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Sample records for a1298c mtr a2756g

  1. Methionine Synthase A2756G Polymorphism and Risk of Colorectal Adenoma and Cancer: Evidence Based on 27 Studies

    PubMed Central

    Jiang, Xun; Lu, Lie-sheng

    2013-01-01

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

  2. Lack of association between methionine synthase A2756G polymorphism and digestive system cancer risk: evidence from 3,9327 subjects.

    PubMed

    Zhao, Yuan; Chen, Zixian; Ma, Yushui; Xia, Qing; Zhang, Feng; Fu, Da; Wang, Xiao-Feng

    2013-01-01

    Polymorphisms in genes involved in the metabolism of folate and methyl groups have been implicated with risk of digestive system cancer. Methionine synthase (MTR) plays a central role in folate metabolism, thereby affecting DNA methylation. The association between A2756G polymorphism (rs1805087) in MTR and digestive system cancer susceptibility was inconsistent in previous studies. To investigate this inconsistency, we performed this meta-analysis. Databases including Pubmed, EMBASE, ISI Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression. A total of 29 articles with 15,368 patients and 23,959 controls were included. We found no association between MTR A2756G polymorphism and digestive system cancer in overall population (G allele: OR = 1.03, 95% CI = 0.98-1.09, P = 0.25; dominant model: OR = 1.03, 95% CI = 0.97-1.10, P = 0.33; recessive model: OR = 1.02, 95% CI = 0.89-1.17, P = 0.79). In the stratified analyses according to cancer type, sample size and genotyping method, no evidence of any gene-disease association was obtained in almost all genetic models. However, marginal significant associations were found for East Asians and hospital-based studies. This meta-analysis suggests that there is no significant association between the MTR A2756G polymorphism and digestive system cancer risk.

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

    PubMed

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

    2008-08-01

    To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

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

    USDA-ARS?s Scientific Manuscript database

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

  5. Methylenetetrahydrofolate reductase A1298C genetic variant & risk of schizophrenia: A meta-analysis

    PubMed Central

    Rai, Vandana; Yadav, Upendra; Kumar, Pradeep; Yadav, Sushil K.; Gupta, Sanjay

    2017-01-01

    Background & objectives: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia. Methods: PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure. Results: The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04). Interpretation & conclusions: MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia. PMID:28862175

  6. Association between MTHFR A1298C polymorphism and male infertility: A meta-analysis.

    PubMed

    Zhang, Qiang; Yin, Guo-Ying; Liu, Juan; Liang, Yue; Li, Yao-Yan; Zhao, Jing-Yu; Zhang, Li-Wen; Wang, Bai-Qi; Tang, Nai-Jun

    2017-04-01

    There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility. However, the results obtained were inconsistent. Therefore, we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th, 2016. A total of 20 studies with 4293 cases and 4507 controls were included. An odds ratio (OR) and a 95% confidence interval (95% CI) were calculated to assess the strength of the association. A cumulative meta-analysis, sensitivity analysis and assessment of the publication bias were also performed in this study. The results showed that in the overall analysis, the association between the MTHFR A1298C polymorphism and male infertility was not significant. A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model: OR=1.20, 95% CI=1.01-1.44, P=0.994; the dominant model: OR=1.23, 95% CI=1.04-1.45, P=0.996; and the allele model: OR=1.20, 95% CI=1.04-1.39, P=0.985) but not in the Caucasian population. In the stratified analyses, no significant association was observed between the different types of male infertility. This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility, especially in the Asian population.

  7. Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.

    PubMed

    Rai, Vandana; Yadav, Upendra; Kumar, Pradeep; Yadav, Sushil K; Gupta, Sanjay

    2017-04-01

    Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia. PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure. The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04). MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia.

  8. Does the MTHFR A1298C Polymorphism Modulate the Cardiorespiratory Response to Training?

    PubMed

    Cięszczyk, Paweł; Zarębska, Aleksandra; Jastrzębski, Zbigniew; Sawczyn, Michał; Kozakiewicz-Drobnik, Izabela; Leońska-Duniec, Agata; Kaczmarczyk, Mariusz; Maciejewska-Skrendo, Agnieszka; Żmijewski, Piotr; Trybek, Grzegorz; Smółka, Wojciech; Pilch, Jan; Leźnicka, Katarzyna; Lulińska-Kuklik, Ewelina; Sawczuk, Marek; Massidda, Myosotis

    2016-12-01

    The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphic variant is a candidate to explain the individual differences in trainability and response to exercise training. Therefore, the aim of the study was to verify whether the A1298C polymorphism influenced the aerobic and anaerobic performance as well as body and mass composition in young Polish women following low-high impact aerobic exercise training. Two hundred and one women aged 21 ± 1 years (range 19-24) were included in the study. All of them completed a 12-week exercise training program and were measured for selected somatic features, aerobic capacity and cardiorespiratory fitness indices as well as peak anaerobic power and anaerobic capacity, before and after the intervention. A mixed 2 x 2 ANOVA for 20 dependent variables grouped in three categories was conducted. No significant interaction of the genotype with training for body mass and body composition variables was observed. Although, there were three significant genotype x training interactions for maximal oxygen uptake variables, regardless of body mass i.e.: for VO2max (p < 0.05), HRmax (p < 0.0001) and HRAT/HRmax (p < 0.0001). Significantly greater improvement in VO2max was gained by the CC+AC group compared to the AA genotype group. The present results support the hypothesis that individual differences in trainability are at least in part determined by the genetic component and MTHFR A1298C seems to be one of the many polymorphisms involved.

  9. Combined genotype and haplotype distributions of MTHFR C677T and A1298C polymorphisms

    PubMed Central

    Fan, Shujun; Yang, Boyi; Zhi, Xueyuan; Wang, Yanxun; Zheng, Quanmei; Sun, Guifan

    2016-01-01

    Abstract Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are, independently and/or in combination, associated with many disorders. However, data on the combined genotype and haplotype distributions of the 2 polymorphisms in Chinese population were limited. We recruited 13,473 adult women from 9 Chinese provinces, collected buccal cell samples, and determined genotypes, to estimate the combined genotype and haplotype distributions of the MTHFR C677T and A1298C polymorphisms. In the total sample, the 6 common combined genotypes were CT/AA (29.5%), TT/AA (21.9%), CC/AA (15.4%), CC/AC (14.9%), CT/AC (13.7%), and CC/CC (3.4%); the 3 frequent haplotypes were 677T-1298A (43.6%), 677C-1298A (37.9%), and 677C-1298C (17.6%). Importantly, we observed that there were 51 (0.4%) individuals with the CT/CC genotype, 92 (0.7%) with the TT/AC genotype, 17 (0.1%) with the TT/CC genotype, and that the frequency of the 677T-1298C haplotype was 0.9%. In addition, the prevalence of some combined genotypes and haplotypes varied among populations residing in different areas and even showed apparent geographical gradients. Further linkage disequilibrium analysis showed that the D’ and r2 values were 0.883 and 0.143, respectively. In summary, the findings of our study provide further strong evidence that the MTHFR C677T and A1298C polymorphisms are usually in trans and occasionally in cis configurations. The frequencies of mutant genotype combinations were relatively higher in Chinese population than other populations, and showed geographical variations. These baseline data would be useful for future related studies and for developing health management programs. PMID:27902594

  10. Synergistic effect of methyltetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphism as risk modifiers of pediatric acute lymphoblastic leukemia.

    PubMed

    Kamel, Azza M; Moussa, Heba S; Ebid, Gamal T; Bu, Rong R; Bhatia, Kishor G

    2007-06-01

    ALL is the most common pediatric cancer. The causes of the majority of pediatric acute leukemia are unknown and are likely to involve an interaction between genetic and environmental factors. Therefore, unfavourable gene-environmental interactions might be involved in the genesis of ALL. The aim of this work was to evaluate, in a case-control study, whether the common polymorphisms in 5, 10-methylenetetrahydrofolate reductase (MTHFR) namely (C677T and A1298C) and methionine synthase (MS) (A2756G) genes may play a role in altering susceptibility to pediatric ALL as individual genes and in combination. DNA of 88 ALL patients (age < or = 18 years) and 311 healthy control subjects was analyzed for the polymorphisms of MTHFR and MS genes using PCR-RFLP method. The frequencies of the wild types of MTHFR 677CC, MTHFR 1298AA and MS 2756AA, the homozygous genotypes of MTHFR 677TT, MTHFR 1298CC and MS 2756GG and heterozygous genotypes of MTHFR 677CT and MS 2756AG showed no statistically significant differences between patients and controls. The frequency of the MTHFR 1298AC heterozygous genotype was 25% among patients compared to 45.0% among controls; the difference was found to be statistically significant (p value =0.001, O.R=0.382 & 95% C.I=0.222-0.658). The frequency of the MTHFR1298AC heterozygous genotype plus 1298CC homozygous genotype was 34% among patients compared to 54.3% among controls and the difference was statistically significant (p value =0.001). A synergistic effect of 677CT and1298AC (CTAC) was observed, (p value=0.002) with 3.65 fold protection (OR 0.273 & 95% C.I=0.155-0.9) compared to 2.6 folds for MTHFR 1298AC alone. This protective effect of CTAC polymorphism was abolished when combined with MS 2756AA or AG. The present study provided further evidence for the protective role of MTHFR 1298AC mutant alleles in acute lymphoblastic leukemia in children (2.6 fold protection). This suggests that folate and methionine metabolism play an important role in the

  11. A literature review of MTHFR (C677T and A1298C polymorphisms) and cancer risk.

    PubMed

    Izmirli, Muzeyyen

    2013-01-01

    5,10-Methlenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folate metabolism. This enzyme is mapped on chromosome 1, which is located at the end of the short arm (1p36.3). The C677T and A1298C are MTHFR polymorphisms that decrease in vitro MTHFR enzyme activity. Folate metabolism plays a key role in cell metabolism. These reactions are associated with purine-pyrimidine synthesis: DNA, RNA, and protein methylation. Polymorphism is also a factor in biodiversity, and be affected by ethnic heritage and geographic locale. In the case of unknown outcomes, not only should all geographical regions be investigated to ascertain biodiversity, but all populations as well to fully understand the variations in the effect. PUBMED was searched from January 2006 to December 2011 to develop an investigatory pursuit strategy. MTHFR, cancer, C677T, A1298C, and polymorphisms were key words used to focus the search. The literature review included all published relevant cancer types and MTHFR polymorphisms for that 5 years period. All selected polymorphisms data for cancer types was listed in tables for easy access and retrieval.

  12. Association between the MTHFR A1298C polymorphism and risk of cancer: evidence from 265 case-control studies.

    PubMed

    Zhu, Xin-Li; Liu, Zhi-Zhong; Yan, Sen-Xiang; Wang, Wei; Chang, Rui-Xia; Zhang, Chun-Yan; Guo, Yan

    2016-02-01

    Many molecular, epidemiological studies have been performed to explore the association between MTHFR A1298C polymorphism and cancer risk. However, the results were inconsistent or even contradictory. Hence, we performed a meta-analysis to investigate the association between cancer risk and MTHFR A1298C (81,040 cases and 114,975 controls from 265 studies) polymorphism. Overall, significant association was observed between MTHFR A1298C polymorphism and cancer risk when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased cervical cancer (dominant model: OR 1.46, 95 % CI 1.13-1.90; AC vs. AA: OR 1.48, 95 % CI 1.13-1.92) and lymphoma (dominant model: OR 1.22, 95 % CI 1.04-1.44; recessive model: OR 1.66, 95 % CI 1.15-2.39; CC vs. AA: OR 1.75, 95 % CI 1.21-2.53) risk were observed in Asians, and significantly decreased colorectal cancer risk was found in Asians (recessive model: OR 0.75, 95 % CI 0.59-0.96; CC vs. AA: OR 0.77, 95 % CI 0.60-1.00). In summary, this meta-analysis suggests that MTHFR A1298C polymorphism is associated with increased cervical cancer and lymphoma risk in Asians, and MTHFR A1298C polymorphism is associated with decreased colorectal cancer risk in Asians. Moreover, this meta-analysis also points out the importance of new studies, such as oral cancer and chronic myeloid leukemia, because they had high heterogeneity in this meta-analysis (I (2) > 75 %).

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

    PubMed

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

    2014-06-01

    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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Association of Methylenetetrahydrofolate Reductase C677T and A1298C Gene Polymorphisms With Recurrent Pregnancy Loss in Syrian Women.

    PubMed

    Al-Achkar, Walid; Wafa, Abdulsamad; Ammar, Samer; Moassass, Faten; Jarjour, Rami A

    2017-09-01

    C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene was a risk factor for recurrent pregnancy loss (RPL), but few studies have confirmed a possible role of MTHFR A1298C polymorphism in RPL risk. This study was carried out to determine the influence of the MTHFR gene polymorphisms in RPL Syrian women. A case-control study was performed on 2 groups (106 healthy and 100 RPL women). The frequency of the MTHFR gene polymorphisms was determined by polymerase chain reaction based on restriction fragment length gene polymorphism. In the RPL group, the genotype frequencies of MTHFR C677T were CC (41%), CT (41%), and TT (18%), and in the control group, the frequencies were CC (62.2%), CT (36.7%), and TT (1%). Statistical analysis showed a homozygous TT genotype and T allele were significantly different in the RPL group ( P = .000003 and P = .000019, respectively). The genotype frequencies of MTHFR A1298C were AA (53%), AC (44%), and CC (8%) in the RPL group, whereas in the control group, these were AA (61.3%), AC (37.8%), and CC (1%). A significant difference in the CC genotype and C allelic frequencies in the RPL women was observed ( P = .014 and P = .064, respectively). The patients having compound heterozygous (677 CT/1298AC) were associated with an estimated 4.86-fold increase in risk of pregnancy loss compared to individuals with a wild type ( P = .012). Our findings indicate that RPL women with homozygous genotype for (C677T and A1298C) either alone or compound heterozygous genotypes have a high risk of pregnancy loss in Syrian women.

  17. Plasma homocysteine levels, methylene tetrahydrofolate reductase A1298C gene polymorphism and risk of retinal vein thrombosis.

    PubMed

    Ghaznavi, Habib; Soheili, Zahra; Samiei, Shahram; Soltanpour, Mohammad Soleiman

    2016-09-01

    There are limited data regarding the role of methylene tetrahydrofolate reductase (MTHFR) A1298C polymorphism and hyperhomocysteinemia as risk factors for retinal vein thrombosis (RVT) in Iranians. This study aimed to examine a possible association between fasting plasma total homocysteine (tHcy) levels, MTHFR A1298C polymorphism and RVT development in Iranian patients. Our study population consisted of 73 patients with a diagnosis of RVT (52.7 ± 16.2 years) and 73 age and sex-matched healthy controls (49.1 ± 14.6 years). Genotyping for the MTHFR A1298Cpolymorphism was conducted by PCR-RFLP technique and plasma tHcy levels were measured by an enzyme immunoassay method. Fasting plasma tHcy levels were 20.29 ± 8.5 μmol/l in RVT patients and 10.9 ± 3.1 μmol/l in control subjects. The number of cases with abnormal tHcy values (hyperhomocysteinemia) was significantly higher in the RVT patients than control subjects (P = 0.0001). The prevalence of MTHFR 1298CC homozygote genotype was similar in RVT patients and controls (17.8 vs.15.1%, P = 0.45). There were no significant differences in genotype distribution of MTHFR A1298C polymorphism between males and females in both RVT patients and controls (P > 0.05). The frequency of the 1298C allele was 39.1 and 35.6% in patients and controls, respectively, and did not differ significantly between them (P = 0.23). Moreover, heterozygote and homozygote genotypes in the RVT patients had significantly higher abnormal tHcy values than corresponding genotypes in control subjects (P < 0.001). Our study demonstrated that hyperhomocysteinemia but not homozygosity for MTHFR A1298C polymorphism is a significant risk factor for RVT in the Iranian population.

  18. Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and susceptibility to acute lymphoblastic leukemia in a cohort of Egyptian children.

    PubMed

    Mosaad, Youssef M; Abousamra, Nashwa K; Elashery, Rasha; Fawzy, Iman M; Eldein, Omar A Sharaf; Sherief, Doaa M; El Azab, Hend M M

    2015-01-01

    This case-control study was planned to investigate the possible role of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as a risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children. Typing of MTHFR C677T and A1298C polymorphisms was done using restriction fragment length polymorphism (RFLP) for 100 children with ALL and 100 age- and sex-matched healthy controls. No significant differences were found between patients with ALL and controls for the frequency of MTHFR C677T and A1298C alleles, genotypes, combined genotypes or haplotypes. The C677T and A1298C genotype frequency was different from that in Korean and Chinese populations (p < 0.5) and was similar to that in British, French-Canadian and German-Caucasian populations (p > 0.5). Our findings suggest that MTHFR C677T and A1298C polymorphisms are unlikely to affect the development of childhood ALL in an Egyptian population from Delta.

  19. Methylenetetrahydrofolate Reductase Gene Polymorphisms (C677T and A1298C) and Hemorrhagic Stroke in Moroccan Patients.

    PubMed

    Abidi, Omar; Haissam, Mohammed; Nahili, Halima; El Azhari, Abdessamad; Hilmani, Said; Barakat, Abdelhamid

    2018-07-01

    The number of deaths from hemorrhagic strokes is about twice as high than the number of deaths from ischemic strokes. Genetic risk assessment could play important roles in preventive and therapeutic strategies. The present study was aimed to evaluate whether the MTHFR gene polymorphisms could increase the risk of cerebral hemorrhage in Moroccan patients. A total of 113 patients with hemorrhagic stroke and 323 healthy controls were included in this case-control study. The C677T (rs1801133) and A1298C (rs1801131) MTHFR gene polymorphisms were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in all patients and controls. The genotype and allele frequencies were compared between groups using appropriate statistical analyses. Both groups, patients and controls, were in accordance with the Hardy-Weinberg Equilibrium. For the C677T polymorphism, the frequencies of the CC, CT, and TT genotypes were 50.44% versus 46.13%, 39.82% versus 43.03, and 9.73% versus 10.84% in controls versus patients, respectively, whereas for the A1298C polymorphism, the frequencies of the AA, AC, and CC genotypes were 56.64% versus 57.59%, 40.71% versus 37.15, and 2.65% versus 5.26% in controls versus patients, respectively. No statistically significant difference has been proved between patients and controls frequencies (P >.05) for all additive, recessive, and dominant models. Additional analyses including genotypes combination, allelic frequencies, and hemorrhagic stroke patient subtypes did not show any statistically significant difference between controls and patients/subgroup patients. Our findings suggested no association between MTHFR gene polymorphisms and susceptibility to hemorrhagic strokes in Moroccan patients. Further investigations should be conducted to elucidate the roles of other gene variants in the pathogenesis of this condition. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation.

    PubMed

    Yang, Yi; Luo, Yunyao; Yuan, Jing; Tang, Yidan; Xiong, Lang; Xu, MangMang; Rao, XuDong; Liu, Hao

    2016-06-01

    Numerous studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss (RPL); however, the results remain controversial. The aim of this study is to drive a more precise estimation of association between MTHFR gene polymorphisms and risk of RPL. We searched PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and RPL risk. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in the homozygous model, heterozygous model, dominant model, recessive model and an additive model. The software STATA (Version 13.0) was used for statistical analysis. Overall, 57 articles were included in the final meta-analysis. In maternal group the MTHFR C677T polymorphism showed pooled odds ratios for the homozygous comparison [OR = 2.285, 95 % CI (1.702, 3.067)] and the MTHFR A1298C polymorphism showed pooled odds ratios for recessive model [OR = 1.594, 95 % CI (1.136, 2.238)]. In fetal group the MTHFR C677T polymorphism showed pooled odds ratios for dominant model [OR = 1.037, 95 % CI (0.567, 1.894)] and the MTHFR A1298C polymorphism showed pooled odds ratios for dominant model [OR = 1.495, 95 % CI (1.102, 2.026)]. In summary, the results of our meta-analysis indicate that maternal and paternal MTHFR gene C677T and A1298C polymorphisms are associated with RPL. We also observed a significant association between fetal MTHFR A1298C polymorphism and RPL but not C677T.

  1. Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma.

    PubMed

    Kantar, Mehmet; Kosova, Buket; Cetingul, Nazan; Gumus, Sevinc; Toroslu, Ertug; Zafer, Nur; Topcuoglu, Nejat; Aksoylar, Serap; Cinar, Mehtap; Tetik, Asli; Eroglu, Zuhal

    2009-06-01

    This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24 h (p = 0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48 h (p = 0.02), and had more grade III/IV anemia (p = 0.02), thrombocytopenia (p = 0.0001), elevated AST levels (p = 0.04) and frequent febrile neutropenic episodes (p = 0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.

  2. Association of the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) polymorphisms in Korean patients with adult acute lymphoblastic leukemia.

    PubMed

    Oh, Doyeun; Kim, Nam Keun; Jang, Moon Ju; Kim, Hugh Chul; Lee, Jae Hoon; Lee, Jung Ae; Ahn, Myung Ju; Kim, Chul Soo; Kim, Heung Sik; Park, Seonyang; Chio, Hyun Sook; Min, Yoo Hong

    2007-01-01

    Methylenetetrahydrofolate reductase (MTHFR) plays a central role in converting folate to methyl donor for DNA methylation. Because MTHFR is a key enzyme in folate metabolism, changes in its activity resulting from polymorphisms in the MTHFR gene could modify the susceptibility to cancer. Recently, the C677T and A1298C mutations of MTHFR were discovered to be associated with susceptibility in acute lymphoblastic leukemia (ALL). The association between MTHFR polymorphisms and susceptibility and clinical outcome in ALL was studied in 118 adult ALL patients and matched healthy controls (n =427). DNA samples taken from patients with ALL and controls were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays to detect the MTHFR C677T and A1298C mutations. No significant difference was found in the development of adult ALL among those with different MTHFR genotypes of the C677T or A1298C polymorphisms. However, the MTHFR 677CT+TT genotype showed a tendency to be associated with adult ALL [crude odds ratio (OR), 0.67; 95% confidence interval (CI), 0.44-1.02; adjusted OR, 0.74 95% CI, 0.47-1.14]. The MTHFR C677T and A1298C polymorphisms are not significant risk factors in adult acute leukemia in the Korean population.

  3. Association between C677T and A1298C polymorphisms of the MTHFR gene and risk of male infertility: a meta-analysis.

    PubMed

    Yang, Y; Luo, Y Y; Wu, S; Tang, Y D; Rao, X D; Xiong, L; Tan, M; Deng, M Z; Liu, H

    2016-04-26

    Published studies on the association between the C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene and male infertility risk are controversial. To obtain a more precise evaluation, we performed a meta-analysis based on published case-control studies. We conducted an electronic search of PubMed, EMBASE, the Cochrane Library, the Web of Science, and the China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and male infertility risk. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were used to assess the strength of association in homozygote, heterozygote, dominant, recessive, and additive models. Statistical heterogeneity, test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 13.0). Overall, 21 studies of C677T (4505 cases and 4024 controls) and 13 studies of A1298C (2785 cases and 3094 controls) were included in this meta-analysis. For C677T, the homozygote comparison results were OR = 1.629, 95%CI (1.215- 2.184), and the recessive model results were OR = 1.462 (1.155- 1.850). For A1298C, the homozygote comparison results were OR = 1.289 (1.029-1.616), and the recessive model results were OR = 1.288 (1.034-1.604). In conclusion, the current meta-analysis showed that the MTHFR C677T polymorphism was associated with a significantly increased male infertility risk in the Asian and overall populations, but not in the Caucasian population, and there was a significant association between the A1298C polymorphism and male infertility risk in the Asian, Caucasian, and overall groups.

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

    PubMed

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

    2012-04-01

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

  5. A meta-analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children.

    PubMed

    Yan, Jingrong; Yin, Ming; Dreyer, ZoAnn E; Scheurer, Michael E; Kamdar, Kala; Wei, Qingyi; Okcu, M Fatih

    2012-04-01

    Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have been implicated in childhood acute lymphoblastic leukemia (ALL) risk, but previously published studies were inconsistent and recent meta-analyses were not adequate. In a meta-analysis of 21 publications with 4,706 cases and 7,414 controls, we used more stringent inclusion method and summarized data on associations between MTHFR C677T and A1298C polymorphisms and childhood ALL risk. We found an overall association between 677T variant genotypes and reduced childhood ALL risk. Specifically, in the dominant genetic model, an association was found in a fixed-effect (TT + CT vs. CC: OR = 0.92; 95% CI = 0.85-0.99) but not random-effect model, whereas such an association was observed in both homozygote genetic model (TT vs. CC: OR = 0.80; 95% CI = 0.70-0.93 by fixed effects and OR = 0.78; 95% CI = 0.65-0.93 by random effects) and recessive genetic model (TT vs. CC + CT: OR = 0.83; 95% CI = 0.72-0.95 by fixed effects and OR = 0.84; 95% CI = 0.73-0.97 by random effects). These associations were also observed in subgroups by ethnicity: for Asians in all models except for the dominant genetic model by random effect and for Caucasians in all models except for the recessive genetic model. However, the A1298C polymorphism did not appear to have an effect on childhood ALL risk. These results suggest that the MTHFR C677T, but not A1298C, polymorphism is a potential biomarker for childhood ALL risk. Copyright © 2011 Wiley Periodicals, Inc.

  6. Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean population.

    PubMed

    Hur, M; Park, J Y; Cho, H C; Lee, K M; Shin, H Y; Cho, H I

    2006-06-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. We investigated the association between MTHFR polymorphisms and the risks of acute and chronic leukaemias. MTHFR C677T and A1298C were genotyped in 396 Korean individuals using multiplex polymerase chain reaction/restriction fragment-length polymorphism. They were acute lymphoblastic leukaemia (ALL, n = 89), acute myeloid leukaemia (AML, n = 55), biphenotypic acute leukaemia (n = 12), chronic myelogenous leukaemia (CML, n = 40), and normal controls (n = 200). C677T genotypes were not associated with the risk of each disease. A1298C variants, however, significantly decreased the risks of ALL and CML compared with 1298AA. Odds ratios and 95% confidence intervals of 1298AC and 1298AC + CC were 0.53 (0.31-0.93) and 0.54 (0.31-0.93) in ALL, and 0.34 (0.14-0.80) and 0.40 (0.18-0.89) in CML, respectively, compared with 1298AA. These findings demonstrate that the development of ALL and CML is more dependent on folate status, and more susceptible to DNA instability than that of AML. In addition, A1298C rather than C677T may be a more important genetic risk modifier in leukaemogenesis at least in the Korean population.

  7. C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: effect on methotrexate-related toxicity in adult acute lymphoblastic leukaemia.

    PubMed

    Eissa, Deena Samir; Ahmed, Tamer Mohamed

    2013-03-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism. Two polymorphisms, C677T and A1298C, were described leading to reduced enzyme activity. Methotrexate (MTX) is an antifolate agent of consolidation and maintenance therapy of acute lymphoblastic leukaemia (ALL). Despite its clinical success, MTX can be associated with serious toxicities resulting in treatment interruption or discontinuation, impacting disease outcome. There is evidence that MTX toxicity can be affected by polymorphisms in genes encoding for drug-metabolizing enzymes such as MTHFR. Therefore, we aimed to investigate the influence of MTHFR C677T and A1298C polymorphisms on the frequency of MTX-related toxicity, disease outcome and patients' survival. MTHFR polymorphisms were assessed in 50 adult patients with de novo ALL using real-time PCR. Patients were followed-up for the development of haematologic and/or nonhaematologic toxicity and assessment of clinical outcome. Frequency of C677T polymorphisms was 42% for TT, 24% for CT and 34% for CC; A1298C polymorphisms were 28, 6 and 66% for CC, AC and AA, respectively. MTX therapy was significantly associated with neutropaenia, hepatic and gastrointestinal toxicities, unfavourable response at day 14 of induction therapy, increased relapse and mortality rates and shorter survival in patients with 677 TT genotype than in those with CC and CT, whereas 1298 CC genotype patients had lower frequency of neutropaenia, hepatic toxicity and relapse than in those with AA and AC. Our study suggests MTHFR polymorphism as an attractive predictor of MTX-related toxicity in adult ALL, considering it a potential prognostic factor influencing disease outcome.

  8. Prevalence of factor V leiden, MTHFR C677T and MTHFR A1298C polymorphisms in patients with deep vein thrombosis in Central Iran.

    PubMed

    Ehsani, Majid; Imani, Aida; Moravveji, Alireza

    2018-05-31

    Deep vein thrombosis (DVT) is a common disease, especially among elderly patients, which is associated with high costs of treatment and high rates of recurrence. The risk factors for venous thrombosis are primarily related to hypercoagulability, which can be genetic or acquired, or because of immobilization and venous stasis. Among relevant genetic markers are a number of common polymorphisms and mutations in the genes coding for Factor V leiden and methylenetetrahydrofolate reductase. Differential associations of these polymorphisms have been reported in different populations with DVT due to ethnic variations. However, no study has been reported with respect to these polymorphisms in DVT in Iran. Thus, the aim of the present study is to determine the prevalence of FVL, MTHFR C677T and MTHFR A1298C gene polymorphisms in patients with DVT in central Iran. In the present cross-sectional study, a total of 100 patients with first and recurrent episodes of DVT and age less than 70 years were recruited during 2016-2017. Blood sample was collected from the recruited patients and FVL mutation was screened using ARMS-PCR method, MTHFR C677T and MTHFR A1298C mutations were screened using PCR-RFLP method. The results revealed that MTHFR A1298C gene polymorphism in both homozygote and heterozygote form was found to be most frequent i.e. 77% among cases, followed by MTHFR C677T (67%) and FVL (17%). The study highlights the importance of screening of these genetic markers among patients with DVT in this region.

  9. Evaluation of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C gene polymorphisms in retinopathy of prematurity in a Turkish cohort.

    PubMed

    Aydin, Hatip; Gunay, Murat; Celik, Gokhan; Gunay, Betul Onal; Aydin, Umeyye Taka; Karaman, Ali

    2016-12-01

    To assess Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131) gene mutations as risk factors in the development of retinopathy of prematurity (ROP). A total of 105 children were included in this cross-sectional study. Patients were divided into two groups. The study group consisted of 55 infants with a history of ROP and the control group comprised 50 healthy infants with term birth. All subjects were screened for the presence of certain mutations (FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C) by Real-Time PCR at 1 year of age. The mean gestational age (GA) and birth weight (BW) of the study group were, 28.65 ± 2.85 weeks and 1171 ± 385.74 g, respectively. There were no significant differences of genotype and allele frequency of Prothrombin G20210A, MTHFR A1298C and MTHFR C677T between the study and control groups (p > 0.05). Eight children (14.5 %) had heterozygous and one child (1.8%) had homozygous FVL mutation in the study group. One child (2%) in the control group had heterozygous FVL mutation. There was statistically significant differences of FVL allele and genotype frequencies between the groups (p < 0.05). The prevalence of FVL polymorphism (16.3 %) was higher in ROP patients than control subjects in this Turkish cohort. We suggest a possible association of FVL mutation with ROP at the end of the study.

