAMERA LOOKING NORTHWEST. MTR ...  

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

REACTOR SERVICES BUILDING, TRA-635. EAST SIDE. CAMERA LOOKING NORTHWEST. MTR BUILDING, TRA-603, AT RIGHT OF VIEW. INL NEGATIVE NO. HD46-41-2. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

117

MTR BUILDING INTERIOR, TRA603. CAMERA IS ON SECOND FLOOR BALCONY ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA IS ON SECOND FLOOR BALCONY LOOKING DOWN ON REACTOR FLOOR, FACING NORTHEAST, THE WEST AND SOUTH FACES OF THE REACTOR. MOCK-UP APPARATUS IS AT RIGHT OF VIEW. INL NEGATIVE NO. HD-46-3-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

118

MTR BUILDING INTERIOR, TRA603. CAMERA IS ON SECOND FLOOR BALCONY ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA IS ON SECOND FLOOR BALCONY LOOKING DOWN ON WEST FACE OF REACTOR. SHIELDING BLOCKS IN FOREGROUND ATOP CABINET. INL NEGATIVE NO. HD46-3-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

119

MTR BUILDING INTERIOR, TRA603. CAMERA FACING SOUTHEAST CORNER OF REACTOR ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA FACING SOUTHEAST CORNER OF REACTOR FLOOR. SUPPLIES AND EQUIPMENT RELATE TO MOCK-UP PROJECT. NOTE PRECAST WALL PANELS SUPPORTED BY VERTICAL COLUMNS OF REINFORCED CONCRETE. INL NEGATIVE NO. HD46-4-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

120

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT SOUTH END OF ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT SOUTH END OF THIRD FLOOR BALCONY LOOKING NORTHEAST. BRIDGE BETWEEN BALCONY AND REACTOR TOP AT LEFT OF VIEW. INL NEGATIVE NO. HD46-5-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

121

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED ...  

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

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED BY EAST WALL ON LEFT AND APPARATUS ON RIGHT. CAMERA FACING SOUTH. INL NEGATIVE NO. HD46-1-3. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

122

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT NORTH END OF ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT NORTH END OF THIRD FLOOR BALCONY LOOKING SOUTHEAST. DETAIL OF REACTOR'S NORTH FACE AND ITS TEST HOLES. MOCK-UP APPARATUS IS BEYOND REACTOR. INL NEGATIVE NO. HD46-5-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

123

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. DETAIL OF REACTOR TEST ...  

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

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. DETAIL OF REACTOR TEST HOLE OPENING IN WEST FACE. CAMERA FACING NORTHEAST. INL NEGATIVE NO. HD46-2-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

124

REACTOR SERVICES BUILDING, TRA635. WEST SIDE. CAMERA LOOKING NORTHEAST. MTR ...  

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

REACTOR SERVICES BUILDING, TRA-635. WEST SIDE. CAMERA LOOKING NORTHEAST. MTR (TRA-603) AT LEFT OF VIEW. INL NEGATIVE NO. HD46-41-2. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

125

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. DETAIL OF REACTOR'S SOUTH ...  

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

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. DETAIL OF REACTOR'S SOUTH FACE. CAMERA FACING NORTHWESTERLY. INL NEGATIVE NO. HD46-1-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

126

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

127

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

PubMed

Shewanella oneidensis MR-1 has the ability to use many external terminal electron acceptors during anaerobic respiration, such as DMSO. The pathway that facilitates this electron transfer includes the decahaem cytochrome DmsE, a paralogue of the MtrA family of decahaem cytochromes. Although both DmsE and MtrA are decahaem cytochromes implicated in the long-range electron transfer across a ~300 Å (1 Å=0.1 nm) wide periplasmic 'gap', MtrA has been shown to be only 105 Å in maximal length. In the present paper, DmsE is further characterized via protein film voltammetry, revealing that the electrochemistry of the DmsE haem cofactors display macroscopic potentials lower than those of MtrA by 100 mV. It is possible this tuning of the redox potential of DmsE is required to shuttle electrons to the outer-membrane proteins specific to DMSO reduction. Other decahaem cytochromes found in S. oneidensis, such as the outer-membrane proteins MtrC, MtrF and OmcA, have been shown to have electrochemical properties similar to those of MtrA, yet possess a different evolutionary relationship. PMID:23176466

Bewley, Kathryn D; Firer-Sherwood, Mackenzie A; Mock, Jee-Young; Ando, Nozomi; Drennan, Catherine L; Elliott, Sean J

2012-12-01

128

Towards Electrosynthesis in Shewanella: Energetics of Reversing the Mtr Pathway for Reductive Metabolism  

PubMed Central

Bioelectrochemical systems rely on microorganisms to link complex oxidation/reduction reactions to electrodes. For example, in Shewanella oneidensis strain MR-1, an electron transfer conduit consisting of cytochromes and structural proteins, known as the Mtr respiratory pathway, catalyzes electron flow from cytoplasmic oxidative reactions to electrodes. Reversing this electron flow to drive microbial reductive metabolism offers a possible route for electrosynthesis of high value fuels and chemicals. We examined electron flow from electrodes into Shewanella to determine the feasibility of this process, the molecular components of reductive electron flow, and what driving forces were required. Addition of fumarate to a film of S. oneidensis adhering to a graphite electrode poised at ?0.36 V versus standard hydrogen electrode (SHE) immediately led to electron uptake, while a mutant lacking the periplasmic fumarate reductase FccA was unable to utilize electrodes for fumarate reduction. Deletion of the gene encoding the outer membrane cytochrome-anchoring protein MtrB eliminated 88% of fumarate reduction. A mutant lacking the periplasmic cytochrome MtrA demonstrated more severe defects. Surprisingly, disruption of menC, which prevents menaquinone biosynthesis, eliminated 85% of electron flux. Deletion of the gene encoding the quinone-linked cytochrome CymA had a similar negative effect, which showed that electrons primarily flowed from outer membrane cytochromes into the quinone pool, and back to periplasmic FccA. Soluble redox mediators only partially restored electron transfer in mutants, suggesting that soluble shuttles could not replace periplasmic protein-protein interactions. This work demonstrates that the Mtr pathway can power reductive reactions, shows this conduit is functionally reversible, and provides new evidence for distinct CymA:MtrA and CymA:FccA respiratory units. PMID:21311751

Ross, Daniel E.; Flynn, Jeffrey M.; Baron, Daniel B.; Gralnick, Jeffrey A.; Bond, Daniel R.

2011-01-01

129

MTHFR A1298C polymorphism is associated with cardiovascular risk in end stage renal disease in North Indians  

Microsoft Academic Search

The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism has been shown to be associated with cardiovascular\\u000a disease and in patients with end-stage renal disease (ESRD). However, the relationship between MTHFR polymorphisms and cardiovascular\\u000a disease (CVD) in patients on hemodialysis has not been examined. The aim of this study was to assess the association of polymorphisms\\u000a of MTHFR gene with homocysteine (Hcy)

Aruna Poduri; Debabrata Mukherjee; Kamal Sud; Harbir Singh Kohli; Vinay Sakhuja; Madhu Khullar

2008-01-01

130

Prevalence of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Taiwanese patients with Type 2 diabetic mellitus  

Microsoft Academic Search

ObjectivesDeficiency and\\/or decreased activity of methyltetrahydrofolate reductase (MTHFR) resulted from MTHFR variants are associated with hyperhomocysteinemia, an independent risk factor for vasculopathies in diabetic patients. The aim of this study was to examine MTHFR genotypes between healthy and type 2 diabetes mellitus (T2DM) subjects.

Yih-Hsin Chang; Wen-Mei Fu; Yu-Hui Wu; Chih-Jung Yeh; Chien-Ning Huang; Ming-Yuh Shiau

131

C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation  

Microsoft Academic Search

Pharmacogenetics represents an exciting, new promising tool for the individualisation of therapy. Several genetic polymorphisms and haplotypes have been considered in an attempt to optimise therapy with specific drugs but, up to now, their clinical applications remain limited.5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme of one-carbon metabolism, catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Two common non-synonymous variants, the C677T

Elena De Mattia; Giuseppe Toffoli

2009-01-01

132

Severe Arterial Thrombophilia Associated With a Homozygous MTHFR Gene Mutation (A1298C) in a Young Man With Klinefelter Syndrome  

Microsoft Academic Search

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

Mustafa Ozbek; M. Akif Öztürk; Kemal Ureten; Ozcan Ceneli; Mehmet Erdogan; Ibrahim C. Haznedaroglu

2008-01-01

133

No association between MTHFR A1298C and MTRR A66G polymorphisms, and MS in an Australian cohort  

Microsoft Academic Search

Multiple sclerosis (MS) is a complex neurological disease that affects the central nervous system (CNS) resulting in debilitating neuropathology. Pathogenesis is primarily defined by CNS inflammation and demyelination of nerve axons. Methionine synthase reductase (MTRR) is an enzyme that catalyzes the remethylation of homocysteine (Hcy) to methionine via cobalamin and folate dependant reactions. Cobalamin acts as an intermediate methyl carrier

A. L. Szvetko; J. Fowdar; J. Nelson; N. Colson; L. Tajouri; P. A. Csurhes; M. P. Pender; L. R. Griffiths

2007-01-01

134

Roles of UndA and MtrC of Shewanella putrefaciens W3-18-1 in iron reduction  

PubMed Central

Background The completion of genome sequencing in a number of Shewanella species, which are most renowned for their metal reduction capacity, offers a basis for comparative studies. Previous work in Shewanella oneidensis MR-1 has indicated that some genes within a cluster (mtrBAC-omcA-mtrFED) were involved in iron reduction. To explore new features of iron reduction pathways, we experimentally analyzed Shewanella putrefaciens W3-18-1 since its gene cluster is considerably different from that of MR-1 in that the gene cluster encodes only four ORFs. Results Among the gene cluster, two genes (mtrC and undA) were shown to encode c-type cytochromes. The ?mtrC deletion mutant revealed significant deficiencies in reducing metals of Fe2O3, ?-FeO(OH), ?-FeO(OH), ferric citrate, Mn(IV) and Co(III), but not organic compounds. In contrast, no deficiency of metal reduction was observed in the ?undA deletion mutant. Nonetheless, undA deletion resulted in progressively slower iron reduction in the absence of mtrC and fitness loss under the iron-using condition, which was indicative of a functional role of UndA in iron reduction. Conclusions These results provide physiological and biochemical evidences that UndA and MtrC of Shewanella putrefaciens W3-18-1 are involved in iron reduction. PMID:24274142

2013-01-01

135

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

136

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

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

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

137

MTR BUILDING INTERIOR, TRA603, SECOND FLOOR BALCONY. CAMERA FACING NORTH. ...  

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

MTR BUILDING INTERIOR, TRA-603, SECOND FLOOR BALCONY. CAMERA FACING NORTH. ROOMS 204, 203, 202, AND 201 ARE TO LEFT. VIEW TOWARDS REACTOR FLOOR IS SEEN THROUGH BALCONY RAILING. PLATFORM BETWEEN REACTOR AND THIRD FLOOR BALCONY IS SEEN BEYOND SQUARE PILLAR IN FOREGROUND. INL NEGATIVE NO. HD46-3-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

138

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT NORTH END OF ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT NORTH END OF SECOND FLOOR BALCONY LOOKING TOWARDS WORK PLATFORMS ON NORTH FACE OF REACTOR. BRIDGE TO THIRD FLOOR BALCONY FROM TOP OF REACTOR IS AT UPPER RIGHT OF VIEW. CAMERA FACING EASTERLY. INL NEGATIVE NO. HD-46-4-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

139

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. CAMERA IS IN NORTHEAST ...  

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

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. CAMERA IS IN NORTHEAST CORNER FACING SOUTHWEST. NORTH FACE OF REACTOR IS IN LEFT HALF OF VIEW. WEST WALL CONTAINS CONTROL BALCONIES. BRIDGE FROM REACTOR TO SECOND-FLOOR BALCONY IS IN CENTER OF VIEW. INL NEGATIVE NO. HD46-1-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

140

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT NORTH END OF ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT NORTH END OF THIRD FLOOR BALCONY LOOKING SOUTHEAST AND ACROSS TOP OF REACTOR. MOCK-UP APPARATUS IS BEYOND REACTOR. BRIDGE CONNECTING BALCONY AND REACTOR TOP AT RIGHT OF VIEW. INL NEGATIVE NO. HD46-5-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

141

MTR BUILDING INTERIOR, TRA603. CAMERA IS ON SECOND FLOOR BALCONY ...  

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

MTR BUILDING INTERIOR, TRA-603. CAMERA IS ON SECOND FLOOR BALCONY LOOKING DOWN ON REACTOR FLOOR, FACING EAST. REACTOR IS AT LEFT OF VIEW. APPARATUS DIRECTLY IN FRONT OF CAMERA IS PART OF A MOCK-UP PROJECT. INL NEGATIVE NO. HD46-3-3. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

142

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED ...  

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

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED BY REACTOR (LEFT OF VIEW) AND WEST WALL ON RIGHT. BRIDGE OVERHEAD PROVIDED ACCESS TO TOP OF REACTOR FROM BALCONY. NOTE WIDTH OF BRIDGE. CAMERA FACING SOUTH TOWARDS OPEN DOOR OF REACTOR SERVICE BUILDING, TRA-635. INL NEGATIVE NO. HD46-1-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

143

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

NASA Astrophysics Data System (ADS)

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

Day, Simon E.

144

Studies of mixed HEU-LEU-MTR cores using 3D models  

SciTech Connect

Several different core loadings were assembled at the SAPHIR research reactor in Switzerland combining the available types of MTR-type fuel elements, consisting mainly of both HEU and LEU fuel. Bearing in mind the well known problems which can occur in such configurations (especially power peaking), investigations have been carried out for each new loading with a 2D neutron transport code (BOXER). The axial effects were approximated by a global buckling value and therefore the radial effects could be studied in considerably detail. Some of the results were reported at earlier RERTR meetings and were compared to those obtained by other methods and with experimental values. For the explicit study of the third dimension of the core, another code (SILWER), which has been developed in PSI for LWR power plant cores, has been selected. With the help of an adapted model for the MTR-core of SAPHIR, several important questions have been addressed. Among other aspects, the estimation of the axial contribution to the hot channel factors, the influence of the control rod position and of the Xe-poisoning on the power distribution were studied. Special attention was given to a core position where a new element was assumed placed near a empty, water filled position. The comparison of elements of low and high enrichments at this position was made in terms of the induced power peaks, with explicit consideration of axial effects. The program SILWER has proven to be applicable to MTR-cores for the investigation of axial effects. For routine use as for the support of reactor operation, this 3D code is a good supplement to the standard 2D model.

Haenggi, P.; Lehmann, E.; Hammer, J.; Christen, R. [Paul Scherrer Institute, Villigen (Switzerland)

1997-08-01

145

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

146

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

E-print Network

or in-class demonstration to help illustrate the social psychological theories we will be studying. WePsychology 456: Social Psychology Summer 2011, 102 Peterson Hall, M-TR 12:00 ­ 1:50 Instructor, we will explore some of the most fundamental principles in social psychology--the scientific study

Lockery, Shawn

147

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

E-print Network

all live embedded within a social world, we predict you will find the concepts discussed in class, there will occasionally be a film or in-class demonstration to help illustrate the social psychological theories wePsychology 456: Social Psychology Summer 2012, 107 Esslinger Hall, M-TR 2:00 ­ 3:50 Instructor

Lockery, Shawn

148

Prognostic value of brain tissue pathological changes in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis using magnetization transfer ratio (MTR).  

PubMed

The aim of this study is to investigate abnormalities in the brain tissue of patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). In this method, magnetization transfer ratio (MTR) parameter accompanied with segmentation regional measurements and histogram analysis were used to improve the evaluation of disease progression in CIS patients. Conventional MR imaging protocols such as T1-weighted, T2-weighted, T2-FLAIR as well as MT-2DSPGR were performed on four CIS patients and four normal subjects. White matter, gray matter and lesion masks were segmented from T2-weighted images and superimposed on MTR map using FSL software. Lesions were classified into isontense and severely hypointense according to their signal intensities relative to white matter on the T1-weighted images. MTR parameters of these two lesion types, normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) were analyzed in comparison with those of normal controls. The MTR histograms of NAWM and NAGM were also generated for each segmented brain tissues. A significant reduction was found in mean white matter MTR and the histogram peak position between CIS patients and healthy subjects. The MTR histogram for NAWM showed also a total shift to the left. The MTR value for gray matter in CIS patients was similar to that of controls. Isointense lesions have significantly higher MTR values than severely hypointense lesions. Significant reduction in NAWM-MTR compared to normal subjects shows that pathological changes outside visible lesions on conventional MR images occur among patients with CIS at presentation. Quantitative MT imaging can help to evaluate the extent of global damage in the brain tissue. PMID:18002384

Fooladi, M; Alam, N Riyahi; Harirchyan, M H; Firuznia, K; Oghabian, M A; Shakiba, M; Rafie, B; Bakhtiary, M

2007-01-01

149

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

150

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

151

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

Microsoft Academic Search

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\\u000a that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric\\u000a characterization of MtrC, using protein purified from

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

2007-01-01

152

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

153

Enhancement of the dissolution of albendazole from pellets using MTR technique.  

PubMed

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

2013-04-01

154

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

155

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

156

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

157

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

158

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population  

Microsoft Academic Search

Objectives  Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and\\u000a DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To\\u000a date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective\\u000a of this study was

Li-Na Mu; Wei Cao; Zuo-Feng Zhang; Lin Cai; Qing-Wu Jiang; Nai-Chieh You; Binh Yang Goldstein; Guo-Rong Wei; Chuan-Wei Chen; Qing-Yi Lu; Xue-Fu Zhou; Bao-Guo Ding; Jun Chang; Shun-Zhang Yu

2007-01-01

159

Hyperhomocysteinemia and MTHFR C677T and A1298C polymorphisms are associated with chronic allograft nephropathy in renal transplant recipients  

Microsoft Academic Search

Hyperhomocysteine has been reported to be an important risk factor for the development of atherosclerosis. Identification of risk factors, such as hyperhomocysteinemia, is crucial for a better understanding of the events that lead to degenerative processes in the vascular system and for a correct understanding of the potential role of methylene-tetrahydrofolate reductase enzymes (MTHFR) to help in the treatment of

E. C. Pavarino-Bertelli; M. P. Sanches de Alvarenga; E. M. Goloni-Bertollo; M. A. S. F. Baptista; R. Haddad; N. F. Hoerh; M. N. Eberlin; M. Abbud-Filho

2004-01-01

160

Vitamin B12 Status Is Inversely Associated with Plasma Homocysteine in Young Women with C677T and\\/or A1298C Methylenetetrahydrofolate Reductase Polymorphisms1  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms may negatively influence one-carbon metabolism and increase health risks in women of reproductive age. The effect of MTHFR single nucleotide polymorphisms at bp 677 and\\/or 1298 and differences in folate and vitamin B-12 status on plasma homocysteine concentration in women of reproductive age (20 -30 y; n 186) were investigated. From the multivariate regression model, homozygotes

Lynn B. Bailey; Robert L. Duhaney; David R. Maneval; Gail P. A. Kauwell; Eoin P. Quinlivan; Steven R. Davis; Aisha Cuadras; Alan D. Hutson; Jesse F. Gregory

161

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

Microsoft Academic Search

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

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

2003-01-01

162

Delay Discounting and Frontostriatal Fiber Tracts: A Combined DTI and MTR Study on Impulsive Choices in Healthy Young Adults  

PubMed Central

Delay discounting, a measure of impulsive choice, has been associated with decreased control of the prefrontal cortex over striatum responses. The anatomical connectivity between both brain regions in delaying gratification remains unknown. Here, we investigate whether the quality of frontostriatal (FS) white matter tracts can predict individual differences in delay-discounting behavior. We use tract-based diffusion tensor imaging and magnetization transfer imaging to measure the microstructural properties of FS fiber tracts in 40 healthy young adults (from 18 to 25 years). We additionally explored whether internal sex hormone levels affect the integrity of FS tracts, based on the hypothesis that sex hormones modulate axonal density within prefrontal dopaminergic circuits. We calculated fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity, radial diffusivity (RD), and magnetization transfer ratio (MTR), a putative measure of myelination, for the FS tract. Results showed that lower integrity within the FS tract (higher MD and RD and lower FA), predicts faster discounting in both sexes. MTR was unrelated to delay-discounting performance. In addition, testosterone levels in males were associated with a lower integrity (higher RD) within the FS tract. Our study provides support for the hypothesis that enhanced structural integrity of white matter fiber bundles between prefrontal and striatal brain areas is associated with better impulse control. PMID:22693341

Peper, Jiska S.; Mandl, Rene C.W.; Braams, Barbara R.; de Water, Erik; Heijboer, Annemieke C.; Koolschijn, P. Cedric M.P.; Crone, Eveline A.

2013-01-01

163

Delay discounting and frontostriatal fiber tracts: a combined DTI and MTR study on impulsive choices in healthy young adults.  

PubMed

Delay discounting, a measure of impulsive choice, has been associated with decreased control of the prefrontal cortex over striatum responses. The anatomical connectivity between both brain regions in delaying gratification remains unknown. Here, we investigate whether the quality of frontostriatal (FS) white matter tracts can predict individual differences in delay-discounting behavior. We use tract-based diffusion tensor imaging and magnetization transfer imaging to measure the microstructural properties of FS fiber tracts in 40 healthy young adults (from 18 to 25 years). We additionally explored whether internal sex hormone levels affect the integrity of FS tracts, based on the hypothesis that sex hormones modulate axonal density within prefrontal dopaminergic circuits. We calculated fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity, radial diffusivity (RD), and magnetization transfer ratio (MTR), a putative measure of myelination, for the FS tract. Results showed that lower integrity within the FS tract (higher MD and RD and lower FA), predicts faster discounting in both sexes. MTR was unrelated to delay-discounting performance. In addition, testosterone levels in males were associated with a lower integrity (higher RD) within the FS tract. Our study provides support for the hypothesis that enhanced structural integrity of white matter fiber bundles between prefrontal and striatal brain areas is associated with better impulse control. PMID:22693341

Peper, Jiska S; Mandl, René C W; Braams, Barbara R; de Water, Erik; Heijboer, Annemieke C; Koolschijn, P Cédric M P; Crone, Eveline A

2013-07-01

164

Role of Outer-Membrane Cytochromes MtrC and OmcA in the Biomineralization of Ferrihydrite by Shewanella oneidensis MR-1.  

SciTech Connect

In an effort to improve the understanding of electron transfer mechanisms at the microbe-mineral interface, Shewanella oneidensis MR-1 mutants with in-frame deletions of outer membrane cytochrome genes mtrC, omcA, or both, were characterized for the ability to reduce metal oxides using a suite of microscopic, spectroscopic, and biochemicalr techniques. The results indicate that neither MtrC nor OmcA are essential for the reduction of soluble, complexed Fe(III)-citrate or Fe(III)-NTA; however, at least one of these outer membrane cytochromes is required for the reduction of Fe(III)- and Mn(III/IV)- oxides. In vitro analysis of purified, recombinant protein demonstrated that both cytochromes transfer electrons directly to metal-oxides; however, MtrC transfers electrons at a faster rate than OmcA. Immunolocalization of MtrC and OmcA reveal that both cytochromes are surface-exposed on the cell outer-membrane and co-localize with insoluble iron precipitates when respiring ferrihydrite or cultured aerobically with Fe(III)-citrate. Additionally, during prolonged incubation, wild-type cells promoted biotransformation of ferrihydrite to vivianite [Fe3(PO4)2•8H2O] while the double cytochrome mutant was unable to form any secondary mineral phases. Collectively, our results support a role for direct electron transfer from OMCs to metal oxides by establishing their in vitro electron transfer activities, confirming the requirement of either MtrC or OmcA for in vivo reductive biomineralization of ferrihydrite, and localizing the cytochromes to the cell exterior where they can directly contact mineral substrates.

Reardon, Catherine L.; Dohnalkova, Alice; Nachimuthu, Ponnusamy; Kennedy, David W.; Saffarini, Daad; Arey, Bruce W.; Shi, Liang; Wang, Zheming; Moore, Dean A.; Mclean, Jeffrey S.; Moyles, Dianne M.; Marshall, Matthew J.; Zachara, John M.; Fredrickson, Jim K.; Beliaev, Alex S.

2010-01-01

165

Comparative proteomics reveal the impact of OmcA/MtrC deletion on Shewanella oneidensis MR-1 in response to hexavalent chromium exposure.  