  10. Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms in patients with small cell and non-small cell lung cancer.

    PubMed

    Siemianowicz, Krzysztof; Gminski, Jan; Garczorz, Wojciech; Slabiak, Natalia; Goss, Malgorzata; Machalski, Marek; Magiera-Molendowska, Helena

    2003-01-01

    Two mutations of methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) may lead to a decreased activity of the enzyme. These mutations may change a risk of some cancers. We evaluated these two polymorphisms of MTHFR in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NCSCL). All lung cancer patients had statistically significantly higher percentage of MTHFR 677TT genotype in comparison with non-cancer controls. There were no statistically significant differences in the distribution of MTHFR 1298 genotypes. Neither of the polymorphisms presented any statistically significant differences between SCLC and NSCLC.

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

    PubMed Central

    2014-01-01

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

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

    PubMed

    Li, Xiaolei; Liao, Qingchuan; Zhang, Shunguo; Chen, Minling

    2014-01-29

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

  13. Creatine kinase MM TaqI and methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms influence exercise-induced C-reactive protein levels.

    PubMed

    Miranda-Vilela, Ana Luisa; Akimoto, Arthur K; Lordelo, Graciana S; Pereira, Luiz C S; Grisolia, Cesar K; Klautau-Guimarães, Maria de Nazaré

    2012-01-01

    Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. Results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.

  14. Creatine kinase MM TaqI and methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms influence exercise-induced C-reactive protein levels.

    PubMed

    Miranda-Vilela, Ana Luisa; Akimoto, Arthur K; Lordelo, Graciana S; Pereira, Luiz C S; Grisolia, Cesar K; Klautau-Guimarães, Maria de Nazaré

    2012-03-01

    Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. The results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2009-01-01

    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, χ2=12.6), but not with POAG (CC 71%, CT 28%, TT 1%; p=0.98, χ2=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, χ2=17.2). PCAG in the Punjabi subjects was also significantly associated with the A1298C polymorphism (AA 43%, AC 54%, CC 3%; p<0.001, χ2=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, χ2=20.1). This difference was particularly apparent in the TTAA and TTAC combinations that were completely absent in the control groups (p<0.05. χ2=49.6). Mean serum tHcy levels were found to be significantly increased in the POAG (15.2±1.28 µmol/l, p<0

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

    PubMed

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

    2008-01-01

    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 fasting homocysteine and CAD in 298 CAD patients proved by angiography and 510 control subjects from the Island of Madeira (Portugal). After adjustment for other risk factors, plasma homocysteine remained independently correlated with CAD. Serum homocysteine was significantly higher in individuals with 677TT and 1298AA genotypes. There was no difference in the distribution of MTHFR677 genotypes between cases and controls but a significant increase in 1298AA prevalence was found in CAD patients. In spite of the clear effect of C677T mutation on elevated homocysteine levels we only found an association between 1298AA genotype and CAD in this population. The simultaneous presence of 677CT and 1298AA genotypes provides a significant risk of developing the disease, while the 1298AC genotype, combined with 677CC, shows a significant trend towards a decrease in CAD occurrence. The data shows an independent association between elevated levels of homocysteine and CAD. Both MTHFR polymorphisms are associated with increased fasting homocysteine (677TT and 1298AA genotypes), but only the 1298AA variant shows an increased prevalence in CAD group. Odds ratio seem to indicate that individuals with the MTHFR 1298AA genotype and the 677CT/1298AA compound genotype had a 1.6-fold increased risk for developing CAD suggesting a possible association of MTHFR polymorphisms with the risk of CAD in Madeira population.

  18. Lack of association between MTHFR C677T and A1298C polymorphisms and risk of childhood acute lymphoblastic leukemia in the Kurdish population from Western Iran.

    PubMed

    Azhar, Mohammad-Reza; Rahimi, Zohreh; Vaisi-Raygani, Asad; Akramipour, Reza; Madani, Hamid; Rahimi, Ziba; Parsian, Abbas

    2012-03-01

    Polymorphism in genes involved in folate metabolism may influence the susceptibility to acute lymphoblastic leukemia (ALL). The aim of the present study was to determine the role of the two most common polymorphisms of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene, MTHFR C677T and A1298C, and their interaction on the susceptibility to ALL. Seventy-two children with ALL and 109 age- and sex-matched healthy children from Western Iran were screened for MTHFR C677T and A1298C variants by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of MTHFR 677T and 1298C alleles in patients were 29.9% and 43.1%, respectively, that were higher than those in controls (24.8% and 38.1%, respectively). Logistic regression analysis was performed and its result in the odds ratios (ORs) for possession of either MTHFR 677T or 1298C allele was found to be 1.98 [95% confidence interval (CI) 0.72-5.4, p = 0.18] and 1.48 (95% CI 0.59-3.69, p = 0.4), respectively. Also the concomitant presence of both MTHFR 677T and 1298C alleles was not associated with the risk of ALL [OR = 2.12 (95% CI 0.8-5.7, p = 0.13)]. Our results in a homogenous population with Kurdish ethnic background indicated that neither the MTHFR 677T allele nor the MTHFR 1298C allele is associated with increased risk of ALL.

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

    PubMed Central

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

    2014-01-01

    Objectives Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective of this study was to evaluate the effects of polymorphisms of the MTHFR gene on the risk of primary liver cancer and their possible effect modifications on various environmental risk factors. Methods A population-based case–control study was conducted in Taixing, China. MTHFR C677T and A1298C were assayed by PCR-RFLP techniques. Results The frequency of MTHFR 677 C/C wild homo-zygotes genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratios (ORs) for the MTHFR 677 C/T and T/T genotype were 1.66(95% CI: 1.06–2.61), 1.21(95% CI: 0.65–2.28) respectively when compared with the MTHFR 677 C/C genotype. Subjects carrying any T genotype have the increased risk of 1.55(95% CI: 1.01–2.40) for development of primary hepatocellular carcinoma. A high degree of linkage disequilibrium was observed between the C677T and A1298C polymorphisms, with the D′ of 0.887 and p < 0.01. The MTHFR 677 any T genotype was suggested to have potentially more than multiplicative interactions with raw water drinking with p-value for adjusted interaction of 0.03. Conclusion We observed that the MTHFR 677 C/T genotype was associated with an increased risk of primary liver cancer in a Chinese population. The polymorphism of MTHFR 677 might modify the effects of raw water drinking on the risk of primary hepatocellular carcinoma. PMID:17503006

  20. The effect of RFC G80A polymorphism in Cretan children with acute lymphoblastic leukemia and its interaction with MTHFR C677T and A1298C polymorphisms.

    PubMed

    Karathanasis, N V; Stiakaki, E; Goulielmos, G Ν; Kalmanti, M

    2014-08-01

    The association between the risk of acute lymphoblastic leukemia (ALL) in children and enzymes involved in the folate metabolism has been under investigation lately. The reduced folate carrier gene (RFC) encodes reduced folate carrier, a protein that transports into the cell both folate and methotrexate, a commonly used chemotherapeutic drug, has been proved polymorphic at position 80 (G→A). The role of this polymorphism in childhood ALL and its interaction with other enzymes of the folate metabolic pathway, including MTHFR, has been examined in different populations with diverse results. In the present case-control study, 35 children with ALL and 48 healthy adult blood donors, all originating from the island of Crete (Greece), were screened for the presence of the RFC G80A polymorphism, using PCR/RFLP techniques. The effect on ALL risk and methotrexate-induced toxicities, along with the role of gene-gene interactions in our population, were examined. No significant association was observed between the RFC G80A genotypes and either the development of ALL or the presence of adverse events. However, a significant association was detected between the MTHFR A1298C/ RFC G80A genotype and a nonpredisposition for ALL (P = 0.035). This study suggests that gene-gene interactions in childhood ALL may be of prognostic value in our population. © 2013 John Wiley & Sons Ltd.

  1. MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate

    PubMed Central

    González-Mercado, Mirna Gisel; Rivas, Fernando; Gallegos-Arreola, M. Patricia; Morán-Moguel, M. Cristina; Salazar-Páramo, Mario; González-López, Laura; Gámez-Nava, J. Iván; Muñoz-Valle, J. Francisco; Medina-Coss y León, Ricardo; González-Mercado, Anahí; Aceves, Mario A.; Dávalos, Nory O.; Macías-Chumacera, Agustín

    2017-01-01

    Aim: To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Materials and Methods: Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction. Results: Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations. Conclusion: Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA. PMID:28994615

  2. MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate.

    PubMed

    González-Mercado, Mirna Gisel; Rivas, Fernando; Gallegos-Arreola, M Patricia; Morán-Moguel, M Cristina; Salazar-Páramo, Mario; González-López, Laura; Gámez-Nava, J Iván; Muñoz-Valle, J Francisco; Medina-Coss Y León, Ricardo; González-Mercado, Anahí; Aceves, Mario A; Dávalos, Nory O; Macías-Chumacera, Agustín; Dávalos, Ingrid P

    2017-11-01

    To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction. Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations. Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA.

  3. Role of genetic mutations in folate-related enzyme genes on Male Infertility

    PubMed Central

    Liu, Kang; Zhao, Ruizhe; Shen, Min; Ye, Jiaxin; Li, Xiao; Huang, Yuan; Hua, Lixin; Wang, Zengjun; Li, Jie

    2015-01-01

    Several studies showed that the genetic mutations in the folate-related enzyme genes might be associated with male infertility; however, the results were still inconsistent. We performed a meta-analysis with trial sequential analysis to investigate the associations between the MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G mutations and the MTHFR haplotype with the risk of male infertility. Overall, a total of 37 studies were selected. Our meta-analysis showed that the MTHFR C677T mutation was a risk factor for male infertility in both azoospermia and oligoasthenoteratozoospermia patients, especially in Asian population. Men carrying the MTHFR TC haplotype were most liable to suffer infertility while those with CC haplotype had lowest risk. On the other hand, the MTHFR A1298C mutation was not related to male infertility. MTR A2756G and MTRR A66G were potential candidates in the pathogenesis of male infertility, but more case-control studies were required to avoid false-positive outcomes. All of these results were confirmed by the trial sequential analysis. Finally, our meta-analysis with trial sequential analysis proved that the genetic mutations in the folate-related enzyme genes played a significant role in male infertility. PMID:26549413

  4. Transportation of spent MTR fuels

    SciTech Connect

    Raisonnier, D.

    1997-08-01

    This paper gives an overview of the various aspects of MTR spent fuel transportation and provides in particular information about the on-going shipment of 4 spent fuel casks to the United States. Transnucleaire is a transport and Engineering Company created in 1963 at the request of the French Atomic Energy Commission. The company followed the growth of the world nuclear industry and has now six subsidiaries and affiliated companies established in countries with major nuclear programs.

  5. MTR plates modeling with MAIA

    SciTech Connect

    Marelle, V.; Dubois, S.; Ripert, M.

    2008-07-15

    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 experimentmore » 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)« less

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

    PubMed

    Oztuzcu, Serdar; Ergun, Sercan; Ulaşlı, Mustafa; Nacarkahya, Gülper; Iğci, Yusuf Ziya; Iğci, Mehri; Bayraktar, Recep; Tamer, Ali; Çakmak, Ecir Ali; Arslan, Ahmet

    2014-06-01

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

  7. 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

  8. 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

  9. 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

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

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

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

  11. 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

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

    SciTech Connect

    Edwards, Marcus; Fredrickson, Jim K.; Zachara, John M.

    2012-12-01

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

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

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

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

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

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

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

  15. PRECONSTRUCTION IMAGE OF THE MTR SITE. ABANDONED IRRIGATION CANAL (FROM ...

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

    PRE-CONSTRUCTION IMAGE OF THE MTR SITE. ABANDONED IRRIGATION CANAL (FROM EARLY 1900s) ILLUSTRATES FLATNESS OF MTR/TRA TERRAIN. FEATURE ON HORIZON IN LEFT OF VIEW IS EXPLORATORY WATER DRILLING EQUIPMENT. CAMERA LOOKS SOUTHEAST. INL NEGATIVE NO. 136. Unknown Photographer, 12/5/1949 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  16. 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

  17. 33 CFR 154.1041 - Specific response information to be maintained on mobile MTR facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... be maintained on mobile MTR facilities. 154.1041 Section 154.1041 Navigation and Navigable Waters... maintained on mobile MTR facilities. (a) Each mobile MTR facility must carry the following information as... respond to a discharge from the mobile MTR facility. (3) List of the appropriate persons and agencies...

  18. 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

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

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

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

  20. PRECAST CONCRETE WALL PANELS ARE LIFTED INTO PLACE ON MTR ...

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

    PRECAST CONCRETE WALL PANELS ARE LIFTED INTO PLACE ON MTR STEEL FRAME STRUCTURE. INL NEGATIVE NO. 1330. Unknown Photographer, 1/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

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

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

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

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

    PubMed

    Berger, Thomas; Bilski, Paweł; Hajek, Michael; Puchalska, Monika; Reitz, Günther

    2013-12-01

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

  3. Gene Environment Interactions and Predictors of Colorectal Cancer in Family-Based, Multi-Ethnic Groups.

    PubMed

    Shiao, S Pamela K; Grayson, James; Yu, Chong Ho; Wasek, Brandi; Bottiglieri, Teodoro

    2018-02-16

    For the personalization of polygenic/omics-based health care, the purpose of this study was to examine the gene-environment interactions and predictors of colorectal cancer (CRC) by including five key genes in the one-carbon metabolism pathways. In this proof-of-concept study, we included a total of 54 families and 108 participants, 54 CRC cases and 54 matched family friends representing four major racial ethnic groups in southern California (White, Asian, Hispanics, and Black). We used three phases of data analytics, including exploratory, family-based analyses adjusting for the dependence within the family for sharing genetic heritage, the ensemble method, and generalized regression models for predictive modeling with a machine learning validation procedure to validate the results for enhanced prediction and reproducibility. The results revealed that despite the family members sharing genetic heritage, the CRC group had greater combined gene polymorphism rates than the family controls ( p < 0.05), on MTHFR C677T , MTR A2756G , MTRR A66G, and DHFR 19 bp except MTHFR A1298C. Four racial groups presented different polymorphism rates for four genes (all p < 0.05) except MTHFR A1298C. Following the ensemble method, the most influential factors were identified, and the best predictive models were generated by using the generalized regression models, with Akaike's information criterion and leave-one-out cross validation methods. Body mass index (BMI) and gender were consistent predictors of CRC for both models when individual genes versus total polymorphism counts were used, and alcohol use was interactive with BMI status. Body mass index status was also interactive with both gender and MTHFR C677T gene polymorphism, and the exposure to environmental pollutants was an additional predictor. These results point to the important roles of environmental and modifiable factors in relation to gene-environment interactions in the prevention of CRC.

  4. MTR FAST NEUTRON FLUX MEASUREMENTS FOR CYCLE 146

    SciTech Connect

    Weber, L D; Hogg, C H

    1962-03-20

    The fast neutron fluxes in selected positions of the MTR were measured for Cycle 146. The measurements were made at the beginning, throughout, and at the end of the cycle (564 Mwd). Vertical traverses for each position monitors are shown. (auth)

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

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

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

  6. 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

  7. 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

  8. CANAL EMERGES FROM EAST SIDE OF MTR BUILDING. "EXTRA" LENGTH ...

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

    CANAL EMERGES FROM EAST SIDE OF MTR BUILDING. "EXTRA" LENGTH WAS TO STORE SPENT FUEL THAT WOULD ACCUMULATE BEFORE THE CHEMICAL PROCESSING PLANT WAS READY TO PROCESS IT. INL NEGATIVE NO. 1659. Unknown Photographer, 3/9/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  9. 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

  10. The Role of the Transcription Factors MtrR and MtrA in the Fitness of the Pathogen Neisseria gonorrhoeae

    DTIC Science & Technology

    2007-10-19

    MacA -MacB efflux pump is expressed at very low levels in N. gonorrhoeae; however, experimental alteration of the promoter sequence showed that the...specificity (132). The gonococcus expresses four efflux pump systems, namely MtrC-Mtr-D-MtrE (64), FarA-FarB-MtrE (97), NorM (158), and MacA -MacB (161...2005. Characterization of the MacA -MacB efflux system in Neisseria gonorrhoeae. The Journal of antimicrobial chemotherapy 56:856-860. 162. Rouquette, C

  11. 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

  12. 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

  13. 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

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

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

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

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

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

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

  16. 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

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

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

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

  18. 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

  19. Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex.

    PubMed

    Puno, M Rhyan; Lima, Christopher D

    2018-06-12

    The nuclear exosome-targeting (NEXT) complex functions as an RNA exosome cofactor and is involved in surveillance and turnover of aberrant transcripts and noncoding RNAs. NEXT is a ternary complex composed of the RNA-binding protein RBM7, the scaffold zinc-knuckle protein ZCCHC8, and the helicase MTR4. While RNA interactions with RBM7 are known, it remains unclear how NEXT subunits collaborate to recognize and prepare substrates for degradation. Here, we show that MTR4 helicase activity is enhanced when associated with RBM7 and ZCCHC8. While uridine-rich substrates interact with RBM7 and are preferred, optimal activity is observed when substrates include a polyadenylated 3' end. We identify a bipartite interaction of ZCCHC8 with MTR4 and uncover a role for the conserved C-terminal domain of ZCCHC8 in stimulating MTR4 helicase and ATPase activities. A crystal structure reveals that the ZCCHC8 C-terminal domain binds the helicase core in a manner that is distinct from that observed for Saccharomyces cerevisiae exosome cofactors Trf4p and Air2p. Our results are consistent with a model whereby effective targeting of substrates by NEXT entails recognition of elements within the substrate and activation of MTR4 helicase activity. Copyright © 2018 the Author(s). Published by PNAS.

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

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

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

  1. 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

  2. MtrA of the sodium ion pumping methyltransferase binds cobalamin in a unique mode

    PubMed Central

    Wagner, Tristan; Ermler, Ulrich; Shima, Seigo

    2016-01-01

    In the three domains of life, vitamin B12 (cobalamin) is primarily used in methyltransferase and isomerase reactions. The methyltransferase complex MtrA–H of methanogenic archaea has a key function in energy conservation by catalysing the methyl transfer from methyl-tetrahydromethanopterin to coenzyme M and its coupling with sodium-ion translocation. The cobalamin-binding subunit MtrA is not homologous to any known B12-binding proteins and is proposed as the motor of the sodium-ion pump. Here, we present crystal structures of the soluble domain of the membrane-associated MtrA from Methanocaldococcus jannaschii and the cytoplasmic MtrA homologue/cobalamin complex from Methanothermus fervidus. The MtrA fold corresponds to the Rossmann-type α/β fold, which is also found in many cobalamin-containing proteins. Surprisingly, the cobalamin-binding site of MtrA differed greatly from all the other cobalamin-binding sites. Nevertheless, the hydrogen-bond linkage at the lower axial-ligand site of cobalt was equivalently constructed to that found in other methyltransferases and mutases. A distinct polypeptide segment fixed through the hydrogen-bond linkage in the relaxed Co(III) state might be involved in propagating the energy released upon corrinoid demethylation to the sodium-translocation site by a conformational change. PMID:27324530

  3. Preliminary developments of MTR plates with uranium nitride

    SciTech Connect

    Durand, J.P.; Laudamy, P.; Richter, K.

    1997-08-01

    In the opinion of CERCA, the total weight of Uranium per MTR plate (without changing the external dimensions) cannot be further increased using U{sub 3}Si{sub 2}. Limits have been reached on plates with a thicker meat or loaded to 6g Ut/cm{sup 3}. The use of a denser fuel like Uranium mononitride could permit an increase in these limits. A collaboration between the Institute for Transuranium Elements (ITU), Joint Research Centre of the European Commission, and CERCA has been set ut. The preliminary studies at the ITU to check compatibility between aluminium and UN proved that there are no metallurgical interactionsmore » below 500{degrees}C. Feasibility of the manufacturing, on a laboratory scale at CERCA, of depleted Uranium mononitride plates loaded to 7 g Ut/cm{sup 3} has been demonstrated. The manufacturing process, however, is only one aspect of the development of a new fuel. The experience gained in the case of U{sub 3}Si{sub 2} has shown that the development of a new fuel requires considerable time and financial investment. Such a development certainly represents an effort of about 10 years.« less

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    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.

  5. Mechanical tissue resuscitation (MTR): a nonpharmacological approach to treatment of acute myocardial infarction.

    PubMed

    Jordan, James E; Pereira, Beatriz D; Lane, Magan R; Morykwas, Michael J; McGee, Maria; Argenta, Louis C

    2015-08-01

    Myocardial ischemia-reperfusion injury is known to trigger an inflammatory response involving edema, apoptosis, and neutrophil activation/accumulation. Recently, mechanical tissue resuscitation (MTR) was described as a potent cardioprotective strategy for reduction of myocardial ischemia-reperfusion injury. Here, we further describe the protective actions of MTR and begin to define its therapeutic window. A left ventricular, free-wall ischemic area was created in anesthetized swine for 85 minutes and then reperfused for three hours. Animals were randomized to two groups: (1) untreated controls (Control) and (2) application of MTR that was delayed 90 minutes after the initiation of reperfusion (D90). Hemodynamics and regional myocardial blood flow were assessed at multiple time points. Infarct size and neutrophil accumulation were assessed following the reperfusion period. In separate cohorts, the effect of MTR on myocardial interstitial water (MRI imaging) and blood flow was examined. Both groups had similar areas at risk (AAR), hemodynamics, and arterial blood gas values. MTR, even when delayed 90 minutes into reperfusion (D90, 29.2 ± 5.0% of AAR), reduced infarct size significantly compared to Controls (51.9 ± 2.7%, p = 0.006). This protection was associated with a 33% decrease in neutrophil accumulation (p = 0.047). Improvements in blood flow and interstitial water were also observed. Moreover, we demonstrated that the therapeutic window for MTR lasts for at least 90 minutes following reperfusion. This study confirms our previous observations that MTR is an effective therapeutic approach to reducing reperfusion injury with a clinically useful treatment window. © 2015 Wiley Periodicals, Inc.

  6. L-Area STS MTR/NRU/NRX Grapple Assembly Closure Mechanics Review

    SciTech Connect

    Huizenga, D. J.

    2016-06-08

    A review of the closure mechanics associated with the Shielded Transfer System (STS) MTR/NRU/NRX grapple assembly utilized at the Savannah River Site (SRS) was performed. This review was prompted by an operational event which occurred at the Canadian Nuclear Laboratories (CNL) utilizing a DTS-XL grapple assembly which is essentially identical to the STS MTR/NRU/NRX grapple assembly used at the SRS. The CNL operational event occurred when a NRU/NRX fuel basket containing spent nuclear fuel assemblies was inadvertently released by the DTS-XL grapple assembly during a transfer. The SM review of the STS MTR/NRU/NRX grapple assembly will examine the operational aspectsmore » of the STS and the engineered features of the STS which prevent such an event at the SRS. The design requirements for the STS NRU/NRX modifications and the overall layout of the STS are provided in other documents.« less

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

    PubMed Central

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

    2012-01-01

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

  8. 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

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

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

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

  10. Mutation in a locus linked to penB-nmp causes suppression of the Mtr phenotype of Neisseria gonorrhoeae.

    PubMed Central

    Shinners, E N; Catlin, B W

    1988-01-01

    The chromosomal locus mtr, which encodes low-level resistance to multiple antibacterial agents in Neisseria gonorrhoeae, is subject to phenotypic suppression by env mutations that increase the permeability of the envelope. We have identified a new locus, mom (for modifier of Mtr), which is located on the chromosome very close to penB and nmp, loci known to be linked to each other and to spc. Phenotypic suppression of Mtr was recognized by reductions of resistance to benzylpenicillin and also to oxacillin and the hydrophobic agents novobiocin and erythromycin. The resistance to each of these antibiotics returned to the Mtr levels in mom+ transformants isolated by selection for increased resistance to either novobiocin or erythromycin; the accompanying change of the outer membrane protein I seroreactions confirmed the proximity of nmp and mom. Thus, some mutant gonococci display wild-type antibiotic susceptibilities but can express multiple resistance following a mom+ mutation that releases the suppressed Mtr phenotype. PMID:3142343

  11. [Features of allele polymorphism of genes involved in homocysteine and folate metabolism in patients with atherosclerosis of the lower extremity arteries].

    PubMed

    Klenkova, N A; Kapustin, S I; Saltykova, N B; Shmeleva, V M; Blinov, M N

    2009-01-01

    Under study were features of allele polymorphism of genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A 2756G), methionine synthase reductase (MTRR A66G) and methylenetetrahydrofolate dehydrogenase (MTHFD G1958A) in patients with atherosclerosis of the lower extremity arteries (ALEA). Patients with hyperhomocysteinemia (HHcy) had statistically significant increase of allele MTHFR 677T and MTRR 66GG as compared both with the control group and with the group of patients without HHcy. It suggests that polymorphism of genes involved in homocystein and folate metabolism might affect the risk of HHcy in patients with ALEA.

  12. 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

  13. 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

  14. Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps

    PubMed Central

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

    2015-01-01

    SUMMARY Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually-transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein, which belongs to the AbgT family of transporters for which no structural information is available. Here we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump, mediating bacterial resistance to sulfonamide antimetabolite drugs. PMID:25818299

  15. MTR WING, TRA604, INTERIOR. BASEMENT. WEST CORRIDOR. CAMERA FACES NORTH. ...

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

    MTR WING, TRA-604, INTERIOR. BASEMENT. WEST CORRIDOR. CAMERA FACES NORTH. HVAC AREA IS AT RIGHT OF CORRIDOR. INL NEGATIVE NO. HD46-13-3. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  16. Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps

    DOE PAGES

    Su, Chih -Chia; Bolla, Jani  Reddy; Kumar, Nitin; ...

    2015-04-01

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

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

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

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

  18. Performance of the MTR core with MOX fuel using the MCNP4C2 code.

    PubMed

    Shaaban, Ismail; Albarhoum, Mohamad

    2016-08-01

    The MCNP4C2 code was used to simulate the MTR-22 MW research reactor and perform the neutronic analysis for a new fuel namely: a MOX (U3O8&PuO2) fuel dispersed in an Al matrix for One Neutronic Trap (ONT) and Three Neutronic Traps (TNTs) in its core. Its new characteristics were compared to its original characteristics based on the U3O8-Al fuel. Experimental data for the neutronic parameters including criticality relative to the MTR-22 MW reactor for the original U3O8-Al fuel at nominal power were used to validate the calculated values and were found acceptable. The achieved results seem to confirm that the use of MOX fuel in the MTR-22 MW will not degrade the safe operational conditions of the reactor. In addition, the use of MOX fuel in the MTR-22 MW core leads to reduce the uranium fuel enrichment with (235)U and the amount of loaded (235)U in the core by about 34.84% and 15.21% for the ONT and TNTs cases, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

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

  20. MTR WING, TRA604. BASEMENT FLOOR PLAN. FIREPROOF RECORD ROOM BELOW ...

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

    MTR WING, TRA-604. BASEMENT FLOOR PLAN. FIRE-PROOF RECORD ROOM BELOW COUNTING ROOM. HEATING AND COOLING EQUIPMENT. UNSPECIFIED EXPANSION AREA ALONG WEST WALL. BLAW-KNOX 3150-4-1, 7/1950. INL INDEX NO. 531-0604-00-098-100007, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  1. SOUTH WING, TRA661. SOUTH SIDE. CAMERA FACING NORTH. MTR HIGH ...

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

    SOUTH WING, TRA-661. SOUTH SIDE. CAMERA FACING NORTH. MTR HIGH BAY BEYOND. INL NEGATIVE NO. HD46-45-3. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  2. 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

  3. 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

  4. Characterization of hMTr1, a Human Cap1 2′-O-Ribose Methyltransferase*

    PubMed Central

    Bélanger, François; Stepinski, Janusz; Darzynkiewicz, Edward; Pelletier, Jerry

    2010-01-01

    Cellular eukaryotic mRNAs are capped at their 5′ ends with a 7-methylguanosine nucleotide, a structural feature that has been shown to be important for conferring mRNA stability, stimulating mRNA biogenesis (splicing, poly(A) addition, nucleocytoplasmic transport), and increasing translational efficiency. Whereas yeast mRNAs have no additional modifications to the cap, called cap0, higher eukaryotes are methylated at the 2′-O-ribose of the first or the first and second transcribed nucleotides, called cap1 and cap2, respectively. In the present study, we identify the methyltransferase responsible for cap1 formation in human cells, which we call hMTr1 (also known as FTSJD2 and ISG95). We show in vitro that hMTr1 catalyzes specific methylation of the 2′-O-ribose of the first nucleotide of a capped RNA transcript. Using siRNA-mediated knockdown of hMTr1 in HeLa cells, we demonstrate that hMTr1 is responsible for cap1 formation in vivo. PMID:20713356

  5. 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

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

    SciTech Connect

    Byun, H. S.; Pirbadian, S.; Nakano, Aiichiro

    2014-09-05

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

  7. 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

  8. Flavin binding to the deca-heme cytochrome MtrC: Insights from computational molecular simulation

    DOE PAGES

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

    2015-12-15

    Here, certain dissimilatory bacteria have the remarkable ability to use extracellular metal oxide minerals instead of oxygen as terminal electron sinks, using a process known as “extracellular respiration”. Specialized multiheme cytochromes located on the outer membrane of the microbe were shown to be crucial for electron transfer from the cell surface to the mineral. This process is facilitated by soluble, biogenic flavins secreted by the organism for the purpose of acting as an electron shuttle. However, their interactions with the outer-membrane cytochromes are not established on a molecular scale. Here, we study the interaction between the outer-membrane deca-heme cytochrome MtrCmore » from Shewanella oneidensis and flavin mononucleotide (FMN in fully oxidized quinone form) using computational docking. We find that interaction of FMN with MtrC is significantly weaker than with known FMN-binding proteins, but identify a mildly preferred interaction site close to heme 2 with a dissociation constant (K d) = 490 μM, in good agreement with recent experimental estimates, K d = 255 μM. The weak interaction with MtrC can be qualitatively explained by the smaller number of hydrogen bonds that the planar headgroup of FMN can form with this protein compared to FMN-binding proteins. Molecular dynamics simulation gives indications for a possible conformational switch upon cleavage of the disulphide bond of MtrC, but without concomitant increase in binding affinities according to this docking study. Overall, our results suggest that binding of FMN to MtrC is reversible and not highly specific, which may be consistent with a role as redox shuttle that facilitates extracellular respiration.« less

  9. MTR, TRA603. SECOND FLOOR PLAN. OFFICES AND INSTRUMENT ROOM. STEEL ...

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

    MTR, TRA-603. SECOND FLOOR PLAN. OFFICES AND INSTRUMENT ROOM. STEEL PARTITIONS ON EAST SIDE OF INSTRUMENT ROOM. DETAIL OF COLUMN ENCASEMENTS. STAIRWAYS IN NORTH AND SOUTH CORNERS. PASSENGER ELEVATION. BLAW-KNOX 3150-803-3, 7/1950. INL INDEX NO. 531-0603-00-098-100562, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  10. MTR WING, TRA604. PRECAST CONCRETE PANELS AND DIMENSIONS. TYPES A, ...

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

    MTR WING, TRA-604. PRECAST CONCRETE PANELS AND DIMENSIONS. TYPES A, B, C, D, E, AND F; AND HOW THEY ARE CONNECTED. TYPES C AND D ARE ON WEST SIDE WHERE GLASS BLOCKS SURROUND ENTRY DOOR. BLAW-KNOX 3150-804-20, SHEET #1, 11/1950. INL INDEX NO. 531-0604-62-098-100644, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

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

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

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

  12. 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

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

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

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

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

    SciTech Connect

    Breuer, Marian; Zarzycki, Piotr P.; Blumberger, Jochen

    2012-07-01

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

  15. Targeted Protein Degradation of Outer Membrane Decaheme Cytochrome MtrC Metal Reductase in Shewanella oneidensis MR-1 Measured Using Biarsenical Probe CrAsH-EDT2

    SciTech Connect

    Xiong, Yijia; Chen, Baowei; Shi, Liang

    2011-10-14

    Development of efficient microbial biofuel cells requires an ability to exploit interfacial electron transfer reactions to external electron acceptors, such as metal oxides; such reactions occur in the facultative anaerobic gram-negative bacterium Shewanella oneidensis MR-1 through the catalytic activity of the outer membrane decaheme c-type cytochrome MtrC. Central to the utility of this pathway to synthetic biology is an understanding of cellular mechanisms that maintain optimal MtrC function, cellular localization, and renewal by degradation and resynthesis. In order to monitor trafficking to the outer membrane, and the environmental sensitivity of MtrC, we have engineered a tetracysteine tag (i.e., CCPGCC) atmore » its C-terminus that permits labeling by the cell impermeable biarsenical fluorophore, carboxy-FlAsH (CrAsH) of MtrC at the surface of living Shewanella oneidensis MR-1 cells. In comparison, the cell permeable reagent FlAsH permits labeling of the entire population of MtrC, including proteolytic fragments resulting from incorrect maturation. We demonstrate specific labeling by CrAsH of engineered MtrC which is dependent on the presence of a functional type-2 secretion system (T2S), as evidenced by T2S system gspD or gspG deletion mutants which are incapable of CrAsH labeling. Under these latter conditions, MtrC undergoes proteolytic degradation to form a large 35-38 kDa fragment; this degradation product is also resolved during normal turnover of the CrAsH-labeled MtrC protein. No MtrC protein is released into the medium during turnover, suggesting the presence of cellular turnover systems involving MtrC reuptake and degradation. The mature MtrC localized on the outer membrane is a long-lived protein, with a turnover rate of 0.043 hr-1 that is insensitive to O2 concentration. Maturation of MtrC is relatively inefficient, with substantial rates of turnover of the immature protein prior to export to the outer membrane (i.e., 0.028 hr-1) that are

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

    NASA Astrophysics Data System (ADS)

    Day, Simon E.

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

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

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

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

  18. 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

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

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

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

  20. Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human Nuclear RNA Exosome-MTR4 Complex.

    PubMed

    Weick, Eva-Maria; Puno, M Rhyan; Januszyk, Kurt; Zinder, John C; DiMattia, Michael A; Lima, Christopher D

    2018-06-14

    The ribonucleolytic RNA exosome interacts with RNA helicases to degrade RNA. To understand how the 3' to 5' Mtr4 helicase engages RNA and the nuclear exosome, we reconstituted 14-subunit Mtr4-containing RNA exosomes from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human and show that they unwind structured substrates to promote degradation. We loaded a human exosome with an optimized DNA-RNA chimera that stalls MTR4 during unwinding and determined its structure to an overall resolution of 3.45 Å by cryoelectron microscopy (cryo-EM). The structure reveals an RNA-engaged helicase atop the non-catalytic core, with RNA captured within the central channel and DIS3 exoribonuclease active site. MPP6 tethers MTR4 to the exosome through contacts to the RecA domains of MTR4. EXOSC10 remains bound to the core, but its catalytic module and cofactor C1D are displaced by RNA-engaged MTR4. Competition for the exosome core may ensure that RNA is committed to degradation by DIS3 when engaged by MTR4. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Nuclear Proximity of Mtr4 with RNA exosome restricts DNA mutational asymmetry

    PubMed Central

    Lim, Junghyun; Giri, Pankaj Kumar; Kazadi, David; Laffleur, Brice; Zhang, Wanwei; Grinstein, Veronika; Pefanis, Evangelos; Brown, Lewis M.; Ladewig, Erik; Martin, Ophélie; Chen, Yuling; Rabadan, Raul; Boyer, François; Rothschild, Gerson; Cogné, Michel; Pinaud, Eric; Deng, Haiteng; Basu, Uttiya

    2017-01-01

    SUMMARY The distribution of sense and antisense strand DNA mutations on transcribed duplex DNA contributes to the development of immune and neural systems along with the progression of cancer. Because developmentally matured B cells undergo biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid structures, they make a convenient system to investigate strand-specific mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA mutagenesis at the immunoglobulin heavy chain locus and some other regions of the B cell genome depends upon localized RNA processing protein complex formation in the nucleus. Both the physical proximity and coupled activities of RNA helicase Mtr4 (and Senataxin) with the noncoding RNA processing function of RNA exosome determine the strand specific distribution of DNA mutations. Our study suggests that strand-specific DNA mutagenesis-associated mechanisms will play major roles in other undiscovered aspects of organismic development. PMID:28431250

  2. Influence of Combined Methionine Synthase (MTR 2756A > G) and Methylenetetrahydrofolate Reductase (MTHFR 677C > T) Polymorphisms to Plasma Homocysteine Levels in Korean Patients with Ischemic Stroke

    PubMed Central

    Kim, Ok Joon; Hong, Sun Pyo; Ahn, Jung Yong; Hong, Seung Ho; Hwang, Tae Sun; Kim, Soo Ok; Yoo, Wangdon; Oh, Doyeun

    2007-01-01

    Purpose Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case-control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. Materials and Methods DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p = 0.04 for MTR, p = 0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p = 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p = 0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p = 0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. Conclusion The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke. PMID:17461517

  3. Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase

    SciTech Connect

    Wasmuth, Elizabeth V.; Zinder, John C.; Zattas, Dimitrios

    Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome. Mpp6-exosomes can recruit Mtr4, while Mpp6 and Rrp47 each contribute to Mtr4-dependent RNA decay, with maximal Mtr4-dependent decay observed with bothmore » cofactors. The 3.3 Å structure of a twelve-subunit nuclear Mpp6 exosome bound to RNA shows the central region of Mpp6 bound to the exosome core, positioning its Mtr4 recruitment domain next to Rrp6 and the exosome central channel. Genetic analysis reveals interactions that are largely consistent with our model.« less

  4. Structure and reconstitution of yeast Mpp6-nuclear exosome complexes reveals that Mpp6 stimulates RNA decay and recruits the Mtr4 helicase.

    PubMed

    Wasmuth, Elizabeth V; Zinder, John C; Zattas, Dimitrios; Das, Mom; Lima, Christopher D

    2017-07-25

    Nuclear RNA exosomes catalyze a range of RNA processing and decay activities that are coordinated in part by cofactors, including Mpp6, Rrp47, and the Mtr4 RNA helicase. Mpp6 interacts with the nine-subunit exosome core, while Rrp47 stabilizes the exoribonuclease Rrp6 and recruits Mtr4, but it is less clear if these cofactors work together. Using biochemistry with Saccharomyces cerevisiae proteins, we show that Rrp47 and Mpp6 stimulate exosome-mediated RNA decay, albeit with unique dependencies on elements within the nuclear exosome. Mpp6-exosomes can recruit Mtr4, while Mpp6 and Rrp47 each contribute to Mtr4-dependent RNA decay, with maximal Mtr4-dependent decay observed with both cofactors. The 3.3 Å structure of a twelve-subunit nuclear Mpp6 exosome bound to RNA shows the central region of Mpp6 bound to the exosome core, positioning its Mtr4 recruitment domain next to Rrp6 and the exosome central channel. Genetic analysis reveals interactions that are largely consistent with our model.

  5. High temperature ultrasonic sensor for fission gas characterization in MTR harsh environment

    NASA Astrophysics Data System (ADS)

    Gatsa, O.; Combette, P.; Rozenkrantz, E.; Fourmentel, D.; Destouches, C.; Ferrandis, J. Y. AD(; )

    2018-01-01

    In the contemporary world, the measurements in hostile environment is one of the predominant necessity for automotive, aerospace, metallurgy and nuclear plant. The measurement of different parameters in experimental reactors is an important point in nuclear power strategy. In the near past, IES (Institut d'Électronique et des Systèmes) on collaboration with CEA (Commissariat à l'Energie Atomique et aux Energies Alternatives) have developed the first ultrasonic sensor for the application of gas quantity determination that has been tested in a Materials Testing Reactor (MTR). Modern requirements state to labor with the materials that possess stability on its parameters around 350°C in operation temperature. Previous work on PZT components elaboration by screen printing method established the new basis in thick film fabrication and characterization in our laboratory. Our trials on Bismuth Titanate ceramics showed the difficulties related to high electrical conductivity of fabricated samples that postponed further research on this material. Among piezoceramics, the requirements on finding an alternative solution on ceramics that might be easily polarized and fabricated by screen printing approach were resolved by the fabrication of thick film from Sodium Bismuth Titanate (NBT) piezoelectric powder. This material exhibits high Curie temperature, relatively good piezoelectric and coupling coefficients, and it stands to be a good solution for the anticipated application. In this paper, we present NBT thick film fabrication by screen printing, characterization of piezoelectric, dielectric properties and material parameters studies in dependence of temperature. Relatively high resistivity in the range of 1.1013 Ohm.cm for fabricated thick film is explained by Aurivillius structure in which a-and b-layers form perovskite structure between oxides of c-layer. Main results of this study are presented and discussed in terms of feasibility for an application to a new sensor

  6. Membrane topology analysis of Escherichia coli K-12 Mtr permease by alkaline phosphatase and beta-galactosidase fusions.

    PubMed

    Sarsero, J P; Pittard, A J

    1995-01-01

    The mtr gene of Escherichia coli K-12 encodes an inner membrane protein which is responsible for the active transport of trypotophan into the cell. It has been proposed that the Mtr permease has a novel structure consisting of 11 hydrophobic transmembrane spans, with a cytoplasmically disposed amino terminus and a carboxyl terminus located in the periplasmic space (J.P. Sarsero, P. J. Wookey, P. Gollnick, C. Yanofsky, and A.J. Pittard, J. Bacteriol. 173:3231-3234, 1991). The validity of this model was examined by the construction of fusion proteins between the Mtr permease and alkaline phosphatase or beta-galactosidase. In addition to the conventional methods, in which the reporter enzyme replaces a carboxyl-terminal portion of the membrane protein, the recently developed alkaline phosphatase sandwich fusion technique was utilized, in which alkaline phosphatase is inserted into an otherwise intact membrane protein. A cluster of alkaline phosphatase fusions to the carboxyl-terminal end of the Mtr permease exhibited high levels of alkaline phosphatase activity, giving support to the proposition of a periplasmically located carboxyl terminus. The majority of fusion proteins produced enzymatic activities which were in agreement with the positions of the fusion sites on the proposed topological model of the permease. The synthesis of a small cluster of hybrid proteins, whose enzymatic activity did not agree with the location of their fusion sites within putative transmembrane span VIII or the preceding periplasmic loop, was not detected by immunological techniques and did not necessitate modification of the proposed model in this region. Slight alterations may need to be made in the positioning of the carboxyl-terminal end of transmembrane span X.

  7. Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export

    PubMed Central

    Chatterjee, Kunal; Majumder, Shubhra; Wan, Yao; Shah, Vijay; Wu, Jingyan; Huang, Hsiao-Yun

    2017-01-01

    Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67–Mtr2 (TAP–p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67–Mtr2 can substitute for Los1 in los1Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67–Mtr2 functions in primary nuclear export for a subset of yeast tRNAs. PMID:29212662

  8. Sharing the load: Mex67-Mtr2 cofunctions with Los1 in primary tRNA nuclear export.

    PubMed

    Chatterjee, Kunal; Majumder, Shubhra; Wan, Yao; Shah, Vijay; Wu, Jingyan; Huang, Hsiao-Yun; Hopper, Anita K

    2017-11-01

    Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67-Mtr2 (TAP-p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67-Mtr2 can substitute for Los1 in los1 Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67-Mtr2 functions in primary nuclear export for a subset of yeast tRNAs. © 2017 Chatterjee et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Draft genome sequence of Janthinobacterium lividum strain MTR reveals its mechanism of capnophilic behavior.

    PubMed

    Valdes, Natalia; Soto, Paola; Cottet, Luis; Alarcon, Paula; Gonzalez, Alex; Castillo, Antonio; Corsini, Gino; Tello, Mario

    2015-01-01

    Janthinobacterium lividum is a Gram-negative bacterium able to produce violacein, a pigment with antimicrobial and antitumor properties. Janthinobacterium lividum colonizes the skin of some amphibians and confers protection against fungal pathogens. The mechanisms underlying this association are not well understood. In order to identify the advantages for the bacterium to colonize amphibian skin we sequenced Janthinobacterium lividum strain MTR, a strain isolated from Cajón del Maipo, Chile. The strain has capnophilic behavior, with growth favored by high concentrations (5 %) of carbon dioxide. Its genome is 6,535,606 bp in size, with 5,362 coding sequences and a G + C content of 62.37 %. The presence of genes encoding for products that participate in the carbon fixation pathways (dark CAM pathways), and the entire set of genes encoding for the enzymes of the glyoxylate cycle may explain the capnophilic behavior and allow us to propose that the CO2 secreted by the skin of amphibians is the signal molecule that guides colonization by Janthinobacterium lividum.

  10. GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis.

    PubMed

    Nantes, Julia C; Proulx, Sébastien; Zhong, Jidan; Holmes, Scott A; Narayanan, Sridar; Brown, Robert A; Hoge, Richard D; Koski, Lisa

    2017-08-15

    Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings

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

    PubMed Central

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

    2013-01-01

    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

  12. Metabolism and gene polymorphisms of the folate pathway in Brazilian women with history of recurrent abortion.

    PubMed

    Boas, Wendell Vilas; Gonçalves, Rozana Oliveira; Costa, Olívia Lúcia Nunes; Goncalves, Marilda Souza

    2015-02-01

    To investigate the association between polymorphisms in genes that encode enzymes involved in folate- and vitamin B12-dependent homocysteine metabolism and recurrent spontaneous abortion (RSA). We investigated the C677T and A1298C polymorphisms of the methylenetetrahydrofalate reductase gene (MTHFR), the A2756G polymorphism of the methionine synthase gene (MS) and the 844ins68 insertion of the cystathionine beta synthetase gene (CBS). The PCR technique followed by RFLP was used to assess the polymorphisms; the serum levels of homocysteine, vitamin B12 and folate were investigated by chemiluminescence. The EPI Info Software version 6.04 was used for statistical analysis. Parametric variables were compared by Student's t-test and nonparametric variables by the Wilcoxon rank sum test. The frequencies of gene polymorphisms in 89 women with a history of idiopathic recurrent miscarriage and 150 controls were 19.1 and 19.6% for the C677T, insertion, 20.8 and 26% for the A1298C insertion, 14.2 and 21.9% for the A2756G insertion, and 16.4 and 18% for the 844ins68 insertion, respectively. There were no significant differences between case and control groups in any of the gene polymorphisms investigated. However, the frequency of the 844ins68 insertion in the CBS gene was higher among women with a history of loss during the third trimester of pregnancy (p=0.003). Serum homocysteine, vitamin B12 and folate levels id not differ between the polymorphisms studied in the case and control groups. However, linear regression analysis showed a dependence of serum folate levels on the maintenance of tHcy levels. The investigated gene polymorphisms and serum homocysteine, vitamin B12 and folate levels were not associated with idiopathic recurrent miscarriage in the present study. Further investigations are needed in order to confirm the role of the CBS 844ins68 insertion in recurrent miscarriage.

  13. Exosome cofactor hMTR4 competes with export adaptor ALYREF to ensure balanced nuclear RNA pools for degradation and export.

    PubMed

    Fan, Jing; Kuai, Bin; Wu, Guifen; Wu, Xudong; Chi, Binkai; Wang, Lantian; Wang, Ke; Shi, Zhubing; Zhang, Heng; Chen, She; He, Zhisong; Wang, Siyuan; Zhou, Zhaocai; Li, Guohui; Cheng, Hong

    2017-10-02

    The exosome is a key RNA machine that functions in the degradation of unwanted RNAs. Here, we found that significant fractions of precursors and mature forms of mRNAs and long noncoding RNAs are degraded by the nuclear exosome in normal human cells. Exosome-mediated degradation of these RNAs requires its cofactor hMTR4. Significantly, hMTR4 plays a key role in specifically recruiting the exosome to its targets. Furthermore, we provide several lines of evidence indicating that hMTR4 executes this role by directly competing with the mRNA export adaptor ALYREF for associating with ARS2, a component of the cap-binding complex (CBC), and this competition is critical for determining whether an RNA is degraded or exported to the cytoplasm. Together, our results indicate that the competition between hMTR4 and ALYREF determines exosome recruitment and functions in creating balanced nuclear RNA pools for degradation and export. © 2017 The Authors.

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

    SciTech Connect

    Breuer, Marian; Zarzycki, Piotr P.; Shi, Liang

    2012-12-01

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

  15. Lidocaine Injection in the Intramuscular Innervation Zone Can Effectively Treat Chronic Neck Pain Caused by MTrPs in the Trapezius Muscle.

    PubMed

    Xie, Peng; Qin, Bangyong; Yang, Fangjiu; Yu, Tian; Yu, Jin; Wang, Jiang; Zheng, Hong

    2015-01-01

    An increasing number of people suffer from neck pain due to life style and prolonged use of computers. Research has revealed that myofascial trigger points (MTrPs) and the intramuscular innervation zone (IZ) are involved in neck pain. MTrPs are induced mainly by IZ dysfunction of the affected skeletal muscle and the 2 do not overlap in location. The question is whether injection treatment in MTrPs or in the IZ is more effective to relieve MTrPs-associated pains. The precise location and body-surface map of the intramuscular IZ in the trapezius muscle and a clinical injection study in the IZ may provide a useful answer to the question. This study aimed to investigate the efficacy of lidocaine injection in the intramuscular IZ for the treatment of chronic neck pain caused by MTrPs in the trapezius muscle. Prospective observational study, approved by the local research ethics. University hospital, departments of Anesthesiology and Anatomy. First, for the determination of IZ distribution and body-surface mapping, a modified intramuscular Sihler's neural staining technique was applied to elucidate nerve distribution patterns of the trapezius muscle. Then, 120 patients with myofascial pain syndrome (MPS) of the trapezius muscle were randomly divided into 5 groups for analysis. Group 1 (n = 24) received injections of saline (0.9% NaCl) at the MTrPs. Group 2 (n = 24) received injections of 0.5% lidocaine at the MTrPs. Group 3 (n = 24) received injections of saline (0.9% NaCl) at the mid-upper trapezius (Point E). Group 4 (n = 24) received injections of 0.5% lidocaine at Point E. Group 5 (n = 24) received a combined injection of 0.5% lidocaine treatment at both Point E and the lower trapezius (Point F). The injection dose was 4 mL at each injection site. All patients received injections once a week for 4 weeks. The visual analogue scale (VAS) and the frequency of painful days per month (FPD) were obtained before treatment and at 2, 4, and 6 months after treatment. The

  16. Comparison Of 252Cf Time Correlated Induced Fisssion With AmLi Induced Fission On Fresh MTR Research Reactor Fuel

    SciTech Connect

    Joshi, Jay Prakash

    The effective application of international safeguards to research reactors requires verification of spent fuel as well as fresh fuel. To accomplish this goal various nondestructive and destructive assay techniques have been developed in the US and around the world. The Advanced Experimental Fuel Counter (AEFC) is a nondestructive assay (NDA) system developed at Los Alamos National Laboratory (LANL) combining both neutron and gamma measurement capabilities. Since spent fuel assemblies are stored in water, the system was designed to be watertight to facilitate underwater measurements by inspectors. The AEFC is comprised of six 3He detectors as well as a shielded andmore » collimated ion chamber. The 3He detectors are used for active and passive neutron coincidence counting while the ion chamber is used for gross gamma counting. Active coincidence measurement data is used to measure residual fissile mass, whereas the passive coincidence measurement data along with passive gamma measurement can provide information about burnup, cooling time, and initial enrichment. In the past, most of the active interrogation systems along with the AEFC used an AmLi neutron interrogation source. Owing to the difficulty in obtaining an AmLi source, a 252Cf spontaneous fission (SF) source was used during a 2014 field trail in Uzbekistan as an alternative. In this study, experiments were performed to calibrate the AEFC instrument and compare use of the 252Cf spontaneous fission source and the AmLi (α,n) neutron emission source. The 252Cf source spontaneously emits bursts of time-correlated prompt fission neutrons that thermalize in the water and induce fission in the fuel assembly. The induced fission (IF) neutrons are also time correlated resulting in more correlated neutron detections inside the 3He detector, which helps reduce the statistical errors in doubles when using the 252Cf interrogation source instead of the AmLi source. In this work, two MTR fuel assemblies varying both in

  17. CymA and Exogenous Flavins Improve Extracellular Electron Transfer and Couple It to Cell Growth in Mtr-Expressing Escherichia coli

    SciTech Connect

    Jensen, Heather M.; TerAvest, Michaela A.; Kokish, Mark G.

    Introducing extracellular electron transfer pathways into heterologous organisms offers the opportunity to explore fundamental biogeochemical processes and to biologically alter redox states of exogenous metals for various applications. While expression of the MtrCAB electron nanoconduit from Shewanella oneidensis MR-1 permits extracellular electron transfer in Escherichia coli, the low electron flux and absence of growth in these cells limits their practicality for such applications. In this paper, we investigate how the rate of electron transfer to extracellular Fe(III) and cell survival in engineered E. coli are affected by mimicking different features of the S. oneidensis pathway: the number of electron nanoconduits,more » the link between the quinol pool and MtrA, and the presence of flavin-dependent electron transfer. While increasing the number of pathways does not significantly improve the extracellular electron transfer rate or cell survival, using the native inner membrane component, CymA, significantly improves the reduction rate of extracellular acceptors and increases cell viability. Strikingly, introducing both CymA and riboflavin to Mtr-expressing E. coli also allowed these cells to couple metal reduction to growth, which is the first time an increase in biomass of an engineered E. coli has been observed under Fe 2O 3 (s) reducing conditions. Overall and finally, this work provides engineered E. coli strains for modulating extracellular metal reduction and elucidates critical factors for engineering extracellular electron transfer in heterologous organisms.« less

  18. CymA and Exogenous Flavins Improve Extracellular Electron Transfer and Couple It to Cell Growth in Mtr-Expressing Escherichia coli

    DOE PAGES

    Jensen, Heather M.; TerAvest, Michaela A.; Kokish, Mark G.; ...

    2016-03-22

    Introducing extracellular electron transfer pathways into heterologous organisms offers the opportunity to explore fundamental biogeochemical processes and to biologically alter redox states of exogenous metals for various applications. While expression of the MtrCAB electron nanoconduit from Shewanella oneidensis MR-1 permits extracellular electron transfer in Escherichia coli, the low electron flux and absence of growth in these cells limits their practicality for such applications. In this paper, we investigate how the rate of electron transfer to extracellular Fe(III) and cell survival in engineered E. coli are affected by mimicking different features of the S. oneidensis pathway: the number of electron nanoconduits,more » the link between the quinol pool and MtrA, and the presence of flavin-dependent electron transfer. While increasing the number of pathways does not significantly improve the extracellular electron transfer rate or cell survival, using the native inner membrane component, CymA, significantly improves the reduction rate of extracellular acceptors and increases cell viability. Strikingly, introducing both CymA and riboflavin to Mtr-expressing E. coli also allowed these cells to couple metal reduction to growth, which is the first time an increase in biomass of an engineered E. coli has been observed under Fe 2O 3 (s) reducing conditions. Overall and finally, this work provides engineered E. coli strains for modulating extracellular metal reduction and elucidates critical factors for engineering extracellular electron transfer in heterologous organisms.« less

  19. The use of MOX caramel fuel mixed with 241Am, 242mAm and 243Am as burnable absorber actinides for the MTR research reactors.

    PubMed

    Shaaban, Ismail; Albarhoum, Mohamad

    2017-07-01

    The MOX (UO 2 &PuO 2 ) caramel fuel mixed with 241 Am, 242m Am and 243 Am as burnable absorber actinides was proposed as a fuel of the MTR-22MW reactor. The MCNP4C code was used to simulate the MTR-22MW reactor and estimate the criticality and the neutronic parameters, and the power peaking factors before and after replacing its original fuel (U 3 O 8 -Al) by the MOX caramel fuel mixed with 241 Am, 242m Am and 243 Am actinides. The obtained results of the criticality, the neutronic parameters, and the power peaking factors for the MOX caramel fuel mixed with 241 Am, 242m Am and 243 Am actinides were compared with the same parameters of the U 3 O 8 -Al original fuel and a maximum difference is -6.18% was found. Additionally, by recycling 2.65% and 2.71% plutonium and 241 Am, 242m Am and 243 Am actinides in the MTR-22MW reactor, the level of 235 U enrichment is reduced from 4.48% to 3% and 2.8%, respectively. This also results in the reduction of the 235 U loading by 32.75% and 37.22% for the 2.65%, the 2.71% plutonium and 241 Am, 242m Am and 243 Am actinides, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Role of outer membrane c-type cytochromes MtrC and OmcA in Shewanella oneidensis MR-1 cell production, accumulation and detachment during respiration on hematite

    USDA-ARS?s Scientific Manuscript database

    The iron-reducing bacterium Shewanella oneidensis MR-1 has the capacity to contribute to iron cycling over the long term by respiring on crystalline iron oxides such as hematite when poorly crystalline phases are depleted. The ability of outer membrane cytochromes OmcA and MtrC of MR-1 to bind to an...

  1. 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

    Mitchell, Andrew C.; Peterson, L.; Reardon, Catherine L.

    2012-07-01

    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 indicatedmore » 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.« less

  2. Acoustic sensors for fission gas characterization: R and D skills devoted to innovative instrumentation in MTR, non-destructive devices in hot lab facilities and specific transducers for measurements of LWR rods in nuclear plants

    SciTech Connect

    Ferrandis, J.Y.; Leveque, G.; Rosenkrantz, E.

    2015-07-01

    irradiation. The instrumented fuel rod incorporating the ultrasonic gas composition sensor was finally irradiated during 2 weeks in nominal conditions. Neutronics calculation will be performed in order to calculate the thermal and fast neutron fluence and the gamma dose absorbed by acoustic sensor. A first evaluation gives a thermal fluence about 4,5.10{sup 19} n/cm{sup 2}, a fast neutrons fluence about 4,5.1018 n/cm{sup 2} and a total gamma dose up to 0,25 MGy The maximal temperature during the irradiation test was about 150 C. Although the ultrasonic sensor appears to be damaged, the optimization of the electrical attack parameters and the development of a new signal processing maintain the measurement feasibility up the end of the irradiation campaign. It was the first time that the composition of fission gas has been monitored all along an irradiation experiment in a MTR, giving access to the gas release kinetics. New researches involve thick film transducers produced by screen-printing process in order to propose piezoelectric structures for harsh temperature and irradiation measurements. The second project consists in the development of a non-destructive device that can be directly applied on a LWR fuel rod. The problem to be solved relates to the measurement of the fission gas pressure and composition in a fuel rod using a non-destructive method. Fuel rod internal pressure is one of the safety criteria applied in nuclear power analyses. This criterion must be verified in order to avoid any fuel-cladding gap reopening risk and therefore any local clad ballooning. Apart from the safety implications, this parameter is also a fuel behaviour indicator and reflects the overall fuel performance in operation, but also during shipping and long-term storage. Rod internal pressure is one criterion amongst others, like cladding corrosion, against which the acceptable fuel burn-up limit is set. A sensor has been achieved in 2007. A full-scale hot cell test of the internal gas

  3. Genetic polymorphisms of genes involved in DNA repair and metabolism influence micronucleus frequencies in human peripheral blood lymphocytes.

    PubMed

    Dhillon, Varinderpal S; Thomas, Philip; Iarmarcovai, G; Kirsch-Volders, Micheline; Bonassi, Stefano; Fenech, Michael

    2011-01-01

    The cytokinesis-block micronucleus cytome (CBMNCyt) assay is a widely used technique for measuring DNA damage in human populations. The formation of micronuclei (MN) in dividing cells can result from chromosome breakage due to unrepaired or mis-repaired DNA lesions or chromosome malsegregation due to mitotic malfunction. The sensitivity of the MN assay to polymorphisms in various genes involved in DNA repair, activation/deactivation of carcinogens/chemicals/drugs/alcohol, folate metabolism pathway and micronutrient transport has been extensively reported in the literature. MN frequency is also an important index for determining DNA repair efficiency phenotype (including mis-repair), response to environmental exposure and identifying various dietary factors required for optimal genome stability. The aim of the present study is to review the reported in vivo associations between genotype and MN frequency in humans taking into considerations the presence of interactions with nutrients levels and/or exposure to genotoxins. One hundred and eleven publications linking MN frequency in peripheral blood lymphocytes to gene polymorphism were retrieved from PubMed. After applying exclusion criteria, only 37 studies were evaluated in the present review. Polymorphisms in XRCC1 (Arg280His), ERCC2 (Lys751Gln), CYP2E1 (c1/c2) and MTR (A2756G) were consistently associated with the MN formation. These results contribute substantial evidence to the hypothesis that genotype may influence MN frequency in human cells.

  4. Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

    PubMed

    Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

    2016-04-15

    In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The Folate Pathway and Nonsyndromic Cleft Lip and Palate

    PubMed Central

    Blanton, Susan H.; Henry, Robin R.; Yuan, Quiping; Mulliken, John B.; Stal, Samuel; Finnell, Richard H.; Hecht, Jacqueline T.

    2013-01-01

    Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth malformation caused by genetic, environmental and gene-environment interactions. Periconceptional supplementation with folic acid, a key component in DNA synthesis and cell division, has reduced the birth prevalence of neural tube defects (NTDs) and may similarly reduce the birth prevalence of other complex birth defects including NSCLP. Past studies investigating the role of two common methylenetetrahydrofolate reductase (MTHFR) SNP polymorphisms, C677T (rs1801133) and A1298C (rs1801131), in NSCLP have produced conflicting results. Most studies of folate pathway genes have been limited in scope, as few genes/SNPs have been interrogated. In this study, we asked whether variations in a more comprehensive group of folate pathway genes were associated with NSCLP and, if so, were there detectable interactions between these genes and environmental exposures. In addition, we evaluated the data for a sex effect. Fourteen folate metabolism related genes were interrogated using eighty-nine SNPs in multiplex and simplex non-Hispanic White (NHW) (317) and Hispanic (128) NSCLP families. Evidence for a risk association between NSCLP and SNPs in nitrous oxide 3 (NOS3) and thymidylate synthetase (TYMS) was detected in the NHW group, whereas associations with methionine synthase (MTR), betaine-homocysteine methyltransferase (BHMT2), MTHFS and SLC19A1 were detected in the Hispanic group. Evidence for over-transmission of haplotypes and gene interactions in the methionine arm was detected. These results suggest that perturbations of the genes in the folate pathway may contribute to NSCLP. There was evidence for an interaction between several SNPs and maternal smoking, and for one SNP with sex of the offspring. These results provide support for other studies that suggest that high maternal homocysteine levels may contribute to NSCLP and should be further investigated. PMID:21254359

  6. Evaluation of the use of nodal methods for MTR neutronic analysis

    SciTech Connect

    Reitsma, F.; Mueller, E.Z.