PubMed

Hexavalent chromium [Cr(VI)] is a priority pollutant causing serious environmental issues. Microbial reduction provides an alternative strategy for Cr(VI) remediation. The dissimilatory metal-reducing bacterium, Shewanella oneidensis MR-1, was employed to study Cr(VI) reduction and toxicity in this work. To understand the effect of membrane cytochromes on Cr(VI) response, a comparative protein profile analysis from S. oneidensis MR-1 wild type and its mutant of deleting OmcA and MtrC (?omcA/mtrC) was conducted using two-dimensional electrophoresis (2-DE) technology. The 2-DE patterns were compared, and the proteins with abundant changes of up to twofold in the Cr(VI) treatment were detected. Using mass spectrometry, 38 and 45 differentially abundant proteins were identified in the wild type and the mutant, respectively. Among them, 25 proteins were shared by the two strains. The biological functions of these identified proteins were analyzed. Results showed that Cr(VI) exposure decreased the abundance of proteins involved in transcription, translation, pyruvate metabolism, energy production, and function of cellular membrane in both strains. There were also significant differences in protein expressions between the two strains under Cr(VI) treatment. Our results suggest that OmcA/MtrC deletion might result in the Cr(VI) toxicity to outer membrane and decrease assimilation of lactate, vitamin B12, and cystine. When carbohydrate metabolism was inhibited by Cr(VI), leucine and sulfur metabolism may act as the important compensatory mechanisms in the mutant. Furthermore, the mutant may regulate electron transfer in the inner membrane and periplasm to compensate for the deletion of OmcA and MtrC in Cr(VI) reduction. PMID:25341401

Wang, Chao; Chen, Juan; Hu, Wen-Jun; Liu, Ji-Yun; Zheng, Hai-Lei; Zhao, Feng

2014-12-01

166

Kinetic Characterization of OmcA and MtrC, Terminal Reductases Involved in Respiratory Electron Transfer for Dissimilatory Iron Reduction in Shewanella oneidensis MR-1?  

PubMed Central

We have used scaling kinetics and the concept of kinetic competence to elucidate the role of hemeproteins OmcA and MtrC in iron reduction by Shewanella oneidensis MR-1. Second-order rate constants for OmcA and MtrC were determined by single-turnover experiments. For soluble iron species, a stopped-flow apparatus was used, and for the less reactive iron oxide goethite, a conventional spectrophotometer was used to measure rates. Steady-state experiments were performed to obtain molecular rate constants by quantifying the OmcA and MtrC contents of membrane fractions and whole cells by Western blot analysis. For reduction of soluble iron, rates determined from transient-state experiments were able to account for rates obtained from steady-state experiments. However, this was not true with goethite; rate constants determined from transient-state experiments were 100 to 1,000 times slower than those calculated from steady-state experiments with membrane fractions and whole cells. In contrast, addition of flavins to the goethite experiments resulted in rates that were consistent with both transient- and steady-state experiments. Kinetic simulations of steady-state results with kinetic constants obtained from transient-state experiments supported flavin involvement. Therefore, we show for the first time that OmcA and MtrC are kinetically competent to account for catalysis of soluble iron reduction in whole Shewanella cells but are not responsible for electron transfer via direct contact alone with insoluble iron-containing minerals. This work supports the hypothesis that electron shuttles are important participants in the reduction of solid Fe phases by this organism. PMID:19542342

Ross, Daniel E.; Brantley, Susan L.; Tien, Ming

2009-01-01

167

Hyperhomocysteinemia Due to Methionine Synthase Deficiency, cblG: Structure of the MTR Gene, Genotype Diversity, and Recognition of a Common Mutation, P1173L  

PubMed Central

Mutations in the MTR gene, which encodes methionine synthase on human chromosome 1p43, result in the methylcobalamin deficiency G (cblG) disorder, which is characterized by homocystinuria, hyperhomocysteinemia, and hypomethioninemia. To investigate the molecular basis of the disorder, we have characterized the structure of the MTR gene, thereby identifying exon-intron boundaries. This enabled amplification of each of the 33 exons of the gene, from genomic DNA from a panel of 21 patients with cblG. Thirteen novel mutations were identified. These included five deletions (c.12-13delGC, c.381delA, c.2101delT, c.2669-2670delTG, and c.2796-2800delAAGTC) and two nonsense mutations (R585X and E1204X) that would result in synthesis of truncated proteins that lack portions critical for enzyme function. One mutation was identified that resulted in conversion of A to C of the invariant A of the 3? splice site of intron 9. Five missense mutations (A410P, S437Y, S450H, H595P, and I804T) were identified. The latter mutations, as well as the splice-site mutation, were not detected in a panel of 50 anonymous DNA samples, suggesting that these sequence changes are not polymorphisms present in the general population. In addition, a previously described missense mutation, P1173L, was detected in 16 patients in an expanded panel of 24 patients with cblG. Analysis of haplotypes constructed using sequence polymorphisms identified within the MTR gene demonstrated that this mutation, a C?T transition in a CpG island, has occurred on at least two separate genetic backgrounds. PMID:12068375

Watkins, David; Ru, Ming; Hwang, Hye-Yeon; Kim, Caroline D.; Murray, Angus; Philip, Noah S.; Kim, William; Legakis, Helen; Wai, Timothy; Hilton, John F.; Ge, Bing; Dore, Carole; Hosack, Angela; Wilson, Aaron; Gravel, Roy A.; Shane, Barry; Hudson, Thomas J.; Rosenblatt, David S.

2002-01-01

168

Hearing impairment risk and interaction of folate metabolism related gene polymorphisms in an aging study  

PubMed Central

Background Recent investigations demonstrated many genetic contributions to the development of human age-related hearing impairment (ARHI), however, reports of factors associated with a reduction in the ARHI risk are rare. Folate metabolism is essential for cellular functioning. Despite the extensive investigations regarding the roles of folate metabolism related gene polymorphisms in the pathophysiology of complex diseases, such as cancer, cardio-cerebrovascular disease, and atherosclerosis, little is known about the association with ARHI. The aim of this study is to investigate the effects of the methionine synthase (MTR) A2756G and methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms on the risk of hearing impairment in middle-aged and elderly Japanese. Methods Data were collected from community-dwelling Japanese adults aged 40-84 years who participated in the Longitudinal Study of Aging biennially between 1997 and 2008. We analyzed cumulative data (5,167 samples in accumulated total) using generalized estimating equations. Results The MTHFR 677T allele was significantly associated with a reduced risk of hearing impairment only when the subjects were wild-type homozygotes for MTR A2756G. The per-T allele odds ratio of MTHFR for the risk of developing hearing impairment was 0.7609 (95% CI: 0.6178-0.9372) in the MTR AA genotype. In addition, a subgroup analysis demonstrated that the favorable effect of the MTHFR 677T allele on the risk of developing hearing impairment was independent of folate and homocysteine level, whereas plasma total homocysteine level was independently associated with an increased risk of developing hearing impairment. The interactive effect of gene polymorphisms associated with folate metabolism may modify the risk of developing hearing impairment after middle age. These results contribute to the elucidation of the causes of ARHI. Conclusions The present study has found that the MTHFR 677T allele has a favorable effect on a risk of hearing impairment in the middle-aged and elderly population, only when the individuals were wild-type homozygotes for MTR A2756G. PMID:21385350

2011-01-01

169

Effects of Bio-Au Nanoparticles on Electrochemical Activity of Shewanella oneidensis Wild Type and ?omcA/mtrC Mutant  

PubMed Central

Both Shewanella oneidensis MR-1 wild type and its mutant ?omcA/mtrC are capable of transforming AuIII into Au nanoparticles (AuNPs). Cyclic voltammetry reveals a decrease in redox current after the wild type is exposed to AuIII but an increase in oxidation current for the mutant. The peak current of the wild type is much higher than that of the mutant before the exposure of AuIII, but lower than that of the mutant after the formation of AuNPs. This suggests that damage to the electron transfer chain in the mutant could be repaired by AuNPs to a certain extent. Spectroscopy and SDS-PAGE analysis indicate a decrease in cell protein content after the formation of AuNPs, which provides a convenient way to detect intracellular information on cells. PMID:24264440

Wu, Ranran; Cui, Li; Chen, Lixiang; Wang, Chao; Cao, Changli; Sheng, Guoping; Yu, Hanqing; Zhao, Feng

2013-01-01

170

The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study  

Microsoft Academic Search

Total blood levels of homocysteine (tHcy) have been shown to depend on both environmental and genetic factors, and to be associated with the risk of developing atherosclerosis with its complications of coronary heart disease (CHD) and stroke. In this study, 408 men and 346 women from two towns, Dewsbury and Maidstone were examined for tHcy levels and genotyped for the

V. Dekou; P. Whincup; O. Papacosta; S. Ebrahim; L. Lennon; P. M. Ueland; H. Refsum; S. E. Humphries; V. Gudnason

2001-01-01

171

Flow cytometric determination of mitochondrial membrane potential changes during apoptosis of T lymphocytic and pancreatic beta cell lines: Comparison of tetramethylrhodamineethylester (TMRE), chloromethyl-X-rosamine (H 2-CMX-Ros) and MitoTracker Red 580 (MTR580)  

Microsoft Academic Search

The mitochondria-specific dyes, TMRE, H2-CMX-Ros and MTR580 were determined for their suitability to measure mitochondrial potential changes of the T cell leukemia cell line Jurkat and insulin-secreting beta cell line NIT-1 during apoptosis. Both freshly harvested Jurkat and NIT-1 cells induced to undergo apoptosis displayed poor retention of the potential-sensitive, intrinsically fluorescent dye, TMRE. Treatment with formaldehyde or paraformaldehyde completely

Sundararajan Jayaraman

2005-01-01

172

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

PubMed

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

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

2014-11-01

173

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

174

Maternal Gene Polymorphisms Involved in Folate Metabolism as Risk Factors for Down Syndrome Offspring in Southern Brazil  

PubMed Central

This study aimed to investigate the role of maternal polymorphisms, as well as their risk genotypes combinations of MTR A2756G, MTRR A66G, CBS 844ins68, and RFC A80G, involved in folate/homocysteine metabolism, as possible risk factors for Down syndrome (DS) in Southern Brazil. A case-control study was conducted with 239~mothers of DS children and 197 control mothers. The investigation of polymorphisms was performed by PCR and PCR-RFLP. The distribution of genotypic variants was similar in both groups when they were analyzed separately. An investigation of combined risk genotypes showed that the risk of having a DS child for one, two or three risk genotypes was 6.23, 6.96 and 5.84 (95%CI 1.48–26.26; 1.69–28.66; 1.37–24.86), respectively. The combined MTRR 66G and MTHFR 677T alleles were significantly more common among mothers of children with DS than among control mothers (OR 1.55; IC 95% 1.03–2.35). The results show that individual polymorphisms studied in this work are not associated with DS; however, the effects of the combined risk genotypes among MTR, MTRR, CBS and RFC genes are considered maternal risk factors for DS offspring in our population. PMID:21045269

Brandalize, Ana Paula Carneiro; Bandinelli, Eliane; Santos, Pollyanna Almeida Dos; Schuler-Faccini, Lavinia

2010-01-01

175

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

E-print Network

(MTHFR) gene at positions C677T and A1298C were associated with lower risk of adult acute lymphocytic an association between polymorphic variants at positions C677T and A1298C in the folate-metabolizing gene 5,10- methylenetetrahydrofolate reductase (MTHFR), and a decreased risk of adult acute lymphocytic leukemia (ALL).1 Similar

California at Berkeley, University of

176

28 MTR October 2009 Ocean gliders are autonomous underwater vehicles that  

E-print Network

coordinates. In addition, any sensor added to a glider must be small, light weight, and require very little- erence to current velocity data is very difficult due to the glider motion in the horizontal and vertical, number of dives, and types of observational sensors. Since 2005, Nortek has collaborated with leading

Fratantoni, David

177

University MTR Station (Northern Exit)> 1. Fong Yun Wah Hall > 2. Yasumoto International  

E-print Network

Block) (lift to 4/F) > 10. Pentecostal Mission Hall Complex (High Block) (footbridge) > 11. Basic (lift to 9/F) > 9. Ho Sin-Hang Engineering Building (footbridge) > 10. Lady Shaw Building (footbridge Medical Sciences Building > 12. Mong Man Wai Building (lift to 8/F) > 13. Staff Student Centre ­ Leung

Huang, Jianwei

178

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

SciTech Connect

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

Baxter, D.E.

1994-10-01

179

Gene Polymorphisms of Homocysteine Metabolism-Related Enzymes in Chinese Patients with Occlusive Coronary Artery or Cerebral Vascular Diseases  

Microsoft Academic Search

The mutations in homocysteine (Hcy) metabolism-related enzyme genes including methylenetetrahydrofolate reductase (MTHFR) C677T, cystathionine ?-synthase (CBS) 844ins68, and methionine synthase (MS) A2756G have been identified as genetic risk factors for thromboembolic events. It has been noticed that these gene mutations have heterogeneous distributions among different ethnic groups or geographic areas. The data on the prevalence of the gene mutations in

Guangsen Zhang; Chongwen Dai

2001-01-01

180

Investigation of genetic polymorphisms and smoking in a bladder cancer casecontrol study in Argentina  

E-print Network

: the T variant at nucleotide 677 (MTHFR C677T) and the C variant at nucleotide 1298 (MTHFR A1298C). Variant C677T investigated the role of glutathione S-transferase (GST) enzymes (M1, T1), methylenetetrahydrofolate (MTHFR conferred the highest risks. The MTHFR 677 CT and TT polymorphisms appeared protective against bladder

California at Berkeley, University of

181

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

182

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

E-print Network

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

Bewley, Kathryn D.

183

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

184

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.

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

2013-01-01

185

Evidence for the Assembly of a Bacterial Tripartite Multidrug Pump with a Stoichiometry of 3:6:3*  

PubMed Central

The multiple transferable resistance (mTR) pump from Neisseria gonorrhoeae MtrCDE multidrug pump is assembled from the inner and outer membrane proteins MtrD and MtrE and the periplasmic membrane fusion protein MtrC. Previously we established that while there is a weak interaction of MtrD and MtrE, MtrC binds with relatively high affinity to both MtrD and MtrE. MtrD conferred antibiotic resistance only when it was expressed with MtrE and MtrC, suggesting that these proteins form a functional tripartite complex in which MtrC bridges MtrD and MtrE. Furthermore, we demonstrated that MtrC interacts with an intraprotomer groove on the surface of MtrE, inducing channel opening. However, a second groove is apparent at the interface of the MtrE subunits, which might also be capable of engaging MtrC. We have now established that MtrC can be cross-linked to cysteines placed in this interprotomer groove and that mutation of residues in the groove impair the ability of the pump to confer antibiotic resistance by locking MtrE in the closed channel conformation. Moreover, MtrE K390C forms an intermolecular disulfide bond with MtrC E149C locking MtrE in the open channel conformation, suggesting that a functional salt bridge forms between these residues during the transition from closed to open channel conformations. MtrC forms dimers that assemble into hexamers, and electron microscopy studies of single particles revealed that these hexamers are arranged into ring-like structures with an internal aperture sufficiently large to accommodate the MtrE trimer. Cross-linking of single cysteine mutants of MtrC to stabilize the dimer interface in the presence of MtrE, trapped an MtrC-MtrE complex with a molecular mass consistent with a stoichiometry of 3:6 (MtrE3MtrC6), suggesting that dimers of MtrC interact with MtrE, presumably by binding to the two grooves. As both MtrE and MtrD are trimeric, our studies suggest that the functional pump is assembled with a stoichiometry of 3:6:3. PMID:21610073

Janganan, Thamarai K.; Bavro, Vassiliy N.; Zhang, Li; Matak-Vinkovic, Dijana; Barrera, Nelson P.; Venien-Bryan, Catherine; Robinson, Carol V.; Borges-Walmsley, Maria Ines; Walmsley, Adrian R.

2011-01-01

186

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

PubMed Central

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

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

2014-01-01

187

Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer  

Microsoft Academic Search

The aim of this study was to investigate the association of environmental factors (dietary folate, methionine and drinking status) and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) gene, as well as the combination of these factors, with the risk of colon cancer and rectal cancer. A case-control study of 53 colon cancer patients, 73 rectal cancer patients and

Qinting Jiang; Kun Chen; Xinyuan Ma; Qilong Li; Weiping Yu; Guotong Shu; Kaiyan Yao

2005-01-01

188

Methylenetetrahydrofolate reductase (MTHFR) c677t gene variant modulates the homocysteine folate correlation in a mild folate-deficient population  

Microsoft Academic Search

Background: A large body of evidence links plasma concentrations of homocysteine and cardiovascular disease. Several genetic and environmental variables may modulate such relationship. We investigated the influence of methylenetetrahydrofolate reductase (MTHFR) gene variants C677T, A1298C, and T1317C on homocysteine, folate, and cobalamin concentrations in a sample of individuals from a mild folate deficiency population to better clarify the complex interactions

Alexandre C. Pereira; Isolmar Tadeu Schettert; Antônio Alberto F. Morandini Filho; Elvira Maria Guerra-Shinohara; José E. Krieger

2004-01-01

189

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

190

Association between methylenetetrahydrofolate reductase polymorphisms and the relapse of acute lymphoblastic leukemia: a meta-analysis.  

PubMed

Relapse is a threat in patients treated for acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) activity may affect the sensitivity of patients to folate-based chemotherapeutic drugs, thus influencing the relapse risk. Two polymorphisms of the gene encoding MTHFR, C677T and A1298C, alter MTHFR enzyme activity and may be associated with ALL relapse. The aim of this meta-analysis was to clarify the correlation between the C677T and A1298C polymorphisms and ALL relapse. To this end, data were collected from studies of the association between these two polymorphisms and ALL relapse. Analysis of the data revealed a serious contradiction among the results. A recessive model demonstrated that the ALL relapse risk was significantly increased in carriers of the 677?TT genotype, especially for pediatric ALL, but was unaffected by the A1298C polymorphism. These findings confirm that the MTHFR C677T polymorphism could be considered as a good marker of the pediatric ALL relapse risk. PMID:24637499

He, H-R; Chen, S-Y; You, H-S; Hu, S-S; Sun, J-Y; Dong, Y-L; Lu, J

2014-10-01

191

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

192

Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.  

PubMed

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

Qin, Yu-Tao; Zhang, Yong; Wu, Fang; Su, Yan; Lu, Ge-Ning; Wang, Ren-Sheng

2014-01-01

193

98 U3BEl&RABJSAC1'KWSON MICROWAVR THEQRY AND TiiCHNIQUBS, VU, MTr-28, NW,~, FIIMWAW 1980 Effects of Fringing Fields on the Capacitance  

E-print Network

of Fringing Fields on the Capacitance of Circular Microstrip Disk WINGCHO CHEW mm JIPJ AU K(3NG A*#m-m computed the capacitance for small plate separation, For practical usage, Shen et al. [10] devised

Leung, Ka-Cheong

194

Solution-Based Structural Analysis of the Decaheme Cytochrome, MtrA, by Small-Angle X-ray Scattering and Analytical Ultracentrifugation  

E-print Network

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 ...

Firer-Sherwood, Mackenzie A.

195

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

PubMed

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 (OM), 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-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and 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-OM spanning beta-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. 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. PMID:20018742

Hartshorne, Robert S; Reardon, Catherine L; Ross, Daniel; 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; Butt, Julea N; Richardson, David J

2009-12-29

196

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

197

Migraine and Genetic Polymorphisms: An Overview  

PubMed Central

The relationship between genetic polymorphisms and migraine as a cause of an increased risk of thrombotic disorders development is still debated In this respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII (V34L), ?-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and ACE I/D seem to play a determinant role in vascular diseases related to migraine. The present review analyzes both the incidence of the above genetic vascular mutations in migraineurs and the most re-cent developments related to genetic polymorphisms and migraine. PMID:22962564

Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna

2012-01-01

198

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

199

A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in breast cancer.  

PubMed

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To derive a more precise estimation, we carried out not only an updated meta-analysis but also a combined analysis based on all the available studies estimating the association between MTHFR C677T and/or A1298C and breast cancer risk. With respect to C677T polymorphism, the results suggested that 677T allele was associated with significantly elevated breast cancer risk in overall analysis (T vs. C: OR 1.073, 95 % CI 1.028-1.120; TT vs. CC: OR 1.177, 95 % CI 1.072-1.293; TT vs. CC + CT: OR 1.175, 95 % CI 1.073-1.288); Stratifying by ethnicity, significantly increased risk was only found in East Asians (T vs. C: OR 1.150, 95 % CI 1.039-1.273; TT vs. CC: OR 1.441, 95 % CI 1.145-1.814; TT vs. CC + CT: OR 1.413, 95 % CI 1.148-1.739); When stratified by menopausal status, statistically significant association was found for postmenopausal women (CT + TT vs. CC: OR 1.092, 95 % CI 1.011-1.179). In regard to A1298C polymorphism, no significant associations were found between the polymorphism and breast cancer risk. With respect to MTHFR haplotypes, significantly elevated breast cancer risk was associated with 677T-1298C for overall result (OR 1.498, 95 % CI 1.143-1.962) and for Caucasians (OR 2.088, 95 % CI 1.277-3.416) when compared with 677C-1298A; Haplotype 677C-1298C might provide higher protection than 677C-1298A in East Asians (OR 0.840, 95 % CI 0.742-0.949). The combined genotypes for C677T and A1298C produced a significant OR for the 677TT/1298AC relative to 677CC/1298AA in overall population (OR 2.047, 95 % CI 1.275-3.288); When stratified by ethnicity, significant ORs were only found for East Asians (677CC/1298CC vs. 677CC/1298AA: OR 0.686, 95 % CI 0.478-0.985; 677TT/1298AC vs. 677CC/1298AA: OR 2.181, 95 % CI 1.179-4.035). The findings suggest that the MTHFR C677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer. PMID:24973876

Zhong, Shanliang; Chen, Zhiyuan; Yu, Xinnian; Li, Wenjing; Tang, Jinhai; Zhao, Jianhua

2014-09-01

200

Prevalence of Myofascial Trigger Points in Fibromyalgia: The Overlap of Two Common Problems  

Microsoft Academic Search

With the objective evidence of their existence, myofascial trigger points (MTrPs) contribute to an increasing number of chronic\\u000a regional and widespread pain conditions. The widespread spontaneous pain pattern in fibromyalgia (FM) is a summation of multiple\\u000a regional pains due to active MTrPs. A regional pain in FM is from local active MTrPs and\\/or referred from remote active MTrPs.\\u000a Positive tender

Hong-You Ge

2010-01-01

201

Treatment of myofascial pain syndrome  

Microsoft Academic Search

Myofascial pain syndrome (MPS) is caused by myofascial trigger points (MTrPs) located within taut bands of skeletal muscle\\u000a fibers. Treating the underlying etiologic lesion responsible for MTrP activation is the most important strategy in MPS therapy.\\u000a If the underlying pathology is not given the appropriate treatment, the MTrP cannot be completely and permanently inactivated.\\u000a Treatment of active MTrPs may be

Chang-Zern Hong

2006-01-01

202

Masters of Science Translational Research  

E-print Network

student is $3,101 · Cost of living stipend of $22,032 to offset delay to earing · For students receiving in 2008 · Enrolls on average 15 students per year ­ MD Students, Residents, Fellows, Pre 30th 5 MTR Module 5 + MTR MD tuition Finances #12;Funding the tuition costs · Cost of MTR ($4,286 per

Bushman, Frederic

203

Serial Magnetization Transfer Imaging in Acute Optic Neuritis  

ERIC Educational Resources Information Center

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

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

2004-01-01

204

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

Microsoft Academic Search

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

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

2005-01-01

205

Characterization of Protein-Protein Interactions Involved in Iron Reduction by Shewanella oneidensis MR1  

Microsoft Academic Search

The interaction of proteins implicated in dissimilatory metal reduction by Shewanella oneidensis MR-1 (outer membrane (OM) proteins OmcA, MtrB, and MtrC; OM-associated protein MtrA; periplasmic protein CctA; and cytoplasmic membrane protein CymA) were characterized by protein purification, analytical ultracentrif- ugation, and cross-linking methods. Five of these proteins are heme proteins, OmcA (83 kDa), MtrC (75 kDa), MtrA (32 kDa), CctA

Daniel E. Ross; Shane S. Ruebush; Susan L. Brantley; Robert S. Hartshorne; Thomas A. Clarke; David J. Richardson; Ming Tien

2007-01-01

206

Evaluation of the contribution of methylenetetrahydrofolate reductase genotypes to Taiwan breast cancer.  

PubMed

The aim of the present study was to evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and its interaction with early-onset breast cancer risk in Taiwan. Two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed and their joint effects with individual age- and estrogen-related factors on breast cancer risk were discussed. In total, 1,232 patients with breast cancer and 1,232 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The MTHFR C677T genotype, but not the A1298C, was differently distributed between cancer and control groups. The T allele of MTHFR C677T was significantly more frequently found in controls than in patients with cancer. In addition, females carrying MTHFR C677T CT or TT genotypes had a higher odds ratio of 1.21 (95% confidence interval=1.03-1.42, p=1.85E-5) for breast cancer, especially before the age of 45.4 years (odds ratio=1.51 and 95% confidence interval=1.20-1.90). Our results indicate that MTHFR C677T T allele was associated with increased risk of breast cancer in Taiwan, especially in cases who were 45.4 old or younger and with earlier menarche age (<12.2 years). PMID:25075036

Huang, Chung-Yu; Chang, Wen-Shin; Shui, Hao-Ai; Hsieh, Yung-Hung; Loh, Ching-Hui; Wang, Hwei-Chung; Ji, Hong-Xue; Hsiao, Chieh-Lun; Hsu, Chin-Mu; Tsai, Chia-Wen; Bau, Da-Tian

2014-08-01

207

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

PubMed

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

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

2014-01-01

208

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

PubMed

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

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

2014-05-01

209

Methylenetetrahydrofolate reductase gene haplotypes affect toxicity during maintenance therapy for childhood acute lymphoblastic leukemia in Japanese patients.  