    1997-08-01

    Although modern nodal methods are used extensively in the nuclear power industry, their use for research reactor analysis has been very limited. The suitability of nodal methods for material testing reactor analysis is investigated with the emphasis on the modelling of the core region (fuel assemblies). The nodal approach`s performance is compared with that of the traditional finite-difference fine mesh approach. The advantages of using nodal methods coupled with integrated cross section generation systems are highlighted, especially with respect to data preparation, simplicity of use and the possibility of performing a great variety of reactor calculations subject to strict timemore » limitations such as are required for the RERTR program.« less

  7. Methylenetetrahydrofolate reductase gene polymorphisms contribute to acute myeloid leukemia and chronic myeloid leukemia susceptibilities: evidence from meta-analyses.

    PubMed

    He, Hairong; He, Gonghao; Wang, Taotao; Cai, Jiangxia; Wang, Yan; Zheng, Xiaowei; Dong, Yalin; Lu, Jun

    2014-10-01

    The expression of methylenetetrahydrofolate reductase (MTHFR) is associated with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Most studies have linked the common functional C677T and A1298C polymorphisms of the MTHFR gene and susceptibility to AML and CML, but the results were not consistent. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses assessing the association of MTHFR C677T and A1298C variations with AML and CML were conducted. Eligible articles were identified from the PubMed and EMBASE databases. All statistical analyses were conducted using Review Manager Software. 10 and 10 studies were included in the meta-analysis about the role of C677T polymorphism on the AML and CML risks, respectively; 6 and 4 studies were included about the role of A1298C polymorphism on the AML and CML risks, respectively. Overall, both the C677T and A1298C polymorphisms were significantly associated with CML risk under the recessive model (P=0.04, OR=1.35, 95% CI=1.02-1.79 for C677T and P=0.003, OR=2.17, 95% CI=1.29-3.63 for A1298C). In addition, the risk of CML was higher in 1298CC genotype carriers than in 1298AA genotype carriers (P=0.004, OR=2.17, 95%=1.28-3.69). Conversely, the overall data failed to indicate a significant association of C677T or A1298C polymorphisms with AML risk under any model. The findings provide evidence that C677T and A1298C polymorphisms are risk factors for CML risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Association of the methylenetetrahydrofolate reductase polymorphism in Korean patients with childhood acute lymphoblastic leukemia.

    PubMed

    Kim, Nam Keun; Chong, So Young; Jang, Moon Ju; Hong, Seung Ho; Kim, Heung Sik; Cho, Eun Kyung; Lee, Jung Ae; Ahn, Myung Ju; Kim, Chul Soo; Oh, Doyeun

    2006-01-01

    Methylenetetrahydrofolate reductase plays a central role in converting folate to methyl donor for DNA methylation. Recently, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations were discovered to be associated with childhood acute lymphoblastic leukemia (ALL), as well as colon cancer, lymphoma, esophageal and stomach cancer. Therefore, it was hypothesized that the MTHFR polymorphisms are associated with the risk of childhood ALL in the Korean population. DNA samples taken from 66 patients with ALL and 100 age-matched controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for detection of MTHFR C677T and A1298C mutations. The frequency of the AC genotype for MTHFR A1298C polymorphism was significantly different between the controls and the cases (OR, 2.22; CI, 95% 1.09-4.51, p=0.03). The 1298AC+CC genotype was also significantly different (OR, 2.11; 95% CI, 1.06-4.22; p=0.049). There was, however, no significant difference for MTHFR C677T polymorphism and combined genotype frequencies between the two groups. Although no consistent results on associations between MTHFR A 1298C polymorphism and ALL in the populations studied were obtained, the A1298C polymorphism, at least in Koreans, may be a genetic determinant among childhood ALL patients.

  9. A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia.

    PubMed

    Lopez-Lopez, E; Martin-Guerrero, I; Ballesteros, J; Garcia-Orad, A

    2013-12-01

    Methotrexate (MTX) is an important component of therapy used to treat childhood acute lymphoblastic leukemia (ALL). Two single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect MTHFR activity. A large body of studies has investigated the potential role of MTHFR SNPs in MTX toxicity in pediatric ALL. However, the results are controversial. In this review and meta-analysis, we critically evaluate the relationship between the C677T and A1298C polymorphisms of MTHFR and MTX toxicity in pediatric ALL. The majority of published reports do not find associations between MTHFR polymorphisms and toxicity in pediatric ALL. When associations are reported, often the results are contradictory to each other. The meta-analysis confirms a lack of association. In conclusion, MTHFR, C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity in pediatric ALL.

  10. Pharmacogenetic predictors of toxicity to platinum based chemotherapy in non-small cell lung cancer patients.

    PubMed

    Pérez-Ramírez, Cristina; Cañadas-Garre, Marisa; Alnatsha, Ahmed; Villar, Eduardo; Delgado, Juan Ramón; Faus-Dáder, María José; Calleja-Hernández, Miguel Ÿngel

    2016-09-01

    Platinum-based chemotherapy is the standard treatment for NSCLC patients with EGFR wild-type, and as alternative to failure to EGFR inhibitors. However, this treatment is aggressive and most patients experience grade 3-4 toxicities. ERCC1, ERCC2, ERCC5, XRCC1, MDM2, ABCB1, MTHFR, MTR, SLC19A1, IL6 and IL16 gene polymorphisms may contribute to individual variation in toxicity to chemotherapy. The aim of this study was to evaluate the effect of these polymorphisms on platinum-based chemotherapy in NSCLC patients. A prospective cohorts study was conducted, including 141 NSCLC patients. Polymorphisms were analyzed by PCR Real-Time with Taqman(®) probes and sequencing. Patients with ERCC1 C118T-T allele (p=0.00345; RR=26.05; CI95%=4.33, 515.77) and ERCC2 rs50872-CC genotype (p=0.00291; RR=4.06; CI95%=1.66, 10.65) had higher risk of general toxicity for platinum-based chemotherapy. ERCC2 Asp312Asn G-alelle, ABCB1 C1236T-TT and the IL1B rs12621220-CT/TT genotypes conferred a higher risk to present multiple adverse events. The subtype toxicity analysis also revealed that ERCC2 rs50872-CC genotype (p=0.01562; OR=3.23; CI95%=1.29, 8.82) and IL16 rs7170924-T allele (p=0.01007; OR=3.19; CI95%=1.35, 7.97) were associated with grade 3-4 hematological toxicity. We did not found the influence of ERCC1 C8092A, ERCC2 Lys751Gln, ERCC2 Asp312Asn, ERCC5 Asp1104His, XRCC1 Arg194Trp, MDM2 rs1690924, ABCB1 C3435T, ABCB1 Ala893Ser/Thr, MTHFR A1298C, MTHFR C677T, IL1B rs1143623, IL1B rs16944, and IL1B rs1143627 on platinum-based chemotherapy toxicity. In conclusion, ERCC1 C118T, ERCC2 rs50872, ERCC2 Asp312Asn, ABCB1 C1236T, IL1B rs12621220 and IL16 rs7170924 polymorphisms may substantially act as prognostic factors in NSCLC patients treated with platinum-based chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2014-03-24

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

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

    PubMed

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

    2012-03-01

    In order to determine the influence of polymorphism in thymidylate synthase (TS 28-bp repeat) and methionine synthase (MS A2756G) genes on the susceptibility to acute lymphoblastic leukemia (ALL), 73 children with ALL and 128 age and sex matched unrelated healthy individuals from the Kermanshah Province of Iran were screened. The genotyping of TS 28-bp repeat and MS A2756G polymorphisms were performed by polymerase chain reaction (PCR) and PCR-RFLP, respectively. The frequency of TS 2R allele in patients and controls were 41.5 and 38%, respectively (Odds ratios (OR) = 1.13, 95%CI 0.73-1.74, P = 0.56). The allelic frequency of G allele of MS was higher (25%) in patients compared with healthy subjects (23%) (OR = 1.09, 95%CI 0.67-1.75, P = 0.71). Considering MS AA and TS 3R3R genotypes as reference indicated that individuals with MS GG + TS 2R2R genotypes have 1.3-fold increase in the risk of ALL (OR = 1.3, 95%CI 0.6-2.7, P = 0.5). Our results showed that neither TS 28-bp repeat nor MS A2756G polymorphisms are risk factors for susceptibility to ALL in Western Iran.

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

    PubMed

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

    2014-01-01

    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.

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

    USDA-ARS?s Scientific Manuscript database

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

  15. Methylenetetrahydrofolate reductase gene polymorphisms: association with risk for pediatric acute lymphoblastic leukemia in north Indians.

    PubMed

    Sood, Swati; Das, Reena; Trehan, Amita; Ahluwalia, Jasmina; Sachdeva, Man Updesh; Varma, Neelam; Bansal, Deepak; Marwaha, Ram Kumar

    2010-05-01

    Genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. We conducted a case-control study in 95 north Indian children with acute lymphoblastic leukemia (ALL) and 255 controls, to investigate the role of MTHFR C677T and A1298C polymorphisms as risk factors in the development of ALL. PCR-RFLP on genomic DNA was carried out to determine C677T and A1298C genotypes. The frequency of MTHFR C677T for the T allele was found to be 23.2% among patients and 18.2% among controls. The frequency of the C allele in MTHFR A1298C was 44.2% among cases and 48.2% in controls. Patients showed a higher frequency of heterozygosity for the MTHFR C677T polymorphism as compared to controls (40% vs 27.8%; OR = 1.73, 95% CI 1.02-2.91, p = 0.02), and the A1298C polymorphism did not show any difference in genotype frequency between cases and controls. MTHFR 677CC/1298AC genotype frequencies showed a statistically significant difference between cases and controls (OR = 0.58, 95% CI 0.34-1.01, p = 0.04). In conclusion, our study in north Indian controls and patients with pediatric ALL showed increased frequency for MTHFR C677T in the heterozygous state and no significant difference in the frequency of A1298C genotype between the two groups.

  16. Methylenetetrahydrofolate reductase polymorphisms and risk of acute lymphoblastic leukemia-evidence from an updated meta-analysis including 35 studies.

    PubMed

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

    2012-09-04

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

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

    PubMed Central

    2012-01-01

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

  18. Development and experimental qualification of a calculation scheme for the evaluation of gamma heating in experimental reactors. Application to MARIA and Jules Horowitz (JHR) MTR Reactors

    SciTech Connect

    Tarchalski, M.; Pytel, K.; Wroblewska, M.

    2015-07-01

    Precise computational determination of nuclear heating which consists predominantly of gamma heating (more than 80 %) is one of the challenges in material testing reactor exploitation. Due to sophisticated construction and conditions of experimental programs planned in JHR it became essential to use most accurate and precise gamma heating model. Before the JHR starts to operate, gamma heating evaluation methods need to be developed and qualified in other experimental reactor facilities. This is done inter alia using OSIRIS, MINERVE or EOLE research reactors in France. Furthermore, MARIA - Polish material testing reactor - has been chosen to contribute to themore » qualification of gamma heating calculation schemes/tools. This reactor has some characteristics close to those of JHR (beryllium usage, fuel element geometry). To evaluate gamma heating in JHR and MARIA reactors, both simulation tools and experimental program have been developed and performed. For gamma heating simulation, new calculation scheme and gamma heating model of MARIA have been carried out using TRIPOLI4 and APOLLO2 codes. Calculation outcome has been verified by comparison to experimental measurements in MARIA reactor. To have more precise calculation results, model of MARIA in TRIPOLI4 has been made using the whole geometry of the core. This has been done for the first time in the history of MARIA reactor and was complex due to cut cone shape of all its elements. Material composition of burnt fuel elements has been implemented from APOLLO2 calculations. An experiment for nuclear heating measurements and calculation verification has been done in September 2014. This involved neutron, photon and nuclear heating measurements at selected locations in MARIA reactor using in particular Rh SPND, Ag SPND, Ionization Chamber (all three from CEA), KAROLINA calorimeter (NCBJ) and Gamma Thermometer (CEA/SCK CEN). Measurements were done in forty points using four channels. Maximal nuclear heating evaluated from measurements is of the order of 2.5 W/g at half of the possible MARIA power - 15 MW. The approach and the detailed program for experimental verification of calculations will be presented. The following points will be discussed: - Development of a gamma heating model of MARIA reactor with TRIPOLI 4 (coupled neutron-photon mode) and APOLLO2 model taking into account the key parameters like: configuration of the core, experimental loading, control rod location, reactor power, fuel depletion); - Design of specific measurement tools for MARIA experiments including for instance a new single-cell calorimeter called KAROLINA calorimeter; - MARIA experimental program description and a preliminary analysis of results; - Comparison of calculations for JHR and MARIA cores with experimental verification analysis, calculation behavior and n-γ 'environments'. (authors)« less

  19. Methylenetetrahydrofolate Reductase Gene Polymorphisms in Children with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Gokcen, Cem; Kocak, Nadir; Pekgor, Ahmet

    2011-01-01

    Objective: The purpose of this study was to evaluate the relationship between 5,10- methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Attention Deficit Hyperactivity Disorder (ADHD) in a sample of Turkish children. Study Design: MTHFR gene polymorphisms were assessed in 40 patients with ADHD and 30 healty controls. Two mutations in the MTHFR gene were investigated using polymerase chain reactions and restriction fragment length polymorphisms. Results: Although there were no statistically significant differences in genotype distributions of the C677T alleles between the ADHD and the control groups (p=0,678) but the genotypic pattern of the distributions of the A1298C alleles was different between the ADHD patients and the controls (p=0,033). Conclusions: Preliminary data imply a possible relationship between A1298C MTHFR polymorphisms and the ADHD. PMID:21897766

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

    PubMed Central

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

    2013-01-01

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

  1. Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans.

    PubMed

    Gutiérrez-Álvarez, Ossyneidee; Lares-Asseff, Ismael; Galaviz-Hernández, Carlos; Reyes-Espinoza, Elio-Aarón; Almanza-Reyes, Horacio; Sosa-Macías, Martha; Chairez Hernández, Isaías; Salas-Pacheco, José-Manuel; Bailón-Soto, Claudia E

    2016-03-01

    Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single-nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study. DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1-15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT*2 and TPMT*3A genotypes. The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found. The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found.

  2. 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children.

    PubMed

    Alcasabas, Patricia; Ravindranath, Yaddanapudi; Goyette, Gerard; Haller, Andrew; Del Rosario, Luz; Lesaca-Medina, Maria Ysabel; Darga, Linda; Ostrea, Enrique M; Taub, Jeffrey W; Everson, Richard B

    2008-08-01

    5,10-Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism. Polymorphisms at the C677T and A1298C loci are associated with reduced activity; consequently more folate substrates are shunted toward thymidylate and DNA synthesis. Several studies have reported a reduced risk of developing ALL in children with MTHFR polymorphisms. The objective of this study was to determine the association between MTHFR polymorphisms and ALL in Filipino children. We conducted a case control study in children diagnosed with ALL at the Philippine General Hospital from 1/2001 through 12/2005. Bone marrow aspirate slides were reviewed by two expert hematologists to verify the morphologic diagnosis of ALL. DNA was isolated from the slides and MTHFR polymorphisms, C677T and A1298C, were determined using Taqman real-time PCR. Cord blood of healthy Filipino newborns served as control. There were a total of 191 ALL and 394 controls genotyped. The distribution of C677T polymorphisms was similar in the two groups (P = 1.0). However, for A1298C, there was significantly more AC and CC genotypes in the ALL compared to controls (P = 0.02; OR 1.57; CI: 1.08-2.28). The 1298C allele frequency for the control group was 36.8% and 677T allele frequency was 9.9%. A1298C polymorphisms is associated with an increased risk for ALL in Filipino children. This may be due to a difference in leukemia biology or to a high prevalence of folate deficiency in Filipinos. Our study reiterates the gene and environment interaction in leukemogenesis.

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

    PubMed

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

    2012-12-01

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

  4. Vitamin B6 and homocysteine levels in carbamazepine treated epilepsy of Khyber Pakhtunkhwa.

    PubMed

    Shakir, Shakirullah; Ali, Niaz; Udin, Zia; Nazish, Haleema; Nabi, Muhammad

    2017-06-01

    The study focused on the plasma levels of vitamin B 6 and homocysteine in different genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes in carbamazepine resistant epilepsy in the population of Khyber Pakhtunkhwa. Patients who were possible candidates for carbamazepine therapy were followed for six months for their seizure control. Plasma levels of vitamin B 6 and homocysteine were determined using immunoassay based techniques at baseline and after six months. MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes were genotyped using restriction fragment length polymorphisms. Seizure control during therapy was recorded on a standardized proforma. Low vitamin B 6 levels and hyperhomocysteinemia were found in 61.7% of resistant patients (n=34). Resistant patients had the following frequencies of variant genotypes (677CT=38.1% and 677TT=24.4%; 1298AC=42.2% and 1298CC=26.1%; 588CT= 47.6% and 315TT= 33.3%) of MTHFR (C677T and A1298C) and GABRG2 (C588T and C315T) genes. A significant decline in vitamin B 6 (P<0.0001) and hyperhomocysteinemia were found in variant genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes. Following six months of carbamazepine of therapy in heterozygous variant genotypes of MTHFR (677CT and 1298AC) and GABRG2 (588CT and 315CT) genes, we observed a significant fall in vitamin B 6 levels and hyperhomocysteinemia.

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

    PubMed Central

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

    2014-01-01

    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

  6. No evidence of association of methylenetetrahydrofolate reductase polymorphism with occurrence of second neoplasms after treatment of childhood leukemia.

    PubMed

    Jazbec, Janez; Kitanovski, Lidija; Aplenc, Richard; Debeljak, Marusa; Dolzan, Vita

    2005-06-01

    Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been associated not only with the risk for acute lymphoblastic leukemia (ALL) in adults and children, but also with increased methotrexate toxicity. The present study aimed to investigate whether MTHFR polymorphisms modify the risk for development of secondary malignancies in children treated for ALL with protocols that included high-dose methotrexate. MTHFR genotypes were determined in DNA samples isolated from archived bone marrow smears of 15 patients with a second malignancy and a matched control group of 30 patients who did not developed a second malignancy after the treatment for ALL. The frequencies of MTHFR C677T and A1298C genotypes in all patients were: C677T: CC 40%, CT 46.7% and TT 13.3% and A1298C: AA 46.7%, AC 44.4% and CC 8.9%. The relative risk for second malignancy was not significantly increased in ALL patients having at least one polymorphic C667T [odds ratio (OR) 1.51; 95% confidence interval (CI) 0.43-5.31] or one polymorphic A1298C allele (OR 1; 95% CI 0.29?-?3.46). Our study suggests that MTHFR polymorphisms are not associated with increased risk of second cancer in children treated with high-dose methotrexate.

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

    PubMed

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

    2014-01-01

    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.

  8. The role of the methylenetetrahydrofolate reductase 677 and 1298 polymorphisms in Cretan children with acute lymphoblastic leukemia.

    PubMed

    Karathanasis, Nikolaos V; Stiakaki, Eftichia; Goulielmos, George N; Kalmanti, Maria

    2011-01-01

    Acute lymphoblastic leukemia (ALL) is the most common form of malignancy in children. Recently, many studies have examined factors influencing both the susceptibility to ALL and the metabolism of widely used chemotherapeutic agents. These factors include, among others, single-nucleotide polymorphisms in various genes, such as the gene encoding for methylenetetrahydrofolate reductase (MTHFR), which has been proven polymorphic at the nucleotide positions 677 and 1298. Thirty-five children with ALL and 48 healthy adults of Cretan origin were genotyped for the presence of the MTHFR 677 and 1298 single-nucleotide polymorphisms. The possible correlation of the polymorphisms with the risk for ALL and the presence of methotrexate-induced toxicities were examined. No significant association between the MTHFR genotypes and the susceptibility to ALL was observed. A borderline statistically significant relationship was detected after methotrexate administration, between the C677T genotype (polymorphisms) and leukopenia (p = 0.050) and between the A1298C polymorphism and normal aspartate transaminase and alanine transaminase values (p = 0.065 and p = 0.053, respectively), which was strengthened for aspartate transaminase, after grouping the A1298A and A1298C genotypes together (p = 0.039). In our population the MTHFR C677T and A1298C polymorphisms are related with hematologic toxicity and hepatotoxicity, respectively, and could be suggested as prognostic factors for these adverse events.

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

    PubMed

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

    2014-10-01

    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.

  10. Methylenetetrahydrofolate reductase gene polymorphism and risk of chronic myelogenous leukemia: a meta-analysis.

    PubMed

    Li, Chen; Yichao, Jin; Jiaxin, Lin; Yueting, Zhang; Qin, Lu; Tonghua, Yang

    2015-01-01

    Reported evidence supports a role for methylenetetrahydrofolate reductase (MTHFR) in the risk of chronic myelogenous leykemia (CML). However, these reports arrived at non-conclusive and even conflicting results regarding the association between two common MTHFR polymorphisms (C677T and A1298C) and CML risk. Thus, a meta-analysis was carried out to clarify a more precise association between these two polymorphisms and the CML risk by updating the available publications. Pooled odds ratios (OR) with corresponding 95% confidence interval (95% CI) and stratification analysis were performed to estimate the relationship between MTHFR polymorphisms and the risk of CML under different genetic comparison models. Data from the meta-analysis showed no significant association between MTHFR C677T polymorphism and CML risk. However, significant associations were found between MTHFR A1298C variants and CML risk under homozygous comparison model (CC vs AA, OR=1.62, 95% CI=1.11-2.36, p=0.01) and dominant comparison model (CC+AC vs AA, OR=1.68, 95% CI=1.17-2.43, p=0.005) in overall population; especially more obvious impacts were noticed for Asian populations in subgroup analysis for homozygous model (CC vs AA, OR=2.00, 95% CI=1.25-3.21, p=0.004) and dominant model (CC+AC vs AA, OR=2.49, 95% CI=1.42-4.36, p=0.001), but this did not apply in Caucasian populations. The results of this meta-analysis suggested no significant association between MTHFR C677T polymorphism and CML risk, while an increased CML risk was noticed for 1298C variant carriers, especially in Asian populations but not in Caucasian populations, which suggested ethnicity differences between MTHFR A1298C polymorphisms and risk of CML.

  11. 5,10-Methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic leukemia risk: a meta-analysis.

    PubMed

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

    2006-10-01

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

  12. TS Gene Polymorphisms Correlate with Susceptibility to Acute Lymphocytic Leukemia in Children.

    PubMed

    Zou, Runyin; He, Xiangling; Wu, Yanpeng; Tian, Xin; You, Yalan; Zheng, Mincui; Li, Wanli; Zou, Hui; Liu, Hua; Zhu, Xiujuan; Zhu, Chengguang

    2017-06-24

    BACKGROUND Acute lymphocytic leukemia (ALL) in children is a clonal disease of bone marrow hematopoietic stem cells. This study aimed to explore the associations between MTHFR or TS genetic polymorphisms and susceptibility to acute lymphocytic leukemia (ALL) in children. MATERIAL AND METHODS This case-control study included 79 ALL patients (case group) and 102 non-ALL patients (control group). Post-PCR genomic DNA sequencing revealed MTHFR C677T and MTHFR A1298C genotypes and TS polymorphisms. The χ² test was used to compare differences in MTHFR and TS polymorphisms (including genotypic and allelic distributions) between groups. Logistic regression analysis was used to determine genetic polymorphisms and ALL risk associations. RESULTS The results indicated that TS 3R allele frequency was significantly higher in the case group than in the control group (χ²=7.45, P<0.05). The MTHFR C677T and MTHFR A1298C polymorphisms were not associated with ALL risk. Compared to the TS 2R/2R genotype, subjects carrying TS 2R/3R were twice as likely to develop ALL, and the TS 3R/3R+3R/4R genotype carried a 4-fold higher risk of developing ALL (OR=1.96, CI: 1.14-3.36). CONCLUSIONS The TS genetic polymorphisms increase the ALL risk. The TS 3R allele was a risk factor for ALL. There were no associations between MTHFR C677T or MTHFR A1298C polymorphisms and ALL susceptibility.

  13. Correlation between methyltetrahydrofolate reductase (MTHFR) polymorphisms and isolated patent ductus arteriosus in Taiwan.

    PubMed

    Chao, Chia-Sheng; Wei, Jeng; Huang, Hurng-Wern; Yang, Shyh-Chyun

    2014-07-01

    Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene polymorphisms are associated with the risk of patent ductus arteriosus (PDA) congenital heart defects. This study aimed to determine the association of these polymorphisms in patients with isolated PDA and in non-PDA patients group without congenital heart disease. This retrospective case-controlled study was undertaken in 17 patients with isolated PDA and a control non-PDA group consisting of 34 subjects without congenital heart disease. MTHFR gene polymorphisms were analysed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, the genotype distribution of the MTHFR gene was compared among different ethnicities using the HapMap database. In contrast to the MTHFR C677T polymorphism, differences in the MTHFR A1298C genotype were observed between the two groups (P=0.002); a greater proportion of the PDA patients had the MTHFR 1298CC and 1298AA genotypes as compared to the non-PDA control group. After merging the data obtained from the Taiwanese participants with that from the HapMap database, genetic diversity of the MTHFR 1298AA genotype was observed. Thus, the MTHFR A1298C polymorphism is associated with isolated PDA in Taiwan. Larger studies are necessary to evaluate the prognostic value of determining MTHFR polymorphism in PDA. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  14. The rs4846049 polymorphism in the 3'UTR region of the MTHFR gene increases the migraine susceptibility in an Iranian population.

    PubMed

    Salehi, Mohaddeseh; Amin-Beidokhti, Mona; Safarpour Lima, Behnam; Gholami, Milad; Javadi, Gholam-Reza; Mirfakhraie, Reza

    2018-01-01

    Migraine is a painful complex neurovascular disease characterized by recurrent moderate-to-severe headaches. Increased level of homocysteine is related to dilation of cerebral vessels and endothelial injury that could trigger migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine metabolism and, therefore, play an important role in the etiology of the disease. We aimed to investigate the possible association between MTHFR gene rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian population. In this genetic association study, 498 individuals were enrolled, including 223 migraine patients and 275 healthy controls. Genotyping was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction fragment length polymorphism for C677T and A1298C polymorphisms. The association between rs4846049 and C677T polymorphisms and migraine was observed. For the rs4846049 polymorphism, the association was detected under a dominant model ( P =0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41-0.87), and for the C677T polymorphism, the TT genotype frequency was significantly different in the studied groups ( P =0.009; OR =2.48; 95% CI, 1.25-4.92). No significant differences in the genotype or allele frequencies were found for the A1298C polymorphism between the migraineurs and controls. Present data provide evidence for the association of rs4846049 and C677T polymorphisms in the MTHFR gene and migraine. Further studies are required to validate the significance of the studied genetic variations in diverse ethnic populations.

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

    PubMed

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

    2014-11-01

    Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL and may be modified by thiopurine methyltransferase activity as well as by MTHFR genotype. We assessed TPMT *3A, *3B, *3C, and MTHFR C677T and A1298C germline genetic polymorphisms among 351 patients enrolled in the thioguanine treatment arm of CCG-1952 clinical trial. TPMT and MTHFR C677T genotypes were not associated with SOS risk. The combination of MTHFR and TPMT variant genotypes was not associated with SOS risk. These suggest that germline genetic variation in TPMT and MTHFR do not significantly alter SOS risk in patients exposed to thioguanine. © 2014 Wiley Periodicals, Inc.

  16. Methylene tetrahydrofolate reductase gene polymorphism in Egyptian children with acute lymphoblastic leukemia.

    PubMed

    Tantawy, Azza A G; El-Bostany, Eman A; Adly, Amira A M; Abou El Asrar, Mohammed; El-Ghouroury, Eman A; Abdulghaffar, Esmat E

    2010-01-01

    Genetic variations of the enzymes involved in chemotherapy metabolism in cancer patients may play a role in determining relapse and toxicity risks. Methotrexate is a key drug in acute lymphoblastic leukemia (ALL) treatment; it inhibits DNA replication by blocking the conversion of 5,10 methylene tetrahydrofolate to 5-methylene tetrahydrofolate by methylene tetrahydrofolate reductase (MTHFR). MTHFR is central to folate metabolism and has two common functional polymorphisms (C677>T and A1298>C). The present study aimed to assess the prevalence of MTHFR polymorphisms C677>T and A1298>C in Egyptian children with ALL and the relation to the frequency of drug-induced complications and relapse rate. Forty ALL patients were included in the study. They were treated according to modified ALL-BFM 90 protocol, and were followed up for 3.1-6.5 years. The severity and duration of hepatic, mucosal and infectious complications during therapy were reported. MTHFR genotyping was done with a PCR-based restriction fragment length polymorphism assay. The MTHFR C677>T polymorphic allele frequencies were 40, 27.5, and 32.5% for TT, CT, and CC genotypes, respectively among the studied ALL patients. The MTHFR A1298>C polymorphic allele frequencies were 40, 35, and 25% for AA, AC, and CC genotypes, respectively. Methotrexate therapy was significantly associated with increased grade III/IV toxicity in TT genotype: diarrhea in 81.3%, oral mucositis in 81.3%, elevated transaminases in 87.5%, neutropenia in 78.7% compared to values of 7.7, 7.7, 15.3, and 7.7% in CC genotype, respectively (P < 0.0001, P < 0.0001, P < 0.0001, and P = 0.03). The 677 TT genotype was significantly associated with relapse in 5 years in 56.3%, compared to 18.2% in CT and 0% in CC alleles. The overall 5 years survival was significantly lower in 677 TT (50%) compared with CC genotypes (92.3%) (P = 0.001). No significant relation was found between MTHFR A1298C polymorphism and the risks of therapy induced complications

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

    PubMed

    Kiyohara, Chikako; Horiuchi, Takahiko; Takayama, Koichi; Nakanishi, Yoichi

    2011-10-25

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

  18. Migraine and genetic polymorphisms: an overview.

    PubMed

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

    2012-01-01

    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), β-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.

  19. Migraine and Genetic Polymorphisms: An Overview

    PubMed Central

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

    2012-01-01

    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), β-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

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

    PubMed

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

    2015-05-01

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

  1. Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies.

    PubMed

    Zintzaras, Elias; Doxani, Chrysoula; Rodopoulou, Paraskevi; Bakalos, Georgios; Ziogas, Dimitris C; Ziakas, Panayiotis; Voulgarelis, Michael

    2012-04-01

    Acute lymphoblastic leukemia (ALL) is a complex disease with genetic background. The genetic association studies (GAS) that investigated the association between ALL and the MTHFR C677T and A1298C gene variants have produced contradictory or inconclusive results. In order to decrease the uncertainty of estimated genetic risk effects, a meticulous meta-analysis of published GAS related the variants in the MTFHR gene with susceptibility to ALL was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR(G)). Cumulative and recursive cumulative meta-analyses were also performed. The analysis showed marginal significant association for the C677T variant, overall [OR=0.91 (0.82-1.00) and OR(G)=0.89 (0.79-1.01)], and in Whites [OR=0.88 (0.77-0.99) and OR(G)=0.85 (0.73-0.99)]. The A1298C variant produced non-significant results. For both variants, the cumulative meta-analysis did not show a trend of association as evidence accumulates and the recursive cumulative meta-analysis indicated lack of sufficient evidence for denying or claiming an association. The current evidence is not sufficient to draw definite conclusions regarding the association of MTHFR variants and development of ALL. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2007-09-01

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

  3. Methylenetetrahydrofolate reductase gene polymorphisms and acute lymphoblastic leukemia risk: a meta-analysis based on 28 case-control studies.

    PubMed

    Tong, Na; Sheng, Xiaojing; Wang, Meilin; Fang, Yongjun; Shi, Danni; Zhang, Zhizhong; Zhang, Zhengdong

    2011-10-01

    Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation and nucleotide synthesis. Accumulated evidence has demonstrated that C677T and A1298C polymorphisms of the MTHFR gene are associated with acute lymphoblastic leukemia (ALL) risk, but the results have been inconclusive. To determine a more precise estimation, we performed a meta-analysis of 28 studies with 4240 cases and 9289 controls. We found that the 677TT genotype showed a reduced risk of ALL compared with the 677CC genotype in the overall population (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.61-0.92). The reduced risk was pronounced only among the Caucasian population (OR 0.68, 95% CI 0.51-0.90), not the Asian (OR 0.89, 95% CI 0.75-1.05). For the MTHFR A1298C polymorphism, no significant association with ALL susceptibility was observed in the pooled analyses. However, significantly increased ALL risk was found in childhood in the comparison of 1298CA versus AA genotype. This study provides evidence that MTHFR polymorphisms may play an important role in the development of ALL.

  4. Methylenetetrahydrofolate reductase polymorphisms and susceptibility to acute lymphoblastic leukemia in a Chinese population: a meta-analysis.

    PubMed

    Xiao, Yi; Deng, Tao-Ran; Su, Chang-Liang; Shang, Zhen

    2014-01-01

    Although many epidemiologic studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their association with acute lymphoblastic leukemia (ALL), definitive conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of ALL, a meta-analysis was performed in a Chinese population. A computerized literature search was carried out in PubMed, the Chinese Biomedicine (CBM) database, China National Knowledge Infrastructure (CNKI) platform, and the Wanfang database (Chinese) to collect relevant articles. A total of 11 articles including 1,738 ALL cases and 2,438 controls were included in this meta-analysis. Overall, a significantly decreased association was found between the MTHFR C677T polymorphism and ALL risk when all studies in Chinese populations were pooled into the meta-analysis. In subgroup analyses stratified by age, ethnicity, and source of controls, the same results were observed in children, in population-based studies, and in people with no stated ethnicity. However, a significantly increased association was also found for MTHFR C677T in hospital-based studies, and for MTHFR A1298C in people with no stated ethnicity. Our results suggest that the MTHFR C677T and A1298C polymorphisms may be potential biomarkers for ALL risk in Chinese populations, and studies with a larger sample size and wider population spectrum are required before definitive conclusions can be drawn. © 2014 S. Karger GmbH, Freiburg.

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

    PubMed

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

    2014-05-01

    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.

  6. Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico

    PubMed Central

    Contreras-Cubas, Cecilia; Sánchez-Hernández, Beatríz E.; García-Ortiz, Humberto; Martínez-Hernández, Angélica; Barajas-Olmos, Francisco; Cid, Miguel; Mendoza-Caamal, Elvia C.; Centeno-Cruz, Federico; Ortiz-Cruz, Gabriela; Jiménez-López, José Concepción; Córdova, Emilio J.; Salas-Bautista, Eva Gabriela; Saldaña-Alvarez, Yolanda; Fernández-López, Juan Carlos; Mutchinick, Osvaldo M.

    2016-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Folate deficiency has been related to several conditions, including neural tube defects (NTDs) and cardiovascular diseases. Hence, MTHFR genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C MTHFR polymorphisms in Mexican Amerindians (MAs), from the largest sample included in a genetic study (n = 2026, from 62 ethnic groups), and in a geographically-matched Mexican Mestizo population (MEZ, n = 638). The 677T allele was most frequent in Mexican individuals, particularly in MAs. The frequency of this allele in both MAs and MEZs was clearly enriched in the South region of the country, followed by the Central East and South East regions. In contrast, the frequency of the 1298C risk allele in Mexicans was one of the lowest in the world. Both in MAs and MEZs the variants 677T and 1298C displayed opposite allele frequency gradients from southern to northern Mexico. Our findings suggest that in Mestizos the 677T allele was derived from Amerindians while the 1298C allele was a European contribution. Some subgroups showed an allele frequency distribution that highlighted their genetic diversity. Notably, the distribution of the frequency of the 677T allele was consistent with that of the high incidence of NTDs reported in MEZ. PMID:27649570

  7. Polymorphisms in the methylene tetrahydrofolate reductase and methionine synthase reductase genes and their correlation with unexplained recurrent spontaneous abortion susceptibility.

    PubMed

    Zhu, L

    2015-07-28

    We aimed to explore the correlation between unexplained recurrent spontaneous abortion and polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes. A case control study was conducted in 118 patients with unexplained recurrent spontaneous abortion (abortion group) and 174 healthy women (control group). The genetic material was extracted from the oral mucosal epithelial cells obtained from all subjects. The samples were subjected to fluorescence quantitative PCR to detect the single nucleotide polymorphisms (SNPs) in the MTHFR (C677T and A1298C) and MTRR (A66G) gene loci. The distribution frequency (18/118, 15.3%) of the MTHFR 677TT genotype was significantly higher in the abortion group (χ2 = 11.006, P = 0.004) than in the control group (2/174, 1.1%); on the other hand, the distribution frequency of the MTHFR A1298C genotype did not significantly differ between the abortion and control groups (χ(2) = 0.441, P = 0.507). The distribution frequency of the MTRR A66G genotype was also significantly higher in the abortion group (14/118, 11.9%; χ(2) = 10.503, P = 0.005) than in the control group (8/174, 4.6%). The MTHFR C677T and MTRR A66G polymorphisms are significantly correlated with the occurrence of spontaneous abortion.

  8. Hyperhomocysteinemia and MTHFR polymorphisms as antenatal risk factors of white matter abnormalities in two cohorts of late preterm and full term newborns.

    PubMed

    Marseglia, Lucia M; Nicotera, Antonio; Salpietro, Vincenzo; Giaimo, Elisa; Cardile, Giovanna; Bonsignore, Maria; Alibrandi, Angela; Caccamo, Daniela; Manti, Sara; D'Angelo, Gabriella; Mamì, Carmelo; Di Rosa, Gabriella

    2015-01-01

    Higher total homocysteine (tHcy) levels, and C677T and A1298C methylenetetrahydrofolate (MTHFR) polymorphisms, have been reported in preterm or full term newborns with neonatal encephalopathy following perinatal hypoxic-ischemic insult. This study investigated the causal role of tHcy and MTHFR polymorphisms together with other acquired risk factors on the occurrence of brain white matter abnormalities (WMA) detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. A total of 171 newborns (81 M, 47.4%), 45 (26.3%) born <37 wks, and 126 (73.7%) born ≥37 wks were recruited in the study. cUS detected predominant WMA pattern in 36/171 newborns (21.1%) mainly characterized by abnormal periventricular white matter signal and mild-to-moderate periventricular white matter volume loss with ventricular dilatation (6/36, 16.6%). WMA resulted in being depending on tHcy levels (P < 0.014), lower GA (P < 0.000), lower Apgar score at 1 minutes (P < 0.000) and 5 minutes (P < 0.000), and 1298AC and 677CT/1298AC genotypes (P < 0.000 and P < 0.000). In conclusion, both acquired and genetic predisposing antenatal factors were significantly associated with adverse neonatal outcome and WMA. The role of A1298C polymorphism may be taken into account for prenatal assessment and treatment counseling.

  9. CBS mutations and MTFHR SNPs causative of hyperhomocysteinemia in Pakistani children.

    PubMed

    Ibrahim, Shahnaz; Maqbool, Saadia; Azam, Maleeha; Iqbal, Mohammad Perwaiz; Qamar, Raheel

    2018-03-29

    Three index patients with hyperhomocysteinemia and ocular anomalies were screened for cystathionine beta synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Genotyping of hyperhomocysteinemia associated MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) was done by PCR-restriction fragment length polymorphism. Sanger sequencing was performed for CBS exonic sequences along with consensus splice sites. In the case of MTHFR polymorphisms, all the patients were heterozygous CT for the single nucleotide polymorphism (SNP) C677T and were therefore carriers of the risk allele (T), while the patients were homozygous CC for the risk genotype of the SNP A1298C. CBS sequencing resulted in the identification of two novel mutations, a missense change (c.467T>C; p.Leu156Pro) in exon 7 and an in-frame deletion (c.808_810del; p.Glu270del) in exon 10. In addition, a recurrent missense mutation (c.770C>T; p.Thr257Met) in exon 10 of the gene was also identified. The mutations were present homozygously in the patients and were inherited from the carrier parents. This is the first report from Pakistan where novel as well as recurrent CBS mutations causing hyperhomocysteinemia and lens dislocation in three patients from different families are being reported with the predicted effect of the risk allele of the MTHFR SNP in causing hyperhomocysteinemia.

  10. Methylenetetrahydrofolate reductase (MTHFR) genotype, smoking habit, metastasis and oral cancer in Taiwan.

    PubMed

    Tsai, Chia-Wen; Hsu, Chia-Fang; Tsai, Ming-Hsui; Tsou, Yung-An; Hua, Chun-Hung; Chang, Wen-Shin; Lin, Cheng-Chieh; Bau, Da-Tian

    2011-06-01

    The aim of this study was to evaluate the association and interaction of genotypic polymorphism in methylenetetrahydrofolate reductase (MTHFR) with smoking habits and oral cancer in Taiwan. Two well-known polymorphic variants of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed in association with oral cancer risk, and their joint effects with individual smoking habits on oral cancer risk are discussed. In total, 620 oral cancer patients and 620 non-cancer controls in central Taiwan were recruited and genotyped. The MTHFR C677T genotype, but not the A1298C, was differently distributed between the oral cancer and control groups. The T allele of MTHFR C677T was significantly more frequently found in controls than in oral cancer patients. Joint effects of smoking and MTHFR C677T genotype significantly affected oral cancer susceptibility. The MTHFR C677T CT and TT genotypes in association with smoking conferred lower odds ratios of 0.66 and 0.54 (95% confidence interval=0.49-0.82 and 0.39-0.86), respectively. Those patients with MTHFR C677T CT and TT genotypes also had a lower risk of oral cancer metastasis. MTHFR C677T genotype may have joint effects with smoking on oral carcinogenesis, and may be a useful biomarker for prediction and prognosis of oral cancer.

  11. The importance of folate, vitamins B6 and B12 for the lowering of homocysteine concentrations for patients with recurrent pregnancy loss and MTHFR mutations.

    PubMed

    Serapinas, Danielius; Boreikaite, Evelina; Bartkeviciute, Agne; Bandzeviciene, Rita; Silkunas, Mindaugas; Bartkeviciene, Daiva

    2017-09-01

    In patients with MTHFR (methylenetetrahydrofolate reductase) mutations and hyperhomocysteinemia, recurrent pregnancy loss is a frequent feature. The aim of the study was to evaluate the impact of folic acid, vitamins B6 and B12 supplementation for the lowering of total homocysteine concentrations and pregnancy. 16 patients who had had 3 or more miscarriages and MTHFR mutations were used in the study. They received methylfolate (5mg/day), vitamin B6 (50mg/day) and vitamin B12 (1mg/week). Supplementation induced a decrease in homocysteine from 19.4±5.3μmol/L to 6.9±2.2μmol/L after folate supplementation (p<0.05). During one year 7 women became pregnant and delivered. Two women delivered from the homozygous C677T mutations group (7 patients) and combined heterozygous C677T/A1298C mutations group (5 patients), while 3 deliveries were in A1298C homozygous mutations group (4 patients). In conclusion, supraphysiologic methylfolate, vitamins B6 and B12 supplementation in woman with MTHFR mutations has a beneficial effect on pregnancy outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Association between Thrombophilic Genes Polymorphisms and Recurrent Pregnancy Loss Susceptibility in the Iranian Population: a Systematic Review and Meta-Analysis

    PubMed Central

    Kamali, Mahdieh; Hantoushzadeh, Sedigheh; Borna, Sedigheh; Neamatzadeh, Hossein; Mazaheri, Mahta; Noori-Shadkam, Mahmood; Haghighi, Fatemeh

    2018-01-01

    Studies have indicated that thrombophilic genes polymorphisms are associated with recurrent pregnancy loss (RPL) in the Iranian population. We aimed to evaluate the precise association between thrombophilic genes polymorphisms (MTHFR C677T, MTHFR A1298C, Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G) and RPL risk in the Iranian population. PubMed, Web of Science, Google Scholar, and ISC were searched for eligible articles published up to April 1, 2017. In total, 37 case-control studies in 18 relevant publications were selected: 1,199, 1,194, 630, 830, and 955 RPL cases and 1,079, 1079, 594, 794, and 499 controls for MTHFR C677T, MTHFR A1298C,Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G, respectively. The results indicated a significant increased risk of RPL in all genetic models in the population. Also, Prothrombin G20210A and FVL G1691A as well as PAI-1 4G/5G polymorphisms were associated with RPL risk in the Iranian population. Hence, thrombophilic genes polymorphisms are associated with an increased RPL risk in the Iranian population. PMID:28734273

  13. Novel Applications of Ultrasound Technology to Visualize and Characterize Myofascial Trigger Points and Surrounding Soft Tissue

    PubMed Central

    Sikdar, Siddhartha; Shah, Jay P.; Gebreab, Tadesse; Yen, Ru-Huey; Gilliams, Elizabeth; Danoff, Jerome; Gerber, Lynn H.

    2009-01-01

    Objective Apply ultrasound (US) imaging techniques to better describe the characteristics of myofascial trigger points (MTrPs) and the immediately adjacent soft tissue. Design Descriptive (exploratory) study. Setting Biomedical research center. Participants 9 subjects meeting Travell and Simons’s criteria for MTrPs in a taut band in the upper trapezius. Interventions (None) Main Outcome Measures MTrPs were evaluated by 1) physical examination, 2) pressure algometry, and 3) three types of ultrasound imaging including grayscale (2D US), vibration sonoelastography (VSE), and Doppler. Methods Four sites in each patient were labeled based on physical examination as either active MTrP (spontaneously-painful, A-MTrP), latent MTrP (non-painful, L-MTrP), or normal myofascial tissue. US examination was performed on each subject by a team blinded to the physical findings. A 12-5 MHz US transducer was used. VSE was performed by color Doppler variance imaging while simultaneously inducing vibrations (~92Hz) with a handheld massage vibrator. Each site was assigned a tissue imaging score (TIS) as follows: 0 = uniform echogenicity and stiffness; 1 = focal hypoechoic region with stiff nodule; 2 = multiple hypoechoic regions with stiff nodules. Blood flow in the neighborhood of MTrPs was assessed using Doppler imaging. Each site was assigned a blood flow waveform score (BFS) as follows: 0 = normal arterial flow in muscle; 1 = elevated diastolic flow; 2 = high-resistance flow waveform with retrograde diastolic flow. Results MTrPs appeared as focal, hypoechoic regions on 2D US, indicating local changes in tissue echogenicity, and as focal regions of reduced vibration amplitude on VSE, indicating a localized stiff nodule. MTrPs were elliptical in shape, with a size of 0.16 ± 0.11 cm2. There were no significant differences in size between A-MTrPs and L-MTrPs. Sites containing MTrPs were more likely to have higher TIS compared to normal myofascial tissue (p<0.002). Small arteries (or

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

    PubMed Central

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

    2013-01-01

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

  15. The first step in using a robot in brain injury rehabilitation: patients' and health-care professionals' perspective.

    PubMed

    Boman, Inga-Lill; Bartfai, Aniko

    2015-01-01

    To evaluate the usability of a mobile telepresence robot (MTR) in a hospital training apartment (HTA). The MTR was manoeuvred remotely and was used for communication when assessing independent living skills, and for security monitoring of cognitively impaired patients. Occupational therapists (OTs) and nurses received training in how to use the MTR. The nurses completed a questionnaire regarding their expectations of using the MTR. OTs and patients staying in the HTA were interviewed about their experiences of the MTR. Interviews and questionnaires were analysed qualitatively. The HTA patients were very satisfied with the MTR. The OTs and nurses reported generally positive experiences. The OT's found that assessment via the MTR was more neutral than being physically present. However, the use of the MTR implied considerable difficulties for health-care professionals. The main obstacle for the nurses was the need for fast and easy access in emergency situations while protecting the patients' integrity. The results indicate that the MTR could be a useful tool to support daily living skills and safety monitoring of HTA patients. However, when designing technology for multiple users, such as health-care professionals, the needs of all users, their routines and support services involved, should also be considered. Implications for Rehabilitation A mobile telepresence robot (MTR) can be a useful tool for assessments and communication in rehabilitation. The design of the robot has to allow easy use by remote users, particularly in emergency situations. When designing MTRs the needs of ALL users have to be taken into consideration.

  16. Charge carrier transport in polycrystalline organic thin film based field effect transistors

    NASA Astrophysics Data System (ADS)

    Rani, Varsha; Sharma, Akanksha; Ghosh, Subhasis

    2016-05-01

    The charge carrier transport mechanism in polycrystalline thin film based organic field effect transistors (OFETs) has been explained using two competing models, multiple trapping and releases (MTR) model and percolation model. It has been shown that MTR model is most suitable for explaining charge carrier transport in grainy polycrystalline organic thin films. The energetic distribution of traps determined independently using Mayer-Neldel rule (MNR) is in excellent agreement with the values obtained by MTR model for copper phthalocyanine and pentacene based OFETs.

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

    PubMed

    Ge, Hong-You

    2010-10-01

    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.

  18. Hospital-based epidemiological and clinical characterisation of the malignant transformation of oral leukoplakia in a Chinese population.

    PubMed

    Lyu, Ming-Yue; Guo, Yu-Si; Li, Shuo; Yang, Di; Hua, Hong

    2017-08-01

    The aim of this review was to analyse, systematically, hospital-based epidemiological information concerning the malignant transformation rate (MTR) of oral leukoplakia (OL) in a Chinese population, as well as the associated risk factors. Four electronic databases were searched for studies dealing with OL and related risk factors, including age, gender, type of lesion, site, and smoking and drinking habits. The MTR of OL in the hospital-based Chinese population ranged from 4% to 13%, based on the studies analysed. Regarding risk factors, we found that female patients had a higher MTR than male patients, and that patients older than 50 years of age also had a higher MTR. Patients who smoked had a lower MTR, while alcohol consumption seemed to have no association with MTR. Malignant transformation occurred most commonly on the tongue. Regarding lesion type, non-homogeneous OL had a higher MTR, with the granular type having the highest MTR. Our results regarding the epidemiology of OL showed a similar trend to those reported in western populations and provided preliminary epidemiological information on the Chinese population. Our findings show that female gender, age >50 years and non-homogeneous OL are risk factors for malignant transformation. It is important to develop clinical strategies to educate, diagnose and treat patients with OL and to minimise the MTR of OL. © 2017 FDI World Dental Federation.

  19. Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability.

    PubMed

    Khaleeli, Z; Cercignani, M; Audoin, B; Ciccarelli, O; Miller, D H; Thompson, A J

    2007-08-01

    Disability in primary progressive multiple sclerosis (PPMS) has been correlated with damage to the normal appearing brain tissues. Magnetization transfer ratio (MTR) and volume changes indicate that much of this damage occurs in the normal appearing grey matter, but the clinical significance of this remains uncertain. We aimed to localize these changes to distinct grey matter regions, and investigate the clinical impact of the MTR changes. 46 patients with early PPMS and 23 controls underwent MT and high-resolution T1-weighted imaging. Patients were scored on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite and subtests (Nine-Hole Peg Test, Timed Walk Test, Paced Auditory Serial Addition Test [PASAT]). Grey matter volume and MTR were compared between patients and controls, adjusting for age. Mean MTR for significant regions within the motor network and in areas relevant to PASAT performance were correlated with appropriate clinical scores, adjusting for grey matter volume. Patients showed reduced MTR and atrophy in the right pre- and left post-central gyri, right middle frontal gyrus, left insula, and thalamus bilaterally. Reduced MTR without significant atrophy occurred in the left pre-central gyrus, left superior frontal gyri, bilateral superior temporal gyri, right insula and visual cortex. Higher EDSS correlated with lower MTR in the right primary motor cortex (BA 4). In conclusion, localized grey matter damage occurs in early PPMS, and MTR change is more widespread than atrophy. Damage demonstrated by reduced MTR is clinically eloquent.

  20. The NASA modern technology rotors program

    NASA Technical Reports Server (NTRS)

    Watts, M. E.; Cross, J. L.

    1986-01-01

    Existing data bases regarding helicopters are based on work conducted on 'old-technology' rotor systems. The Modern Technology Rotors (MTR) Program is to provide extensive data bases on rotor systems using present and emerging technology. The MTR is concerned with modern, four-bladed, rotor systems presently being manufactured or under development. Aspects of MTR philosophy are considered along with instrumentation, the MTR test program, the BV 360 Rotor, and the UH-60 Black Hawk. The program phases include computer modelling, shake test, model-scale test, minimally instrumented flight test, extensively pressure-instrumented-blade flight test, and full-scale wind tunnel test.

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

    PubMed

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

    2014-05-01

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

  2. More severe toxicity of genetic polymorphisms on MTHFR activity in osteosarcoma patients treated with high-dose methotrexate

    PubMed Central

    Xie, Lu; Guo, Wei; Yang, Yi; Ji, Tao; Xu, Jie

    2018-01-01

    5,10-Methylenetrahydrofolate reductase (MTHFR), a key enzyme for folate metabolism, catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is located at the end of the short arm (1p36.3). Two common non-synonymous variants, the C677T (Ala222Val) and A1298C (Glu429Ala), were mainly described with decreased enzymatic activity and an alteration of intracellular folate distribution. Osteosarcomas are currently treated with high dose of methotrexate (MTX). The decreased enzyme activity of MTHFR theoretically could increase the drug action of MTX and at the same time increase toxic and side effect. Germline variants of C677T and A1298C were studied in 59 osteosarcoma patients, with whom the A1298C is detected with particularly low rate of mutant genotype (N = 1, 0.8%) and could not proceed with statistical calculations. 15 patients were wild type of C677T (CC, 25.4%), 20 were heterozygous mutant genotype (CT, 33.9%) and 24 were homozygous mutant genotype (TT, 40.7%). Patients harboring the TT/CT genotype had the same progression-free survival and tumor necrosis rate in comparison with patients having the CC genotype (P = 0.349 and P = 0.465 respectively). And the C677T polymorphisms had no significant correlation with MTX initial plasma concentration (P = 0.867; r = 0.024) and delayed elimination (P = 0.305; r = −0.136). However patients with mutant genotype of C677T were associated with higher degree of liver toxicity (P = 0.043) and fever reaction of MTX (P = 0.050) while G3/G4 hematologic toxicity were more likely to be noticed with TT than CT/CC (P = 0.095). The study suggests that genetic polymorphism of MTHFR C677T in the MTX metabolic pathway seems to be associated with the trend for more side effects statistically, but has no obvious effect on histologic response and survival. PMID:29545912

  3. Associations between Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms and Non-Alcoholic Fatty Liver Disease (NAFLD) Risk: A Meta-Analysis

    PubMed Central

    Sun, Man-Yi; Zhang, Li; Shi, Song-Li; Lin, Jing-Na

    2016-01-01

    Background C677T and A1298C are the most common allelic variants of Methylenetetrahydrofolate Reductase (MTHFR) gene. The association between MTHFR polymorphisms and the occurrence of non-alcoholic fatty liver disease (NAFLD) remains controversial. This study was thus performed to examine whether MTHFR mutations are associated with the susceptibility to NAFLD. Methods A first meta-analysis on the association between the MTHFR polymorphisms and NAFLD risks was carried out via Review Manager 5.0 and Stata/SE 12.0 software. The on-line databases, such as PubMed, EMBASE, CENTRAL, WOS, Scopus and EBSCOhost (updated to April 1st, 2016), were searched for eligible case-control studies. The odd radio (OR), 95% confidence interval (CI) and P value were calculated through Mantel-Haenszel statistics under random- or fixed-effect model. Results Eight articles (785 cases and 1188 controls) contributed data to the current meta-analysis. For C677T, increased NAFLD risks were observed in case group under homozygote model (T/T vs C/C, OR = 1.49, 95% CI = 1.03~2.15, P = 0.04) and recessive model (T/T vs C/C+C/T, OR = 1.42, 95% CI = 1.07~1.88, P = 0.02), but not the other genetics models, compared with control group. For A1298C, significantly increased NAFLD risks were detected in allele model (C vs A, OR = 1.53, 95% CI = 1.13~2.07, P = 0.006), homozygote model (C/C vs A/A, OR = 2.81, 95% CI = 1.63~4.85, P = 0.0002), dominant model (A/C+C/C vs A/A, OR = 1.60, 95% CI = 1.06~2.41, P = 0.03) and recessive model (C/C vs A/A+A/C, OR = 2.08, 95% CI = 1.45~3.00, P<0.0001), but not heterozygote model. Conclusion T/T genotype of MTHFR C677T polymorphism and C/C genotype of MTHFR A1298C are more likely to be associated with the susceptibility to NAFLD. PMID:27128842

  4. Test-retest reliability of myofascial trigger point detection in hip and thigh areas.

    PubMed

    Rozenfeld, E; Finestone, A S; Moran, U; Damri, E; Kalichman, L

    2017-10-01

    Myofascial trigger points (MTrP's) are a primary source of pain in patients with musculoskeletal disorders. Nevertheless, they are frequently underdiagnosed. Reliable MTrP palpation is the necessary for their diagnosis and treatment. The few studies that have looked for intra-tester reliability of MTrPs detection in upper body, provide preliminary evidence that MTrP palpation is reliable. Reliability tests for MTrP palpation on the lower limb have not yet been performed. To evaluate inter- and intra-tester reliability of MTrP recognition in hip and thigh muscles. Reliability study. 21 patients (15 males and 6 females, mean age 21.1 years) referred to the physical therapy clinic, 10 with knee or hip pain and 11 with pain in an upper limb, low back, shin or ankle. Two experienced physical therapists performed the examinations, blinded to the subjects' identity, medical condition and results of the previous MTrP evaluation. Each subject was evaluated four times, twice by each examiner in a random order. Dichotomous findings included a palpable taut band, tenderness, referred pain, and relevance of referred pain to patient's complaint. Based on these, diagnosis of latent MTrP's or active MTrP's was established. The evaluation was performed on both legs and included a total of 16 locations in the following muscles: rectus femoris (proximal), vastus medialis (middle and distal), vastus lateralis (middle and distal) and gluteus medius (anterior, posterior and distal). Inter- and intra-tester reliability (Cohen's kappa (κ)) values for single sites ranged from -0.25 to 0.77. Median intra-tester reliability was 0.45 and 0.46 for latent and active MTrP's, and median inter-tester reliability was 0.51 and 0.64 for latent and active MTrPs, respectively. The examination of the distal vastus medialis was most reliable for latent and active MTrP's (intra-tester k = 0.27-0.77, inter-tester k = 0.77 and intra-tester k = 0.53-0.72, inter-tester k = 0.72, correspondingly

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

    PubMed Central

    2011-01-01

    Background Shoulder pain is reported to be highly prevalent and tends to be recurrent or persistent despite medical treatment. The pathophysiological mechanisms of shoulder pain are poorly understood. Furthermore, there is little evidence supporting the effectiveness of current treatment protocols. Although myofascial trigger points (MTrPs) are rarely mentioned in relation to shoulder pain, they may present an alternative underlying mechanism, which would provide new treatment targets through MTrP inactivation. While previous research has demonstrated that trained physiotherapists can reliably identify MTrPs in patients with shoulder pain, the percentage of patients who actually have MTrPs remains unclear. The aim of this observational study was to assess the prevalence of muscles with MTrPs and the association between MTrPs and the severity of pain and functioning in patients with chronic non-traumatic unilateral shoulder pain. Methods An observational study was conducted. Subjects were recruited from patients participating in a controlled trial studying the effectiveness of physical therapy on patients with unilateral non-traumatic shoulder pain. Sociodemographic and patient-reported symptom scores, including the Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire, and Visual Analogue Scales for Pain were compared with other studies. To test for differences in age, gender distribution, and education level between the current study population and the populations from Dutch shoulder studies, the one sample T-test was used. One observer examined all subjects (n = 72) for the presence of MTrPs. Frequency distributions, means, medians, standard deviations, and 95% confidence intervals were calculated for descriptive purposes. The Spearman's rank-order correlation (ρ) was used to test for association between variables. Results MTrPs were identified in all subjects. The median number of muscles with MTrPs per subject was 6 (active MTrPs) and 4 (latent MTr

  6. [Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia].

    PubMed

    Zheng, Miao-Miao; Yue, Li-Jie; Chen, Xiao-Wen; Wen, Fei-Qiu; Li, Chang-Gang; Yang, Chun-Lan; Xie, Cai; Ding, Hui

    2013-03-01

    To study the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and toxicities after high-dose methotrexate (HD-MTX) infusion in children with acute lymphocytic leukemia (ALL). MTHFR variants in 52 children with ALL were determined by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. Toxicities of children who received HD-MTX chemotherapy were evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). The children carrying MTHFR 1298AC had a higher risk of developing thrombocytopenia compared with the carriers of the 1298 AA genotype (OR=13.7, 95%CI=1.18-159.36, P=0.036). There was no significant difference in HD-MTX chemotherapy-related adverse effects between the patients with different MTHFR C677T or G1793A genotypes. MTHFR A1298C polymorohism may associate with the toxicity of HD-MTX chemotherapy in children with ALL.

  7. Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors.

    PubMed

    Turan, Özden; Anuk-İnce, Deniz; Olcay, Lale; Sezer, Taner; Gülleroğlu, Kaan; Yılmaz-Çelik, Zerrin; Ecevit, Ayşe

    2017-01-01

    Turan Ö, Anuk-İnce D, Olcay L, Sezer T, Gülleroğlu K, Yılmaz-Çelik Z, Ecevit A. Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors. Turk J Pediatr 2017; 59: 71-75. Cerebral sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also the greatest risk of neonatal mortality and morbidity. In this report, we presented two cases with CSVT and different risk factors. One of these cases had methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator inhibitor-1 (PAI-1) 4G/ 5G polymorphism and elevated lipoprotein a. Early diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal mortality and poor long-term neurodevelopmental outcomes.