PubMed

Abstract The aim of this study was to investigate the influence of daily 6-mercaptopurine (6-MP) and low-dose weekly methotrexate (MTX) combination treatment and methylenetetrahydrofolate reductase (MTHFR) haplotypes on toxicity during maintenance therapy in Japanese childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed the MTHFR C677T and A1298C polymorphisms and influence of haplotypes on toxicity in 73 patients. Patients with the MTHFR 677TT and 677CT + 1298AC were associated with severe liver toxicity (p = 0.014, odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.27-11.46) and more rapid onset of liver toxicity (p = 0.010). Patients with MTHFR 677TT and 677CT + 1298AC were associated with lower frequency of 6-MP and MTX dose reduction due to leukopenia (p < 0.05). No difference was observed in average drug doses in the MTHFR genotypes. In conclusion, the MTHFR C677T and A1298C haplotypes might be useful for monitoring adverse effects in childhood ALL maintenance therapy in Japanese patients. PMID:23865834

Tanaka, Yoichi; Manabe, Atsushi; Nakadate, Hisaya; Kondoh, Kensuke; Nakamura, Kozue; Koh, Katsuyoshi; Kikuchi, Akira; Komiyama, Takako

2014-05-01

210

The MTHFR C677T polymorphism modifies age at onset in Parkinson's disease.  

PubMed

Hyperhomocysteinemia is a risk factor for Parkinson's disease (PD) and may result from genetic mutations or/and environmental factors. 5,10-methylenetetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme that catalyzed remethylation of homocysteine (Hcy) and the MTHFR C677T polymorphism makes the MTHFR enzyme thermolabile causing hyperhomocysteinemia. In this study we analyzed whether two functional polymorphisms of MTHFR gene, A1298C and C677T, affect age of onset in PD. We enrolled 120 patients with sporadic PD. Patients were divided into three groups based on MTHFR C677T polymorphisms: (a) homozygotes wild type (CC) (b) heterozygotes (CT) and (c) homozygotes carriers of mutation (TT). MTHFR SNPs were analyzed using High-Resolution Melt analysis and ANOVA was performed to assess whether polymorphisms of MTHFR gene could influence age of onset. The MTHFR A1298C polymorphism had no effect on PD age at onset (p = 1.0) while there was a significant association with MTHFR C677T (p = 0.019 Bonferroni-adjusted post hoc) showing an earlier onset in CC as compared with TT. (p = 0.024). No differences were found for vascular load assessed with magnetic resonance imaging, pharmacological therapy and cognitive state for two MTHFR SNPs. Our results suggest a possible association of MTHFR C677T with age at onset of PD and may have important implications regarding the role of MTHFR. PMID:24052451

Vallelunga, Annamaria; Pegoraro, Valentina; Pilleri, Manuela; Biundo, Roberta; De Iuliis, Angela; Marchetti, Mauro; Facchini, Silvia; Formento Dojot, Patrizia; Antonini, Angelo

2014-01-01

211

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

PubMed

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

Diri, Halit; Sener, Elif Funda; Bayram, Fahri; Tascioglu, Nazife; Simsek, Yasin; Dundar, Munis

2014-01-01

212

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

213

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

214

Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase  

Microsoft Academic Search

Telomerase, the essential enzyme that maintains telomere length, contains two core components, TERT and TR. Early studies in yeast and mouse showed that loss of telomerase leads to phenotypes only after several generations, due to telomere shortening. However, recent studies have sug- gested additional roles for telomerase components in transcription and the response to DNA damage. To examine these potential

Sofia L. Vidal-Cardenas; Carol W. Greider

2010-01-01

215

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

SciTech Connect

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

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

2007-01-01

216

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

217

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

PubMed Central

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 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 MtrA either directly or indirectly through other periplasmic proteins. 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). In addition to Fe(III) oxides, Mtr pathway is also involved in reduction of manganese oxides and other metals. 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. PMID:22363328

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

2012-01-01

218

Increased H-reflex response induced by intramuscular electrical stimulation of latent myofascial trigger points  

Microsoft Academic Search

Background:Myofascial trigger points (MTrPs) present with mechanical hyperalgesia and allodynia. No electrophysiological evidence exists as to the excitability of muscle spindle afferents at myofascial trigger points MTrPs. The purpose of this current study was to explore whether an H-reflex response could be elicited from intramuscular electrical stimulation. If so, to assess the possibility of increased reflex response at MTrPs.Methods:The H-reflex

Hong-You Ge; Mariano Serrao; Ole K Andersen; Thomas Graven-Nielsen; Lars Arendt-Nielsen

2009-01-01

219

Identification and characterization of mesotocin and V1a-like vasotocin receptors in a urodele amphibian, Taricha granulosa  

Microsoft Academic Search

The cDNA sequences encoding the mesotocin receptor (MTR) and vasotocin 1a receptor (VTR-1a) were identified in a urodele amphibian, the rough-skinned newt, Taricha granulosa. Saturation binding of [3H]oxytocin (OT) to the Taricha MTR (tMTR) was best fit by a two-state model; a high affinity-low abundance site and a lower affinity-high abundance site. Competition-binding studies found the following rank-order affinities for

Brian T. Searcy; C. Samuel Bradford; Richmond R. Thompson; Theresa M. Filtz; Frank L. Moore

2011-01-01

220

Short Telomeres and Ataxia-Telangiectasia Mutated Deficiency Cooperatively Increase Telomere Dysfunction and Suppress Tumorigenesis  

Microsoft Academic Search

To examine the role of ataxia-telangiectasia mutated (Atm) in telomere function, we generated Atm and telomerase null mice (Atm\\/ mTR\\/ iG6 mice). These mice exhibited increased germ cell death and chromo- some fusions compared with either Atm\\/ or mTR\\/ iG6 mice. Further- more, the Atm\\/ mTR iG6 mice had a delayed onset and reduced incidence of thymic lymphoma compared with

Ling Qi; Margaret A. Strong; Baktiar O. Karim; Mary Armanios; David L. Huso; Carol W. Greider

2003-01-01

221

Current studies on myofascial pain syndrome  

Microsoft Academic Search

Recent studies have clarified the nature of myofascial trigger points (MTrPs). In an MTrP region, multiple hyperirritable\\u000a loci can be found. The sensory components of the MTrP locus are sensitized nociceptors that are responsible for pain, referred\\u000a pain, and local twitch responses. The motor components are dysfunctional endplates that are responsible for taut band formation\\u000a as a result of excessive

Ta-Shen Kuan

2009-01-01

222

Prevalence of myofascial trigger points in fibromyalgia: the overlap of two common problems.  

PubMed

With the objective evidence of their existence, myofascial trigger points (MTrPs) contribute to an increasing number of chronic regional and widespread pain conditions. The widespread spontaneous pain pattern in fibromyalgia (FM) is a summation of multiple regional pains due to active MTrPs. A regional pain in FM is from local active MTrPs and/or referred from remote active MTrPs. Positive tender points specified in FM are MTrPs, either active or latent. Manual stimulation of active MTrPs located in the muscles in different body regions completely reproduced overall spontaneous FM pain pattern. Active MTrPs as tonic peripheral nociceptive input contribute tremendously to the initiation and maintenance of central sensitization, to the impairment of descending inhibition, to the increased excitability of motor units, and to the induction of sympathetic hyperactivity observed in FM. The considerable overlap of MTrPs and FM in pain characteristics and pathophysiology suggests that FM pain is largely due to MTrPs. PMID:20607459

Ge, Hong-You

2010-10-01

223

[Frequently associated genotypes to thrombophilia].  

PubMed

Venous thromboembolism is an important pathological entity that causes high morbidity due either to the disease or its complications. The incidence in the world ranges between 1:100 in adults and 1:100,000 in children. Risk factors for the disease include genetic as well as environmental factors. Among them, factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR C677T and A1298C (which until recently were considered risk factors), have been widely studied given their impact in the world. This review presents in a clear and concise way what a thrombous is and how it is formed; how a clot is able to produce thromboembolic disease; what are the main nosological entities involved, and their main genetic causes. The most epidemiologically important genetic alterations and studies conducted in Colombia will be emphasized. PMID:24967866

Hernández-Cuervo, Helena; Usme, Solangy; Yunis, Juan J

2014-01-01

224

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

PubMed

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

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

2014-07-01

225

Ocular vascular thrombotic events: a diagnostic window to familial thrombophilia (compound factor V Leiden and prothrombin gene heterozygosity) and thrombosis.  

PubMed

In a 12-member, 3-generation kindred with conjoint inheritance of G1691A factor V Leiden (FVL) and G20210A prothrombin gene (PTG) mutations, identified through a proband with amaurosis fugax and his father with nonarteritic ischemic optic neuropathy (NAION), the authors' hypothesis was that ocular thrombosis was a diagnostic window to familial thrombophilia-thrombosis. The authors used polymerase chain reaction (PCR) measures for thrombophilia (FVL, PTG, C677T-A1298C methylenetetrahydrofolate reductase [MTHFR], platelet glycoprotein PLA1A2) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G). The 39-year-old white male proband, with amaurosis fugax and transient ischemic attacks (TIA), was found to be a compound heterozygote for FVL and PTG mutations. His symptoms resolved only after coumadin. His 44-year-old brother (deep venous thrombosis [DVT]) and 46-year-old sister (DVT, pulmonary embolus [PE]) were compound FVL-PTG gene heterozygotes. Of 4 asymptomatic children born to these 3 siblings, 2 were FVL heterozygotes and 2 PTG heterozygotes. The proband's 69-year-old father, with NAION and ischemic stroke, had PTG heterozygosity, familial high factor VIII, and compound MTHFR C677T-A1298C mutation with homocysteinemia. The proband's 61-year-old aunt had PTG heterozygosity, recurrent DVT, and mesenteric artery thrombosis. The proband's 67-year-old mother, free of thrombotic events, was a FVL heterozygote, had high factor VIII, and PAI-1 4G4G homozygosity. In this extended kindred, ocular thrombotic events (amaurosis fugax, NAION) were associated with variegated thrombotic events, including TIA, ischemic stroke, DVT, PE, and mesenteric artery thrombosis, and opened a diagnostic window to family screening and treatment for complex thrombophilias, which had previously been undiagnosed. PMID:18796459

Glueck, Charles J; Wang, Ping

2009-02-01

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

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia  

PubMed Central

Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C?T) and 1,298 (A?C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15–0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07–0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20–1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia. PMID:11274424

Wiemels, Joseph L.; Smith, Rosalyn N.; Taylor, G. Malcolm; Eden, Osborn B.; Alexander, Freda E.; Greaves, Mel F.

2001-01-01

228

Maternal MTHFR genotype and haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico City1234  

PubMed Central

Background: Maternal folate nutritional status and prenatal lead exposure can influence fetal development and subsequent health. The methylenetetrahydrofolate reductase (MTHFR) gene is important for folate metabolism, and 2 common polymorphisms, C677T and A1298C, reduce enzymatic activity; C677T is present at high penetrance in Mexican populations. Objective: The objective of this study was to examine potential links between maternal and child MTHFR polymorphisms and child neurodevelopment in a lead-exposed population. Design: Data regarding MTHFR polymorphisms C677T and A1298C, peri- and postnatal lead measures, and Bayley Mental Development Index at 24 mo of age (MDI-24) scores were available for 255 mother-child pairs who participated in the ELEMENT (Early Life Exposures in Mexico to Environmental Toxicants) study during 1994–1995. Results: In covariate-adjusted regression models, maternal MTHFR 677 genotype predicted MDI-24 scores, in which each copy of the maternal MTHFR 677T variant allele was associated with lower MDI-24 scores (? = ?3.52; 95% CI: ?6.12, ?0.93; P = 0.004). Maternal MTHFR haplotype also predicted MDI-24 scores (mean ± SE: 93.3 ± 1.2 for 677C-1298A compared with 89.9 ± 0.8 for 677T-1298A; P < 0.05). MDI-24 scores were not associated with maternal MTHFR 1298 genotype or child MTHFR genotypes. We did not observe significant MTHFR genotype × lead interactions with respect to any of the subject biomarkers of lead exposure. Conclusions: The maternal MTHFR 677T allele is an independent predictor of poorer child neurodevelopment at 24 mo. These results suggest that maternal genetic variations in folate metabolism during pregnancy may program offspring neurodevelopment trajectories. Further research is warranted to determine the generalizability of these results across other populations. PMID:20504979

Hu, Howard; Wright, Robert O; Kordas, Katarzyna; Ettinger, Adrienne S; Sanchez, Brisa N; Cantonwine, David; Lazarus, Alicia L; Cantoral, Alejandra; Schnaas, Lourdes; Tellez-Rojo, Martha Maria; Hernandez-Avila, Mauricio

2010-01-01

229

The allele frequency of mutations in four genes that confer enhanced susceptibility to venous thromboembolism in an unselected group of New York State newborns.  

PubMed

The frequencies of Factor V G1691A (FVL), prothrombin (PT) G20210A, 5'10'methylenetetrahydrofolate reductase (MTHFR) C677T, and methionine synthase (MS) A2756G (four mutations associated with an increased risk of venous thromboembolism [VTE]) were determined in a sample of approximately 1500 New York State residents. Dried blood spots from approximately equal numbers of Caucasians, African-Americans and Hispanics were anonymously obtained from the New York State Department of Health Newborn Screening Program. Following PCR amplification of dried blood spot DNA, allele-specific oligonucleotide hybridization was used to detect mutant alleles. The total number of individuals at increased genetic risk for VTE was 271 (17.5%) of the 1553 persons tested. Increased genetic risk was defined as the heterozygous state for FVL or PT and the homozygous state for the MTHFR or MS polymorphisms. Sixteen individuals had more than one genetic risk factor. The MS gene variant allele frequencies for African-Americans and Hispanics are the first to be reported. This report also provides an estimate of the variant PT allele in the largest group of Hispanics studied to date. PMID:10963782

Conroy, J M; Trivedi, G; Sovd, T; Caggana, M

2000-08-15

230

Basic Res Cardiol 97: 365 373 (2002) DOI 10.1107/s00395-002-0361-z ORIGINAL CONTRIBUTION  

E-print Network

Basic Res Cardiol 97: 365 ­ 373 (2002) DOI 10.1107/s00395-002-0361-z ORIGINAL CONTRIBUTION Maike cells (A7r5) were incubated with 1 µM reduced MTR (non-fluorescent) and the MTR oxidation product trans- port (myxothiazol) or uncoupling of oxidative phosphorylation (dinitrophe- nol) also blocked

Garlid, Keith

231

A new-generation 5-nitroimidazole can induce highly metronidazole-resistant Giardia lamblia in vitro  

PubMed Central

The 5-nitroimidazole (NI) compound C17, with a side chain carrying a remote phenyl group in the 2-position of the imidazole ring, is at least 14-fold more active against the gut protozoan parasite Giardia lamblia than the 5-NI drug metronidazole (MTR), with a side chain in the 1-position of the imidazole ring, which is the primary drug for the treatment of giardiasis. Over 10 months, lines resistant to C17 were induced in vitro and were at least 12-fold more resistant to C17 than the parent strains. However, these lines had ID90 values (concentration of drug at which 10% of control parasite ATP levels are detected) for MTR of >200 ?M, whilst lines induced to be highly resistant to MTR in vitro have maximum ID90 values around 100 ?M (MTR-susceptible isolates typically have an ID90 of 5–12.8 ?M). The mechanism of MTR activation in Giardia apparently involves reduction to toxic radicals by the activity of pyruvate:ferredoxin oxidoreductase (PFOR) and the electron acceptor ferredoxin. MTR-resistant Giardia have decreased PFOR activity, which is consistent with decreased activation of MTR in these lines, but C17-resistant lines have normal levels of PFOR. Therefore, an alternative mechanism of resistance in Giardia must account for these super-MTR-resistant cells. PMID:20456926

Dunn, Linda A.; Burgess, Anita G.; Krauer, Kenia G.; Eckmann, Lars; Vanelle, Patrice; Crozet, Maxime D.; Gillin, Frances D.; Upcroft, Peter; Upcroft, Jacqueline A.

2010-01-01

232

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 United States. The goals of this study were to 1) compare the structure and function of natural and constructed stream channels in forested and MTR/VF catch...

233

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 ...

234

MTRETR MAINTENANCE SHOP, TRA653. FLOOR PLAN FOR MEZZANINE: LUNCH AND ...  

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

MTR-ETR MAINTENANCE SHOP, TRA-653. FLOOR PLAN FOR MEZZANINE: LUNCH AND CONFERENCE ROOM, STORAGE AREA, OFFICES FOR FOREMEN, STENOS, ENGINEERS, DISPATCHER, WOMEN'S RESTROOM. HUMMEL HUMMEL & JONES 810-MTR-ETR-653-A-12, 2/1958. INL INDEX NO. 532-0653-00-381-102837, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

235

FAST CHOPPER BUILDING, TRA665. CONTEXTUAL VIEW: CHOPPER BUILDING IN CENTER. ...  

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

FAST CHOPPER BUILDING, TRA-665. CONTEXTUAL VIEW: CHOPPER BUILDING IN CENTER. MTR REACTOR SERVICES BUILDING,TRA-635, TO LEFT; MTR BUILDING TO RIGHT. CAMERA FACING WEST. INL NEGATIVE NO. HD42-1. Mike Crane, Photographer, 3/2004 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

236

Development of metronidazole-resistant lines of Blastocystis sp.  

PubMed

Metronidazole (MTR) is frequently used for the treatment of Blastocystis infections, but with variable effectiveness, and often with treatment failures as a possible result of drug resistance. We have developed two Blastocystis MTR-resistant (MTR(R)) subtype 4 WR1 lines (WR1-M4 and WR1-M5), with variable susceptibility to a panel of anti-protozoal agents including various 5-nitroimidazoles, nitazoxanide and furazolidone. WR1-M4 and WR1-M5 were developed and assessed over an 18-month period and displayed persistent MTR resistance, being more than 2.5-fold less susceptible to MTR than the parent isolate. The MTR(R) lines grew with a similar g time to WR1, but were morphologically less consistent with a mixture of size. All Blastocystis isolates and the MTR(R) lines were most susceptible to the 5-nitroimidazole drug ronidazole. WR1-M5 was apparently cross-resistant to satranidazole and furazolidone, and WR1-M4 was cross-resistant to nitazoxanide. These MTR(R) lines now provide a valuable tool for the continued assessment of the efficacy and mechanism of action of new and established drugs against a range of Blastocystis sp. subtypes, in order to identify a universally effective drug and to facilitate understanding of the mechanisms of drug action and resistance in Blastocystis. PMID:22362365

Dunn, L A; Tan, K S W; Vanelle, P; Juspin, T; Crozet, M D; Terme, T; Upcroft, P; Upcroft, J A

2012-07-01

237

Ultrasonic characterization of the upper trapezius muscle in patients with chronic neck pain.  

PubMed

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

2013-04-01

238

Identification and characterization of mesotocin and V1a-like vasotocin receptors in a urodele amphibian, Taricha granulosa.  

PubMed

The cDNA sequences encoding the mesotocin receptor (MTR) and vasotocin 1a receptor (VTR-1a) were identified in a urodele amphibian, the rough-skinned newt, Taricha granulosa. Saturation binding of [(3)H]oxytocin (OT) to the Taricha MTR (tMTR) was best fit by a two-state model; a high affinity-low abundance site and a lower affinity-high abundance site. Competition-binding studies found the following rank-order affinities for the tMTR: mesotocin (MT)>OT?vasotocin (VT)>vasopressin (VP)>isotocin (IT). Inositol phosphate (IP) accumulation studies demonstrated functional activity of both the tMTR and Taricha VTR-1a (tVTR-1a) in a heterologous cell culture system. The rank-order potencies for the tMTR were MT>OT>VT?VP>IT. The combined binding and IP results indicate that VT may act as a partial agonist of the tMTR. Rank-order potencies for the tVTR-1a were VT>VP>MT?OT>IT. For both receptors, stimulation of IP accumulation was blocked by d(CH(2))(5)[Tyr(Me)(2)]AVP (Manning compound) and d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2)]OVT (OTA). OTA was a more potent antagonist for the transiently expressed tMTR while Manning compound was relatively more potent at inhibiting IP accumulation in tVTR-1a expressing cells. In contradiction to earlier assumptions, the absolute IC(50) of Manning compound was lower for the tMTR (27nM±13) than the tVTR-1a (586nM±166) indicating its potential higher affinity for the tMTR, a finding with special relevance to interpretation of comparative studies investigating the behavioral and physiological actions of neurohypophysial peptides in non-mammalian species. PMID:20920503

Searcy, Brian T; Bradford, C Samuel; Thompson, Richmond R; Filtz, Theresa M; Moore, Frank L

2011-01-01

239

Metabolism of 5-Methylthioribose to Methionine 1  

PubMed Central

During ethylene biosynthesis, the H3CS- group of S-adenosylmethionine is released as 5?-methylthioadenosine, which is recycled to methionine via 5-methylthioribose (MTR). In mungbean hypocotyls and cell-free extracts of avocado, [14C]MTR was converted into labeled methionine via 2-keto-4-methylthiobutyric acid (KMB) and 2-hydroxy-4-methylthiobutyric acid (HMB), as intermediates. Incubation of [ribose-U-14C]MTR with avocado extract resulted in the production of [14C]formate, indicating the conversion of MTR to KMB involves a loss of formate, presumably from C-1 of MTR. Tracer studies showed that KMB was converted readily in vivo and in vitro to methionine, while HMB was converted much more slowly. The conversion of KMB to methionine by dialyzed avocado extract requires an amino donor. Among several potential donors examined, l-glutamine was the most efficient. Anaerobiosis inhibited only partially the oxidation of MTR to formate, KMB/HMB, and methionine by avocado extract. The role of O2 in the conversion of MTR to methionine is discussed. PMID:16665430

Miyazaki, John H.; Yang, Shang Fa

1987-01-01

240

Association of antitumor antibiotic Mithramycin with Mn(2+) and the potential cellular targets of Mithramycin after association with Mn(2+).  

PubMed

Mithramycin (MTR), an aureolic acid group of antitumor antibiotic is used for the treatment of several types of tumors. We have reported here the association of MTR with an essential micronutrient, manganese (Mn(2+)). Spectroscopic methods have been used to characterize and understand the kinetics and mechanism of complex formation between them. MTR forms a single type of complex with Mn(2+) in the mole ratio of 2:1 [MTR: Mn(2+)] via a two step kinetic process. Circular dichroism (CD) spectroscopic study indicates that the complex [(MTR)2 Mn(2+)] has a right-handed twist conformation similar in structure with the complexes reported for Mg(2+) and Zn(2+). This conformation allows binding via minor groove of DNA with (G, C) base preference during the interaction with double-stranded B-DNA. Using absorbance, fluorescence, and CD spectroscopy we have shown that [(MTR)2 Mn(2+)] complex binds to double-stranded DNA with an apparent dissociation constant of 32??M and binding site size of 0.2 (drug/nucleotide). It binds to chicken liver chromatin with apparent dissociation constant value 298??M. Presence of histone proteins in chromatin inhibits the accessibility of the complex for chromosomal DNA. We have also shown that MTR binds to Mn(2+) containing metalloenzyme manganese superoxide dismutase from Escherichia coli. PMID:24559512

Dutta, Shreyasi; Lahiri, Shibojyoti; Banerjee, Amrita; Saha, Shriya; Dasgupta, Dipak

2015-02-01

241

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

242

Role of plasma homocysteine levels and MTHFR polymorphisms on IQ scores in children and young adults with epilepsy treated with antiepileptic drugs.  