  8. Serial Magnetization Transfer Imaging in Acute Optic Neuritis

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  9. A Decaheme Cytochrome as a Molecular Electron Conduit in Dye-Sensitized Photoanodes

    PubMed Central

    Hwang, Ee Taek; Sheikh, Khizar; Orchard, Katherine L; Hojo, Daisuke; Radu, Valentin; Lee, Chong-Yong; Ainsworth, Emma; Lockwood, Colin; Gross, Manuela A; Adschiri, Tadafumi; Reisner, Erwin; Butt, Julea N; Jeuken, Lars J C

    2015-01-01

    In nature, charge recombination in light-harvesting reaction centers is minimized by efficient charge separation. Here, it is aimed to mimic this by coupling dye-sensitized TiO2 nanocrystals to a decaheme protein, MtrC from Shewanella oneidensis MR-1, where the 10 hemes of MtrC form a ≈7-nm-long molecular wire between the TiO2 and the underlying electrode. The system is assembled by forming a densely packed MtrC film on an ultra-flat gold electrode, followed by the adsorption of approximately 7 nm TiO2 nanocrystals that are modified with a phosphonated bipyridine Ru(II) dye (RuP). The step-by-step construction of the MtrC/TiO2 system is monitored with (photo)electrochemistry, quartz-crystal microbalance with dissipation (QCM-D), and atomic force microscopy (AFM). Photocurrents are dependent on the redox state of the MtrC, confirming that electrons are transferred from the TiO2 nanocrystals to the surface via the MtrC conduit. In other words, in these TiO2/MtrC hybrid photodiodes, MtrC traps the conduction-band electrons from TiO2 before transferring them to the electrode, creating a photobioelectrochemical system in which a redox protein is used to mimic the efficient charge separation found in biological photosystems. PMID:26180522

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

    PubMed

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

    2015-03-11

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

  11. 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...

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

    PubMed Central

    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

    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 μM, whilst lines induced to be highly resistant to MTR in vitro have maximum ID90 values around 100 μM (MTR-susceptible isolates typically have an ID90 of 5–12.8 μM). 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

  13. 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 ...

  14. Comparison of adherence to generic multi-tablet regimens vs. brand multi-tablet and brand single-tablet regimens likely to incorporate generic antiretroviral drugs by breaking or not fixed-dose combinations in HIV-infected patients.

    PubMed

    Rwagitinywa, Joseph; Lapeyre-Mestre, Maryse; Bourrel, Robert; Montastruc, Jean-Louis; Sommet, Agnès

    2018-03-05

    Adherence to antiretroviral (ARV) is crucial to achieve viral load suppression in HIV-infected patients. This study aimed to compare adherence to generic multi-tablet regimens (MTR) vs. brand MTR likely to incorporate ARV drugs without breaking fixed-dose combinations (FDC) and brand single-tablet regimens (STR) likely to incorporate generics by breaking the FDC. Patients aged of 18 years or over exposed to one of the generic or the brand of lamivudine (3TC), zidovudine/lamivudine (AZT/TC), nevirapine (NVP), or efavirenz (EFV), or the brand STR of efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Adherence was measured by medication possession ratio (MPR) using both defined daily dose (DDD) and daily number of tablet recommended for adults (DNT). Adherence to generic MTR vs. brand MTR and brand STR was compared using Kruskal-Wallis. The overall median adherence was 0.97 (IQR 0.13) by DNT method and 0.97 (0.14) by DDD method. Adherence in patients exposed to generic MTR (n = 165) vs. brand MTR (n = 481) and brand STR (n = 470) was comparable by DNT and DDD methods. In conclusion, adherence to generic MTR was high and comparable with adherence to brand MTR and to STR. Utilization of DDD instead DNT to measure the MPR led to small but nonsignificant difference that has no clinical impact. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  15. 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

  16. Use of Mixer Torque Rheometer to Clarify the Relationship between the Kneading States of Wet Mass and the Dissolution of Final Product in High Shear Granulation.

    PubMed

    Otsuka, Tomoko; Kuroiwa, Yosuke; Sato, Kazunari; Yamashita, Kazunari; Hakomori, Tadashi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-01-01

    The properties of wet mass, which indicate the progress of high shear granulation processes, usually have an effect on final product properties, such as tablet dissolution. The mixer torque rheometer (MTR) is a useful tool for quantitatively measuring the 'kneading state' of wet mass and detecting differences in granules. However, there have been no studies of the relationship between the MTR torque and the final product properties to date. In this study, we measured the MTR torque of wet granules at different kneading states, which were prepared by changing the granulation conditions. We then evaluated the relationship between the MTR torque and the dissolution rate of the final product properties. The amperage of the high shear granulator is usually monitored during granulation, but we could not detect a difference in the kneading state through the amperage. However, using MTR torque we were able to quantify the difference of the wet mass. Moreover, MTR torque showed a high correlation with dissolution, compared with the correlations with other intermediate properties, such as granules particle size and tablet hardness. These other properties are affected by following processes and are not properties that directly relate to the kneading state. Thus, MTR torque is a property of wet mass after granulation, and it can be used to directly evaluate differences of the kneading state, and as a result, dissolution. These results indicate the importance of controlling the kneading state, i.e., the progress of granulation, and the utility of MTR for detecting differences in wet mass.

  17. 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

  18. Are the methylenetetrahydrofolate reductase 1298 and 677 gene polymorphisms related to optic glioma and hamartoma risk in neurofibromatosis type 1 patients?

    PubMed

    Tanyıldız, Hikmet Gülşah; Yeşil, Şule; Bozkurt, Ceyhun; Çandır, Mehmet Onur; Akpınar-Tekgündüz, Sibel; Toprak, Şule; Yüksel, Deniz; Şahin, Gürses

    2016-01-01

    The methylenetetrahydrofolate reductase (MTHFR) gene plays a key role in carcinogenesis through its effects on DNA synthesis and methylation and also has a significant role in the etiology of many disorders, such as diabetes, migraine, and cardiovascular disease. Neurofibromatoses (NF) are autosomal dominant inherited diseases that can affect tissues such as bone and skin and predispose individuals to tumor development in various parts of the nervous system or body. Optic nerve glioma and brain tumors are common in children with NF, and leukemia and lymphoma incidence is also higher than normal. We therefore aimed to investigate the possible relationship between the MTHFR gene polymorphism and accompanying tumors such as neurofibroma, hamartoma, and optic glioma in children with NF1 found to have the MTHFR 677 and MTHFR 1298 gene polymorphism in this study. We included 55 pediatric patients diagnosed with NF1 between 2005 and 2014 in the study group. The control group included 44 healthy subjects without acute or chronic disease findings. A significant relationship was found between the MTHFR A1298C polymorphism and the incidence of optic glioma (p=0.014) (AA vs. AC: OR 11, 95% CI 1.27-95.17; AA vs. CC: OR 7.33, 95% CI 0.35-150.70). We also found a significant relationship between the MTHFR C1298C polymorphism and the incidence of hamartoma (p=0.019) (AA vs. AC: OR 2.12, 95% CI 0.662-6.809; p=0.203). Epilepsy incidence was high in subjects with MTHFR C677C. The MTHFR A1298C, C1298C, and C677C gene polymorphisms can be associated with a higher optic glioma, hamartoma, and epilepsy incidence, respectively, in patients diagnosed with neurofibromatosis type 1.

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

    PubMed Central

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

    2015-01-01

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

  20. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis.

    PubMed

    Yang, Lin; Hu, Xin; Xu, Luhang

    2012-10-01

    The associations between methylenetetrahydrofolate reductase (MTHFR) polymorphism and methotrexate (MTX)-induced toxicities in patients with acute lymphoblastic leukemia (ALL) have been evaluated in various populations, with the results remained conflicting. Therefore, we conducted a meta-analysis by combining available data to derive a more precise estimation of the association. PubMed, Embase, and China National Knowledge Infrastructure were searched until 21 September 2011 to identify eligible studies. A total of 14 studies were included, with all studies investigating MTHFR C677T polymorphism while nine of them investigating MTHFR A1298C polymorphism only. Results suggested that MTHFR C677T polymorphism was associated with significantly increased risk of MTX-induced toxicity, specifically liver toxicity (TT/CT vs. CC: odds ratio (OR) = 1.70, 95 % confidence interval (CI) = 1.05-2.75), myelosuppression (TT vs. CT/CC: OR = 2.82, 95 %CI = 1.25-6.34), oral mucositis (TT/CT vs. CC: OR = 3.68, 95 %CI = 1.73-7.85), gastrointestinal toxicity (TT/CT vs. CC: OR = 2.36, 95 %CI = 1.36-4.11), and skin toxicity (T vs. C: OR = 2.26, 95 %CI = 1.07-4.74). MTHFR A1298C polymorphism was found to be associated with decreased risk of skin toxicity (CC/AC vs. AA: OR = 0.11, 95 %CI = 0.01-0.85). Genotyping of MTHFR polymorphism, C677T particularly, prior to treatment for ALL is likely to be useful with the aim of tailoring MTX therapy and thus reducing the MTX-related toxicities. However, further studies with larger data set and well-designed models are required to validate our findings.

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. The relationship between methylenetetrahydrofolate reductase polymorphism and hematological malignancy.

    PubMed

    Jiang, Ni; Zhu, Xishan; Zhang, Hongmei; Wang, Xiaoli; Zhou, Xinna; Gu, Jiezhun; Chen, Baoan; Ren, Jun

    2014-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for folate metabolism. Previous studies suggest a relationship between its single nucleotide polymorphisms (SNP) of C677T and A1298C with a variety of tumor susceptibility including hematological malignancy. SNP frequency distribution in different ethnic populations might lead to differences in disease susceptibility. There has been little research in Chinese people on the MTHFR SNP with the susceptibility of the hematological malignancy. Therefore, this study investigated the relationship between MTHFR SNPs and hematological malignancy in Jiangsu province in China. Gene microarray was used to detect MTHFR C677T and A1298C single nucleotide polymorphism loci on 157 healthy controls and 127 patients from Jiangsu province with hematological malignancies (30 with multiple myeloma, 28 with non-Hodgkin's lymphoma, 22 with acute lymphoblastic leukemia, 40 with acute myeloid leukemia, and seven with chronic myeloid leukemia). The allele frequency of 677T was 41.3% in patients and 33.1% in controls, showed significant difference (chi2 = 4.08, p = 0.043); 677TT genotype with a high susceptibility to hematological malignancy (OR 1.96, 95% CI 1.01 - 4.45, p = 0.041). In subgroup analyses, the genotypes 677TT and 1298CC were associated with significantly increased multiple myeloma risk (TT vs. CC: OR 8.92, 95% CI 1.06 - 75.24, p = 0.006; CC vs. AA: OR = 4.80, 95% CI 1.56 - 14.73, p = 0.044). No associations were found between polymorphisms and susceptibilities to acute lymphoblastic leukemia, acute myeloid leukemia, or non-Hodgkin's lymphoma. MTHFRC677T polymorphisms influence the risk of hematological malignancy among the population in Jiangsu province. Both MTHFR 677TT and MTHFR 1298CC genotypes increase susceptibility to myeloid leukemia.

  4. The association of methylenetetrahydrofolate reductase genotypes with the risk of childhood leukemia in Taiwan.

    PubMed

    Pei, Jen-Sheng; Hsu, Chin-Mu; Tsai, Chia-Wen; Chang, Wen-Shin; Ji, Hong-Xue; Hsiao, Chieh-Lun; Miao, Chia-En; Hsu, Yuan-Nian; Bau, Da-Tian

    2015-01-01

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

  5. The methylenetetrahydrofolate reductase 677T-1298C haplotype is a risk factor for acute lymphoblastic leukemia in children.

    PubMed

    Kałużna, Ewelina Maria; Strauss, Ewa; Świątek-Kościelna, Bogna; Zając-Spychała, Olga; Gowin, Ewelina; Nowak, Jerzy S; Rembowska, Jolanta; Januszkiewicz-Lewandowska, Danuta

    2017-12-01

    The etiology of acute lymphoblastic leukemia (ALL) is complex, linked with both environmental exposures and genetic factors. Functional variants of the methylenetetrahydrofolate reductase (MTHFR) gene result in disturbance in folate metabolism and may affect susceptibility to cancer. The study was performed to evaluate whether MTHFR C677T and A1298C polymorphisms, analyzed separately and together, are associated with the development of ALL in a population under 18 years of age of Caucasian ancestry.The study included 117 pediatric patients (59% males, mean age at diagnosis 7.4 ± 5.2 years) with ALL, confirmed by conventional immunophenotyping surface-marker analysis and 404 healthy control subjects (48.5% men, mean age 37.7 ± 11.3 years). The MTHFR C677T and A1298C genotypes were analyzed using allele discrimination tests with Taq-Man fluorescent probes.The MTHFR 677TT genotype was related to a 2-fold increase in risk of ALL (P = .014). The 677T-1298C haplotype was found in ALL patients but not in controls (frequency 0.598%; P <.0001). The observed frequency of carriers of this rare haplotype was 12%, including 677CT/1298CC (1.7%), 677TT/1298AC (6.0%), and 677CT/1298AC (4.3%) genotypes.The MTHFR 677T allele alone or in combination with the MTHFR 1298C allele significantly increases the risk of development of ALL in Polish population under 18 years of age. Further studies of haplotype composition in subjects with the 677CT/1298AC genotype are necessary to assess the risk of childhood ALL. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  6. The methylenetetrahydrofolate reductase 677T-1298C haplotype is a risk factor for acute lymphoblastic leukemia in children

    PubMed Central

    Kałużna, Ewelina Maria; Strauss, Ewa; Świątek-Kościelna, Bogna; Zając-Spychała, Olga; Gowin, Ewelina; Nowak, Jerzy S.; Rembowska, Jolanta; Januszkiewicz-Lewandowska, Danuta

    2017-01-01

    Abstract The etiology of acute lymphoblastic leukemia (ALL) is complex, linked with both environmental exposures and genetic factors. Functional variants of the methylenetetrahydrofolate reductase (MTHFR) gene result in disturbance in folate metabolism and may affect susceptibility to cancer. The study was performed to evaluate whether MTHFR C677T and A1298C polymorphisms, analyzed separately and together, are associated with the development of ALL in a population under 18 years of age of Caucasian ancestry. The study included 117 pediatric patients (59% males, mean age at diagnosis 7.4 ± 5.2 years) with ALL, confirmed by conventional immunophenotyping surface-marker analysis and 404 healthy control subjects (48.5% men, mean age 37.7 ± 11.3 years). The MTHFR C677T and A1298C genotypes were analyzed using allele discrimination tests with Taq-Man fluorescent probes. The MTHFR 677TT genotype was related to a 2-fold increase in risk of ALL (P = .014). The 677T-1298C haplotype was found in ALL patients but not in controls (frequency 0.598%; P <.0001). The observed frequency of carriers of this rare haplotype was 12%, including 677CT/1298CC (1.7%), 677TT/1298AC (6.0%), and 677CT/1298AC (4.3%) genotypes. The MTHFR 677T allele alone or in combination with the MTHFR 1298C allele significantly increases the risk of development of ALL in Polish population under 18 years of age. Further studies of haplotype composition in subjects with the 677CT/1298AC genotype are necessary to assess the risk of childhood ALL. PMID:29390492

  7. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis.

    PubMed

    Chen, Hui; Yang, Xiaorong; Lu, Ming

    2016-02-01

    Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses before the 20th week of gestation with the same partner. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms were reported to have an effect on embryonic development and pregnancy success. To clarify the effects of MTHFR polymorphisms on the risk of RPL in the Chinese population, a meta-analysis was performed. Related studies were identified from Medline, Embase, Web of Science, and Chinese Databases up to March 7th, 2015. We extracted the number of both C677T and A1298C genotypes in the cases and controls. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to estimate the associations. Data analysis was performed using Stata 13.1. Sixteen articles involving 1420 RPL cases and 1408 controls were included in this meta-analysis. MTHFR C677T polymorphism was significantly associated with RPL risk under dominant (TT + CT vs. CC; OR 2.10, 95 % CI 1.76-2.50), recessive (TT vs. CC + CT; OR 2.36, 95 % CI 1.92-2.90), heterozygote (CT vs. CC; OR 1.77, 95 % CI 1.32-2.37), homozygote (TT vs. CC; OR 3.55, 95 % CI 2.76-4.56), and additive (T vs. C; OR 1.83, 95 % CI 1.64-2.05) model. Sensitivity analyses excluding studies that deviated from HWE did not change the direction of effect. For the A1298C mutation, no significant association was found. The Egger's regression asymmetry test showed no significant publication bias. Identification of MTHFR C677T mutation would have some implication for primary prevention of RPL and screening of high-risk individuals in China. Large well-designed researches are needed to fully describe the associations.

  8. Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

    PubMed

    Campbell, Jared M; Bateman, Emma; Stephenson, Matthew D; Bowen, Joanne M; Keefe, Dorothy M; Peters, Micah D J

    2016-07-01

    Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies.

  9. Inherited thrombophilia in pregnant women with intrauterine growth restriction.

    PubMed

    Coriu, Letitia; Copaciu, Elena; Tulbure, Dan; Talmaci, Rodica; Secara, Diana; Coriu, Daniel; Cirstoiu, Monica

    2014-12-01

    Intrauterine growth restriction (IUGR) is a major cause of fetal morbidity and mortality during pregnancy. The role of mutation in the factor V gene, prothrombin gene, MTHFR gene, as risk factors for intrauterine growth restriction during pregnancy, is not very well known so far. This is a retrospective study of 151 pregnant women with a history of complicated pregnancy: intrauterine growth restriction, preeclampsia, recurrent pregnancy loss or maternal venous thromboembolism, who were admitted in Bucharest Emergency University Hospital, during the period January 2010 to July 2014. Genetic testing was performed for all the cases to detect: factor V Leiden mutation, G20210A mutation in the prothrombin gene, C677T mutation and A1298C mutation in methylenetetrahydrofolate reductase (MTHFR) gene. Blood samples were obtained as soon as the diagnosis of intrauterine growth restriction was established with ultrasonography. The following gene mutations were associated with increased risk of IUGR: G20210A prothrombin gene mutation (OR 4.81, 95% CI 1.05 - 2.22, p= 0.043), G1691A factor V gene mutation (factor V Leiden) (OR 1.58, 95% CI 0.61 - 4.080, p= 0.347), C677T MTHFR gene mutation (OR 1.61, 95% CI 0.79 to 3.26, p= 0.186), compound heterozygous MTHFR C677T and A1298C (OR 1.66, 95% CI 0.81- 3.42, p= 0.169). Particularly, for G20210A prothrombin gene mutation we found statistically significant risk (p≤0.05) of IUGR.

  10. Cilioretinal artery: Vasculogenesis might be promoted by plasminogen activator inhibitor-1 5G allele.

    PubMed

    Yilmaz, Sarenur; Ardagil, Aylin; Akalin, Ibrahim; Altinel, Meltem Guzin; Dag, Yasar; Kurum, Esra; Koyun, Efe; Ari Yaylali, Sevil; Bayramlar, Huseyin

    2017-01-01

    Cilioretinal arteries (CAs) represent enlargements of microscopic and early established collaterals formed via vasculogenesis between choroidal and retinal circulations. We aimed to investigate whether genetic tendency to thrombosis due to well-known gene polymorphisms may induce CA vasculogenesis in embryonic life. We assessed plasminogen activator inhibitor-1 (PAI-1) 4G/5G, methylenetetrahydrofolatereductase (MTHFR), FACTOR V LEIDEN and PROTHROMBIN gene polymorphisms on 130 patients [82/48 females/males; Median age: 57 (18-84) with visible CAs and 100 (64/36: female/male; Median age: 55 (19-90)] without visible CAs. Using multiple logistic regression models, we found PAI-1 4G/5G; MTHFR (C677T and A1298C) polymorphisms to have significant effects on the probability of visible CAs, that having at least one 5G allele would increase the odds of having visible cilioretinal artery by 98.4% [Odds ratio: 1984 (95% CI: 1.320-3.000, p = 0.001)], and having at least one MTHFR C677T or A1298C allele would decrease the odds of having visible CAs by approximately 38% (OR = 0.618, 95% CI: 0.394-0.961, p = 0.035) or 44% (OR = 0.558, 95% CI: 0.354-0.871, p = 0.011), respectively. This is the first study to test the existence of significant association between presence of enlarged and visible CAs and genetic factors predisposing to thrombosis, according to the literature. Here we suggest that not only the lack of genetic predisposition to thrombosis by MTHFR gene polymorphisms, but also the PAI-1 5G allele might promote vasculogenesis of CAs.

  11. Margin to tumor thickness ratio - A predictor of local recurrence and survival in oral squamous cell carcinoma.

    PubMed

    Heiduschka, Gregor; Virk, Sohaib A; Palme, Carsten E; Ch'ng, Sydney; Elliot, Michael; Gupta, Ruta; Clark, Jonathan

    2016-04-01

    To assess whether small oral squamous cell carcinomas (OSCC) require the same margin clearance as large tumors. We evaluated the association between the ratio of the closest margin to tumor size (MSR) and tumor thickness (MTR) with local control and survival. The clinicopathologic and follow up data were obtained for 501 OSCC patients who had surgical resection with curative intent at our institution. MTR and MSR were computed and their associations with local control and survival were assessed using multivariable Cox-regression model. Survival curves were generated using the Kaplan-Meier method. MTR was a better predictor of disease control than MSR. MTR was a predictor of local failure (p=0.033) and disease specific death (p=0.038) after adjusting for perineural invasion, lymphovascular involvement, nodal status, and radiotherapy. A threshold MTR value of 0.3 was identified, above which the risk of local recurrence was low. The ratio of margin to tumor thickness was an independent predictor for local recurrence and disease specific death in this cohort. A MTR>0.3 can serve as a useful tool for adjuvant therapy planning as it combines tumor thickness and margin clearance, two well established prognostic factors. The minimum safe margin can be calculated by multiplying the tumor thickness by 0.3. Further prospective studies in other institutions are warranted to confirm the prognostic utility of MTR and assess the generalizability of our threshold values. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Regional patterns of grey matter atrophy and magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups: a voxel-based analysis study.

    PubMed

    Mallik, Shahrukh; Muhlert, Nils; Samson, Rebecca S; Sethi, Varun; Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

    2015-04-01

    In multiple sclerosis (MS), demyelination and neuro-axonal loss occur in the brain grey matter (GM). We used magnetic resonance imaging (MRI) measures of GM magnetisation transfer ratio (MTR) and volume to assess the regional localisation of reduced MTR (reflecting demyelination) and atrophy (reflecting neuro-axonal loss) in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). A total of 98 people with MS (51 RRMS, 28 SPMS, 19 PPMS) and 29 controls had T1-weighted volumetric and magnetisation transfer scans. SPM8 was used to undertake voxel-based analysis (VBA) of GM tissue volumes and MTR. MS subgroups were compared with controls, adjusting for age and gender. A voxel-by-voxel basis correlation analysis between MTR and volume within each subject group was performed, using biological parametric mapping. MTR reduction was more extensive than atrophy. RRMS and SPMS patients showed proportionately more atrophy in the deep GM. SPMS and PPMS patients showed proportionately greater cortical MTR reduction. RRMS patients demonstrated the most correlation of MTR reduction and atrophy in deep GM. In SPMS and PPMS patients, there was less extensive correlation. These results suggest that in the deep GM of RRMS patients, demyelination and neuro-axonal loss may be linked, while in SPMS and PPMS patients, neuro-axonal loss and demyelination may occur mostly independently. © The Author(s), 2014.

  13. Regional patterns of grey matter atrophy and magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups: A voxel-based analysis study

    PubMed Central

    Muhlert, Nils; Samson, Rebecca S; Sethi, Varun; Wheeler-Kingshott, Claudia AM; Miller, David H; Chard, Declan T

    2015-01-01

    Background: In multiple sclerosis (MS), demyelination and neuro-axonal loss occur in the brain grey matter (GM). We used magnetic resonance imaging (MRI) measures of GM magnetisation transfer ratio (MTR) and volume to assess the regional localisation of reduced MTR (reflecting demyelination) and atrophy (reflecting neuro-axonal loss) in relapsing–remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). Methods: A total of 98 people with MS (51 RRMS, 28 SPMS, 19 PPMS) and 29 controls had T1-weighted volumetric and magnetisation transfer scans. SPM8 was used to undertake voxel-based analysis (VBA) of GM tissue volumes and MTR. MS subgroups were compared with controls, adjusting for age and gender. A voxel-by-voxel basis correlation analysis between MTR and volume within each subject group was performed, using biological parametric mapping. Results: MTR reduction was more extensive than atrophy. RRMS and SPMS patients showed proportionately more atrophy in the deep GM. SPMS and PPMS patients showed proportionately greater cortical MTR reduction. RRMS patients demonstrated the most correlation of MTR reduction and atrophy in deep GM. In SPMS and PPMS patients, there was less extensive correlation. Conclusions: These results suggest that in the deep GM of RRMS patients, demyelination and neuro-axonal loss may be linked, while in SPMS and PPMS patients, neuro-axonal loss and demyelination may occur mostly independently. PMID:25145689

  14. Photoreduction of Shewanella oneidensis Extracellular Cytochromes by Organic Chromophores and Dye‐Sensitized TiO2

    PubMed Central

    Ainsworth, Emma V.; Lockwood, Colin W. J.; White, Gaye F.; Hwang, Ee Taek; Sakai, Tsubasa; Gross, Manuela A.; Richardson, David J.; Clarke, Thomas A.

    2016-01-01

    Abstract The transfer of photoenergized electrons from extracellular photosensitizers across a bacterial cell envelope to drive intracellular chemical transformations represents an attractive way to harness nature's catalytic machinery for solar‐assisted chemical synthesis. In Shewanella oneidensis MR‐1 (MR‐1), trans‐outer‐membrane electron transfer is performed by the extracellular cytochromes MtrC and OmcA acting together with the outer‐membrane‐spanning porin⋅cytochrome complex (MtrAB). Here we demonstrate photoreduction of solutions of MtrC, OmcA, and the MtrCAB complex by soluble photosensitizers: namely, eosin Y, fluorescein, proflavine, flavin, and adenine dinucleotide, as well as by riboflavin and flavin mononucleotide, two compounds secreted by MR‐1. We show photoreduction of MtrC and OmcA adsorbed on RuII‐dye‐sensitized TiO2 nanoparticles and that these protein‐coated particles perform photocatalytic reduction of solutions of MtrC, OmcA, and MtrCAB. These findings provide a framework for informed development of strategies for using the outer‐membrane‐associated cytochromes of MR‐1 for solar‐driven microbial synthesis in natural and engineered bacteria. PMID:27685371

  15. Metabolism of 5-methylthioribose to methionine

    SciTech Connect

    Miyazaki, J.H.; Yang, S.F.

    1987-06-01

    During ethylene biosynthesis, the H/sub 3/CS-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, (/sup 14/C)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-/sup 14/C)MTR with avocado extract resulted in the production of (/sup 14/C)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 conversionmore » 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 O/sub 2/ in the conversion of MTR to methionine is discussed.« less

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

    EPA Science Inventory

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

  17. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  18. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  19. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  20. 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...

  1. High Performance Reduction of H2O2 with an Electron Transport Decaheme Cytochrome on a Porous ITO Electrode

    PubMed Central

    2017-01-01

    The decaheme cytochrome MtrC from Shewanella oneidensis MR-1 immobilized on an ITO electrode displays unprecedented H2O2 reduction activity. Although MtrC showed lower peroxidase activity in solution compared to horseradish peroxidase, the ten heme cofactors enable excellent electronic communication and a superior activity on the electrode surface. A hierarchical ITO electrode enabled optimal immobilization of MtrC and a high current density of 1 mA cm–2 at 0.4 V vs SHE could be obtained at pH 6.5 (Eonset = 0.72 V). UV–visible and Resonance Raman spectroelectrochemical studies suggest the formation of a high valent iron-oxo species as the catalytic intermediate. Our findings demonstrate the potential of multiheme cytochromes to catalyze technologically relevant reactions and establish MtrC as a new benchmark in biotechnological H2O2 reduction with scope for applications in fuel cells and biosensors. PMID:28221032

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

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

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

  3. Myofascial trigger points, pain, disability, and sleep quality in individuals with mechanical neck pain.

    PubMed

    Muñoz-Muñoz, Sonsoles; Muñoz-García, María T; Alburquerque-Sendín, Francisco; Arroyo-Morales, Manuel; Fernández-de-las-Peñas, César

    2012-10-01

    The purpose of this study was to investigate the presence of active myofascial trigger points (MTrPs) in a greater number of muscles than previous studies and the relation between the presence of MTrPs, the intensity of pain, disability, and sleep quality in mechanical neck pain. Fifteen patients with mechanical neck pain (80% women) and 12 comparable controls participated. Myofascial trigger points were bilaterally explored in the upper trapezius, splenius capitis, semispinalis capitis, sternocleidomastoid, levator scapulae, and scalene muscles in a blinded design. Myofascial trigger points were considered active if the subject recognized the elicited referred pain as a familiar symptom. Myofascial trigger points were considered latent if the elicited referred pain was not recognized as a symptom. Pain was collected with a numerical pain rate scale (0-10); disability was assessed with Neck Disability Index; and sleep quality, with the Pittsburgh Sleep Quality Index. Patients exhibited a greater disability and worse sleep quality than controls (P < .001). The Pittsburgh Sleep Quality Index score was associated with the worst intensity of pain (r = 0.589; P = .021) and disability (r = 0.552; P = .033). Patients showed a greater (P = .002) number of active MTrPs (mean, 2 ± 2) and similar number (P = .505) of latent MTrPs (1.6 ± 1.4) than controls (latent MTrPs, 1.3 ± 1.4). No significant association between the number of latent or active MTrPs and pain, disability, or sleep quality was found. The referred pain elicited by active MTrPs in the neck and shoulder muscles contributed to symptoms in mechanical neck pain. Patients exhibited higher disability and worse sleep quality than controls. Sleep quality was associated with pain intensity and disability. No association between active MTrPs and the intensity of pain, disability, or sleep quality was found. Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  4. Chemical exchange rotation transfer (CERT) on human brain at 3 Tesla.

    PubMed

    Lin, Eugene C; Li, Hua; Zu, Zhongliang; Louie, Elizabeth A; Lankford, Christopher L; Dortch, Richard D; Does, Mark D; Gore, John C; Gochberg, Daniel F

    2018-05-25

    To test the ability of a novel pulse sequence applied in vivo at 3 Tesla to separate the contributions to the water signal from amide proton transfer (APT) and relayed nuclear Overhauser enhancement (rNOE) from background direct water saturation and semisolid magnetization transfer (MT). The lack of such signal source isolation has confounded conventional chemical exchange saturation transfer (CEST) imaging. We quantified APT and rNOE signals using a chemical exchange rotation transfer (CERT) metric, MTR double . A range of duty cycles and average irradiation powers were applied, and results were compared with conventional CEST analyses using asymmetry (MTR asym ) and extrapolated magnetization transfer (EMR). Our results indicate that MTR double is more specific than MTR asym and, because it requires as few as 3 data points, is more rapid than methods requiring a complete Z-spectrum, such as EMR. In white matter, APT (1.5 ± 0.5%) and rNOE (2.1 ± 0.7%) were quantified by using MTR double with a 30% duty cycle and a 0.5-µT average power. In addition, our results suggest that MTR double is insensitive to B 0 inhomogeneity, further magnifying its speed advantage over CEST metrics that require a separate B 0 measurement. However, MTR double still has nontrivial sensitivity to B 1 inhomogeneities. We demonstrated that MTR double is an alternative metric to evaluate APT and rNOE, which is fast, robust to B 0 inhomogeneity, and easy to process. © 2018 International Society for Magnetic Resonance in Medicine.

  5. Breast Mucin Tumor-Specific Epitopes for Cancer Immunotherapy

    DTIC Science & Technology

    1998-09-01

    reactivity with tumor-specific monoclonal antibodies show that antigenicity is maximized with the 40 amino acid MUC1-mtr2. By contrast, the MUC1-mtr3...associated mucins (7). The presence of tumor-specific epitopes is evidenced by the development of many monoclonal antibodies (mAb) that recognize...P1-P5 in the tandem repeat sequence (7). This epitope was identified by competition of antibody binding to tumor- specific mucin by synthetic

  6. FAST CHOPPER BUILDING, TRA665. CAMERA FACING NORTH. NOTE BRICKEDIN WINDOW ...

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

    FAST CHOPPER BUILDING, TRA-665. CAMERA FACING NORTH. NOTE BRICKED-IN WINDOW ON RIGHT SIDE (BELOW PAINTED NUMERALS "665"). SLIDING METAL DOOR ON COVERED RAIL AT UPPER LEVEL. SHELTERED ENTRANCE TO STEEL SHIELDING DOOR. DOOR INTO MTR SERVICE BUILDING, TRA-635, STANDS OPEN. MTR BEHIND CHOPPER BUILDING. 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

  7. 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

  8. Characteristics of lesional and extra-lesional cortical grey matter in relapsing-remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study.

    PubMed

    Yaldizli, Özgür; Pardini, Matteo; Sethi, Varun; Muhlert, Nils; Liu, Zheng; Tozer, Daniel J; Samson, Rebecca S; Wheeler-Kingshott, Claudia Am; Yousry, Tarek A; Miller, David H; Chard, Declan T

    2016-02-01

    In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. Seventy-two people with MS (46 relapsing-remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability. © The Author(s), 2015.

  9. Modified pectic polysaccharide from turmeric (Curcuma longa): A potent dietary component against gastric ulcer.

    PubMed

    Harsha, Mysore R; Chandra Prakash, Serkad V; Dharmesh, Shylaja M

    2016-03-15

    Native, intact (TrPP) and modified, low-molecular-weight (MTrPP) forms of pectic polysaccharides isolated from turmeric were evaluated for ulcer-preventive potentials in in vitro and in vivo models. Data indicated that MTrPP possessed significantly better ulcer-preventive property than TrPP; inhibiting ulcer scores up to 85%. Results were substantiated by effective muco-protection, H(+),K(+)-ATPase down-regulation, inhibition of H. pylori growth/adherence, higher antioxidant/cytoprotective mechanisms. Structural data indicated TrPP and MTrPP differ in their molecular weights and structural characteristics with different sugar compositions and side chain ratios. MTrPP was rich in galacturonic acid (687mg/g; TrPP-544mg/g) and galactose (52.9%; TrPP-21.7%). Results were substantiated by NMR/FTIR data indicating the presence of homogalacturonan and rhamnogalacturonam-I containing galactans. By virtue of binding to inflammatory marker (galectin-3), galactans may reduce inflammation induced ulcerations. The low molecular weight of MTrPP (155kDa; TrPP-13kDa) may increase its bioavailability than TrPP, thus MTrPP may possess higher antiulcer potential. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Probable Mechanisms of Needling Therapies for Myofascial Pain Control

    PubMed Central

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

    2012-01-01

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

  11. Decreased Spontaneous Electrical Activity and Acetylcholine at Myofascial Trigger Spots after Dry Needling Treatment: A Pilot Study.

    PubMed

    Liu, Qing-Guang; Liu, Lin; Huang, Qiang-Min; Nguyen, Thi-Tham; Ma, Yan-Tao; Zhao, Jia-Min

    2017-01-01

    The aims of this study are to investigate the changes in spontaneous electrical activities (SEAs) and in acetylcholine (ACh), acetylcholine receptor (AChR), and acetylcholine esterase (AChE) levels after dry needling at myofascial trigger spots in model rats. Forty-eight male Sprague-Dawley rats were divided into four groups. Thirty-six rats were assigned to three model groups, which underwent MTrSs modeling intervention. Twelve rats were assigned to the blank control (BC) group. After model construction, the 36 model rats were randomly subdivided into three groups according to treatment: MTrSs model control (MC) and two dry needling groups. One dry needling group received puncturing at MTrSs (DN-M), whereas the other underwent puncturing at non-MTrSs (DN-nM). Dry needling treatment will last for two weeks, once a week. SEAs and ACh, AChR, and AChE levels were measured after one-week rest of dry needling treatment. The amplitudes and frequencies of endplate noise (EPN) and endplate spike (EPS) significantly decreased after dry needling treatment in the DN-M group. Moreover, ACh and AChR levels significantly decreased, whereas AChE significantly increased after dry needling treatment in the DN-M group. Dry needling at the exact MTrSs is more effective than dry needling at non-MTrSs.

  12. Decreased Spontaneous Electrical Activity and Acetylcholine at Myofascial Trigger Spots after Dry Needling Treatment: A Pilot Study

    PubMed Central

    2017-01-01

    Objective The aims of this study are to investigate the changes in spontaneous electrical activities (SEAs) and in acetylcholine (ACh), acetylcholine receptor (AChR), and acetylcholine esterase (AChE) levels after dry needling at myofascial trigger spots in model rats. Materials and Methods Forty-eight male Sprague-Dawley rats were divided into four groups. Thirty-six rats were assigned to three model groups, which underwent MTrSs modeling intervention. Twelve rats were assigned to the blank control (BC) group. After model construction, the 36 model rats were randomly subdivided into three groups according to treatment: MTrSs model control (MC) and two dry needling groups. One dry needling group received puncturing at MTrSs (DN-M), whereas the other underwent puncturing at non-MTrSs (DN-nM). Dry needling treatment will last for two weeks, once a week. SEAs and ACh, AChR, and AChE levels were measured after one-week rest of dry needling treatment. Results The amplitudes and frequencies of endplate noise (EPN) and endplate spike (EPS) significantly decreased after dry needling treatment in the DN-M group. Moreover, ACh and AChR levels significantly decreased, whereas AChE significantly increased after dry needling treatment in the DN-M group. Conclusion Dry needling at the exact MTrSs is more effective than dry needling at non-MTrSs. PMID:28592980

  13. Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats

    PubMed Central

    Zhang, Jianying; Yuan, Ting; Wang, James H-C.

    2016-01-01

    The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down-regulated PPAR-γ, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients. PMID:26885754

  14. Multi-trigger resist patterning with ASML NXE3300 EUV scanner

    NASA Astrophysics Data System (ADS)

    Vesters, Yannick; McClelland, Alexandra; De Simone, Danilo; Popescu, Carmen; Dawson, Guy; Roth, John; Theis, Wolfgang; Vandenberghe, Geert; Robinson, Alex P. G.

    2018-03-01

    Irresistible Materials (IM) is developing novel resist systems based on the multi-trigger concept, which incorporates a dose dependent quenching-like behaviour. The Multi Trigger Resist (MTR) is a negative tone crosslinking resist that does not need a post exposure bake (PEB), and during the past years, has been mainly tested using interference lithography at PSI. In this study, we present the results that have been obtained using MTR resists, performing EUV exposures on ASML NXE3300B EUV scanner at IMEC. We present the lithography performance of the MTR1 resist series in two formulations - a high-speed baseline, and a formulation designed to enhance the multi-trigger behaviour. Additionally, we present results for the MTR2 resist series, which has been designed for lower line edge roughness. The high-speed baseline resist (MTR1), showed 18 nm resolution at 20mJ/cm2. The MTR2 resist shows 16nm half pitch lines patterned with a dose of 38mJ/cm2, giving a LER of 3.7 nm. Performance across multiple process conditions are discussed. We performed etch rate measurement and the multi-trigger resist showed etch resistance equivalent or better than standard chemically amplified resist. This could compensate for the lower film thickness required to avoid pattern collapse at pitch 32nm.

  15. Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats.

    PubMed

    Zhang, Jianying; Yuan, Ting; Wang, James H-C

    2016-02-23

    The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down-regulated PPAR-γ, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients.

  16. The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene-Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients.

    PubMed

    Wu, Xiayu; Xu, Weijiang; Zhou, Tao; Cao, Neng; Ni, Juan; Zou, Tianning; Liang, Ziqing; Wang, Xu; Fenech, Michael

    2016-06-24

    Folate-mediated one-carbon metabolism (FMOCM) is linked to DNA synthesis, methylation, and cell proliferation. Vitamin B6 (B6) is a cofactor, and genetic polymorphisms of related key enzymes, such as serine hydroxymethyltransferase (SHMT), methionine synthase reductase (MTRR), and methionine synthase (MS), in FMOCM may govern the bioavailability of metabolites and play important roles in the maintenance of genomic stability and cell viability (GSACV). To evaluate the influences of B6, genetic polymorphisms of these enzymes, and gene-nutrient interactions on GSACV, we utilized the cytokinesis-block micronucleus assay (CBMN) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques in the lymphocytes from female breast cancer cases and controls. GSACV showed a significantly positive correlation with B6 concentration, and 48 nmol/L of B6 was the most suitable concentration for maintaining GSACV in vitro. The GSACV indexes showed significantly different sensitivity to B6 deficiency between cases and controls; the B6 effect on the GSACV variance contribution of each index was significantly higher than that of genetic polymorphisms and the sample state (tumor state). SHMT C1420T mutations may reduce breast cancer susceptibility, whereas MTRR A66G and MS A2756G mutations may increase breast cancer susceptibility. The role of SHMT, MS, and MTRR genotype polymorphisms in GSACV is reduced compared with that of B6. The results appear to suggest that the long-term lack of B6 under these conditions may increase genetic damage and cell injury and that individuals with various genotypes have different sensitivities to B6 deficiency. FMOCM metabolic enzyme gene polymorphism may be related to breast cancer susceptibility to a certain extent due to the effect of other factors such as stress, hormones, cancer therapies, psychological conditions, and diet. Adequate B6 intake may be good for maintaining genome health and preventing breast cancer.

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

    PubMed Central

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

    2001-01-01

    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

  18. Ex vivo study for the assessment of behavioral factor and gene polymorphisms in individual susceptibility to oxidative DNA damage metals-induced.

    PubMed

    Di Pietro, Angela; Baluce, Barbara; Visalli, Giuseppa; La Maestra, Sebastiano; Micale, Rosanna; Izzotti, Alberto

    2011-06-01

    Transition metals in fine particulate matter generated by combustion induce oxidative DNA damage and inflammation. However, there is remarkable inter-individual variability in susceptibility to these damages. To assess this variability, an ex vivo study was performed using lymphocytes of 47 Caucasian healthy subjects. Cell samples were exposed to a water solution of oil fly ash (OFA). This was formed by the distinctive transition metals vanadium, iron, and nickel. Oxidative DNA damage was evaluated by testing cell viability, intracellular ROS production and 8-oxo-dG. DNA fragmentation and DNA repair capacity were assessed by using the Alkaline-Halo assay. GSTM1, GSTT1, hOGG1, and C677T and A1298C MTHFR gene polymorphisms were tested. Demographic and behavioral factors, collected by questionnaire, were also considered. OFA induced damages showed: (a) a 20-fold variation in range among different subjects in ROS production, (b) a 7-fold variation in range of 8-oxo-dG, and (c) a 25-fold variation in range in DNA repair capacity. A significant increase in DNA damage was detected in GSTT1-deficent subjects compared with wild type genotype carriers. Increases in cytoplasmic ROS and decreases in DNA repair capacity (P<0.05) were observed in C677T and A1298C variants of MTHFR. A remarkable protective effect of high fruits and vegetable intake was observed for ROS production and DNA damage. Conversely, an adverse effect of meat intake was observed on ROS increase, DNA damage and repair capacity, probably due to the increased intake of bioavailable iron. Smoking decreased DNA repair capacity, while age increased OFA-induced DNA damage. The wide comparative analysis of the complex interactions network, between genetic and behavioral factors provides evidence of the remarkable role of several lifestyle factors. In comparison to genetic polymorphisms they seem to have a higher weight in determining individual susceptibility to the adverse effects of airborne pollutants as

  19. MTHFR C677T Polymorphism is Associated with Tumor Response to Preoperative Chemoradiotherapy: A Result Based on Previous Reports.

    PubMed

    Zhao, Yue; Li, Xingde; Kong, Xiangjun

    2015-10-12

    Preoperative chemoradiotherapy (pRCT) followed by surgery has been widely practiced in locally advanced rectal cancer, esophageal cancer, gastric cancer and other cancers. However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response. It is very important to develop biomarkers (e.g., gene polymorphisms) to identify patients who have a higher likelihood of responding to pRCT. Recently, a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and epidermal growth factor receptor (EGFR) genes with the tumor response to pRCT; however, the results were inconsistent and inconclusive. A systematic review and meta-analysis was performed by searching relevant studies about the association of MTHFR and EGFR polymorphisms with the tumor regression grade (TRG) in response to pRCT in databases of PubMed, EMBAS, Web of science, Chinese National Knowledge Infrastructure, and Wanfang database up to March 30, 2015. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the association under 5 genetic models. A total of 11 eligible articles were included in the present meta-analysis, of which 8 studies were performed in rectal cancer and 3 studies were performed in esophageal cancer. We finally included 8 included studies containing 839 cases for MTHFR C677T, 5 studies involving 634 cases for MTHFR A1298C, 3 studies containing 340 cases for EGFR G497A, and 4 studies containing 396 cases for EGFR CA repeat. The pooled analysis results indicated that MTHFR C677T might be correlated with the tumor response to pRCT under the recessive model (CC vs. CTTT) in overall analysis (OR=1.426(1.074-1.894), P=0.014), rectal cancer (OR=1.483(1.102-1.996), P=0.009), and TRG 1-2 vs. 3-5 group (OR=1.423(1.046-1.936), P=0.025), while other polymorphism including MTHFR A1298C, EGFR G497A, and EGFR CA repeat

  20. Systematic review of community health impacts of mountaintop removal mining.

    PubMed

    Boyles, Abee L; Blain, Robyn B; Rochester, Johanna R; Avanasi, Raghavendhran; Goldhaber, Susan B; McComb, Sofie; Holmgren, Stephanie D; Masten, Scott A; Thayer, Kristina A

    2017-10-01

    The objective of this evaluation is to understand the human health impacts of mountaintop removal (MTR) mining, the major method of coal mining in and around Central Appalachia. MTR mining impacts the air, water, and soil and raises concerns about potential adverse health effects in neighboring communities; exposures associated with MTR mining include particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), metals, hydrogen sulfide, and other recognized harmful substances. A systematic review was conducted of published studies of MTR mining and community health, occupational studies of MTR mining, and any available animal and in vitro experimental studies investigating the effects of exposures to MTR-mining-related chemical mixtures. Six databases (Embase, PsycINFO, PubMed, Scopus, Toxline, and Web of Science) were searched with customized terms, and no restrictions on publication year or language, through October 27, 2016. The eligibility criteria included all human population studies and animal models of human health, direct and indirect measures of MTR-mining exposure, any health-related effect or change in physiological response, and any study design type. Risk of bias was assessed for observational and experimental studies using an approach developed by the National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT). To provide context for these health effects, a summary of the exposure literature is included that focuses on describing findings for outdoor air, indoor air, and drinking water. From a literature search capturing 3088 studies, 33 human studies (29 community, four occupational), four experimental studies (two in rat, one in vitro and in mice, one in C. elegans), and 58 MTR mining exposure studies were identified. A number of health findings were reported in observational human studies, including cardiopulmonary effects, mortality, and birth defects. However, concerns for risk of bias were identified, especially

  1. Myofascial Trigger Points Then and Now: A Historical and Scientific Perspective

    PubMed Central

    Shah, Jay P.; Thaker, Nikki; Heimur, Juliana; Aredo, Jacqueline V.; Sikdar, Siddhartha; Gerber, Lynn H.

    2015-01-01

    The intent of this paper is to discuss the evolving role of the myofascial trigger point (MTrP) in myofascial pain syndrome (MPS) from both a historical and scientific perspective. MTrPs are hard, discrete, palpable nodules in a taut band of skeletal muscle that may be spontaneously painful (i.e. active), or painful only on compression (i.e. latent). MPS is a term used to describe a pain condition which can be acute or, more commonly, chronic and involves the muscle and its surrounding connective tissue (e.g. fascia). According to Travell and Simons, MTrPs are central to the syndrome—but are they necessary? Although the clinical study of muscle pain and MTrPs has proliferated over the past two centuries, the scientific literature often seems disjointed and confusing. Unfortunately, much of the terminology, theories, concepts, and diagnostic criteria are inconsistent, incomplete, or controversial. In order to address these deficiencies, investigators have recently applied clinical, imaging (of skeletal muscle and brain), and biochemical analyses to systematically and objectively study the MTrP and its role in MPS. Data suggest that the soft tissue milieu around the MTrP, neurogenic inflammation, sensitization, and limbic system dysfunction may all play a role in the initiation, amplification, and perpetuation of MPS. The authors will chronicle the advances that have led to the current understanding of MTrP pathophysiology and its relationship to MPS, and review the contributions of clinicians and researchers who have influenced and expanded our contemporary level of clinical knowledge and practice. PMID:25724849

  2. Functional variants of gene encoding folate metabolizing enzyme and methotrexate-related toxicity in children with acute lymphoblastic leukemia.

    PubMed

    Kałużna, Ewelina; Strauss, Ewa; Zając-Spychała, Olga; Gowin, Ewelina; Świątek-Kościelna, Bogna; Nowak, Jerzy; Fichna, Marta; Mańkowski, Przemysław; Januszkiewicz-Lewandowska, Danuta

    2015-12-15

    Methotrexate (MTX) is commonly used agent in therapy of malignancies, including acute lymphoblastic leukemia (ALL). Based on the literature data it is known that MTX elimination and toxicity can be affected by polymorphisms in genes encoding enzymes involved in MTX metabolism. The aim of our study was to investigate the influence of C677T and A1298C polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene on MTX-induced toxicity during treatment of children with ALL. We also tried to answer the question whether simultaneous occurrence of these two polymorphisms has a clinical significance. MTHFR polymorphisms were assessed in 47 pediatric ALL patients, treated according to intensive chemotherapy for childhood ALL, ALL IC BFM 2009. Prolonged MTX elimination and higher incidence of toxicity were observed for patients with 677T-1298A haplotype. On the other hand, occurrence of 677C-1298A haplotype had protective effect on MTX clearance and toxicity, that was not observed in carriers of 677C-1298C haplotype. In patients with coexistence of studied variants 677CT/1298AC heterozygotes as well as in 677TT/1298AA homozygotes more frequently toxicity incidents were noted. The obtained results suggest that occurrence of 677T allele and coexistence of 677T and 1298C alleles may be associated with lower MTX clearance and elevated risk of adverse effects during MTX-treatment of pediatric ALL patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population.

    PubMed

    Lordelo, G S; Miranda-Vilela, A L; Akimoto, A K; Alves, P C Z; Hiragi, C O; Nonino, A; Daldegan, M B; Klautau-Guimarães, M N; Grisolia, C K

    2012-04-19

    Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.

  4. The role of methylenetetrahydrofolate reductase in acute lymphoblastic leukemia in a Brazilian mixed population.

    PubMed

    Zanrosso, Crisiane Wais; Hatagima, Ana; Emerenciano, Mariana; Ramos, Flávio; Figueiredo, Alexandre; Félix, Têmis Maria; Segal, Sandra L; Giugliani, Roberto; Guigliani, Roberto; Muniz, Maria Tereza Cartaxo; Pombo-de-Oliveira, Maria S

    2006-04-01

    The polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with leukemogenesis. In order to investigate the influence of two polymorphisms in the MTHFR gene, 677C>T and 1298A>C, on the risk of acute lymphoblastic leukemia (ALL) we performed a case-control study in children from different Brazilians' regions. Genotyping of 176 ALL and 199 unselected healthy subjects was performed using PCR-RFLP assay. There was no association between the 677C>T or 1298A>C and risk of ALL in total case-control sample. However, 677T allele was linked to a decrease risk of ALL [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.22-0.86], whereas the 1298A>C polymorphism presents an elevated risk factor [OR, 2.01; 95% CI, 1.01-3.99] in non-White children. Our investigation provides interesting data concerning the opposite effect of A1298C polymorphisms, particularly in the light of relatively scarce data regarding the MTHFR role in leukemia susceptibility in different populations.

  5. [Association of single nucleotide polymorphism of methylenetetrahydrofolate reductase gene with susceptibility to acute leukemia].

    PubMed

    Zheng, Miao-miao; Yue, Li-jie; Zhang, Hong-hong; Yang, Chun-lan; Xie, Cai

    2013-08-01

    To assess whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene is associated with susceptibility to acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) in Chinese Han children. The study has included 87 patients with ALL, 22 patients with AML and 120 healthy controls. All subjects were analyzed with reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. A 677CT genotype of the MTHFR gene was associated with decreased risk of ALL (OR=0.23, 95%CI: 0.07-0.79). However, MTHFR A1298C genotypes were not associated with the risk of either disease. 677TT/1298AA and 677CC/1298AC genotypes were associated with increased risk of ALL(OR=3.78, 95% CI: 1.38-10.40; OR=3.17, 95% CI: 1.18-8.53, respectively), whereas the genotype 677CT/1298AA was associated with susceptibility to AML (OR=0.23, 95% CI: 0.06-0.97). Our data suggested that C677T polymorphism of MTHFR gene may increase the risk of childhood AML.

  6. Methylenetetrahydrofolate reductase polymorphisms, serum methylenetetrahydrofolate reductase levels, and risk of childhood acute lymphoblastic leukemia in a Chinese population.

    PubMed

    Tong, Na; Fang, Yongjun; Li, Jie; Wang, Meilin; Lu, Qin; Wang, Shizhi; Tian, Yuanyuan; Rong, Liucheng; Sun, Jielin; Xu, Jianfeng; Zhang, Zhengdong

    2010-03-01

    Methylenetetrahydrofolate reductase (MTHFR), involved in DNA methylation and nucleotide synthesis, is thought to be associated with a decreased risk of adult and childhood acute lymphoblastic leukemia (ALL). Accumulating evidence has indicated that two common genetic variants, C677T and A1298C, are associated with cancer risk. We hypothesized that these two variants were associated with childhood ALL susceptibility and influence serum MTHFR levels. We genotyped these two polymorphisms and detected MTHFR levels in a case-control study of 361 cases and 508 controls. Compared with the 677CC and 677CC/CT genotypes, the 677TT genotype was associated with a statistically significantly decreased risk of childhood ALL (odds ratio = 0.53, 95% confidence interval = 0.32-0.88, and odds ratio = 0.55, 95% confidence interval = 0.35-0.88, respectively). In addition, a pronounced reduced risk of ALL was observed among low-risk ALL and B-phenotype ALL. Moreover, the mean serum MTHFR level was 8.01 ng/mL (+/-4.38) in cases and 9.27 ng/mL (+/-4.80) in controls (P < 0.001). MTHFR levels in subjects with 677TT genotype was significantly higher than those with 677CC genotype (P = 0.010) or 677CT genotype (P = 0.043) in controls. In conclusion, our results provide evidence that the MTHFR polymorphisms might contribute to reduced childhood ALL risk in this population.

  7. Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients.

    PubMed

    Patounakis, George; Bergh, Eric; Forman, Eric J; Tao, Xin; Lonczak, Agnieszka; Franasiak, Jason M; Treff, Nathan; Scott, Richard T

    2016-01-01

    The aim of the study is to determine if thrombophilic single nucleotide polymorphisms (SNPs) affect outcomes in fresh in vitro fertilization (IVF) cycles in a large general infertility population. A prospective cohort analysis was performed at a university-affiliated private IVF center of female patients undergoing fresh non-donor IVF cycles. The effect of the following thrombophilic SNPs on IVF outcomes were explored: factor V (Leiden and H1299R), prothrombin (G20210A), factor XIII (V34L), β-fibrinogen (-455G → A), plasminogen activator inhibitor-1 (4G/5G), human platelet antigen-1 (a/b9L33P), and methylenetetrahydrofolate reductase (C677T and A1298C). The main outcome measures included positive pregnancy test, clinical pregnancy, embryo implantation, live birth, and pregnancy loss. Patients (1717) were enrolled in the study, and a total of 4169 embryos were transferred. There were no statistically significant differences in positive pregnancy test, clinical pregnancy, embryo implantation, live birth, or pregnancy loss in the analysis of 1717 patients attempting their first cycle of IVF. Receiver operator characteristics and logistic regression analyses showed that outcomes cannot be predicted by the cumulative number of thrombophilic mutations present in the patient. Individual and cumulative thrombophilic SNPs do not affect IVF outcomes. Therefore, initial screening for these SNPs is not indicated.

  8. [Patients with inherited trombophilia and recurrent pregnancy loss: incidence].

    PubMed

    Flores-Alatriste, José Daniel; Jacobo-Nájera, Sara; Segura-Rodríguez, Rubén; Stern-Colin y Nunes, Jorge Jaroslav

    2014-06-01

    Inherited thrombophilia is a genetic tendency to suffer thrombotic events clinically evident at an early age, with frequent re- currences without apparent cause. In recent years thrombophilia has earned a place as a primary risk factor for abnormal pregnancy. To determine the incidence of hereditary thrombophilia in patients with recurrent pregnancy loss. A retrospective, linear and descriptive study was conducted at Clinic of Reproduction IMMUNOREP with patients treated from January 2007 to December 2012. The study included patients with a diagnosis of recurrent pregnancy loss and inherited thrombophilia with laboratory studies of thrombophilia including different genes: G1619A (factor V Leiden), R2 H1299R (factor V polymorphism), C677T (methylenetetrahydrofolate reductase enzyme polymorphism), A1298C (methylenetetrahydrofolate reductase enzyme mutation), G20210A (mutation of the prothrombin gene), V34L (factor XIII polymorphism), 455G > A (fibrinogen gene mutation), 4G/5G (plasminogen activator inhibitor) and a/b L33P (ribosomal polymorphism of methylenetetrahydrofolate reductase enzyme). 211 files were reviewed and only 10.4% of patients were negative for hereditary thrombophilia, a percentage that is consistent with the results of different series of studies in patients with unexplained recurrent pregnancy loss. The most prevalent genetic condition was 4G/5G (plasminogen activator inhibitor, 85.5%) in homozygous and heterozygous with 63.4% (120) and 22.4% (42), respectively. It was demonstrated the direct relationship between thrombophilia and recurrent pregnancy loss depending on whether the patient is heterozygous or homozygous for the disease.

  9. Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women.

    PubMed

    Chatzidimitriou, M; Chatzidimitriou, D; Mavridou, M; Anetakis, C; Chatzopoulou, F; Lialiaris, T; Mitka, S

    2017-12-01

    Recurrent pregnancy loss (RPL) is a multifactorial disorder. The aim of this study was the detection of various genetic polymorphisms and their correlation to RPL, in Greek women. The impact of 12 thrombophilic polymorphisms was evaluated, among 48 Greek women with a history of RPL, vs 27 healthy parous women. Multiplex PCR and in situ hybridization on nitrocellulose films were performed, to investigate 12 genetic polymorphisms previously reported as risk factors for RPL. Heterozygous FV Leiden, homozygous PAI-1 4G/4G, heterozygous MTHFR C677T, homozygous MTHFR A1298C, as much as the combined thrombophilic genotypes MTHFR 677T + ACE Ι/D, MTHFR 677T/1298C + ACE D/D, ACE I/D + b-fibrinogen -455 G/A, FV HR2 + b-fibrinogen -455 G/A showed a correlation as risk factors for RPL, whereas the rest of the investigated polymorphisms and their combinations did not render statistically significant differences between the two groups in study. The results of this study, as well as those of similar studies, concerning the detection of genetic, environmental, and physiological factors underlying RPL, will prove of critical significance in the investigation and treatment of thrombophilic predisposition, in cases of RPL. © 2017 John Wiley & Sons Ltd.

  10. Methotrexate pharmacogenetics in Uruguayan adults with hematological malignant diseases.

    PubMed

    Giletti, Andrea; Vital, Marcelo; Lorenzo, Mariana; Cardozo, Patricia; Borelli, Gabriel; Gabus, Raúl; Martínez, Lem; Díaz, Lilian; Assar, Rodrigo; Rodriguez, María Noel; Esperón, Patricia

    2017-11-15

    Individual variability is among the causes of toxicity and interruption of treatment in acute lymphoblastic leukemia (ALL) and severe non-Hodgkin lymphoma (NHL) patients under protocols including Methotrexate (MTX): 2,4-diamino-N10-methyl propyl-glutamic acid. 41 Uruguayan patients were recruited. Gene polymorphisms involved in MTX pathway were analyzed and their association with treatment toxicities and outcome was evaluated. Genotype distribution and allele frequency were determined for SLC19A1 G 80 A, MTHFR C 677 T and A 1298 C, TYMS 28bp copy number variation, SLCO1B1 T 521 C, DHFR C -1610 G/T, DHFR C -680 A, DHFR A -317 G and DHFR 19bp indel. Multivariate analysis showed that DHFR -1610 G/T (OR=0.107, p=0.018) and MTHFR 677 T alleles (OR=0.12, p=0.026) had a strong protective effect against hematologic toxicity, while DHFR -1610 CC genotype increased this toxicity (OR=9, p=0.045). No more associations were found. The associations found between gene polymorphisms and toxicities in this small cohort are encouraging for a more extensive research to gain a better dose individualization in adult ALL and NHL patients. Besides, genotype distribution showed to be different from other populations, reinforcing the idea that genotype data from other populations should not be extrapolated to ours. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2010-03-01

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

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

    PubMed

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

    2014-01-01

    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.

  14. Metabolic dysregulation in first-episode schizophrenia patients with respect to genetic variation in one-carbon metabolism.