PubMed

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial. Cognitive impairment may be associated with epilepsy either as the result of the epileptic syndrome per se or as a side effect induced by the AEDs. High plasma tHcy levels were associated with lower cognitive performances in patients affected by Alzheimer's disease and mild cognitive impairment and in healthy elderly. We searched for a correlation between plasma tHcy levels with the intelligence quotient (IQ) scores in a population of children and young adults with epilepsy treated with old and/or newer AEDs. The study group encompassed 179 patients (92 M, 51.5%) followed at our Unit of Child Neuropsychiatry and aged between 4 and 25years (mean+SD: 14.03±4.25). The inclusion criteria included the following: 1) diagnosis of epilepsy of "unknown cause" (cryptogenic) according to the ILAE classification, 2) age older than 3years, 3) stabilized antiepileptic treatment for at least 6months, and 4) clinical records of cognitive tests, plasma tHcy value, and results of MTHFR polymorphisms. Patients' mean tHcy value was 9.71±3.13?M/L (tHcy<9?M/L as our laboratory cutoff in nonepileptic controls). The mean TIQ score was 85.22 (SD±24.12); the mean VIQ score was 86.32 (SD±20.86); and the mean PIQ score was 86.94 (SD±21.51). C677T and A1298C MTHFR polymorphisms were detected in 74/92 (80%) examined patients and distributed into the following: CT (22.3%), TT (14.9%), CC (10.3%) for C677T, AC (16%), CC (1.1%), and AA (30.3%) for A1298C. Plasma tHcy levels were not significantly related to the IQ scores (TIQ, VIQ, or PIQ). Two significant findings came out. First, patients on AED polytherapy showed significantly lower TIQ, VIQ, and PIQ scores compared with the ones with AED monotherapy (p=0.032; p=0.008; p=0.005, respectively). However, this significant difference was not observed with the plasma tHcy levels compared with AED treatment. Second, patients with the 677TT genotype showed significantly higher tHcy levels versus those with the wt ones (p=0.049). In the latter group of patients, although the mean TIQ score was lower compared with the mean TIQ score in those with the wt ones, the difference only approached statistical significance (p=0.056). To our knowledge, this is the first study investigating the relationship between tHcy levels and cognitive scores in children with epilepsy treated with AEDs. Analysis of wider samples, selective neuropsychological tests, and prospective recruitment of patients might be encouraged. PMID:24183735

Di Rosa, Gabriella; Lenzo, Patrizia; Parisi, Eleonora; Neri, Milena; Guerrera, Silvia; Nicotera, Antonio; Alibrandi, Angela; Germanò, Eva; Caccamo, Daniela; Spanò, Maria; Tortorella, Gaetano

2013-12-01

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

31 CFR 344.7 - What are Demand Deposit securities?  

...auctioned 13-week Treasury bill. MTR = Estimated marginal tax rate, in decimals, of purchasers of tax-exempt bonds. TAC = Treasury administrative costs, in decimals. (ii) Then, you calculate the daily factor for the Demand Deposit rate...

2014-07-01

245

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

Federal Register 2010, 2011, 2012, 2013

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

2010-12-01

246

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

247

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

PubMed Central

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

Fjaer, Sveinung; B?, Lars; Lundervold, Arvid; Myhr, Kjell-Morten; Pavlin, Tina; Torkildsen, ?ivind; Wergeland, Stig

2013-01-01

248

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

249

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

250

Methionine metabolism in apple tissue: implication of s-adenosylmethionine as an intermediate in the conversion of methionine to ethylene.  

PubMed

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

Adams, D O; Yang, S F

1977-12-01

251

Transcriptional Control of themtrEfflux System ofNeisseria gonorrhoeae  

Microsoft Academic Search

The capacity ofNeisseria gonorrhoeaeto resist structurally diverse hydrophobic agents (HAs) because of the mtr(multiple transferrable resistance) efflux system was found to be regulated at the level of transcription by two distinct mechanisms. This was surmised because a deletion that removed >90% of the coding sequence of the mtrR (multiple transferrable resistance regulator) gene or a single-base-pair deletion within a 13-bp

KAYLA E. HAGMAN; ANDWILLIAM M. SHAFER

1995-01-01

252

Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome.  

PubMed

The generalized hypersensitivity associated with fibromyalgia syndrome (FMS) may in part be driven by peripheral nociceptive sources. The aim of the study was to investigate whether local and referred pain from active myofascial trigger points (MTrPs) contributes to fibromyalgia pain. FMS patients and healthy controls (n=22 each, age- and gender-matched) were recruited. The surface area over the upper trapezius muscle on each side was divided into 13 sub-areas (points) of 1cm in diameter for each point. Pressure pain threshold (PPT) and the local and referred pain pattern induced by manual palpation at 13 points bilaterally in the upper trapezius were recorded. Results showed that PPT levels at all measured points were significantly lower in FMS than controls. Multiple active MTrPs (7.4+/-2.2) were identified bilaterally in the muscle in FMS patients, but no active MTrPs were found in controls. The mid-fiber region of the muscle had the lowest PPT level with the largest number of active MTrPs in FMS and with the largest number of latent MTrPs in controls. The local and referred pain pattern induced from active MTrPs bilaterally in the upper trapezius muscle were similar to the ongoing pain pattern in the neck and shoulder region in FMS. In conclusion, active MTrPs bilaterally in the upper trapezius muscle contribute to the neck and shoulder pain in FMS. Active MTrPs may serve as one of the sources of noxious input leading to the sensitization of spinal and supraspinal pain pathways in FMS. PMID:19819074

Ge, Hong-You; Nie, Hongling; Madeleine, Pascal; Danneskiold-Samsøe, Bente; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars

2009-12-15

253

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

254

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

255

Effectiveness of dry needling and injections of myofascial trigger points associated with plantar heel pain: a systematic review  

Microsoft Academic Search

BACKGROUND: Plantar heel pain (plantar fasciitis) is one of the most common musculoskeletal pathologies of the foot. Plantar heel pain can be managed with dry needling and\\/or injection of myofascial trigger points (MTrPs) however the evidence for its effectiveness is uncertain. Therefore, we aimed to systematically review the current evidence for the effectiveness of dry needling and\\/or injections of MTrPs

Matthew P Cotchett; Karl B Landorf; Shannon E Munteanu

2010-01-01

256

Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies.  

PubMed

MRI may provide treatment outcome measures in neuromuscular conditions. The authors assessed MRI magnetisation transfer ratios (MTRs) in lower-limb musculature as markers of pathology in peripheral neuropathies and compared the findings with associated clinical data. Ten patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were compared with 10 healthy subjects. The MTR in the calf muscles was significantly lower than controls in the two patient groups (both p<0.001). The median MTRs (IQR) were 50.5(1.6) percentage units (p.u.) (control), 41.5(10.6) p.u. (CMT1A) and 39.3(8.7) p.u. (CIDP). Moreover, anterior lower leg MTR correlated strongly with strength of ankle dorsiflexion, measured with the Medical Research Council scale, in CIDP (?=0.88, p<0.001) and also in CMT1A (?=0.50, p<0.05), where MTR also showed an association with disease duration (?=-0.86, p<0.001). Short tau inversion recovery MRI of the same muscles showed abnormalities associated with regions of reduced MTR (p<0.001), and MTR was also reduced in other muscles otherwise deemed normal appearing (p<0.001), indicating that MTR may be more sensitive to muscle damaged by denervation than conventional MRI. The significant reductions in muscle MTR in peripheral neuropathies and the associated correlations with clinical measures indicate that MTR has potential as an imaging outcome measure in future therapeutic trials. PMID:21613652

Sinclair, C D J; Morrow, J M; Miranda, M A; Davagnanam, I; Cowley, P C; Mehta, H; Hanna, M G; Koltzenburg, M; Yousry, T A; Reilly, M M; Thornton, J S

2012-01-01

257

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

258

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

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

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

261

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

262

Tract-based Analysis of Magnetization Transfer Ratio and Diffusion Tensor Imaging of the Frontal and Frontotemporal Connections in Schizophrenia  

PubMed Central

Background: In the pathophysiology of schizophrenia, aberrant connectivity between brain regions may be a central feature. Diffusion tensor imaging (DTI) studies have shown altered fractional anisotropy (FA) in white brain matter in schizophrenia. Focal reductions in myelin have been suggested in patients using magnetization transfer ratio (MTR) imaging but to what extent schizophrenia may be related to changes in MTR measured along entire fiber bundles is still unknown. Methods: DTI and MTR images were acquired with a 1.5-T scanner in 40 schizophrenia patients and compared with those of 40 healthy participants. The mean FA and mean MTR were measured along the genu of the corpus callosum and the left and right uncinate fasciculus. Results: A higher mean MTR of 1% was found in the right uncinate fasciculus in patients compared with healthy participants. A significant negative correlation between age and mean FA in the left uncinate fasciculus was found in schizophrenia patients but not in healthy participants. Conclusions: Decreased FA in the left uncinate fasciculus may be more prominent in patients with longer illness duration. The increased mean MTR in the right uncinate fasciculus could reflect a compensatory role for myelin in these fibers or possibly represent aberrant frontotemporal connectivity. PMID:19042913

Mandl, Rene C. W.; Schnack, Hugo G.; Luigjes, Judy; van den Heuvel, Martijn P.; Cahn, Wiepke; Kahn, Rene S.; Hulshoff Pol, Hilleke E.

2010-01-01

263

Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS.  

PubMed

Magnetization transfer and multicomponent T2 imaging techniques were implemented to study guinea pig in vivo. A chronic-progressive model of experimental allergic encephalomyelitis (EAE) was produced, and the inflammatory component of the disease was manipulated using antibodies against integrin. The magnetization transfer ratio (MTR) and T2 relaxation properties were measured in normal-appearing white matter (NAWM) with histological comparisons. Significant reductions in both the mean MTR and the myelin water percentage were measured in NAWM of EAE guinea pig brain. However, the MTR and myelin water percentage appear to measure different aspects of pathology in NAWM in EAE. Reductions in the MTR were prevented or reversed with suppression of inflammation. However, modulation of inflammatory activity was not reflected in the measurement of the myelin water percentage. Since the amount of myelin is not expected to vary with inflammatory-related changes, these observations support our hypothesis that the MTR is sensitive to physiological changes to myelin induced by inflammation, while the short T2 component is a more specific indicator of myelin content in tissue. Pathologic features other than demyelination may be important in the determination of the MTR. PMID:10862056

Gareau, P J; Rutt, B K; Karlik, S J; Mitchell, J R

2000-06-01

264

Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps.  

PubMed

The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B(1)) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B(1) information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two-pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot-Marie-Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within-subject and between-subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram- and region-of-interest-based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B(1) data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle. PMID:21796708

Sinclair, C D J; Morrow, J M; Hanna, M G; Reilly, M M; Yousry, T A; Golay, X; Thornton, J S

2012-02-01

265

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.

Oztop, Didem Behice; Ozkul, Yusuf

2014-01-01

266

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

PubMed

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

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

2014-01-01

267

The Frequent 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphism Is Associated with a Common Haplotype in Whites, Japanese, and Africans  

PubMed Central

The common 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism causes decreased activity of this enzyme and can be associated with mild-to-moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with vascular dementia, arterial thrombosis, venous thrombosis, neural-tube defects, and fetal loss. When folic acid intake is sufficient, homozygotes for MTHFR 677T appear to be protected against colon cancer and acute lymphatic leukemia, and fetuses bearing this genotype have an augmented survival. The distribution of MTHFR 677T is worldwide, but its frequency in different populations varies extensively. In the present study, we addressed the question of whether the MTHFR 677T alteration has an ancestral origin or has occurred repeatedly. We analyzed the frequency distribution of the previously described polymorphism A1298C in exon 7 and of three intronic dimorphisms, in white Israelis (Jews and Arabs), Japanese, and Ghanaian Africans. The 677T allele was, remarkably, associated with one haplotype, G-T-A-C, in white and Japanese homozygotes. Among the Africans, analysis of maximum likelihood also disclosed an association with the G-T-A-C haplotype, although none of the 174 subjects examined was homozygous for MTHFR 677T. These results suggest that the MTHFR 677T alteration occurred on a founder haplotype that may have had a selective advantage. PMID:11781870

Rosenberg, Nurit; Murata, Mitsuru; Ikeda, Yasuo; Opare-Sem, Ohene; Zivelin, Ariella; Geffen, Eli; Seligsohn, Uri

2002-01-01

268

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

269

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

270

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

PubMed Central

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

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

2010-01-01

271

Green tea consumption and breast cancer risk in Japanese women: a case-control study.  

PubMed

Although many in vitro and animal studies have suggested a protective effect of green tea against breast cancer, only a few epidemiological studies have examined this association, and findings have been inconsistent. We examined the association between green tea consumption and breast cancer risk in consideration of the hormone receptor status of tumors and investigated whether the association was modified by dietary and genetic factors based on a hospital-based case-control study in Nagano, Japan. A total of 369 pairs completed a validated food frequency questionnaire and provided blood samples. Four single nucleotide polymorphisms (SNPs) were genotyped: CYP19A1 (rs10046), COMT (rs4680), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131). We found no inverse association between green tea consumption and breast cancer risk. Compared with women who drank less than 120 ml of green tea per day, the adjusted odds ratio for women who drank more than 600 ml was 1.27 (95% confidence interval = 0.75-2.14; P for trend = 0.20). We also found no inverse association for either tumor subtype. No substantial effect modification was observed for menopausal status, 4 SNPs, or dietary intake of folate or isoflavone. This study provides additional evidence that green tea consumption is not associated with a decreased risk. PMID:24274352

Iwasaki, Motoki; Mizusawa, Junki; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Tsugane, Shoichiro

2014-01-01

272

Genomic plasticity enables a secondary electron transport pathway in Shewanella oneidensis.  

PubMed

Microbial dissimilatory iron reduction is an important biogeochemical process. It is physiologically challenging because iron occurs in soils and sediments in the form of insoluble minerals such as hematite or ferrihydrite. Shewanella oneidensis MR-1 evolved an extended respiratory chain to the cell surface to reduce iron minerals. Interestingly, the organism evolved a similar strategy for reduction of dimethyl sulfoxide (DMSO), which is reduced at the cell surface as well. It has already been established that electron transfer through the outer membrane is accomplished via a complex in which ?-barrel proteins enable interprotein electron transfer between periplasmic oxidoreductases and cell surface-localized terminal reductases. MtrB is the ?-barrel protein that is necessary for dissimilatory iron reduction. It forms a complex together with the periplasmic decaheme c-type cytochrome MtrA and the outer membrane decaheme c-type cytochrome MtrC. Consequently, mtrB deletion mutants are unable to reduce ferric iron. The data presented here show that this inability can be overcome by a mobile genomic element with the ability to activate the expression of downstream genes and which is inserted within the SO4362 gene of the SO4362-to-SO4357 gene cluster. This cluster carries genes similar to mtrA and mtrB and encoding a putative cell surface DMSO reductase. Expression of SO4359 and SO4360 alone was sufficient to complement not only an mtrB mutant under ferric citrate-reducing conditions but also a mutant that furthermore lacks any outer membrane cytochromes. Hence, the putative complex formed by the SO4359 and SO4360 gene products is capable not only of membrane-spanning electron transfer but also of reducing extracellular electron acceptors. PMID:23220953

Schicklberger, M; Sturm, G; Gescher, J

2013-02-01

273

Myofascial trigger point needling for whiplash associated pain--a feasibility study.  

PubMed

Clinicians claim that myofascial trigger points (MTrPs) are a primary cause of pain in whiplash injured patients. Pain from MTrPs is often treated by needling, with or without injection. We conducted a placebo controlled study to test the feasibility of a phase III randomised controlled trial investigating the efficacy of MTrP needling in patients with whiplash associated pain. Forty-one patients referred for physiotherapy with a recent whiplash injury, were recruited. Patients were randomised to receive standardised physiotherapy plus either acupuncture or a sham needle control. A trial was judged feasible if: i) the majority of eligible patients were willing to participate; ii) the majority of patients had MTrPs; iii) at least 75% of patients provided completed self-assessment data; iv) no serious adverse events were reported and v) the end of treatment attrition rate was less than 20%. 70% of those patients eligible to participate volunteered to do so; all participants had clinically identified MTrPs; a 100% completion rate was achieved for recorded self-assessment data; no serious adverse events were reported as a result of either intervention; and the end of treatment attrition rate was 17%. A phase III study is both feasible and clinically relevant. This study is currently being planned. PMID:20580303

Tough, Elizabeth A; White, Adrian R; Richards, Suzanne H; Campbell, John L

2010-12-01

274

Trigger point needling: techniques and outcome.  

PubMed

In this review we provide the updates on last years' advancements in basic science, imaging methods, efficacy, and safety of dry needling of myofascial trigger points (MTrPs). The latest studies confirmed that dry needling is an effective and safe method for the treatment of MTrPs when provided by adequately trained physicians or physical therapists. Recent basic studies have confirmed that at the site of an active MTrP there are elevated levels of inflammatory mediators, known to be associated with persistent pain states and myofascial tenderness and that this local milieu changes with the occurrence of local twitch response. Two new modalities, sonoelastography and magnetic resonance elastography, were recently introduced allowing noninvasive imaging of MTrPs. MTrP dry needling, at least partially, involves supraspinal pain control via midbrain periaqueductal gray matter activation. A recent study demonstrated that distal muscle needling reduces proximal pain by means of the diffuse noxious inhibitory control. Therefore, in a patient too sensitive to be needled in the area of the primary pain source, the treatment can be initiated with distal needling. PMID:22610507

Vulfsons, Simon; Ratmansky, Motti; Kalichman, Leonid

2012-10-01

275

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

276

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

PubMed Central

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

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

2008-01-01

277

Mutation of a rice gene encoding a phenylalanine biosynthetic enzyme results in accumulation of phenylalanine and tryptophan.  

PubMed

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

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

2008-05-01

278

ADP-2Ho as a Phasing Tool for Nucleotide-Containing Proteins  

SciTech Connect

Trivalent holmium ions were shown to isomorphously replace magnesium ions to form an ADP-2Ho complex in the nucleotide-binding domain of Bacillus subtilis 5-methylthioribose (MTR) kinase. This nucleotide-holmium complex provided sufficient phasing power to allow SAD and SIRAS phasing of this previously unknown structure using the L{sub III} absorption edge of holmium. The structure of ADP-2Ho reveals that the two Ho ions are approximately 4 {angstrom} apart and are likely to share their ligands: the phosphoryl O atoms of ADP and a water molecule. The structure determination of MTR kinase using data collected using Cu K X-radiation was also attempted. Although the heavy-atom substructure determination was successful, interpretation of the map was more challenging. The isomorphous substitution of holmium for magnesium in the MTR kinase-nucleotide complex suggests that this could be a useful phasing tool for other metal-dependent nucleotide-containing proteins.

Ku,S.; Smith, G.; Howell, P.

2007-01-01

279

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

280

In vivo magnetization transfer measurements of experimental spinal cord injury in the rat.  

PubMed

Magnetization transfer (MT) imaging techniques were implemented to study a clip compression model of spinal cord injury (SCI) in the rat. The purpose of this study was to determine if the magnetization transfer ratio (MTR) could be used to classify the stage and severity of SCI. Two clip compression injuries were studied: mild SCI and severe SCI. MTRs were determined for gray matter (GM) and white matter (WM) regions and the GM-WM contrast was determined on days 1 and 7 following surgery. Despite differences in pathologic features of mild and severe SCI, the GM-WM contrast did not allow discrimination between the two degrees of severity of SCI. WM MTR allowed differentiation of mild and severe SCI on day 1. These preliminary results suggest that WM MTR may provide an indication of the severity of injury in SCI. Magn Reson Med 45:159-163, 2001. PMID:11146498

Gareau, P J; Weaver, L C; Dekaban, G A

2001-01-01

281

Surface-based analysis reveals regions of reduced cortical magnetization transfer ratio in patients with multiple sclerosis: a proposed method for imaging subpial demyelination.  

PubMed

The in vivo detection of subpial cortical gray matter lesions in multiple sclerosis is challenging. We quantified the spatial extent of subpial decreases in the magnetization transfer ratio (MTR) of cortical gray matter in subjects with multiple sclerosis, as such reductions may indicate regions of cortical demyelination. We exploited the unique geometry of cortical lesions by using two-dimensional parametric surface models of the cortex instead of traditional three-dimensional voxel-wise analyses. MTR images were mapped onto intermediate surfaces between the pial and white matter surfaces and were used to compute differences between secondary-progressive MS (n = 12), relapsing-remitting MS (n = 12), and normal control (n = 12) groups as well as between each individual patient and the normal controls. We identified large regions of significantly reduced cortical MTR in secondary-progressive patients when compared with normal controls. We also identified large regions of reduced cortical MTR in 11 individual patients (8 secondary-progressive, 3 relapsing-remitting). The secondary-progressive patients showed larger areas of abnormally low MTR compared with relapsing-remitting patients both at the group level and on an individual basis. The spatial distributions of abnormal MTR preferentially involved cingulate cortex, insula, and the depths of sulci, in agreement with pathological descriptions of subpial gray matter lesion distribution. These findings suggest that our method is a plausible in vivo imaging technique for quantifying subpial cortical demyelinating lesions in patients with multiple sclerosis and, furthermore, can be applied at the typical clinical field strength of 1.5 T. PMID:24356893

Derakhshan, Mishkin; Caramanos, Zografos; Narayanan, Sridar; Arnold, Douglas L; Louis Collins, D

2014-07-01

282

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

PubMed

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

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

2014-12-01

283

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

284

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

285

Longitudinal changes in magnetisation transfer ratio in secondary progressive multiple sclerosis: data from a randomised placebo controlled trial of lamotrigine.  

PubMed

Sodium blockade with lamotrigine is neuroprotective in animal models of central nervous system demyelination. This study evaluated the effect of lamotrigine on magnetisation transfer ratio (MTR), a putative magnetic resonance imaging measure of intact brain tissue, in a group of subjects with secondary progressive multiple sclerosis (MS). In addition, the utility of MTR measures for detecting change in clinically relevant pathology was evaluated. One hundred seventeen people attending the National Hospital for Neurology and Neurosurgery or the Royal Free Hospital, London, UK, were recruited into a double-blind, parallel-group trial. Subjects were randomly assigned by minimisation to receive lamotrigine (target dose 400 mg/day) or placebo for 2 years. Treating and assessing physicians and patients were masked to treatment allocation. Results of the primary endpoint, central cerebral volume, have been published elsewhere. Significant differences between the verum and placebo arms were seen in only two measures [normal appearing grey matter (NAGM) p = 0.036 and lesion peak height (PH) p = 0.004], and in both cases there was a greater reduction in MTR in the verum arm. Significant correlations were found of change in MS functional composite with all MTR measures except lesion and normal appearing white matter (NAWM) PH. However, the change in MTR measures over 2 years were small, with only NAGM mean (p = 0.001), lesion peak location (p = 0.11) and mean (p < 0.0001) changing significantly from baseline. These data did not show that lamotrigine was neuroprotective. The clinical correlation of MTR measures was consistent, but the responsiveness to change was limited. PMID:21904901

Hayton, T; Furby, J; Smith, K J; Altmann, D R; Brenner, R; Chataway, J; Hunter, K; Tozer, D J; Miller, D H; Kapoor, R

2012-03-01

286

Subcellular Distribution of Mitochondrial Ribosomal RNA in the Mouse Oocyte and Zygote  

PubMed Central

Mitochondrial ribosomal RNAs (mtrRNAs) have been reported to translocate extra-mitochondrially and localize to the germ cell determinant of oocytes and zygotes in some metazoa except mammals. To address whether the mtrRNAs also localize in the mammals, expression and distribution of mitochondrion-encoded RNAs in the mouse oocytes and zygotes was examined by whole-mount in situ hybridization (ISH). Both 12S and 16S rRNAs were predominantly distributed in the animal hemisphere of the mature oocyte. This distribution pattern was rearranged toward the second polar body in zygotes after fertilization. The amount of mtrRNAs decreased around first cleavage, remained low during second cleavage and increased after third cleavage. Staining intensity of the 12S rRNA was weaker than that of the 16S rRNA throughout the examined stages. Similar distribution dynamics of the 16S rRNA was observed in strontium-activated haploid parthenotes, suggesting the distribution rearrangement does not require a component from sperm. The distribution of 16S rRNAs did not coincide with that of mitochondrion-specific heat shock protein 70, suggesting that the mtrRNA is translocated from mitochondria. The ISH-scanning electron microscopy confirms the extra-mitochondrial mtrRNA in the mouse oocyte. Chloramphenicol (CP) treatment of late pronuclear stage zygotes perturbed first cleavage as judged by the greater than normal disparity in size of blastomeres of 2-cell conceptuses. Two-third of the CP-treated zygotes arrested at either 2-cell or 3-cell stage even after the CP was washed out. These findings indicate that the extra-mitochondrial mtrRNAs are localized in the mouse oocyte and implicated in correct cytoplasmic segregation into blastomeres through cleavages of the zygote. PMID:18043748

Ninomiya, Youichirou; Ichinose, Shizuko

2007-01-01

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

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

289

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

290

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

291

Maternal and offspring genetic variants of AKR1C3 and the risk of childhood leukemia  

PubMed Central

The aldo-keto reductase 1C3 (AKR1C3) gene located on chromosome 10p15-p14, a regulator of myeloid cell proliferation and differentiation, represents an important candidate gene for studying human carcinogenesis. In a prospectively enrolled population-based case–control study of Han Chinese conducted in Kaohsiung in southern Taiwan, a total of 114 leukemia cases and 221 controls <20 years old were recruited between November 1997 and December 2005. The present study set out to evaluate the association between childhood leukemia and both maternal and offspring's genotypes. To do so, we conducted a systematic assessment of common single-nucleotide polymorphisms (SNPs) at the 5? flanking 10 kb to 3? UTR of AKR1C3 gene. Gln5His and three tagSNPs (rs2245191, rs10508293 and rs3209896) and one multimarker (rs2245191, rs10508293 and rs3209896) were selected with average 90% coverage of untagged SNPs by using the HapMap II data set. Odds ratios and 95% confidence intervals were adjusted for age and gender. After correcting for multiple comparisons, we observed that risk of developing childhood leukemia is significantly associated with rs10508293 polymorphism on intron 4 of the AKR1C3 gene in both offspring alone and in the combined maternal and offspring genotypes (nominal P < 0.0001, permutation P < 0.005). The maternal methylenetetrahydrofolate reductase A1298C polymorphism was found to be an effect modifier of the maternal intron 4 polymorphism of the AKR1C3 gene (rs10508293) and the childhood leukemia risk. In conclusion, this study suggests that AKR1C3 polymorphisms may be important predictive markers for childhood leukemia susceptibility. PMID:18339682

Liu, Chen-yu; Hsu, Yi-Hsiang; Pan, Pi-Chen; Wu, Ming-Tsang; Ho, Chi-Kung; Su, Li; Xu, Xin; Li, Yi; Christiani, David C.

2008-01-01

292

Mountaintop Removal and Job Creation: Exploring the Relationship Using Spatial Regression  

Microsoft Academic Search

This project focused on a new and increasingly contested method of coal extraction, mountaintop removal (MTR), and its effects on central Appalachian residents’ quality of life vis-à-vis increased employment. Attention is given to central Appalachia because its fossil fuel landscapes have undergone major changes as a result of two interrelated forces: (1) a national push for energy independence that led

Brad R. Woods; Jason S. Gordon

2011-01-01

293

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

PubMed

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

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

2014-08-15

294

'Fishing' for Alternatives to Mountaintop Mining in Southern West Virginia  

EPA Science Inventory

Mountaintop removal mining (MTR) is a major industry in southern West Virginia with many detrimental effects for small to mid-sized streams, and interest in alternative, sustainable industries is on the rise. As a first step in a larger effort to assess the value of sport fisheri...

295

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

296

www.emsl.pnl.gov GEOCHEMISTRY/BIOGEOCHEMISTRY  

E-print Network

Shewanella oneidensis MR-1 surface proteins (MtrC and OmcA) that can affect environmental quality. Bacteria such as Shewanella exchange electrons with minerals, yielding effects such as changes in the migra- tion. Louis discovered a novel cluster of genes that encode proteins essential for green plants to thrive

297

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 ...

298

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

PubMed Central

We investigate single-cell reduction of toxic Cr(VI) by the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), an important bioremediation process, using Raman spectroscopy and scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX). Our experiments indicate that the toxic and highly soluble Cr(VI) can be efficiently reduced to the less toxic and non-soluble Cr2O3 nanoparticles by MR-1. Cr2O3 is observed to emerge as nanoparticles adsorbed on the cell surface and its chemical nature is identified by EDX imaging and Raman spectroscopy. Co-localization of Cr2O3 and cytochromes by EDX imaging and Raman spectroscopy suggests a terminal reductase role for MR-1 surface-exposed cytochromes MtrC and OmcA. Our experiments revealed that the cooperation of surface proteins OmcA and MtrC makes the reduction reaction most efficient, and the sequence of the reducing reactivity of the MR-1 is: wild type > single mutant ?mtrC or mutant ?omcA > double mutant (?omcA-?mtrC). Moreover, our results also suggest that the direct microbial Cr(VI) reduction and Fe(II) (hematite)-mediated Cr(VI) reduction mechanisms may co-exist in the reduction processes. PMID:23249294

Wang, Yuanmin; Sevinc, Papatya C.; Balchik, Sara M.; Fridrickson, Jim; Shi, Liang; Lu, H. Peter

2013-01-01

299

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

SciTech Connect

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

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

2013-01-22

300

Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis  

Microsoft Academic Search

The trend to start disease-modifying therapy early in the course of multiple sclerosis makes it important to establish whether the benign form is a real entity. In previous studies, measures of magnetization transfer (MT) ratio (MTr) have been shown to provide good estimates of the amount of tissue damage occurring in multiple sclerosis brains. Thus, with the hypothesis that if

Nicola De Stefano; Marco Battaglini; M. L. Stromillo; Valentina Zipoli; M. L. Bartolozzi; Leonello Guidi; Gianfranco Siracusa; Emilio Portaccio; Antonio Giorgio; Sandro Sorbi; Antonio Federico; Maria Pia Amato

2006-01-01

301

REMORA 3: The first instrumented fuel experiment with on-line gas composition measurement by acoustic sensor  

Microsoft Academic Search

With the aim to improve the knowledge of nuclear fuel behaviour, the development of advanced instrumentation used during in-pile experiments in Material Testing Reactor (MTR) is necessary. To obtain data on high Burn-Up MOX fuel performance under transient operating conditions, especially in order to differentiate between the kinetics of fission gas and helium releases and to acquire data on the

T. Lambert; E. Muller; E. Federici; E. Rosenkrantz; J. Y. Ferrandis; X. Tiratay; V. Silva; D. Machard; G. Trillon

2011-01-01

302

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

PubMed Central

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

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

2013-01-01

303

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...

304

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 ...

305

The Affects of Mountain Top Removal Mining on Headwater Streams in Eastern Kentucky  

Microsoft Academic Search

Mountain Top Removal\\/Valley Fill (MTR\\/VF) coal mining is a relatively new coal extraction technology that is widely utilized throughout the Appalachian region. During this process, the mountaintop is blasted away, the coal removed and the leftover material (spoil) is then deposited into the surrounding valleys. The potential negative ecological effects of these operations on stream biodiversity has received some attention

D. A. Word; J. D. Jack; R. Kelley

2005-01-01

306

PRELIMINARY ANALYSIS OF SPOIL SETTLEMENT AT A MOUNTAIN-TOP-REMOVAL COAL MINE: STAR FIRE TRACT, EASTERN KENTUCKY COAL FIELD1  

Microsoft Academic Search

SETTING The method of mining coal by the mountain top removal (MTR) process can create gently rolling land that may be used for multiple purposes that provide economic diversity for the Eastern Kentucky Coal Field region, part of the Appalachian Plateau physiographic province. A major limiting factor of post- mine development is the settlement of mine spoils over time. Between

J. S. Dinger; R. E. Andrews; D. R. Wunsch; C. D. R. Graham; R. J. Sweigard; P. W. Conrad

307

MATERIALS TESTING REACTOR PROJECT. SITE PLAN. Design Report No. 36  

Microsoft Academic Search

A reactor of the size and having the purposes of the MTR has a number of ; auxiliary functions which must be provided for. In addition to the building ; housing the reactor these include four separate types of water systems, a canal ; for storage and disposal of spent fuel assemblies, a steam plant, an air cooling ; and

R. F. Guzik; L. E. Link

1950-01-01

308

Usability of a virtual reality environment in community facilities for assessment and training in persons with acquired brain injury or older people in Hong Kong  

Microsoft Academic Search

A web-based virtual environment in the use of community facilities like automatic teller machine (ATM), mass transit railway (MTR), and convenient store was designed for assessment and training in people with cognitive disabilities in Hong Kong. A previous study in people with acquired brain injury (ABI) has shown that virtual environment can facilitate the generalization of learned skills to real

Kenneth N. K. Fong; Kathy K. Y. Chow; Asta K. Y. Wong; Elaine W. H. Yan; Serena S. W. Ng; K. W. L. Koo

2010-01-01

309

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

310

ACCURATE NUCLEAR FUEL BURNUP ANALYSES. Quarterly Progress Report No. 6, March-May 1963  

Microsoft Academic Search

Work has continued on the development of accurate methods for ; determining nuclear fuel burnup. Thermal flux capsule GEV-1, has completed its ; irradiation in MTR and its cooling period. Hardened flux capsule GEV-2 is ; presently in the VBWR and has received about 2 x 10¹⁹ nvt. A fast fission ; capsule GEV-3, containing uranium-238 and thorium232 under cadmium,

B. F. Rider; C. P. Ruiz; J. P. Jr. Peterson; P. S. Jr. Luke

1963-01-01

311

Rail + Property Development: A model of sustainable transit finance and urbanism  

E-print Network

Shopping Mall (Up & Big Footbridge w i t h Retails Down) Private Signage SystemSystem PTI at the Ground Level at the Ground Level Vertical Movement A2-19 ShoppingShopping Mall above MTR Footbridge Network PTI at the Ground Level Integrated Entry/Exit Public Signage System

Cervero, Robert; Murakami, Jin

2008-01-01

312

Fiber 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 Fiber Sensors (OFS) can feature unique intrinsic properties that bring substantial advantages over conventional sensing approaches. One of the objectives of the Joint Instrumentation Laboratory (JIL), gathering SCK CEN (Belgium) and CEA (France) resources and know-how,

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

2011-01-01

313

Cell, Vol. 98, 273275, August 6, 1999, Copyright 1999 by Cell Press For Better or Worse? Minireview  

E-print Network

? Minireview Telomerase Inhibition and Cancer subunit of telomerase (called mTR) by the laboratory of Carol Greider in 1995 (Blasco et al., 1995), which fol- lowed the cloning of the human gene by Villeponteau et al., 1995). With this key gene in Howard Hughes Medical Institute hand, Greider teamed up with Ron

de Lange, Titia

314

STORAGE AND RECIEVING, TRA662. ELEVATIONS. LOWBAY SECTION ON SOUTH SIDE ...  

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

STORAGE AND RECIEVING, TRA-662. ELEVATIONS. LOW-BAY SECTION ON SOUTH SIDE WAS FLAMMABLE STORAGE AREA. HUMMEL HUMMEL & JONES 1038-MTR-ETR-662-A-3, 6/1960. INL INDEX NO. 532-0653-00-381-102036, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

315

CAFETERIA, TRA616. EAST AND SOUTH ELEVATIONS. SECTION. C.A. SUNDBERG AND ...  

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

CAFETERIA, TRA-616. EAST AND SOUTH ELEVATIONS. SECTION. C.A. SUNDBERG AND ASSOCIATES 884-MTR-616-A-3, 12/1957. INL INDEX NO. 531-0616-00-822-101881, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

316

ETR COMPRESSOR BUILDING, TRA643. NORTH, EAST AND SOUTH ELEVATIONS. ROOF ...  

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

ETR COMPRESSOR BUILDING, TRA-643. NORTH, EAST AND SOUTH ELEVATIONS. ROOF PLAN. DETAILS. KAISER ETR-5528-MTR-643-A-4, 3/1956. INL INDEX NO. 532-0643-00-486-101270, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

317

STORAGE AND RECEIVING, TRA662. FLOOR PLAN. HUMMEL HUMMEL & JONES ...  

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

STORAGE AND RECEIVING, TRA-662. FLOOR PLAN. HUMMEL HUMMEL & JONES 1038-MTR-ETR-662-A-1, 6/1960. INL INDEX NO. 532-0653-00-381-102034, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

318

ETR COMPRESSOR BUILDING, TRA643. PLAN AND SECTIONS. GRATECOVERED TRENCHES LAY ...  

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

ETR COMPRESSOR BUILDING, TRA-643. PLAN AND SECTIONS. GRATE-COVERED TRENCHES LAY ALONG FLOOR FROM EAST TO WEST AND AROUND MAIN COMPRESSORS. LOCKER ROOM AT NORTHEAST CORNER. KAISER ETR-5528-MTR-643-A-3, 11/1955. INL INDEX NO. 532-0643-00-486-101269, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

319

Do windfall non-debt tax shields from acquisitions affect corporate debt issues?  

Microsoft Academic Search

Purpose – The purpose of this paper is to identify possible tax synergies from acquisitions when the acquiring firm gains a non-debt tax shield (NDTS) not directly associated with its own past performance, or a windfall NDTS. One possible benefit of a windfall NDTS is reduced reliance on interest tax shields to lower the firm's marginal tax rate (MTR). Design\\/methodology\\/approach

Sudip Ghosh; Christine Harrington; Walter Smith

2011-01-01

320

Methionine salvage pathway in relation to ethylene biosynthesis  

SciTech Connect

The recycling of methionine during ethylene biosynthesis (the methionine cycle) was studied. During ethylene biosynthesis, the H/sub 3/CS-group of S-adenosylmethionine (SAM) is released at 5'-methylthioadenosine (MTA), which is recycled to methionine via 5'-methylthioribose (MTS). In mungbean hypocotyls and cell-free extracts of avocado fruit, (/sup 14/C)MTR was converted to labeled methionine via 2-keto-4-methylthiobutyric acid (KMB) and 2-hydroxy-4-methylthiobutyric acid (HMB) as intermediates. Radioactive tracer studies showed that KMB was converted readily in vivo and in vitro to methionine, while HMB was converted much more slowly. The conversion of KMB to methionine by dialyzed avocado extract required an amino group donor. Among several potential donors tested, L-glutamine was the most efficient. Incubation of (ribose-U-/sup 14/C)MTR with avocado extract resulted in the production of (/sup 14/C)formate, with little evolution of other /sup 14/C-labeled one-carbon compounds, indicating that the conversion of MTR to KMB involves a loss of formate, presumably from C-1 of MTR.

Miyazaki, J.H.

1987-01-01

321

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

322

PROCESS WATER BUILDING, TRA605. EAST SIDE. CAMERA FACING WEST. REMOVABLE ...  

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

PROCESS WATER BUILDING, TRA-605. EAST SIDE. CAMERA FACING WEST. REMOVABLE OPENINGS WERE NOT BENEFICIALLY USED FOR FUTURE EXPANSION. PART OF MTR APPEARS BEHIND BUILDING AT LEFT. ATR BUILDING IN BACKGROUND ON RIGHT. INL NEGATIVE NO. HD46-34-4. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

323

SCIENTIST DEMONSTRATES PLACING A "RABBIT CATCHER" INTO ONE OF THE ...  

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

SCIENTIST DEMONSTRATES PLACING A "RABBIT CATCHER" INTO ONE OF THE VERTICAL TEST HOLES AT THE TOP OF THE MTR. CONTROL ROD DRIVES ARE BEHIND HIM TOWARDS LEFT OF VIEW. INL NEGATIVE NO. 56-513. Jack L. Anderson, Photographer, 2/13/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

324

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

325

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

326

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

327

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

328

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

329

System Operational Readiness and Equipment Dependability  

Microsoft Academic Search

The concept of operational readiness of repairable systems is defined in terms of finite queueing theory as the probability that a multidevice, multimodal system will meet specified operational requirements at any given time. The primary determinants are shown to be design parameters and use parameters. Design parameters, which include reliability and maintainability (as measured by MTBF and MTR), can be

Joseph G. Wohl

1966-01-01

330

Published Ahead of Print 20 May 2011. 2011, 193(14):3662. DOI: 10.1128/JB.00201-11.J. Bacteriol.  

E-print Network

oxide minerals as terminal electron acceptors (9). The Mtr respiratory pathway is used by MR-1 to facilitate transfer of electrons from the interior of the cell to these external terminal electron acceptors (2, 6, 12, 18). In addition to naturally oc- curring insoluble electron acceptors, it has been

Li, Yat

331

Canadian Mine Tax System Possible deductions  

E-print Network

· Canadian Mine Tax System · Possible deductions ­ Resource Allowances ­ Capital Cost Allowances MIN E 408: Mining Enterprise Economics Mine Taxation A good 2 page summary: http://www.nrcan.gc.ca/mms-smm/busi-indu/mtr-rdm/mst-rps-eng.htm#lnk15 http://www.pwc.com/en_CA/ca/mining/publications/canadian-mining-taxation

Boisvert, Jeff

332

Canadian Mine Tax System Possible deductions  

E-print Network

08-1 · Canadian Mine Tax System · Possible deductions ­ Resource Allowances ­ Capital Cost Allowances MIN E 408: Mining Enterprise Economics Mine Taxation A good 2 page summary: http://www.nrcan.gc.ca/mms-smm/busi-indu/mtr-rdm/mst-rps-eng.htm#lnk15 http://www.pwc.com/en_CA/ca/mining/publications/canadian-mining-taxation

Boisvert, Jeff

333

REACTOR SERVICE BUILDING, TRA635. CAMERA FACING NORTHWEST. BUILDING PROJECTS FROM ...  

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

REACTOR SERVICE BUILDING, TRA-635. CAMERA FACING NORTHWEST. BUILDING PROJECTS FROM AND CONNECTS TO SOUTH WALL OF MTR BUILDING. EARTH BERM SHIELDING PLUG STORAGE BUILDING IS AT RIGHT OF VIEW. INL NEGATIVE NO. 9913. Unknown Photographer, 2/23/1954 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

334

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

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

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

335

Catalog of experimental projects for a fissioning plasma reactor  

NASA Technical Reports Server (NTRS)

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

Lanzo, C. D.

1973-01-01

336

A MECHANICAL NEUTRON FILTER FOR A CRYSTAL SPECTROMETER  

Microsoft Academic Search

A velocity selector of the Dash-Sommers type with straight slits was ; constructed for use with the MTR crystal spectrometer. The rotor, designed to ; remove undesirable higher order contaninants from the Bragg beam, is built of ; magnesium and fiberglas-epoxy laminate to minimize weight and is driven directly ; by a 1\\/8-hp synchronous motor. Vanes of fiberglas laminate are

J. R. Smith; H. G. Miller

1963-01-01

337

Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and In Vivo Selection for Compensatory Mutations  

PubMed Central

Background.?Quinolone-resistant Neisseria gonorrhoeae (QRNG) arise from mutations in gyrA (intermediate resistance) or gyrA and parC (resistance). Here we tested the consequence of commonly isolated gyrA91/95 and parC86 mutations on gonococcal fitness. Methods.?Mutant gyrA91/95 and parC86 alleles were introduced into wild-type gonococci or an isogenic mutant that is resistant to macrolides due to an mtrR?79 mutation. Wild-type and mutant bacteria were compared for growth in vitro and in competitive murine infection. Results.?In vitro growth was reduced with increasing numbers of mutations. Interestingly, the gyrA91/95 mutation conferred an in vivo fitness benefit to wild-type and mtrR?79 mutant gonococci. The gyrA91/95, parC86 mutant, in contrast, showed a slight fitness defect in vivo, and the gyrA91/95, parC86, mtrR?79 mutant was markedly less fit relative to the parent strains. A ciprofloxacin-resistant (CipR) mutant was selected during infection with the gyrA91/95, parC86, mtrR?79 mutant in which the mtrR?79 mutation was repaired and the gyrA91 mutation was altered. This in vivo–selected mutant grew as well as the wild-type strain in vitro. Conclusions.?gyrA91/95 mutations may contribute to the spread of QRNG. Further acquisition of a parC86 mutation abrogates this fitness advantage; however, compensatory mutations can occur that restore in vivo fitness and maintain CipR. PMID:22492860

Kunz, Anjali N.; Begum, Afrin A.; Wu, Hong; D'Ambrozio, Jonathan A.; Robinson, James M.; Shafer, William M.; Bash, Margaret C.; Jerse, Ann E.

2012-01-01

338

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

339

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

340

Empirical modeling of uranium nitride fuels  

E-print Network

Irradiation Test No. S ec Fuel Average Tem . ('C) [7] Fuel Centerline Tem (o C) Linear Power (kW/m) Fuel Geome PBRF PWAC [High] PWAC [Lo] MTR ORR-UN3 BMI40 I/6 BMI50 4/9 BMI50 10/11 UNI/2, 4/5 29 41 25 41 3 6 36 12 14 890 - 1075... Irradiation Test No. S ec Fuel Average Tem . ('C) [7] Fuel Centerline Tem (o C) Linear Power (kW/m) Fuel Geome PBRF PWAC [High] PWAC [Lo] MTR ORR-UN3 BMI40 I/6 BMI50 4/9 BMI50 10/11 UNI/2, 4/5 29 41 25 41 3 6 36 12 14 890 - 1075...

Brozak, Daniel Edward

2012-06-07

341

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

342

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis.  

PubMed

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations. PMID:25339013

Fang, Xin-Yu; Xu, Wang-Dong; Huang, Qian; Yang, Xiao-Ke; Liu, Yan-Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2014-01-01

343

High shear mixing granulation of ibuprofen and ?-cyclodextrin: Effects of process variables on ibuprofen dissolution  

Microsoft Academic Search

The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on\\u000a wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating\\u000a solvents used (water, isopropanol, and 1:1 vol\\/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM\\u000a were used

Mohamed K. Ghorab; Moji Christianah Adeyeye

2007-01-01

344

Neutronic study on conversion of SAFARI-1 to LEU silicide fuel  

SciTech Connect

This paper marks the initial study into the technical and economic feasibility of converting the SAFARI-1 reactor in South Africa to LEU silicide fuel. Several MTR assembly geometries and LEU uranium densities have been studied and compared with MEU and HEU fuels. Two factors of primary importance for conversion of SAFARI-1 to LEU fuel are the economy of the fuel cycle and the performance of the incore and excore irradiation positions.

Ball, G. [Atomic Energy Corp. of South Africa Ltd., Pretoria (South Africa); Pond, R.; Hanan, N.; Matos, J. [Argonne National Lab., IL (United States)

1995-02-01

345

RRFC hardware operation manual  

SciTech Connect

The Research Reactor Fuel Counter (RRFC) system was developed to assay the {sup 235}U content in spent Material Test Reactor (MTR) type fuel elements underwater in a spent fuel pool. RRFC assays the {sup 235}U content using active neutron coincidence counting and also incorporates an ion chamber for gross gamma-ray measurements. This manual describes RRFC hardware, including detectors, electronics, and performance characteristics.

Abhold, M.E.; Hsue, S.T.; Menlove, H.O.; Walton, G.

1996-05-01

346

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

347

Validation of MCNP&ORIGEN-S 3-D Computational Model for Reactivity Predictions During BR2 Operation  

Microsoft Academic Search

A B S T R A C T The Belgian Material Test Reactor (MTR) BR2 is strongly heterogeneous high flux engineering test reactor at SCK-CEN (Centre d'Etude de l'energie Nucléaire) in Mol at a thermal power 60 to 100 MW. It deploys highly enriched uranium, water cooled concentric plate fuel elements, positioned inside a beryllium reflector with complex hyperboloid arrangement

Silva Kalcheva; Edgar Koonen; Bernard Ponsard

348

Tradeoffs in the utility of learned knowledge  

NASA Technical Reports Server (NTRS)

Planning systems which make use of domain theories can produce more accurate plans and achieve more goals as the quality of their domain knowledge improves. MTR, a multi-strategy learning system, was designed to learn from system failures and improve domain knowledge used in planning. However, augmented domain knowledge can decrease planning efficiency. We describe how improved knowledge that becomes expensive to use can be approximated to yield calculated tradeoffs in accuracy and efficiency.

Kedar, Smadar; Mckusick, Kathleen B.

1992-01-01

349

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

350

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

351

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

PubMed

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 10(4)-10(5) 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

2014-01-14

352

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

353

PROGRESS REPORT ON FUEL ELEMENT DEVELOPMENT AND ASSOCIATED PROJECTS  

Microsoft Academic Search

9 < 4 6 9 7 ; 6 8 7 6 sting Deactor (MTR) has ;\\u000a sought to develop improved, economical, long-life fuel assemblies through a ;\\u000a comprehensive study of various fuel compositions, enrichments, claddings, ;\\u000a burnable poisons, fuel and poison distributions, and fuelelement geometry ;\\u000a optimization. The core materials, including uranium -- aluminum alloys, uranium ;\\u000a oxide -aluminum cermets,

W. C. Francis; S. E. ed. Craig

1960-01-01

354

ETR, TRA642. NORTHSOUTH SECTION, LOOKING WEST. STEELFRAME ROOF, CRANE RAIL, ...  

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

ETR, TRA-642. NORTH-SOUTH SECTION, LOOKING WEST. STEEL-FRAME ROOF, CRANE RAIL, AND CRANES. COOLANT PIPE TUNNEL LEADING TO REACTOR FROM EAST. (THIS WAS A PRELIMINARY CONCEPT DRAWING.) KAISER ETR-5528-MTR-642-A-4, 11/1955. INL INDEX NO. 532-0642-00-486-100912, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

355

Interaction between methionine synthase isoforms and MMACHC: characterization in cblG-variant, cblG and cblC inherited causes of megaloblastic anaemia.  

PubMed

The cblG and cblC disorders of cobalamin (Cbl) metabolism are two inherited causes of megaloblastic anaemia. In cblG, mutations in methionine synthase (MTR) decrease conversion of hydroxocobalamin  (HOCbl) to methylcobalamin, while in cblC, mutations in MMACHC disrupt formation of cob(II)alamin (detected as HOCbl). Cases with undetectable methionine synthase (MS) activity are extremely rare and classified as 'cblG-variant'. In four 'cblG-variant' cases, we observed a decreased conversion of cyanocobalamin to HOCbl that is also seen in cblC cases. To explore this observation, we studied the gene defects, splicing products and expression of MS, as well as MS/MMACHC protein interactions in cblG-variant, cblG, cblC and control fibroblasts. We observed a full-size MS encoded by MTR-001 and a 124 kDa truncated MS encoded by MTR-201 in cblG, cblC, control fibroblasts and HEK cells, but only the MTR-201 transcript and inactive truncated MS in cblG-variant cells. Co-immunoprecipitation and proximity ligation assay showed interaction between truncated MS and MMACHC in cblG-variant cells. This interaction decreased 2.2, 1.5 and 5.0-fold in the proximity ligation assay of cblC cells with p.R161Q and p.R206W mutations, and HEK cells with knock down expression of MS by siRNA, respectively, when compared with control cells. In 3D modelling and docking analysis, both truncated and full-size MS provide a loop anchored to MMACHC, which makes contacts with R-161 and R-206 residues. Our data suggest that the interaction of MS with MMACHC may play a role in the regulation of the cellular processing of Cbls that is required for Cbl cofactor synthesis. PMID:23825108

Fofou-Caillierez, Ma'atem B; Mrabet, Nadir T; Chéry, Céline; Dreumont, Natacha; Flayac, Justine; Pupavac, Mihaela; Paoli, Justine; Alberto, Jean-Marc; Coelho, David; Camadro, Jean-Michel; Feillet, François; Watkins, David; Fowler, Brian; Rosenblatt, David S; Guéant, Jean-Louis

2013-11-15

356

Clinical and imaging correlates of the multiple sclerosis impact scale in secondary progressive multiple sclerosis  

Microsoft Academic Search

The association of pathology and neurological deficit with quality of life (QoL) in multiple sclerosis (MS) is not fully understood.\\u000a In this study, magnetic resonance imaging (MRI) measures of pathology—T1 and T2 lesion volume and ratio; active T2 lesion\\u000a number; global and regional brain volume and atrophy; magnetization transfer ratio (MTR) for lesions, normal appearing grey\\u000a and white matter (NAGM,

T. Hayton; J. Furby; K. J. Smith; D. R. Altmann; R. Brenner; J. Chataway; K. Hunter; D. J. Tozer; D. H. Miller; R. Kapoor

357

Multiple loading and mechanical response of Al6O13Si2-ZrO2/Zn composite coating  

NASA Astrophysics Data System (ADS)

In this paper, Al6O13Si2-ZrO2/Zn composite coatings were prepared by electrolytic co-deposition technique on mild steel surface from sulfate bath. The coatings were investigated using (SEM), micro-hardness tester with MTR-300 dry abrasive wear. Results showed higher micro-hardness, good wear resistance and adhered microstructure. From mechanical response ZrO2 composite has a strong effect on the interaction of the produced alloy.

Fayomi, O. S. I.; Popoola, A. P. I.; Inegbenebor, A. O.

358

Progress in Chile in the development of the fission ⁹⁹Mo production using modified CINTICHEM  

Microsoft Academic Search

Fission ⁹⁹Mo will be produced in Chile irradiating low-enriched uranium (LEU) foil in a MTR research reactor. For the purpose of developing the capability to fabricate the target, which is done of uranium foil enclosed in swaged concentric aluminum tubes, dummy targets are being fabricated using 130 μm copper foil instead of the uranium foil, wrapped in a 14μm nickel

R. Schrader; J. Klein; J. Medel; J. Marin; N. Salazar; M. Barrera; C. Albornoz; M. Chandia; X. Errazu; R. Becerra; G. Sylvester; J. C. Jimenez; E. Vargas

2008-01-01

359

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

360

High prevalence of shoulder girdle muscles with myofascial trigger points in patients with shoulder pain  

Microsoft Academic Search

Background  Shoulder pain is reported to be highly prevalent and tends to be recurrent or persistent despite medical treatment. The pathophysiological\\u000a mechanisms of shoulder pain are poorly understood. Furthermore, there is little evidence supporting the effectiveness of current\\u000a treatment protocols. Although myofascial trigger points (MTrPs) are rarely mentioned in relation to shoulder pain, they may\\u000a present an alternative underlying mechanism, which

Carel Bron; Jan Dommerholt; Boudewijn Stegenga; Michel Wensing; Rob AB Oostendorp

2011-01-01

361

Evidence for Genetic Differentiation and Variable Recombination Rates among Dutch Populations of the Opportunistic Human Pathogen Aspergillus fumigatus  

PubMed Central

As the frequency of antifungal drug resistance continues to increase, understanding the genetic structure of fungal populations, where resistant isolates have emerged and spread, is of major importance. Aspergillus fumigatus is a ubiquitously distributed fungus and the primary causative agent of invasive aspergillosis (IA), a potentially lethal infection in immunocompromised individuals. In the last few years, an increasing number of A. fumigatus isolates has evolved resistance to triazoles, the primary drugs for treating IA infections. In most isolates, this multiple-triazole-resistance (MTR) phenotype is caused by mutations in the cyp51A gene, which encodes the protein targeted by the triazoles. We investigated the genetic differentiation and reproductive mode of A. fumigatus in the Netherlands, the country where the MTR phenotype likely originated, to determine their role in facilitating the emergence and distribution of resistance genotypes. Using 20 genome-wide neutral markers, we genotyped 255 Dutch isolates including 25 isolates with the MTR phenotype. In contrast to previous reports, our results show that Dutch A. fumigatus genotypes are genetically differentiated into five distinct populations. Four of the five populations show significant linkage disequilibrium, indicative of an asexual reproductive mode, whereas the fifth population is in linkage equilibrium, indicative of a sexual reproductive mode. Notably, the observed genetic differentiation among Dutch isolates does not correlate with geography, although all isolates with the MTR phenotype nest within a single, predominantly asexual, population. These results suggest that both reproductive mode and genetic differentiation contribute to the structure of Dutch A. fumigatus populations, and are likely shaping the evolutionary dynamics of drug resistance in this potentially deadly pathogen. PMID:22106836

Klaassen, Corne H.W.; Gibbons, John G.; Fedorova, Natalie D.; Meis, Jacques F.; Rokas, Antonis

2011-01-01

362

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

363

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

364

The use of WIMS-ANL lumped fission product cross sections for burned core analysis with the MCNP Monte Carlo code.  

SciTech Connect

Most Monte Carlo neutronics analyses are performed for fresh cores. To model snapshots of the cores at different stages during burnup using MCNP, a method is presented that uses lumped fission product (LFP) cross sections generated by the WIMS-ANL code and processed for use in MCNP. Results of analyses for four very different reactor cores using MTR-type and Russian-designed fuel assemblies, with LEU and HEU fuels, are provided to demonstrate the use of this method.

Hanan, N. A.

1998-10-14

365

Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging.  

PubMed

The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T1-weighted, T2-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T1 and T2 weighted images were collected in UUO mice on day 0 (~3h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (p<0.05) changes in thickness of cortex and outer medulla, and regional changes in T2 signal intensity and MTR values. Histological changes included tubular cell death, tubular dilation, urine retention, and interstitial fibrosis, assessed by histology. The MRI measures of renal cortical and medullary atrophy, cortical-medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression. PMID:25093632

Wang, Feng; Jiang, Rosie; Takahashi, Keiko; Gore, John; Harris, Raymond C; Takahashi, Takamune; Quarles, C Chad

2014-11-01

366

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

367

'Fishing' for alternatives to mountaintop mining in southern West Virginia.  

PubMed

Mountaintop removal mining (MTR) is a major industry in southern West Virginia with many detrimental effects for small to mid-sized streams, and interest in alternative, sustainable industries is on the rise. As a first step in a larger effort to assess the value of sport fisheries in southern West Virginia, we estimate the potential abundances of two popular sport fishes-smallmouth bass (Micropterus dolomieu) and brook trout (Salvelinus fontinalis)-in the Coal River Basin (CRB). A self-thinning model that incorporates net primary production and terrestrial insect subsidies is first used to predict potential densities of adult (age 1+) smallmouth bass and brook trout. Predicted densities (fish ha(-1)) are then multiplied by the surface area of the CRB stream network (ha) to estimate regional abundance. Median predicted abundances of bass and trout are 38 806 and 118 094 fish (total abundances with the CRB), respectively. However, when streams that intersect permitted MTR areas in the CRB are removed from the dataset, predicted abundances of bass and trout decrease by ~12-14 %. We conclude that significant potential exists in the CRB to capitalize on sport fisheries, but MTR may be undermining this potential. PMID:23001943

McGarvey, Daniel J; Johnston, John M

2013-04-01

368

Linking land use with pesticides in Dutch surface waters.  

PubMed

Compared with other European countries The Netherlands has a relatively high level of pesticide consumption, particularly in agriculture. Many of the compounds concerned end up in surface waters. Surface water quality is routinely monitored and numerous pesticides are found to be present in high concentrations, with various standards being regularly exceeded. Many standards-breaching pesticides exhibit regional patterns that can be traced back to land use. These patterns have been statistically analysed by correlating surface area per land use category with standards exceedance per pesticide, thereby identifying numerous significant correlations with respect to breaches of both the ecotoxicological standard (Maximum Tolerable Risk, MTR) and the drinking water standard. In the case of the MTR, greenhouse horticulture, floriculture and bulb-growing have the highest number as well as percentage of standard-breaching pesticides, despite these market segments being relatively small in terms of area cropped. Cereals, onions, vegetables, perennial border plants and pulses are also associated with many pesticides that exceed the drinking water standard. When a correction is made for cropped acreage, cereals and potatoes also prove to be a major contributor to monitoring sites where the MTR standard is exceeded. Over the period 1998-2006 the land-use categories with the most and highest percentage of standards-exceeding pesticides (greenhouse horticulture, bulb-growing and flower cultivation) showed an increase in the percentage of standards-exceeding compounds. PMID:23885409

Van't, Zelfde M T; Tamis, W L M; Vijver, M G; De Snoo, G R

2012-01-01

369

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 will be working with the company's Randall Gas Technology group, a supplier of equipment and processing technology to the natural gas industry. Randall's engineering group has found a new site for the project at a North Texas Exploration (NTE) gas processing plant. The plant produces about 1 MMscfd of gas containing 24% nitrogen. The membrane unit will bring this gas to 4% nitrogen for delivery to the pipeline. The membrane skid is being built by ABB. NTE has ordered the required compressor and MTR is making the membrane modules. The membrane skid is scheduled to be completed by December 29. Our target is to have the unit installed and optimized by mid-January.

Kaaeid Lokhandwala

2004-09-01

370

Detection and quantification of major toxigenic Microcystis genotypes in Moo-Tan reservoir and associated water treatment plant.  

PubMed

Two molecular methods, denaturing gradient gel electrophoresis (DGGE) and quantitative real-time polymerase chain reaction (qPCR) with the Universal ProbeLibrary (UPL) probe, were developed and used for the characterization and quantification of several microcystin producers in Moo-Tan Reservoir (MTR), Taiwan and its associated water treatment plant (Shih-Men Water Treatment Plant, SMWTP). Internal transcribed spacer (ITS) sequence, a highly diversified region between the 16S rRNA and 23S rRNA genes, was used to further identify the isolated strains from MTR and also used in DGGE for the detection of the specific DNA fragments and biomarkers for 11 strains observed in MTR. These ITS-DGGE biomarkers were successfully applied to monitor the community changes of potential toxigenic Microcystis sp. over a period of five years. Two highly specific primers were combined with UPL probes to measure microcystins synthesis gene (mcyB) and phycocyanin intergenic spacer region (cpcB) concentrations in water samples. The copy concentrations of UPL-mcyB and UPL-cpcB correlated well with MC-RR concentrations/water temperature and Microcystis sp. cell numbers in the water samples, respectively. For SMWTP, toxin concentrations were low, but the DGGE bands clearly demonstrated the presence of potential microcystin producers in both water treatment plants and finished water samples. It was demonstrated that toxigenic Microcystis sp. may penetrate through the treatment processes and pose a potential risk to human health in the drinking water systems. PMID:22234317

Yen, Hung-Kai; Lin, Tsair-Fuh; Tseng, I-Cheng

2012-02-01

371

Application of Ultrasound-Guided Trigger Point Injection for Myofascial Trigger Points in the Subscapularis and Pectoralis Muscles to Post-Mastectomy Patients: A Pilot Study  

PubMed Central

Purpose To investigate the therapeutic effectiveness of ultrasound (US)-guided trigger point injection for myofascial trigger points (MTrPs) in the internal rotator muscles of the shoulder in post-mastectomy patients. Materials and Methods This pilot study was a non-controlled, prospective, clinical trial. Nineteen post-mastectomy patients with a diagnosis of at least one active MTrP in the subscapularis and/or pectoralis muscles were included. We performed trigger point injections into the subscapularis muscle deep behind the scapula as well as the pectoralis muscle for diagnostic and therapeutic purpose by the newly developed US-guided method. Results Visual analogue scale and range of motion of the shoulder for external rotation and of abduction showed significant improvement immediately after the first injection and 3 months after the last injection compared with baseline (p<0.05 for both). Duration from onset to surgery and duration of myofascial pain syndrome in the good responder group were significantly shorter than in the bad responder group (p<0.05). Patients did not report any complications related to the procedure or serious adverse events attributable to the treatment. Conclusion In post-mastectomy patients with shoulder pain, US-guided trigger point injections of the subscapularis and/or pectoralis muscles are effective for both diagnosis and treatment when the cause of shoulder pain is suspected to originate from active MTrPs in these muscles, particularly, the subscapularis. PMID:24719150

Shin, Hyuk Jai; Shin, Ji Cheol; Kim, Wan Sung; Chang, Won Hyuk

2014-01-01

372

Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology.  

PubMed Central

Conventional MRI sequences do not permit the distinction between the different pathological characteristics (oedema, demyelination, gliosis, axonal loss) of the multiple sclerosis plaque. Magnetisation transfer imaging and transverse magnetisation decay curve (tMDC) analysis may be more specific. These techniques have been applied to the optic nerves in 20 patients with optic neuritis and the results correlated with clinical and visual evoked potential (VEP) findings. tMDC analysis failed to identify separate intracellular and extracellular water compartments within the optic nerve but gave a measure of transverse relaxation time (T2) without the confounding effects of CSF in the nerve sheath. Both T2 and magnetisation transfer ratio (MTR) were abnormal after an episode of optic neuritis. T2 did not correlate with visual function or with VEP latency or amplitude. There was a significant correlation between MTR reduction and prolongation of VEP latency: this increased latency may reflect an effect of myelin loss on MTR. Longer lesions were associated with worse visual outcome, implying that the overall extent of pathological involvement is likely to influence the degree of functional deficit. Images PMID:8530932

Thorpe, J W; Barker, G J; Jones, S J; Moseley, I; Losseff, N; MacManus, D G; Webb, S; Mortimer, C; Plummer, D L; Tofts, P S

1995-01-01

373

Conserved SR protein kinase functions in nuclear import and its action is counteracted by arginine methylation in Saccharomyces cerevisiae.  

PubMed

Mammalian serine and arginine-rich (SR) proteins play important roles in both constitutive and regulated splicing, and SR protein-specific kinases (SRPKs) are conserved from humans to yeast. Here, we demonstrate a novel function of the single conserved SR protein kinase Sky1p in nuclear import in budding yeast. The yeast SR-like protein Npl3p is known to enter the nucleus through a composite nuclear localization signal (NLS) consisting of a repetitive arginine- glycine-glycine (RGG) motif and a nonrepetitive sequence. We found that the latter is the site for phosphorylation by Sky1p and that this phosphorylation regulates nuclear import of Npl3p by modulating the interaction of the RGG motif with its nuclear import receptor Mtr10p. The RGG motif is also methylated on arginine residues, but methylation does not affect the Npl3p-Mtr10p interaction in vitro. Remarkably, arginine methylation interferes with Sky1p-mediated phosphorylation, thereby indirectly influencing the Npl3p-Mtr10p interaction in vivo and negatively regulating nuclear import of Npl3p. These results suggest that nuclear import of Npl3p is coordinately influenced by methylation and phosphorylation in budding yeast, which may represent conserved components in the dynamic regulation of RNA processing in higher eukaryotic cells. PMID:10952997

Yun, C Y; Fu, X D

2000-08-21

374

Manganese sulfide formation via concomitant microbial manganese oxide and thiosulfate reduction.  

PubMed

The dissimilatory metal-reducing bacterium, Shewanella oneidensis MR-1 produced ?-MnS (rambergite) nanoparticles during the concurrent reduction of MnO? and thiosulfate coupled to H? oxidation. To investigate effect of direct microbial reduction of MnO? on MnS formation, two MR-1 mutants defective in outer membrane c-type cytochromes (?mtrC/?omcA and ?mtrC/?omcA/?mtrF) were also used and it was determined that direct reduction of MnO? was dominant relative to chemical reduction by biogenic sulfide generated from thiosulfate reduction. Although bicarbonate was excluded from the medium, incubations of strain MR-1 with lactate as the electron donor produced MnCO? (rhodochrosite) as well as MnS in nearly equivalent amounts as estimated by micro X-ray diffraction (micro-XRD) analysis. It was concluded that carbonate released from lactate metabolism promoted MnCO? formation and that Mn(II) mineralogy was strongly affected by carbonate ions even in the presence of abundant sulfide and weakly alkaline conditions expected to favour the precipitation of MnS. Formation of MnS, as determined by a combination of micro-XRD, transmission electron microscopy, energy dispersive X-ray spectroscopy, and selected area electron diffraction analyses was consistent with equilibrium speciation modelling predictions. Biogenic manganese sulfide may be a manganese sink in the Mn biogeochemical cycle in select environments such as deep anoxic marine basins within the Baltic Sea. PMID:21951417

Lee, Ji-Hoon; Kennedy, David W; Dohnalkova, Alice; Moore, Dean A; Nachimuthu, Ponnusamy; Reed, Samantha B; Fredrickson, James K

2011-12-01

375

Recycling of methylthioadenosine is essential for normal vascular development and reproduction in Arabidopsis.  

PubMed

5'-Methylthioadenosine (MTA) is the common by-product of polyamine (PA), nicotianamine (NA), and ethylene biosynthesis in Arabidopsis (Arabidopsis thaliana). The methylthiol moiety of MTA is salvaged by 5'-methylthioadenosine nucleosidase (MTN) in a reaction producing methylthioribose (MTR) and adenine. The MTN double mutant, mtn1-1mtn2-1, retains approximately 14% of the MTN enzyme activity present in the wild type and displays a pleiotropic phenotype that includes altered vasculature and impaired fertility. These abnormal traits were associated with increased MTA levels, altered PA profiles, and reduced NA content. Exogenous feeding of PAs partially recovered fertility, whereas NA supplementation improved fertility and also reversed interveinal chlorosis. The analysis of PA synthase crystal structures containing bound MTA suggests that the corresponding enzyme activities are sensitive to available MTA. Mutant plants that expressed either MTN or human methylthioadenosine phosphorylase (which metabolizes MTA without producing MTR) appeared wild type, proving that the abnormal traits of the mutant are due to MTA accumulation rather than reduced MTR. Based on our results, we propose that the key targets affected by increased MTA content are thermospermine synthase activity and spermidine-dependent posttranslational modification of eukaryotic initiation factor 5A. PMID:22345506

Waduwara-Jayabahu, Ishari; Oppermann, Yasmin; Wirtz, Markus; Hull, Zachary T; Schoor, Sarah; Plotnikov, Alexander N; Hell, Rüdiger; Sauter, Margret; Moffatt, Barbara A

2012-04-01

376

The interstitial location of selenium and arsenic in rocks associated with coal mining using ultrasound extractions and principal component analysis (PCA).  

PubMed

The release of selenium and arsenic from coal mine wastes into main waterways is an environmental cause for concern in the mining industry due to a myriad of subsequent ecotoxicological problems associated with the two metalloids. In a 2002 USEPA study undertaken in a mountaintop removal/valley fill (MTR/VF) mining area in southern West Virginia, measured Se concentrations were higher than the stipulated 5 ng/mL in 66 out of the 213 water samples collected. We studied the chemical composition of forty seven randomly selected pulverized core rock samples collected from depths of 25 ft to 881 ft from MTR/VF sites to determine the amounts of bioaccessible (ultrasound leachable) As and Se concentrations and their tentative locations within the rock matrix. The application of principal component analysis (PCA) to the chemical data, suggested that ultrasound leachable selenium concentrations were associated with 14 ? d-spacing phyllosilicate clays (chlorite, montmorillonite and vermiculite all 2:1 layered clays) whilst ultrasound leachable arsenic concentrations were closely related to the concentration of illite, another 2:1 phyllosilicate clay. Negative correlations between leachable arsenic and selenium with kaolinite a 1:1 layered clay, were also observed. We used the observed negative correlations to rule out the presence of selenium or arsenic in 1:1 kaolinite. Hence mining waste from MTR/VF sites containing substantial amounts of illite and 14 ? d-spacing clays may require to be placed in priority landfills or valley fills. PMID:22056124

Pumure, I; Renton, J J; Smart, R B

2011-12-30

377

Recycling of Methylthioadenosine Is Essential for Normal Vascular Development and Reproduction in Arabidopsis1[W][OA  

PubMed Central

5?-Methylthioadenosine (MTA) is the common by-product of polyamine (PA), nicotianamine (NA), and ethylene biosynthesis in Arabidopsis (Arabidopsis thaliana). The methylthiol moiety of MTA is salvaged by 5?-methylthioadenosine nucleosidase (MTN) in a reaction producing methylthioribose (MTR) and adenine. The MTN double mutant, mtn1-1mtn2-1, retains approximately 14% of the MTN enzyme activity present in the wild type and displays a pleiotropic phenotype that includes altered vasculature and impaired fertility. These abnormal traits were associated with increased MTA levels, altered PA profiles, and reduced NA content. Exogenous feeding of PAs partially recovered fertility, whereas NA supplementation improved fertility and also reversed interveinal chlorosis. The analysis of PA synthase crystal structures containing bound MTA suggests that the corresponding enzyme activities are sensitive to available MTA. Mutant plants that expressed either MTN or human methylthioadenosine phosphorylase (which metabolizes MTA without producing MTR) appeared wild type, proving that the abnormal traits of the mutant are due to MTA accumulation rather than reduced MTR. Based on our results, we propose that the key targets affected by increased MTA content are thermospermine synthase activity and spermidine-dependent posttranslational modification of eukaryotic initiation factor 5A. PMID:22345506

Waduwara-Jayabahu, Ishari; Oppermann, Yasmin; Wirtz, Markus; Hull, Zachary T.; Schoor, Sarah; Plotnikov, Alexander N.; Hell, Rudiger; Sauter, Margret; Moffatt, Barbara A.

2012-01-01

378

Growth of white matter in the adolescent brain: role of testosterone and androgen receptor.  

PubMed

The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath. PMID:18799683

Perrin, Jennifer S; Hervé, Pierre-Yves; Leonard, Gabriel; Perron, Michel; Pike, G Bruce; Pitiot, Alain; Richer, Louis; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomás

2008-09-17

379

Identification and Characterization of MtoA: A Decaheme c-Type Cytochrome of the Neutrophilic Fe(II)-Oxidizing Bacterium Sideroxydans lithotrophicus ES-1  

PubMed Central

The Gram-negative bacterium Sideroxydans lithotrophicus ES-1 (ES-1) grows on FeCO3 or FeS at oxic–anoxic interfaces at circumneutral pH, and the ES-1-mediated Fe(II) oxidation occurs extracellularly. However, the molecular mechanisms underlying ES-1’s ability to oxidize Fe(II) remain unknown. Survey of the ES-1 genome for candidate genes for microbial extracellular Fe(II) oxidation revealed that it contained a three-gene cluster encoding homologs of Shewanella oneidensis MR-1 (MR-1) MtrA, MtrB, and CymA that are involved in extracellular Fe(III) reduction. Homologs of MtrA and MtrB were also previously shown to be involved in extracellular Fe(II) oxidation by Rhodopseudomonas palustris TIE-1. To distinguish them from those found in MR-1, the identified homologs were named MtoAB and CymAES-1. Cloned mtoA partially complemented an MR-1 mutant without MtrA with regards to ferrihydrite reduction. Characterization of purified MtoA showed that it was a decaheme c-type cytochrome and oxidized soluble Fe(II). Oxidation of Fe(II) by MtoA was pH- and Fe(II)-complexing ligand-dependent. Under conditions tested, MtoA oxidized Fe(II) from pH 7 to pH 9 with the optimal rate at pH 9. MtoA oxidized Fe(II) complexed with different ligands at different rates. The reaction rates followed the order Fe(II)Cl2?>? Fe(II)–citrate?>?Fe(II)–NTA?>?Fe(II)–EDTA with the second-order rate constants ranging from 6.3?×?10?3??M?1?s?1 for oxidation of Fe(II)Cl2 to 1.0?×?10?3??M?1?s?1 for oxidation of Fe(II)–EDTA. Thermodynamic modeling showed that redox reaction rates for the different Fe(II)-complexes correlated with their respective estimated reaction-free energies. Collectively, these results demonstrate that MtoA is a functional Fe(II)-oxidizing protein that, by working in concert with MtoB and CymAES-1, may oxidize Fe(II) at the bacterial surface and transfer released electrons across the bacterial cell envelope to the quinone pool in the inner membrane during extracellular Fe(II) oxidation by ES-1. PMID:22347878

Liu, Juan; Wang, Zheming; Belchik, Sara M.; Edwards, Marcus J.; Liu, Chongxuan; Kennedy, David W.; Merkley, Eric D.; Lipton, Mary S.; Butt, Julea N.; Richardson, David J.; Zachara, John M.; Fredrickson, James K.; Rosso, Kevin M.; Shi, Liang

2012-01-01

380

Identification and Characterization of MtoA: A Decaheme c-Type Cytochrome of the Neutrophilic Fe(II)-Oxidizing Bacterium Sideroxydans lithotrophicus ES-1.  

PubMed

The Gram-negative bacterium Sideroxydans lithotrophicus ES-1 (ES-1) grows on FeCO(3) or FeS at oxic-anoxic interfaces at circumneutral pH, and the ES-1-mediated Fe(II) oxidation occurs extracellularly. However, the molecular mechanisms underlying ES-1's ability to oxidize Fe(II) remain unknown. Survey of the ES-1 genome for candidate genes for microbial extracellular Fe(II) oxidation revealed that it contained a three-gene cluster encoding homologs of Shewanella oneidensis MR-1 (MR-1) MtrA, MtrB, and CymA that are involved in extracellular Fe(III) reduction. Homologs of MtrA and MtrB were also previously shown to be involved in extracellular Fe(II) oxidation by Rhodopseudomonas palustris TIE-1. To distinguish them from those found in MR-1, the identified homologs were named MtoAB and CymA(ES-1). Cloned mtoA partially complemented an MR-1 mutant without MtrA with regards to ferrihydrite reduction. Characterization of purified MtoA showed that it was a decaheme c-type cytochrome and oxidized soluble Fe(II). Oxidation of Fe(II) by MtoA was pH- and Fe(II)-complexing ligand-dependent. Under conditions tested, MtoA oxidized Fe(II) from pH 7 to pH 9 with the optimal rate at pH 9. MtoA oxidized Fe(II) complexed with different ligands at different rates. The reaction rates followed the order Fe(II)Cl(2)?>? Fe(II)-citrate?>?Fe(II)-NTA?>?Fe(II)-EDTA with the second-order rate constants ranging from 6.3?×?10(-3)??M(-1)?s(-1) for oxidation of Fe(II)Cl(2) to 1.0?×?10(-3)??M(-1)?s(-1) for oxidation of Fe(II)-EDTA. Thermodynamic modeling showed that redox reaction rates for the different Fe(II)-complexes correlated with their respective estimated reaction-free energies. Collectively, these results demonstrate that MtoA is a functional Fe(II)-oxidizing protein that, by working in concert with MtoB and CymA(ES-1), may oxidize Fe(II) at the bacterial surface and transfer released electrons across the bacterial cell envelope to the quinone pool in the inner membrane during extracellular Fe(II) oxidation by ES-1. PMID:22347878

Liu, Juan; Wang, Zheming; Belchik, Sara M; Edwards, Marcus J; Liu, Chongxuan; Kennedy, David W; Merkley, Eric D; Lipton, Mary S; Butt, Julea N; Richardson, David J; Zachara, John M; Fredrickson, James K; Rosso, Kevin M; Shi, Liang

2012-01-01

381

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

382

Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting  

PubMed Central

Objective In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. Methods The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher’s exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. Results A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/?L, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/?L, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71–€33,570.00) and €14,277.00 (range: €5,908.89–€82,310.30) among MTR patients. At multivariate analysis, after adjustment for age, sex, antibody-hepatitis C virus status, HIV risk factors, baseline CD4+, and HIV-RNA, the cost analysis was significantly lower among patients starting an STR treatment than those starting an MTR (adjusted mean: €12,096.00 vs €16,106.00, P=0.0001). Conclusion STR was associated with a lower annual cost per patient than MTR, thus can be considered a cost-saving strategy in the treatment of HIV patients. This analysis is an important tool for policy makers and health care professionals to make short- and long-term cost projections and thus assess the impact of these on available budgets. PMID:24379676

Colombo, Giorgio L; Castagna, Antonella; Di Matteo, Sergio; Galli, Laura; Bruno, Giacomo; Poli, Andrea; Salpietro, Stefania; Carbone, Alessia; Lazzarin, Adriano

2014-01-01

383

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

384

Identifying the role of cytochromes upon the attachment, growth and detachment of Shewanella oneidensis MR-1 on hematite during dissimilatory iron reduction under natural- flow conditions  

NASA Astrophysics Data System (ADS)

Current understanding of bacterial respiration by dissimilatory iron (Fe) reduction is based primarily on studies of closed systems using soluble Fe(III). However, natural environments likely to support Fe reduction are typically open systems and contain Fe(III) primarily in the form of crystalline (hydr)oxides. Mechanisms by which electrons are transported between bacteria and mineral terminal electron acceptors (TEAs) under open system conditions are still poorly understood. However, a number of cytochromes have been identified as potentially playing a critical role in the electron transport system of some Fe reducing bacteria. Experiments were performed using (i) omcA, (ii) mtrC, or (iii) omcA and mtrC cytochrome deficient mutants of the Fe-reducing bacteria, Shewanella oneidensis MR-1, in transparent-window flow- reactors containing hematite as the only TEA. These were operated under defined hydrodynamic and anaerobic conditions. Cells expressed green fluorescent protein (gfp), allowing real time measurement of cells at the mineral surface by epifluorescence microscopy. Cytochromes which play a critical role in the anaerobic growth of S. Oneidensis by Fe reduction under open system natural-flow conditions could then be identified. Differences in the accumulation, maximum density, detachment and total production of surface-associated cells growing on hematite surfaces were apparent between the mutants, and between the mutants and the wild-type. Mutants deficient in cytochromes grew to a lower max density by up to 2 orders of magnitude than the wild-type, and exhibited no reduced Fe in the reactor effluent or at the surface of the hematite at the conclusion of the experiment, as revealed by X-Ray photoelectron spectroscopy (XPS). Therefore omcA and / or mtrC cytochromes appear critical for electron shuttling and anaerobic growth of S. Oneidensis on hematite under natural-flow conditions.

Mitchell, A. C.; Geesey, G. G.

2006-12-01

385

c-Type Cytochrome-Dependent Formation of U(IV) Nanoparticles by Shewanella oneidensis  

PubMed Central

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 UO 2 nanoparticles. In particular, the outer membrane (OM) decaheme cytochrome MtrC (metal reduction), previously implicated in Mn(IV) and Fe(III) reduction, directly transferred electrons to U(VI). Additionally, deletions of mtrC and/or omcA significantly affected the in vivo U(VI) reduction rate relative to wild-type MR-1. Similar to the wild-type, the mutants accumulated UO 2 nanoparticles extracellularly to high densities in association with an extracellular polymeric substance (EPS). In wild-type cells, this UO 2-EPS matrix exhibited glycocalyx-like properties and contained multiple elements of the OM, polysaccharide, and heme-containing proteins. Using a novel combination of methods including synchrotron-based X-ray fluorescence microscopy and high-resolution immune-electron microscopy, we demonstrate a close association of the extracellular UO 2 nanoparticles with MtrC and OmcA (outer membrane cytochrome). This is the first study to our knowledge to directly localize the OM-associated cytochromes with EPS, which contains biogenic UO 2 nanoparticles. In the environment, such association of UO 2 nanoparticles with biopolymers may exert a strong influence on subsequent behavior including susceptibility to oxidation by O 2 or transport in soils and sediments. PMID:16875436

Marshall, Matthew J; Dohnalkova, Alice C; Kennedy, David W; Shi, Liang; Wang, Zheming; Boyanov, Maxim I; Lai, Barry; Kemner, Kenneth M; McLean, Jeffrey S; Reed, Samantha B; Culley, David E; Bailey, Vanessa L; Simonson, Cody J; Saffarini, Daad A; Romine, Margaret F; Zachara, John M

2006-01-01

386

Structural covariance of superficial white matter in mild Alzheimer's disease compared to normal aging  

PubMed Central

Introduction Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. Methods Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. Results In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. Conclusion This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern. PMID:25328848

Carmeli, Cristian; Fornari, Eleonora; Jalili, Mahdi; Meuli, Reto; Knyazeva, Maria G

2014-01-01

387

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. However, a small test system was installed at a Twin Bottoms Energy well in Kentucky. This unit operated successfully for six months, and demonstrated the technology's reliability on a small scale. MTR then located an alternative test site with much larger gas flow rates and signed a contract with Towne Exploration in the third quarter of 2006, for a demonstration plant in Rio Vista, California, to be run through May 2007. The demonstration for Towne has already resulted in the sale of two commercial skids to the company; both units will be delivered by the end of 2007. Total sales of nitrogen/natural gas membrane separation units from the partnership with ABB are now approaching $4.0 million.

Kaaeid Lokhandwala

2007-03-31

388

Manganese sulfide formation via concomitant microbial manganese oxide and thiosulfate reduction  

SciTech Connect

The dissimilatory metal-reducing bacterium, Shewanella oneidensis MR-1 produced {gamma}-MnS (rambergite) nanoparticles during the concurrent reduction of MnO{sub 2} and thiosulfate coupled to H{sub 2} oxidation. To investigate effect of direct microbial reduction of MnO{sub 2} on MnS formation, two MR-1 mutants defective in outer membrane c-type cytochromes ({Delta}mtrC/{Delta}omcA and {Delta}mtrC/{Delta}omcA/{Delta}mtrF) were also used and it was determined that direct reduction of MnO{sub 2} was dominant relative to chemical reduction by biogenic sulfide generated from thiosulfate reduction. Although bicarbonate was excluded from the medium, incubations of strain MR-1 with lactate as the electron donor produced MnCO{sub 3} (rhodochrosite) as well as MnS in nearly equivalent amounts as estimated by micro X-ray diffraction (micro-XRD) analysis. It was concluded that carbonate released from lactate metabolism promoted MnCO{sub 3} formation and that Mn(II) mineralogy was strongly affected by carbonate ions even in the presence of abundant sulfide and weakly alkaline conditions expected to favor the precipitation of MnS. Formation of MnS, as determined by a combination of micro-XRD, transmission electron microscopy, energy dispersive X-ray spectroscopy, and selected area electron diffraction analyses was consistent with equilibrium speciation modeling predictions. Biogenic manganese sulfide may be a manganese sink in the Mn biogeochemical cycle in select environments such as deep anoxic marine basins within the Baltic Sea.

Lee, Ji-Hoon; Kennedy, David W.; Dohnalkova, Alice; Moore, Dean A.; Nachimuthu, Ponnusamy; Reed, Samantha B.; Fredrickson, Jim K.

2011-12-13

389

Oxygen-dependent autoaggregation in Shewanella oneidensis MR-1  

SciTech Connect

In aerobic chemostat cultures maintained at 50% dissolved O2 tension (123.5 µM dissolved O2), Shewanella oneidensis strain MR-1 rapidly aggregated upon addition of 0.68 mM CaCl2 and retained this multi-cellular phenotype at high dilution rates. Confocal microscopy analysis of the extracellular matrix material contributing to the stability of the aggregate structures revealed the presence of extracellular DNA, protein, and glycoconjugates. Upon onset of O2-limited growth (dissolved O2 below detection) however, the Ca2+-supplemented chemostat cultures of strain MR-1 rapidly disaggregated and grew as motile dispersed cells. Global transcriptome analysis comparing aerobic aggregated to O2-limited unaggregated cells identified genes encoding cell-to-cell and cell-to-surface adhesion factors whose transcription increased upon exposure to increased O2 concentrations. The aerobic aggregated cells also revealed increased expression of putative anaerobic electron transfer and homologs of metal reduction genes, including mtrD (SO1782), mtrE (SO1781), and mtrF (SO1780). Our data indicate that mechanisms involved in autoaggregation of MR-1 are dependent on the function of pilD gene which encodes a putative prepilin peptidase. Mutants of S. oneidensis strain MR-1 deficient in PilD and associated pathways, including type IV and Msh pili biogenesis, displayed a moderate increase in sensitivity to H2O2. Taken together, our evidence indicates that aggregate formation in S. oneidensis MR-1 may serve as an alternative or an addition to biochemical detoxification to reduce the oxidative stress associated with production of reactive oxygen species during aerobic metabolism while facilitating the development of hypoxic conditions within the aggregate interior.

Mclean, Jeffrey S.; Pinchuk, Grigoriy E.; Geydebrekht, Oleg V.; Bilskis, Christina L.; Zakrajsek, Brian A.; Hill, Eric A.; Saffarini, Daad; Romine, Margaret F.; Gorby, Yuri A.; Fredrickson, Jim K.; Beliaev, Alex S.

2008-07-01

390

Reduced magnetisation transfer ratio in cognitively impaired patients at the very early stage of multiple sclerosis: a prospective, multicenter, cross-sectional study  

PubMed Central

Objectives Cognitive impairment belongs to the core symptoms in multiple sclerosis (MS) and can already be present at the very early stages of the disease. The present study evaluated cognitive functioning after the first clinical presentation suggestive of MS and brain tissue damage in a non-lesion focused MRI approach by using magnetisation transfer imaging (MTI). Setting and participants 47 patients (15 men and 32 women; mean age: 31.17?years) after the first clinical event suggestive of MS were recruited in six different MS centres in Germany and underwent a neuropsychological test battery including tests for attention, memory and executive function as well as depression and fatigue. MTI and conventional MRI measures (T1/T2 lesion load) were assessed. In addition, Magnetisation Transfer Ratio (MTR) maps were calculated. Primary outcome measure was the investigation of cognitive dysfunction in very early MS in correlation to MRI data. Results 55.3% of patients with MS failed at least one test parameter. Specifically, 6% were reduced in working memory, 14.9% in focused attention, 25.5% in figural learning and up to 14.9% in executive function. When the sample was subdivided into cognitively impaired and preserved, MTR scores within the cognitively impaired subgroup were significantly lower compared with the preserved group (t(43)=2.346, p=0.02*). No significant differences between the two groups were found in T2-weighted and T1-weighted lesion volume. Conclusions After the first MS-related clinical event, 55.3% of patients showed distinct cognitive deficits. Cognitively impaired patients had significantly lower whole brain MTR, but no differences in focal brain lesion volumes supporting the idea that early cognitive deficits may be related to diffuse loss of brain tissue integrity. PMID:24722197

Faiss, J H; Dähne, D; Baum, K; Deppe, R; Hoffmann, F; Köhler, W; Kunkel, A; Lux, A; Matzke, M; Penner, I K; Sailer, M; Zettl, U K

2014-01-01

391

Grey matter magnetization transfer ratio independently correlates with neurological deficit in secondary progressive multiple sclerosis.  

PubMed

Although there is substantial brain grey matter pathology in secondary progressive multiple sclerosis (MS), there has been limited investigation of its contribution to disability.This study investigated the correlation of magnetization transfer ratio (MTR) measures taken from brain grey matter, normal appearing white matter (NAWM) and lesions with neurological deficit and disability in 113 people with secondary progressive MS. In order to adjust for the potential effects of focal white matter lesions and global brain atrophy, T2 lesion volume and normalized brain volume (NBV) were also calculated for each subject. Clinical measures included the expanded disability status scale (EDSS) and the multiple sclerosis functional composite (MSFC) scores. Linear regression analysis was used to assess the age- and gender-adjusted correlation of MTR histogram mean, peak height and peak location with the MSFC and individual component measures. Logistic regression analysis was used to determine whether imaging measures could be used to predict if subjects were in the higher disability group (EDSS > or = 6.5).Significant correlations were detected between MSFC composite and mean MTR in (i) normal appearing white matter (NAWM; r = 0.327, p < 0.0001), (ii) grey matter (r = 0.460, p < 0.0001) and (iii) lesions (r = 0.394, p < 0.0001). Although NBV and T2 lesion volume correlated significantly with MSFC, grey matter histogram mean emerged as the best predictor of MSFC score. None of the MRI measures significantly predicted higher EDSS.These results suggest that brain grey matter pathology plays an important role in determining neurological impairment. The apparent paucity of correlation between MRI measures and EDSS is likely to represent the relative insensitivity of the latter measure in this study group. PMID:19271108

Hayton, T; Furby, J; Smith, K J; Altmann, D R; Brenner, R; Chataway, J; Hughes, R A C; Hunter, K; Tozer, D J; Miller, D H; Kapoor, R

2009-03-01

392

Global Transcriptional Profiling of Shewanella oneidensis MR-1 during Cr(VI) and U(VI) Reduction†  

PubMed Central

Whole-genome DNA microarrays were used to examine the gene expression profile of Shewanella oneidensis MR-1 during U(VI) and Cr(VI) reduction. The same control, cells pregrown with nitrate and incubated with no electron acceptor, was used for the two time points considered and for both metals. U(VI)-reducing conditions resulted in the upregulation (?3-fold) of 121 genes, while 83 genes were upregulated under Cr(VI)-reducing conditions. A large fraction of the genes upregulated [34% for U(VI) and 29% for Cr(VI)] encode hypothetical proteins of unknown function. Genes encoding proteins known to reduce alternative electron acceptors [fumarate, dimethyl sulfoxide, Mn(IV), or soluble Fe(III)] were upregulated under both U(VI)- and Cr(VI)-reducing conditions. The involvement of these upregulated genes in the reduction of U(VI) and Cr(VI) was tested using mutants lacking one or several of the gene products. Mutant testing confirmed the involvement of several genes in the reduction of both metals: mtrA, mtrB, mtrC, and menC, all of which are involved in Fe(III) citrate reduction by MR-1. Genes encoding efflux pumps were upregulated under Cr(VI)- but not under U(VI)-reducing conditions. Genes encoding proteins associated with general (e.g., groL and dnaJ) and membrane (e.g., pspBC) stress were also upregulated, particularly under U(VI)-reducing conditions, pointing to membrane damage by the solid-phase reduced U(IV) and Cr(III) and/or the direct effect of the oxidized forms of the metals. This study sheds light on the multifaceted response of MR-1 to U(VI) and Cr(VI) under anaerobic conditions and suggests that the same electron transport pathway can be used for more than one electron acceptor. PMID:16269787

Bencheikh-Latmani, Rizlan; Williams, Sarah Middleton; Haucke, Lisa; Criddle, Craig S.; Wu, Liyou; Zhou, Jizhong; Tebo, Bradley M.

2005-01-01

393

Abbreviated sampling and analysis plan for planning decontamination and decommissioning at Test Reactor Area (TRA) facilities  

SciTech Connect

The objective is to sample and analyze for the presence of gamma emitting isotopes and hazardous constituents within certain areas of the Test Reactor Area (TRA), prior to D and D activities. The TRA is composed of three major reactor facilities and three smaller reactors built in support of programs studying the performance of reactor materials and components under high neutron flux conditions. The Materials Testing Reactor (MTR) and Engineering Test Reactor (ETR) facilities are currently pending D/D. Work consists of pre-D and D sampling of designated TRA (primarily ETR) process areas. This report addresses only a limited subset of the samples which will eventually be required to characterize MTR and ETR and plan their D and D. Sampling which is addressed in this document is intended to support planned D and D work which is funded at the present time. Biased samples, based on process knowledge and plant configuration, are to be performed. The multiple process areas which may be potentially sampled will be initially characterized by obtaining data for upstream source areas which, based on facility configuration, would affect downstream and as yet unsampled, process areas. Sampling and analysis will be conducted to determine the level of gamma emitting isotopes and hazardous constituents present in designated areas within buildings TRA-612, 642, 643, 644, 645, 647, 648, 663; and in the soils surrounding Facility TRA-611. These data will be used to plan the D and D and help determine disposition of material by D and D personnel. Both MTR and ETR facilities will eventually be decommissioned by total dismantlement so that the area can be restored to its original condition.

NONE

1994-10-01

394

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

395

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

396

Effects of the Anaerobic Respiration of Shewanella oneidensis MR-1 on the Stability of Extracellular U(VI) Nanofibers  

PubMed Central

Uranium (VI) is considered to be one of the most widely dispersed and problematic environmental contaminants, due in large part to its high solubility and great mobility in natural aquatic systems. We previously reported that under anaerobic conditions, Shewanella oneidensis MR-1 grown in medium containing uranyl acetate rapidly accumulated long, extracellular, ultrafine U(VI) nanofibers composed of polycrystalline chains of discrete meta-schoepite (UO3·2H2O) nanocrystallites. Wild-type MR-1 finally transformed the uranium (VI) nanofibers to uranium (IV) nanoparticles via further reduction. In order to investigate the influence of the respiratory chain in the uranium transformation process, a series of mutant strains lacking a periplasmic cytochrome MtrA, outer membrane (OM) cytochrome MtrC and OmcA, a tetraheme cytochrome CymA anchored to the cytoplasmic membrane, and a trans-OM protein MtrB, were tested in this study. Although all the mutants produced U(VI) nanofibers like the wild type, the transformation rates from U(VI) nanofibers to U(IV) nanoparticles varied; in particular, the mutant with deletion in tetraheme cytochrome CymA stably maintained the uranium (VI) nanofibers, suggesting that the respiratory chain of S. oneidensis MR-1 is probably involved in the stability of extracellular U(VI) nanofibers, which might be easily treated via the physical processes of filtration or flocculation for the remediation of uranium contamination in sediments and aquifers, as well as the recovery of uranium in manufacturing processes. PMID:23719584

Jiang, Shenghua; Hur, Hor-Gil

2013-01-01

397

EXHAUST STACK RISES. STEEL FRAMEWORK FOR FAN HOUSE IN PLACE. ...  

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

EXHAUST STACK RISES. STEEL FRAMEWORK FOR FAN HOUSE IN PLACE. TRENCH IN FOREGROUND IS FOR DUCT THAT WILL CARRY COOLANT AIR FROM MTR'S THERMAL SHIELD. DUCT LINES UP WITH NORTH SIDE OF FAN HOUSE. AT RIGHT OF VIEW, NOTE TRENCH LEADING TO SOUTH SIDE OF FAN HOUSE; IT WILL BRING CONTAMINATED AIR FROM LABORATORY HOODS AND VENTS. CAMERA FACING EAST. INL NEGATIVE NO. 2764. Unknown Photographer, 6/29/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

398

HOT CELL BUILDING, TRA632. CONTEXTUAL VIEW ALONG WALLEYE AVENUE, CAMERA ...  

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

HOT CELL BUILDING, TRA-632. CONTEXTUAL VIEW ALONG WALLEYE AVENUE, CAMERA FACING EASTERLY. HOT CELL BUILDING IS AT CENTER LEFT OF VIEW; THE LOW-BAY PROJECTION WITH LADDER IS THE TEST TRAIN ASSEMBLY FACILITY, ADDED IN 1968. MTR BUILDING IS IN LEFT OF VIEW. HIGH-BAY BUILDING AT RIGHT IS THE ENGINEERING TEST REACTOR BUILDING, TRA-642. INL NEGATIVE NO. HD46-32-1. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

399

Rotary Wing Propulsion Specialists' Meeting, Williamsburg, VA, Nov. 13-15, 1990, Proceedings  

SciTech Connect

Topics presented include sound diffraction at a sharp trailing edge in a supersonic flow, the MTR390 turboshaft development program, progress report of the electrostatic engine monitoring system, some corrosion resistant magnesium alloys, handling severe inlet conditions in aircraft fuel pumps, and an over view of inlet protection systems for Army aircraft. Also presented are the advanced control system architecture for the T800 engine, an expert system to perform on-line controller restructuring for abrupt model changes, an enhanced APU for the H-60 series and Sh-2G helicopters, and a linear theory of the North Atlantic blocking during January 1979.

Not Available

1990-01-01

400

Manual therapies in myofascial trigger point treatment: a systematic review  

Microsoft Academic Search

Abstract Background,and,purpose: Myofascial pain syndrome,(MPS) is thought,by some,authors,the main,cause of headache,and,neck,pain. MPS is characterized,by Myofascial Trigger Points (MTrPs). However, there are not many controlled studies that have,analyzed,the effects of the manual,therapies,in their treatment.,The aim of this systematic,review,is to establish whether,manual,therapies,have,specific efficacy in the management of MPS, based on published studies. Methods: Data sources: PubMed (from 1975), Ovid MEDLINE (from 1975),

Juan Carlos Miangolarra Page; Avenida de Atenas

401

Role of mitochondrial ribosome-dependent translation in germline formation in Drosophila embryos.  

PubMed

In Drosophila, mitochondrially encoded ribosomal RNAs (mtrRNAs) form mitochondrial-type ribosomes on the polar granules, distinctive organelles of the germ plasm. Since a reduction in the amount of mtrRNA results in the failure of embryos to produce germline progenitors, or pole cells, it has been proposed that translation by mitochondrial-type ribosomes is required for germline formation. Here, we report that injection of kasugamycin (KA) and chloramphenicol (CH), inhibitors for prokaryotic-type translation, disrupted pole cell formation in early embryos. The number of mitochondrial-type ribosomes on polar granules was significantly decreased by KA treatment, as shown by electron microscopy. In contrast, ribosomes in the mitochondria and mitochondrial activity were unaffected by KA and CH. We further found that injection of KA and CH impairs production of Germ cell-less (Gcl) protein, which is required for pole cell formation. The above observations suggest that mitochondrial-type translation is required for pole cell formation, and Gcl is a probable candidate for the protein produced by this translation system. PMID:16125913

Amikura, Reiko; Sato, Kimihiro; Kobayashi, Satoru

2005-10-01

402

Outer-membrane cytochrome-independent reduction of extracellular electron acceptors in Shewanella oneidensis.  

PubMed

Dissimilatory metal reduction under pH-neutral conditions is dependent on an extended respiratory chain to the cell surface. The final reduction is catalysed by outer-membrane cytochromes that transfer respiratory electrons either directly to mineral surfaces and metal ions bound in larger organic complexes such as Fe(III) citrate, or indirectly using endogenous or exogenous electron shuttles such as humic acids and flavins. Consequently, a Shewanella oneidensis deletion mutant devoid of outer-membrane cytochromes is unable to reduce Fe(III) citrate or manganese oxide minerals and reduces humic acids at lower rates. Surprisingly, the phenotype of this quintuple deletion mutant can be rescued by a suppressor mutation, which enables metal or humic acid reduction without any outer-membrane cytochrome. Furthermore, the type II secretion system, essential for metal reduction in wild-type S. oneidensis, is not necessary for the suppressor strain. Using genome sequencing we identified two point mutations in key genes for metal reduction: mtrA and mtrB. These mutations are necessary and sufficient to account for the observed phenotype. This study is the first evidence for a catabolic, outer-membrane cytochrome-independent electron transport chain to ferric iron, manganese oxides and humic acid analogues operating in a mesophilic organism. Available bioinformatic data allow the hypothesis that outer-membrane cytochrome-independent electron transfer might resemble an evolutionary intermediate between ferrous iron-oxidizing and ferric iron-reducing micro-organisms. PMID:22493303

Bücking, Clemens; Piepenbrock, Annette; Kappler, Andreas; Gescher, Johannes

2012-08-01

403

High shear mixing granulation of ibuprofen and beta-cyclodextrin: effects of process variables on ibuprofen dissolution.  

PubMed

The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating solvents used (water, isopropanol, and 1:1 vol/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM were used for the granulation. The MTR study showed that the water significantly enhanced the beta-cyclodextrin (beta CD) binding tendency and the strength of liquid bridges formed between the particles, whereas the isopropanol/water mixture yielded more suitable agglomerates. Mini-HSM granulation with the isopropanol/water mixture (1:1 vol/vol) showed a reduction in the extent of torque value rise by increasing the impeller speed as a result of more breakdown of agglomerates than coalescence. In contrast, increasing the impeller speed of the Gral 25 resulted in higher torque readings, larger granule size, and consequently, slower dissolution. This was due to a remarkable rise in temperature during Gral granulation that reduced the isopropanol/water ratio in the granulating solvent as a result of evaporation and consequently increased the beta CD binding strength. In general, the HSM granulation retarded ibuprofen dissolution compared with the physical mixture because of densification and agglomeration. However, a successful HSM granulation scale-up was not achieved due to the difference in the solvent mixture's effect from 1 scale to the other. PMID:18181545

Ghorab, Mohamed K; Adeyeye, Moji Christianah

2007-01-01

404

T?-weighted MRI detects presymptomatic pathology in the SOD1 mouse model of ALS.  

PubMed

Neuroinflammation has been identified as a potential therapeutic target in amyotrophic lateral sclerosis (ALS), but relevant biomarkers are needed. The superoxide dismutase (SOD1)(G93A) transgenic mouse model of ALS offers a unique opportunity to study and potentially manipulate presymptomatic pathology. While T?-weighted magnetic resonance imaging (MRI) has been shown to be sensitive to pathologic changes at symptom onset, no earlier biomarkers were previously identified and the underlying histopathologic correlates remain uncertain. To address these issues, we used a multimodal MRI approach targeting structural (T?, T?, apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR)), vascular (gadolinium diethylene triamine pentaacetic acid), and endothelial (vascular cell adhesion molecule-microparticles of iron oxide) changes, together with histopathologic analysis from presymptomatic to symptomatic stages of disease. Presymptomatic changes in brainstem nuclei were evident on T?-weighted images from as early as 60 days (P<0.05). Histologic indices of vacuolation, astro- and microglial activation all correlated with T?-weighted changes. Significant reductions in ADC (P<0.01) and MTR (P<0.05) were found at 120 days in the same brainstem nuclei. No changes in T? relaxation, vascular permeability, or endothelial activation were found at any stage of disease. These findings suggest that T?-weighted MRI offers the strongest biomarker potential in this model, and that MRI has unique potential for noninvasive and longitudinal assessment of presymptomatically applied therapeutic and neuroprotective agents. PMID:24496176

Evans, Matthew C; Serres, Sébastien; Khrapitchev, Alexandre A; Stolp, Helen B; Anthony, Daniel C; Talbot, Kevin; Turner, Martin R; Sibson, Nicola R

2014-05-01

405

MRI predictors of cognitive outcome in early multiple sclerosis  

PubMed Central

Objective To determine MRI predictors for cognitive outcome in early relapsing remitting multiple sclerosis (MS) patients. Methods Inception Cohort. Forty-four patients recently diagnosed with clinically definite MS, were followed-up with clinical and cognitive evaluations at 1, 2, 5 and 7 years and underwent brain magnetic resonance imaging (MRI) including magnetization transfer (MT) imaging at baseline and two years. Cognitive evaluation was also performed in 56 matched healthy subjects at baseline. Cognitive testing included the Brief Repeatable Battery (BRB). Imaging parameters included lesion load, brain parenchyma fraction, ventricular fraction (VF), mean MT ratio (MTR) of lesion and normal appearing brain tissue (NABT) masks. Results At baseline, patients presented deficits of memory, attention and information processing speed (IPS). Over 2 years all MR parameters deteriorated significantly. Over 7 years, EDSS deteriorated significantly. Fifty percent of patients deteriorated on memory cognitive domain and 22.7% of patients on IPS domain. Seven-year change of memory scores was significantly associated with baseline diffuse brain damage (NABT MTR). IPS z score change over 7 years was correlated with baseline global atrophy (BPF), baseline diffuse brain damage and central brain atrophy (VF) change over 2 years. Conclusion The main predictors of cognitive changes over 7 years are baseline diffuse brain damage and progressive central brain atrophy over the 2 years after MS diagnosis. PMID:21444901

Deloire, Mathilde S. A.; Ruet, Aurelie; Hamel, Delphine; Bonnet, Melissa C.; Dousset, Vincent; Brochet, Bruno

2011-01-01

406

Radioisotopic data of sediment collected in Mobile and Bon Secour Bays, Alabama  

USGS Publications Warehouse

The focus of this study was to determine the extent of natural and (or) anthropogenic impacts on the sedimentary records of Mobile and Bon Secour Bays, Alabama during the last 150 years. These bays are unique in that anthropogenic activities are generally widespread and span both the eastern and western shorelines. However, there is a clear distinction in the types of human development and infrastructure between the western and eastern shorelines. These activities and the differences in land-use and -change influence the overall supply and remobilization of sediment to and within the bay. These factors could subsequently threaten the health and integrity of these environments and their ability to mitigate against long-term processes associated with climate change. In an attempt to characterize long-term accretion rates within the Mobile Bay Estuarine System (MBES), seven box cores were collected and analyzed for excess lead-210 (210Pbxs, the difference between total and supported 210Pb) and cesium-137 (137Cs) activities. The MBES receives sediment and water from the Alabama and Tombigbee River watersheds, which converge into the Mobile-Tensaw River (MTR) system just prior to discharging into Mobile Bay. Riverine discharge from the MTR system to the bay is second only to the Mississippi River discharge to the Gulf of Mexico for the conterminous United States.

Marot, Marci E.; Smith, Christopher G.

2012-01-01

407

Synthesis of oligodeoxyribonucleotide with aliphatic amino or phosphate group at the 5' end by the phosphotriester method on a polystyrene support.  

PubMed Central

Lipophilic protecting groups mTrNH(CH2)n X (mTr:monomethoxytrityl, X = NH,O,S, n = 2,3,4,6) were attached to the 5'-phosphoryl group of 3'-O-protected thymidine. When the diamine derivatives (X = NH2) were used, the time course of the stability of mTr groups on the amino group and the phosphoramidate linkage with 80% aq. AcOH was measured. It was found that the mTr group was removed from the amino group rapidly and that the phosphoramidate linkage was more stable. It's stability depended upon the length of the CH2 linker. Oligonucleotides with an aliphatic amino group at their 5'-ends were synthesized by the phosphotriester method on a polystyrene support using protected nucleotides with P-O or P-S linkages. In the case of product with a P-S linkage, 5'-O-phosphorylated nonadecanucleotide was also prepared by I2-H2O treatment. PMID:3627986

Tanaka, T; Sakata, T; Fujimoto, K; Ikehara, M

1987-01-01

408

T2-weighted MRI detects presymptomatic pathology in the SOD1 mouse model of ALS  

PubMed Central

Neuroinflammation has been identified as a potential therapeutic target in amyotrophic lateral sclerosis (ALS), but relevant biomarkers are needed. The superoxide dismutase (SOD1)G93A transgenic mouse model of ALS offers a unique opportunity to study and potentially manipulate presymptomatic pathology. While T2-weighted magnetic resonance imaging (MRI) has been shown to be sensitive to pathologic changes at symptom onset, no earlier biomarkers were previously identified and the underlying histopathologic correlates remain uncertain. To address these issues, we used a multimodal MRI approach targeting structural (T2, T1, apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR)), vascular (gadolinium diethylene triamine pentaacetic acid), and endothelial (vascular cell adhesion molecule–microparticles of iron oxide) changes, together with histopathologic analysis from presymptomatic to symptomatic stages of disease. Presymptomatic changes in brainstem nuclei were evident on T2-weighted images from as early as 60 days (P<0.05). Histologic indices of vacuolation, astro- and microglial activation all correlated with T2-weighted changes. Significant reductions in ADC (P<0.01) and MTR (P<0.05) were found at 120 days in the same brainstem nuclei. No changes in T1 relaxation, vascular permeability, or endothelial activation were found at any stage of disease. These findings suggest that T2-weighted MRI offers the strongest biomarker potential in this model, and that MRI has unique potential for noninvasive and longitudinal assessment of presymptomatically applied therapeutic and neuroprotective agents. PMID:24496176

Evans, Matthew C; Serres, Sebastien; Khrapitchev, Alexandre A; Stolp, Helen B; Anthony, Daniel C; Talbot, Kevin; Turner, Martin R; Sibson, Nicola R

2014-01-01

409

Structural features of mouse telomerase RNA are responsible for the lower activity of mouse telomerase versus human telomerase  

PubMed Central

Human and mouse telomerases show a high degree of similarity in both the protein and RNA components. Human telomerase is more active and more processive than the mouse telomerase. There are two key differences between hTR [human TR (telomerase RNA)] and mTR (mouse TR) structures. First, the mouse telomerase contains only 2 nt upstream of its template region, whereas the human telomerase contains 45 nt. Secondly, the template region of human telomerase contains a 5-nt alignment domain, whereas that of mouse has only 2 nt. We hypothesize that these differences are responsible for the differential telomerase activities. Mutations were made in both the hTR and mTR, changing the template length and the length of the RNA upstream of the template, and telomerase was reconstituted in vitro using mouse telomerase reverse transcriptase generated by in vitro translation. We show that the sequences upstream of the template region, with a potential to form a double-stranded helix (the P1 helix) as in hTR, increase telomerase activity. The longer alignment domain increases telomerase activity only in the context of the P1 helix. Thus the TR contributes to regulating the level of activity of mammalian telomerases. PMID:16669789

Garforth, Scott J.; Wu, Yan Yun; Prasad, Vinayaka R.

2006-01-01

410

Tri-snRNP-associated proteins interact with subunits of the TRAMP and nuclear exosome complexes, linking RNA decay and pre-mRNA splicing.  

PubMed

Nuclear RNA decay factors are involved in many different pathways including rRNA processing, snRNA and snoRNA biogenesis, pre-mRNA processing, and the rapid decay of cryptic intergenic transcripts. In contrast to its yeast counterpart, the mammalian nuclear decay machinery is largely uncharacterized. Here we report interactions of several putative components of the human nuclear RNA decay machinery, including the TRAMP complex protein Mtr4 and the nuclear exosome constituents PM/Scl-100 and PM/Scl-75, with components of the U4/U6.U5 tri-snRNP complex required for pre-mRNA splicing. The tri-snRNP component Prp31 interacts indirectly with Mtr4 and PM/Scl-100 in a manner that is dependent on the phosphorylation sites in the middle of the protein, while Prp3 and Prp4 interact with the nuclear decay complex independent of Prp31. Together our results suggest recruitment of the nuclear decay machinery to the spliceosome to ensure production of properly spliced mRNA. PMID:22336707

Nag, Anita; Steitz, Joan A

2012-03-01

411

Tri-snRNP-associated proteins interact with subunits of the TRAMP and nuclear exosome complexes, linking RNA decay and pre-mRNA splicing  

PubMed Central

Nuclear RNA decay factors are involved in many different pathways including rRNA processing, snRNA and snoRNA biogenesis, pre-mRNA processing, and the rapid decay of cryptic intergenic transcripts. In contrast to its yeast counterpart, the mammalian nuclear decay machinery is largely uncharacterized. Here we report interactions of several putative components of the human nuclear RNA decay machinery, including the TRAMP complex protein Mtr4 and the nuclear exosome constituents PM/Scl-100 and PM/Scl-75, with components of the U4/U6.U5 tri-snRNP complex required for pre-mRNA splicing. The tri-snRNP component Prp31 interacts indirectly with Mtr4 and PM/Scl-100 in a manner that is dependent on the phosphorylation sites in the middle of the protein, while Prp3 and Prp4 interact with the nuclear decay complex independent of Prp31. Together our results suggest recruitment of the nuclear decay machinery to the spliceosome to ensure production of properly spliced mRNA. PMID:22336707

Nag, Anita; Steitz, Joan A.

2012-01-01

412

Neutron beam studies for a medical therapy reactor.  

PubMed

A conceptual design of a Medical Therapy Reactor (MTR) for neutron capture therapy (NCT) has been performed at the Idaho National Engineering Laboratory (INEL). The initial emphasis of the conceptual design was toward the treatment of glioblastoma multiforme and other presently incurable cancers. The design goal of the facility is to provide routine patient treatments both in brief time intervals (approximately 10 minutes) and inexpensively. The conceptual study has shown this goal to be achievable by locating an MTR at a major medical facility. This paper addresses the next step in the conceptual design process: a guide to the optimization of the epithermal-neutron filter and collimator assembly for the treatment of brain tumors. The current scope includes the sensitivity of the treatment beam to variations in filter length, gamma shield length, and collimator lengths as well as exit beam aperture size. The study shows the areas which can provide the greatest latitude in improving beam intensity and quality. Suggestions are given for future areas of optimization of beam filtering and collimation. PMID:2268234

Neuman, W A

1990-01-01

413

Bell pepper endornavirus: molecular and biological properties, and occurrence in the genus Capsicum.  

PubMed

Bell peppers (Capsicum annuum) harbour a large dsRNA virus. The linear genome (14.7 kbp) of two isolates from Japanese and USA bell pepper cultivars were completely sequenced and compared. They shared extensive sequence identity and contained a single, long ORF encoding a 4815 aa protein. This polyprotein contained conserved motifs of putative viral methyltransferase (MTR), helicase 1 (Hel-1), UDP-glycosyltransferase and RNA-dependent RNA polymerase. This unique arrangement of conserved domains has not been reported in any of the known endornaviruses. Hence this virus, for which the name Bell pepper endornavirus (BPEV) is proposed, is a distinct species in the genus Endornavirus (family Endornaviridae). The BPEV-encoded polyprotein contains a cysteine-rich region between the MTR and Hel-1 domains, with conserved CXCC motifs shared among several endornaviruses, suggesting an additional functional domain. In agreement with general endornavirus features, BPEV contains a nick in the positive-strand RNA molecule. The virus was detected in all bell pepper cultivars tested and transmitted through seed but not by graft inoculations. Analysis of dsRNA patterns and RT-PCR using degenerate primers revealed putative variants of BPEV, or closely related species, infecting other C. annuum genotypes and three other Capsicum species (C. baccatum, C. chinense and C. frutescens). PMID:21775578

Okada, Ryo; Kiyota, Eri; Sabanadzovic, Sead; Moriyama, Hiromitsu; Fukuhara, Toshiyuki; Saha, Prasenjit; Roossinck, Marilyn J; Severin, Ake; Valverde, Rodrigo A

2011-11-01

414

The Molecular Architecture of the TRAMP Complex Reveals the Organization and Interplay of Its Two Catalytic Activities.  

PubMed

The TRAMP complex is involved in the nuclear surveillance and turnover of noncoding RNAs and intergenic transcripts. TRAMP is associated with the nuclear exosome and consists of a poly(A)polymerase subcomplex (Trf4-Air2) and a helicase (Mtr4). We found that N-terminal low-complexity regions of Trf4 and Air2 bind Mtr4 in a cooperative manner. The 2.4 Å resolution crystal structure of the corresponding ternary complex reveals how Trf4 and Air2 wrap around the DExH core of the helicase. Structure-based mutations on the DExH core impair binding to Trf4 and Air2, and also to Trf5 and Air1. The combination of structural, biochemical, and biophysical data suggests that the poly(A)polymerase core of Trf4-Air2 is positioned below the base of the helicase, where the unwound 3' end of an RNA substrate is expected to emerge. The results reveal conceptual similarities between the two major regulators of the exosome, the nuclear TRAMP and cytoplasmic Ski complexes. PMID:25175027

Falk, Sebastian; Weir, John R; Hentschel, Jendrik; Reichelt, Peter; Bonneau, Fabien; Conti, Elena

2014-09-18

415

Clinical implication of latent myofascial trigger point.  

PubMed

Myofascial trigger points (MTrPs) are hyperirritable points located within a taut band of skeletal muscle or fascia, which cause referred pain, local tenderness and autonomic changes when compressed. There are fundamental differences between the effects produced by the two basic types of MTrPs (active and latent). Active trigger points (ATrPs) usually produce referred pain and tenderness. In contrast, latent trigger points (LTrPs) are foci of hyperirritability in a taut band of muscle, which are clinically associated with a local twitch response, tenderness and/or referred pain upon manual examination. LTrPs may be found in many pain-free skeletal muscles and may be "activated" and converted to ATrPs by continuous detrimental stimuli. ATrPs can be inactivated by different treatment strategies; however, they never fully disappear but rather convert to the latent form. Therefore, the diagnosis and treatment of LTrPs is important. This review highlights the clinical implication of LTrPs. PMID:23801006

Celik, Derya; Mutlu, Ebru Kaya

2013-08-01

416

A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice  

PubMed Central

The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations affect telomere function, we generated mice with the equivalent of the TIN2 K280E DC allele (TIN2DC) by gene targeting. Whereas homozygous TIN2DC/DC mice were not viable, first-generation TIN2+/DC mice were healthy and fertile. In the second and third generations, the TIN2+/DC mice developed mild pancytopenia, consistent with hematopoietic dysfunction in DC, as well as diminished fecundity. Bone marrow telomeres of TIN2+/DC mice shortened over the generations, and immortalized TIN2+/DC mouse embryonic fibroblasts (MEFs) showed telomere shortening with proliferation. Unexpectedly, telomere shortening was accelerated in TIN2+/DC mTR?/? mice and MEFs compared with TIN2+/+ mTR?/? controls, establishing that the TIN2DC telomere maintenance defect was not solely due to diminished telomerase action. The TIN2DC allele induced mild ATR kinase signaling at telomeres and a fragile telomere phenotype, suggestive of telomere replication problems. These data suggest that this TIN2-DC mutation could induce telomeric dysfunction phenotypes in telomerase-negative somatic cells and tissues that further exacerbate the telomere maintenance problems in telomerase-positive stem cell compartments. PMID:24449270

Frescas, David; de Lange, Titia

2014-01-01

417

Vascular architecture in shoots of early divergent vascular plants, Lycopodium clavatum and Lycopodium annotinum.  

PubMed

Lycopodium represents a phylogenetically distinct clade of basal vascular plants with anatomical characters that have no parallel in other lineages. Thus, knowledge of lycopod structure and development may reveal important information about the common ancestors of all vascular plants. Here we report the unique architecture of the conducting system in Lycopodium annotinum and Lycopodium clavatum. Based on multiple series of anatomical sections, we reconstructed spatial relationships between microphylls and the stelar system. Analysis revealed that protoxylem ribs (PXR) were vertical, regardless of type of phyllotaxis, and their numbers were variable. Microphyll traces (MTr) were randomly distributed between ribs, resulting in the absence of defined sympodia and varied lengths of MTr. Dichotomous branching contributed to additional features, for example occurrence of mesarch protoxylem, affecting stele structure and PXR numbers. Our data showed limited interrelationships between lycopod vasculature and microphyll phyllotaxis. This may suggest that both systems developed independently, then evolved together to form the integrated supply system. Thus vasculature in extant lycophytes may be less functionally efficient than in seed plants, where consistent leaf-trace lengths guarantee predictable energy utilization during ontogeny. Differences may result from the phylogenetically different origin of microphylls, and the level of vascular complexity. PMID:17504461

Gola, Edyta M; Jernstedt, Judith A; Zagórska-Marek, Beata

2007-01-01

418

An endogenous artificial microRNA system for unraveling the function of root endosymbioses related genes in Medicago truncatula  

PubMed Central

Background Legumes have the unique capacity to undergo two important root endosymbioses: the root nodule symbiosis and the arbuscular mycorrhizal symbiosis. Medicago truncatula is widely used to unravel the functions of genes during these root symbioses. Here we describe the development of an artificial microRNA (amiR)-mediated gene silencing system for M. truncatula roots. Results The endogenous microRNA (miR) mtr-miR159b was selected as a backbone molecule for driving amiR expression. Heterologous expression of mtr-miR159b-amiR constructs in tobacco showed that the backbone is functional and mediates an efficient gene silencing. amiR-mediated silencing of a visible marker was also effective after root transformation of M. truncatula constitutively expressing the visible marker. Most importantly, we applied the novel amiR system to shed light on the function of a putative transcription factor, MtErf1, which was strongly induced in arbuscule-containing cells during mycorrhizal symbiosis. MtPt4 promoter driven amiR-silencing led to strongly decreased transcript levels and deformed, non-fully truncated arbuscules indicating that MtErf1 is required for arbuscule development. Conclusions The endogenous amiR system demonstrated here presents a novel and highly efficient tool to unravel gene functions during root endosymbioses. PMID:23679580

2013-01-01

419

Pronounced and Extensive Microtubule Defects in a Saccharomyces cerevisiae DIS3 Mutant  

PubMed Central

Subunits of the RNA processing exosome assemble into structurally distinct protein complexes that function in disparate cellular compartments and RNA metabolic pathways. Here, in a genetic, cell biological, and transcriptomic analysis, we examine the role of Dis3 – an essential polypeptide with endo- and 3’ to 5’ exo-ribonuclease activity – in cell cycle progression. We present several lines of evidence that perturbation of DIS3 affects microtubule (MT) localization and structure in Saccharomyces cerevisiae. Cells with a DIS3 mutant: (i) accumulate anaphase and pre-anaphase mitotic spindles; (ii) exhibit spindles that are mis-oriented and displaced from the bud neck; (iii) harbor elongated spindle-associated astral MTs; (iv) have an increased G1 astral MT length and number; and (v) are hypersensitive to MT poisons. Mutations in the core exosome genes RRP4 and MTR3 and the exosome cofactor gene MTR4 – but not other exosome subunit gene mutants – also elicit MT phenotypes. RNA deep sequencing analysis (RNA-seq) shows broad changes in the levels of cell cycle- and MT-related transcripts in mutant strains. Collectively, the data presented in this study suggests an evolutionarily conserved role for Dis3 in linking RNA metabolism, MTs, and cell cycle progression. PMID:21919057

Smith, Sarah B.; Kiss, Daniel L.; Turk, Edward; Tartakoff, Alan M.; Andrulis, Erik D.

2012-01-01

420

Three-dimensional Computational Fluid Dynamics (CFD) modeling of dry spent nuclear fuel storage canisters  

SciTech Connect

One of the interim storage configurations being considered for aluminum-clad foreign research reactor fuel, such as the Material and Testing Reactor (MTR) design, is in a dry storage facility. To support design studies of storage options, a computational and experimental program was conducted at the Savannah River Site (SRS). The objective was to develop computational fluid dynamics (CFD) models which would be benchmarked using data obtained from a full scale heat transfer experiment conducted in the SRS Experimental Thermal Fluids Laboratory. The current work documents the CFD approach and presents comparison of results with experimental data. CFDS-FLOW3D (version 3.3) CFD code has been used to model the 3-dimensional convective velocity and temperature distributions within a single dry storage canister of MTR fuel elements. For the present analysis, the Boussinesq approximation was used for the consideration of buoyancy-driven natural convection. Comparison of the CFD code can be used to predict reasonably accurate flow and thermal behavior of a typical foreign research reactor fuel stored in a dry storage facility.

Lee, S.Y.

1997-06-01

421

Nuclear data production, calculation and measurement: a global overview of the gamma heating issue  

NASA Astrophysics Data System (ADS)

The gamma heating evaluation in different materials found in current and future generations of nuclear reactor (EPRTM, GENIV, MTR-JHR), is becoming an important issue especially for the design of many devices (control rod, heavy reflector, in-core & out-core experiments…). This paper deals with the works started since 2009 in the Reactor Studies Department of CEA Cadarache in ordre to answer to several problematic which have been identified as well for nuclear data production and calculation as for experimental measurement methods. The selected subjects are: Development of a Monte Carlo code (FIFRELIN) to simulate the prompt fission gamma emission which represents the major part of the gamma heating production inside the core Production and qualification of new evaluations of nuclear data espec