    PubMed

    Misiak, Błażej; Łaczmański, Łukasz; Słoka, Natalia Kinga; Szmida, Elżbieta; Piotrowski, Patryk; Loska, Olga; Ślęzak, Ryszard; Kiejna, Andrzej; Frydecka, Dorota

    2016-04-30

    The aim of this study was to investigate the prevalence of metabolic disturbances in patients with first-episode schizophrenia (FES) and test the hypothesis that genetic variation in one-carbon metabolism may account for metabolic dysregulation in early psychosis. We measured fasting glucose, lipid profile parameters, homocysteine, folate and vitamin B12 in 135 patients with FES and 146 healthy controls (HCs). Polymorphisms in the following genes were determined: MTHFR (C677T and A1298C), MTHFD1 (G1958A), MTRR (A66G) and BHMT (G742A). Serum levels of folate and high-density lipoproteins (HDL) were significantly lower in patients with FES compared to HCs. In turn, serum levels of homocysteine and triglycerides were significantly higher in patients with FES than in HCs. Prevalence of hyperhomocysteinemia, low folate and HDL levels together with dyslipidemia was significantly higher in patients with FES compared to HCs. Higher homocysteine levels, lower vitamin B12 levels and the presence of metabolic syndrome were associated with higher severity of negative symptoms. None of studied polymorphisms was associated with schizophrenia risk. Several associations between studied polymorphisms and cardio-metabolic parameters were found. None of them remained significant after Bonferroni correction. Our results indicate that metabolic dysregulation in patients with FES is not associated with genetic variation in one-carbon metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

  16. The Location of Peak Upper Trapezius Muscle Activity During Submaximal Contractions is not Associated With the Location of Myofascial Trigger Points: New Insights Revealed by High-density Surface EMG.

    PubMed

    Barbero, Marco; Falla, Deborah; Mafodda, Luca; Cescon, Corrado; Gatti, Roberto

    2016-12-01

    To apply topographical mapping of the electromyography (EMG) amplitude recorded from the upper trapezius muscle to evaluate the distribution of activity and the location of peak activity during a shoulder elevation task in participants with and without myofascial pain and myofascial trigger points (MTrP) and compare this location with the site of the MTrP. Thirteen participants with myofascial pain and MTrP in the upper trapezius muscle and 12 asymptomatic individuals participated. High-density surface EMG was recorded from the upper trapezius muscle using a matrix of 64 surface electrodes aligned with an anatomic landmark system (ALS). Each participant performed a shoulder elevation task consisting of a series of 30 s ramped contractions to 15% or 60% of their maximal voluntary contraction (MVC) force. Topographical maps of the EMG average rectified value were computed and the peak EMG amplitude during the ramped contractions was identified and its location determined with respect to the ALS. The location of the MTrP was also determined relative to the ALS and Spearman correlation coefficients were used to examine the relationship between MTrP and peak EMG amplitude location. The location of the peak EMG amplitude was significantly (P<0.05) different between groups (participants with pain/MTrP: -0.32±1.2 cm at 15% MVC and -0.35±0.9 cm at 60% MVC relative to the ALS; asymptomatic participants: 1.0±1.3 cm at 15% MVC and 1.3±1.1 cm relative to the ALS). However, no correlation was observed between the position of the MTrP and peak EMG amplitude during the ramped contractions at either force level (15%: rs=0.039, P=0.9; 60%: rs=-0.087, P=0.778). People with myofascial pain and MTrP displayed a caudal shift of the distribution of upper trapezius muscle activity compared with asymptomatic individuals during a submaximal shoulder elevation task. For the first time, we show that the location of peak muscle activity is not associated with the location of the MTrP.

  17. A Distinct and Parallel Pathway for the Nuclear Import of an mRNA-binding Protein

    PubMed Central

    Pemberton, Lucy F.; Rosenblum, Jonathan S.; Blobel, Günter

    1997-01-01

    Three independent pathways of nuclear import have so far been identified in yeast, each mediated by cognate nuclear transport factors, or karyopherins. Here we have characterized a new pathway to the nucleus, mediated by Mtr10p, a protein first identified in a screen for strains defective in polyadenylated RNA export. Mtr10p is shown to be responsible for the nuclear import of the shuttling mRNA-binding protein Npl3p. A complex of Mtr10p and Npl3p was detected in cytosol, and deletion of Mtr10p was shown to lead to the mislocalization of nuclear Npl3p to the cytoplasm, correlating with a block in import. Mtr10p bound peptide repeat-containing nucleoporins and Ran, suggesting that this import pathway involves a docking step at the nuclear pore complex and is Ran dependent. This pathway of Npl3p import is distinct and does not appear to overlap with another known import pathway for an mRNA-binding protein. Thus, at least two parallel pathways function in the import of mRNA-binding proteins, suggesting the need for the coordination of these pathways. PMID:9412460

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

    PubMed Central

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

    2013-01-01

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

  19. Physiological and transcriptional approaches reveal connection between nitrogen and manganese cycles in Shewanella algae C6G3

    PubMed Central

    Aigle, Axel; Bonin, Patricia; Iobbi-Nivol, Chantal; Méjean, Vincent; Michotey, Valérie

    2017-01-01

    To explain anaerobic nitrite/nitrate production at the expense of ammonium mediated by manganese oxide (Mn(IV)) in sediment, nitrate and manganese respirations were investigated in a strain (Shewanella algae C6G3) presenting these features. In contrast to S. oneidensis MR-1, a biotic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during anaerobic growth with Mn(IV) under condition of limiting electron acceptor, concomitantly, with a higher electron donor stoichiometry than expected. This low and reproducible transitory accumulation is the result of production and consumption since the strain is able to dissimilative reduce nitrate into ammonium. Nitrite production in Mn(IV) condition is strengthened by comparative expression of the nitrate/nitrite reductase genes (napA, nrfA, nrfA-2), and rates of the nitrate/nitrite reductase activities under Mn(IV), nitrate or fumarate conditions. Compared with S. oneidensis MR-1, S. algae contains additional genes that encode nitrate and nitrite reductases (napA-α and nrfA-2) and an Outer Membrane Cytochrome (OMC)(mtrH). Different patterns of expression of the OMC genes (omcA, mtrF, mtrH and mtrC) were observed depending on the electron acceptor and growth phase. Only gene mtrF-2 (SO1659 homolog) was specifically expressed under the Mn(IV) condition. Nitrate and Mn(IV) respirations seem connected at the physiological and transcriptional levels. PMID:28317859

  20. Physiological and transcriptional approaches reveal connection between nitrogen and manganese cycles in Shewanella algae C6G3.

    PubMed

    Aigle, Axel; Bonin, Patricia; Iobbi-Nivol, Chantal; Méjean, Vincent; Michotey, Valérie

    2017-03-20

    To explain anaerobic nitrite/nitrate production at the expense of ammonium mediated by manganese oxide (Mn(IV)) in sediment, nitrate and manganese respirations were investigated in a strain (Shewanella algae C6G3) presenting these features. In contrast to S. oneidensis MR-1, a biotic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during anaerobic growth with Mn(IV) under condition of limiting electron acceptor, concomitantly, with a higher electron donor stoichiometry than expected. This low and reproducible transitory accumulation is the result of production and consumption since the strain is able to dissimilative reduce nitrate into ammonium. Nitrite production in Mn(IV) condition is strengthened by comparative expression of the nitrate/nitrite reductase genes (napA, nrfA, nrfA-2), and rates of the nitrate/nitrite reductase activities under Mn(IV), nitrate or fumarate conditions. Compared with S. oneidensis MR-1, S. algae contains additional genes that encode nitrate and nitrite reductases (napA-α and nrfA-2) and an Outer Membrane Cytochrome (OMC)(mtrH). Different patterns of expression of the OMC genes (omcA, mtrF, mtrH and mtrC) were observed depending on the electron acceptor and growth phase. Only gene mtrF-2 (SO1659 homolog) was specifically expressed under the Mn(IV) condition. Nitrate and Mn(IV) respirations seem connected at the physiological and transcriptional levels.

  1. Physiological and transcriptional approaches reveal connection between nitrogen and manganese cycles in Shewanella algae C6G3

    NASA Astrophysics Data System (ADS)

    Aigle, Axel; Bonin, Patricia; Iobbi-Nivol, Chantal; Méjean, Vincent; Michotey, Valérie

    2017-03-01

    To explain anaerobic nitrite/nitrate production at the expense of ammonium mediated by manganese oxide (Mn(IV)) in sediment, nitrate and manganese respirations were investigated in a strain (Shewanella algae C6G3) presenting these features. In contrast to S. oneidensis MR-1, a biotic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during anaerobic growth with Mn(IV) under condition of limiting electron acceptor, concomitantly, with a higher electron donor stoichiometry than expected. This low and reproducible transitory accumulation is the result of production and consumption since the strain is able to dissimilative reduce nitrate into ammonium. Nitrite production in Mn(IV) condition is strengthened by comparative expression of the nitrate/nitrite reductase genes (napA, nrfA, nrfA-2), and rates of the nitrate/nitrite reductase activities under Mn(IV), nitrate or fumarate conditions. Compared with S. oneidensis MR-1, S. algae contains additional genes that encode nitrate and nitrite reductases (napA-α and nrfA-2) and an Outer Membrane Cytochrome (OMC)(mtrH). Different patterns of expression of the OMC genes (omcA, mtrF, mtrH and mtrC) were observed depending on the electron acceptor and growth phase. Only gene mtrF-2 (SO1659 homolog) was specifically expressed under the Mn(IV) condition. Nitrate and Mn(IV) respirations seem connected at the physiological and transcriptional levels.

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

    PubMed Central

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

    2014-01-01

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

  3. Multiparameter MR imaging in the 6-OPRI variant of inherited prion disease.

    PubMed

    De Vita, E; Ridgway, G R; Scahill, R I; Caine, D; Rudge, P; Yousry, T A; Mead, S; Collinge, J; Jäger, H R; Thornton, J S; Hyare, H

    2013-09-01

    Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology.

  4. A Cajal body-independent pathway for telomerase trafficking in mice

    SciTech Connect

    Tomlinson, Rebecca L.; Li, Jian; Culp, Bradley R.

    2010-10-15

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

  5. SciTech Connect

    Jackson, R.N.; Robinson, H.; Klauer, A. A.

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

  6. Multi-parameter MRI in the 6-OPRI variant of inherited prion disease

    PubMed Central

    De Vita, Enrico; Ridgway, Gerard R.; Scahill, Rachael I; Caine, Diana; Rudge, Peter; Yousry, Tarek A; Mead, Simon; Collinge, John; Jäger, H R; Thornton, John S; Hyare, Harpreet

    2013-01-01

    Background and Purpose To define the distribution of cerebral volumetric and microstructural parenchymal tissue changes in a specific mutation within inherited human prion diseases (IPD) combining voxel-based morphometry (VBM) with voxel-based analysis (VBA) of cerebral magnetization transfer ratio (MTR) and mean diffusivity (MD). Materials and Methods VBM and VBA of cerebral MTR and MD were performed in 16 healthy controls and 9 patients with the 6-octapeptide repeat insertion (6-OPRI) mutation. An ANCOVA consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. Results On VBM there was significant grey matter (GM) volume reduction in patients compared with controls in the basal ganglia, perisylvian cortex, lingual gyrus and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. Conclusions GM and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomical distribution of MTR-VBA and MDVBA changes compared to VBM, likely to reflect regional variations in the type and degree of the respective pathophysiological substrates. Combined analysis of complementary multi-parameter MRI data furthers our understanding of prion disease pathophysiology. PMID:23538406

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

    PubMed Central

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

    2008-01-01

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

  8. SciTech Connect

    Sarta, Jose A.; Castiblanco, Luis A

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

  9. Effect of lidocaine patches on upper trapezius EMG activity and pain intensity in patients with myofascial trigger points: A randomized clinical study.

    PubMed

    Firmani, Mónica; Miralles, Rodolfo; Casassus, Rodrigo

    2015-04-01

    To compare the effects of 5% lidocaine patches and placebo patches on pain intensity and electromyographic (EMG) activity of an active myofascial trigger point (MTrP) of the upper trapezius muscle. Thirty-six patients with a MTrP in the upper trapezius muscle were randomly divided into two groups: 20 patients received lidocaine patches (lidocaine group) and 16 patients received placebo patches (placebo group). They used the patches for 12 h each day, for 2 weeks. The patch was applied to the skin over the upper trapezius MTrP. Spontaneous pain, pressure pain thresholds, pain provoked by a 4-kg pressure applied to the MTrP and trapezius EMG activity were measured before and after treatment. Baseline spontaneous pain values were similar in both groups and significantly lower in the lidocaine group than the placebo group after treatment. The baseline pressure pain threshold was significantly lower in the lidocaine group, but after treatment it was significantly higher in this group. Baseline and final values of the pain provoked by a 4-kg pressure showed no significant difference between the groups. Baseline EMG activity at rest and during swallowing of saliva was significantly higher in the lidocaine group, but no significant difference was observed after treatment. Baseline EMG activity during maximum voluntary clenching was similar in both groups, but significantly higher in the lidocaine group after treatment. These clinical and EMG results support the use of 5% lidocaine patches for treating patients with MTrP of the upper trapezius muscle.

  10. Profiles of gonadotropin-inhibitory hormone and melatonin during the sex change and maturation of cinnamon clownfish, Amphiprion melanopus.

    PubMed

    Choi, Young Jae; Habibi, Hamid R; Choi, Cheol Young

    2016-06-24

    The present study aimed to determine the relationship between melatonin and gonadotropin-inhibitory hormone (GnIH) and their effect on reproduction in cinnamon clownfish, Amphiprion melanopus. Accordingly, we investigated the expression pattern of GnIH, GnIH receptor (GnIH-R), and melatonin receptor (MT-R1) mRNA and protein, as well as the plasma levels of melatonin, during sex change in cinnamon clownfish. We found that GnIH and MT-R1 mRNA and melatonin activity were higher in fish with mature brain than in fish with developing gonads, and using double immunofluorescence staining, we found that both GnIH and MT-R1 proteins were co-expressed in the hypothalamus of cinnamon clownfish. These findings support the hypothesis that melatonin plays an important role in the negative regulation of maturation and GnIH regulation during reproduction. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery

    NASA Astrophysics Data System (ADS)

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

    2000-02-01

    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.

  12. Do Individuals Perceive Income Tax Rates Correctly?

    PubMed Central

    Gideon, Michael

    2017-01-01

    This article uses data from survey questions fielded on the 2011 wave of the Cognitive Economics Study to uncover systematic errors in perceptions of income tax rates. First, when asked about the marginal tax rates (MTRs) for households in the top tax bracket, respondents underestimate the top MTR on wages and salary income, overestimate the MTR on dividend income, and therefore significantly underestimate the currently tax-advantaged status of dividend income. Second, when analyzing the relationship between respondents' self-reported average tax rates (ATRs) and MTRs, many people do not understand the progressive nature of the federal income tax system. Third, when comparing self-reported tax rates with those computed from self-reported income, respondents systematically overestimate their ATR while reported MTR are accurate at the mean, the responses are consistent with underestimation of tax schedule progressivity. PMID:29238156

  13. Do Individuals Perceive Income Tax Rates Correctly?

    PubMed

    Gideon, Michael

    2017-01-01

    This article uses data from survey questions fielded on the 2011 wave of the Cognitive Economics Study to uncover systematic errors in perceptions of income tax rates. First, when asked about the marginal tax rates (MTRs) for households in the top tax bracket, respondents underestimate the top MTR on wages and salary income, overestimate the MTR on dividend income, and therefore significantly underestimate the currently tax-advantaged status of dividend income. Second, when analyzing the relationship between respondents' self-reported average tax rates (ATRs) and MTRs, many people do not understand the progressive nature of the federal income tax system. Third, when comparing self-reported tax rates with those computed from self-reported income, respondents systematically overestimate their ATR while reported MTR are accurate at the mean, the responses are consistent with underestimation of tax schedule progressivity.

  14. Predictors of upper trapezius pain with myofascial trigger points in food service workers: The STROBE study.

    PubMed

    Hwang, Ui-Jae; Kwon, Oh-Yun; Yi, Chung-Hwi; Jeon, Hye-Seon; Weon, Jong-Hyuck; Ha, Sung-Min

    2017-06-01

    Shoulder pain occurs commonly in food service workers (FSWs) who repetitively perform motions of the upper limbs. Myofascial trigger points (MTrPs) on the upper trapezius (UT) are among the most common musculoskeletal shoulder pain syndromes. This study determined the psychological, posture, mobility, and strength factors associated with pain severity in FSWs with UT pain due to MTrPs.In this cross-sectional study, we measured 17 variables in 163 FSWs with UT pain due to MTrPs: a visual analog scale (VAS) pain score, age, sex, Borg rating of perceived exertion (BRPE) scale, beck depression inventory, forward head posture angle, rounded shoulder angle (RSA), shoulder slope angle, scapular downward rotation ratio, cervical lateral-bending side difference angle, cervical rotation side difference angle, glenohumeral internal rotation angle, shoulder horizontal adduction angle, serratus anterior (SA) strength, lower trapezius (LT) strength, bicep strength, and glenohumeral external rotator strength, in 163 FSWs with UT pain due to MTrPs.The model for factors influencing UT pain with MTrPs included SA strength, age, BRPE, LT strength, and RSA as predictor variables that accounted for 68.7% of the variance in VAS (P < .001) in multiple regression models with a stepwise selection procedure. The following were independent variables influencing the VAS in the order of standardized coefficients: SA strength (β = -0.380), age (β = 0.287), BRPE (β = 0.239), LT strength (β = -0.195), and RSA (β = 0.125).SA strength, age, BRPE, LT strength, and RSA variables should be considered when evaluating and intervening in UT pain with MTrPs in FSWs.

  15. Predictors of upper trapezius pain with myofascial trigger points in food service workers

    PubMed Central

    Hwang, Ui-Jae; Kwon, Oh-Yun; Yi, Chung-Hwi; Jeon, Hye-Seon; Weon, Jong-Hyuck; Ha, Sung-Min

    2017-01-01

    Abstract Shoulder pain occurs commonly in food service workers (FSWs) who repetitively perform motions of the upper limbs. Myofascial trigger points (MTrPs) on the upper trapezius (UT) are among the most common musculoskeletal shoulder pain syndromes. This study determined the psychological, posture, mobility, and strength factors associated with pain severity in FSWs with UT pain due to MTrPs. In this cross-sectional study, we measured 17 variables in 163 FSWs with UT pain due to MTrPs: a visual analog scale (VAS) pain score, age, sex, Borg rating of perceived exertion (BRPE) scale, beck depression inventory, forward head posture angle, rounded shoulder angle (RSA), shoulder slope angle, scapular downward rotation ratio, cervical lateral-bending side difference angle, cervical rotation side difference angle, glenohumeral internal rotation angle, shoulder horizontal adduction angle, serratus anterior (SA) strength, lower trapezius (LT) strength, bicep strength, and glenohumeral external rotator strength, in 163 FSWs with UT pain due to MTrPs. The model for factors influencing UT pain with MTrPs included SA strength, age, BRPE, LT strength, and RSA as predictor variables that accounted for 68.7% of the variance in VAS (P < .001) in multiple regression models with a stepwise selection procedure. The following were independent variables influencing the VAS in the order of standardized coefficients: SA strength (β = −0.380), age (β = 0.287), BRPE (β = 0.239), LT strength (β = −0.195), and RSA (β = 0.125). SA strength, age, BRPE, LT strength, and RSA variables should be considered when evaluating and intervening in UT pain with MTrPs in FSWs. PMID:28658117

  16. Changes in blood flow and cellular metabolism at a myofascial trigger point with trigger point release (ischemic compression): a proof-of-principle pilot study

    PubMed Central

    Moraska, Albert F.; Hickner, Robert C.; Kohrt, Wendy M.; Brewer, Alan

    2012-01-01

    Objective To demonstrate proof-of-principle measurement for physiological change within an active myofascial trigger point (MTrP) undergoing trigger point release (ischemic compression). Design Interstitial fluid was sampled continuously at a trigger point before and after intervention. Setting A biomedical research clinic at a university hospital. Participants Two subjects from a pain clinic presenting with chronic headache pain. Interventions A single microdialysis catheter was inserted into an active MTrP of the upper trapezius to allow for continuous sampling of interstitial fluid before and after application of trigger point therapy by a massage therapist. Main Outcome Measures Procedural success, pain tolerance, feasibility of intervention during sample collection, determination of physiologically relevant values for local blood flow, as well as glucose and lactate concentrations. Results Both patients tolerated the microdialysis probe insertion into the MTrP and treatment intervention without complication. Glucose and lactate concentrations were measured in the physiological range. Following intervention, a sustained increase in lactate was noted for both subjects. Conclusions Identifying physiological constituents of MTrP’s following intervention is an important step toward understanding pathophysiology and resolution of myofascial pain. The present study forwards that aim by showing proof-of-concept for collection of interstitial fluid from an MTrP before and after intervention can be accomplished using microdialysis, thus providing methodological insight toward treatment mechanism and pain resolution. Of the biomarkers measured in this study, lactate may be the most relevant for detection and treatment of abnormalities in the MTrP. PMID:22975226

  17. In Vitro Activity of Delafloxacin against Clinical Neisseria gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance

    PubMed Central

    Salipante, Stephen J.; No, David; Duffy, Erin; Roberts, Marilyn C.

    2016-01-01

    We evaluated the in vitro activity of delafloxacin against a panel of 117 Neisseria gonorrhoeae strains, including 110 clinical isolates collected from 2012 to 2015 and seven reference strains, compared with the activities of seven antimicrobials currently or previously recommended for treatment of gonorrhea. We examined the potential for delafloxacin to select for resistant mutants in ciprofloxacin-susceptible and ciprofloxacin-resistant N. gonorrhoeae. We characterized mutations in the gyrA, gyrB, parC, and parE genes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) by PCR and sequencing and by whole-genome sequencing. The MIC50, MIC90, and MIC ranges of delafloxacin were 0.06 μg/ml, 0.125 μg/ml, and ≤0.001 to 0.25 μg/ml, respectively. The frequency of spontaneous mutation ranged from 10−7 to <10−9. The multistep delafloxacin resistance selection of 30 daily passages resulted in stable resistant mutants. There was no obvious cross-resistance to nonfluoroquinolone comparator antimicrobials. A mutant with reduced susceptibility to ciprofloxacin (MIC, 0.25 μg/ml) obtained from the ciprofloxacin-susceptible parental strain had a novel Ser91Tyr alteration in the gyrA gene. We also identified new mutations in the gyrA and/or parC and parE genes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) of two mutant strains with elevated delafloxacin MICs of 1 μg/ml. Although delafloxacin exhibited potent in vitro activity against N. gonorrhoeae isolates and reference strains with diverse antimicrobial resistance profiles and demonstrated a low tendency to select for spontaneous mutants, it is important to establish the correlation between these excellent in vitro data and treatment outcomes through appropriate randomized controlled clinical trials. PMID:26976873

  18. Migraineurs without aura show microstructural abnormalities in the cerebellum and frontal lobe.

    PubMed

    Granziera, C; Romascano, D; Daducci, A; Roche, A; Vincent, M; Krueger, G; Hadjikhani, N

    2013-12-01

    The involvement of the cerebellum in migraine pathophysiology is not well understood. We used a biparametric approach at high-field MRI (3 T) to assess the structural integrity of the cerebellum in 15 migraineurs with aura (MWA), 23 migraineurs without aura (MWoA), and 20 healthy controls (HC). High-resolution T1 relaxation maps were acquired together with magnetization transfer images in order to probe microstructural and myelin integrity. Clusterwise analysis was performed on T1 and magnetization transfer ratio (MTR) maps of the cerebellum of MWA, MWoA, and HC using an ANOVA and a non-parametric clusterwise permutation F test, with age and gender as covariates and correction for familywise error rate. In addition, mean MTR and T1 in frontal regions known to be highly connected to the cerebellum were computed. Clusterwise comparison among groups showed a cluster of lower MTR in the right Crus I of MWoA patients vs. HC and MWA subjects (p = 0.04). Univariate and bivariate analysis on T1 and MTR contrasts showed that MWoA patients had longer T1 and lower MTR in the right and left pars orbitalis compared to MWA (p < 0.01 and 0.05, respectively), but no differences were found with HC. Lower MTR and longer T1 point at a loss of macromolecules and/or micro-edema in Crus I and pars orbitalis in MWoA patients vs. HC and vs. MWA. The pathophysiological implications of these findings are discussed in light of recent literature.

  19. Therapeutic effects of dry needling in patients with upper trapezius myofascial trigger points

    PubMed Central

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

    2017-01-01

    Background Active myofascial trigger points (MTrPs) are major pain generators in myofascial pain syndrome. Dry needling (DN) is an effective method for the treatment of MTrPs. Objective To assess the immediate neurophysiological and clinical effects of DN in patients with upper trapezius MTrPs. Methods This was a prospective, clinical trial study of 20 patients with upper trapezius MTrPs and 20 healthy volunteers (matched for height, weight, body mass index and age), all of whom received one session of DN. Primary outcome measures were neuromuscular junction response (NMJR) and sympathetic skin response (SSR). Secondary outcomes were pain intensity (PI) and pressure pain threshold (PPT). Data were collected at baseline and immediately post-intervention. Results At baseline, SSR amplitude was higher in patients versus healthy volunteers (p<0.003). With respect to NMJR, a clinically abnormal increment and normal reduction was observed in patients and healthy volunteers, respectively. Moreover, PPT of patients was less than healthy volunteers (p<0.0001). After DN, SSR amplitude decreased significantly in patients (p<0.01), but did not change in healthy volunteers. A clinically important reduction in the NMJR of patients and increment in healthy volunteers was demonstrated after DN. PPT increased after DN in patients, but decreased in healthy volunteers (p<0.0001). PI improved after DN in patients (p<0.001). Conclusions The results of this study showed that one session of DN targeting active MTrPs appears to reduce hyperactivity of the sympathetic nervous system and irritability of the motor endplate. DN seems effective at improving symptoms and deactivating active MTrPs, although further research is needed. Trial registration number IRCT20130316128. PMID:27697768

  20. Effectiveness of dry needling on the lower trapezius in patients with mechanical neck pain: a randomized controlled trial.

    PubMed

    Pecos-Martín, Daniel; Montañez-Aguilera, F Javier; Gallego-Izquierdo, Tomás; Urraca-Gesto, Alicia; Gómez-Conesa, Antonia; Romero-Franco, Natalia; Plaza-Manzano, Gustavo

    2015-05-01

    To evaluate the effect of dry needling into a myofascial trigger point (MTrP) in the lower trapezius muscle of patients with mechanical idiopathic neck pain. A single-center, randomized, double-blinded controlled study. Patients were recruited from the student population of a local hospital by advertisement in the university clinic from January 2010 to December 2011. Patients (N=72) with unilateral neck pain, neck pain for ≥3 months, and active trigger points in the lower trapezius muscle were randomly assigned to 1 of 2 treatment groups. All the patients completed the study. Dry needling in an MTrP in the lower trapezius muscle, or dry needling in the lower trapezius muscle but not at an MTrP. The visual analog scale (VAS), Neck Pain Questionnaire (NPQ), and pressure-pain threshold (PPT) were assessed before the intervention and 1 week and 1 month postintervention. Treatment with dry needling of the lower trapezius muscle close to the MTrP showed decreases in pain and PPT as well as an improvement in the degree of disability (P<.001) compared with the baseline and control group measurements (P<.001). The dry-needling technique performed in the MTrP showed more significant therapeutic effects (P<.001). The application of dry needling into an active MTrP of the lower trapezius muscle induces significant changes in the VAS, NPQ, and PPT levels compared with the application of dry needling in other locations of the same muscle in patients with mechanical neck pain. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. Therapeutic effects of dry needling in patients with upper trapezius myofascial trigger points.

    PubMed

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

    2017-04-01

    Active myofascial trigger points (MTrPs) are major pain generators in myofascial pain syndrome. Dry needling (DN) is an effective method for the treatment of MTrPs. To assess the immediate neurophysiological and clinical effects of DN in patients with upper trapezius MTrPs. This was a prospective, clinical trial study of 20 patients with upper trapezius MTrPs and 20 healthy volunteers (matched for height, weight, body mass index and age), all of whom received one session of DN. Primary outcome measures were neuromuscular junction response (NMJR) and sympathetic skin response (SSR). Secondary outcomes were pain intensity (PI) and pressure pain threshold (PPT). Data were collected at baseline and immediately post-intervention. At baseline, SSR amplitude was higher in patients versus healthy volunteers (p<0.003). With respect to NMJR, a clinically abnormal increment and normal reduction was observed in patients and healthy volunteers, respectively. Moreover, PPT of patients was less than healthy volunteers (p<0.0001). After DN, SSR amplitude decreased significantly in patients (p<0.01), but did not change in healthy volunteers. A clinically important reduction in the NMJR of patients and increment in healthy volunteers was demonstrated after DN. PPT increased after DN in patients, but decreased in healthy volunteers (p<0.0001). PI improved after DN in patients (p<0.001). The results of this study showed that one session of DN targeting active MTrPs appears to reduce hyperactivity of the sympathetic nervous system and irritability of the motor endplate. DN seems effective at improving symptoms and deactivating active MTrPs, although further research is needed. IRCT20130316128. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. White and gray matter damage in primary progressive MS

    PubMed Central

    Chard, Declan; Altmann, Daniel R.; Tozer, Daniel; Miller, David H.; Thompson, Alan J.; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

    2016-01-01

    Objective: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex (“primary WM damage model”); and (2) cortical abnormalities predict later changes in connected WM tracts (“primary GM damage model”). Methods: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. Results: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. Conclusion: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID:26674332

  3. White and gray matter damage in primary progressive MS: The chicken or the egg?

    PubMed

    Bodini, Benedetta; Chard, Declan; Altmann, Daniel R; Tozer, Daniel; Miller, David H; Thompson, Alan J; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

    2016-01-12

    The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. © 2015 American Academy of Neurology.

  4. A myofascial component of pain in knee osteoarthritis.

    PubMed

    Dor, Adi; Kalichman, Leonid

    2017-07-01

    Osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability. The knee is the most common site of OA. Numerous studies have shown an inconsistency between patients' reports of pain and their radiographic findings. This inconsistency may be partially explained by the fact that a portion of the pain originates from the myofascial trigger points (MTrPs) located in the surrounding muscles. To assess the role of myofascial pain in OA patients. Critical review. PubMed, Google Scholar, Scopus, and PEDro databases were searched from inception until December 2016 for the following keywords: "myofascial pain", "osteoarthritis", "trigger points", "knee" or any combination of these words. The reference lists of all articles retrieved were searched as well. The current review included two observational studies evaluating the prevalence of MTrPs in OA patients and six interventional studies describing the treatment of myofascial pain in OA patients. Data from two of the interventional studies also included an observational section. The reviewed observational studies offered initial evidence as to the assumption that myofascial pain and the presence of MTrPs may play a role in pain and disability of knee OA. Because of the cross-sectional design of these studies, the causal relationships could not be established. Additional studies are needed to confirm this assumption as well as to clarify if MTrPs are a portion of OA etiology or that OA is the basis for MTrPs formation. Each interventional study elaborated on various myofascial treatment techniques. However, treatment focusing on MTrPs seems to be effective in reducing pain and improving function in OA patients. Due to the heterogeneity in treatment methods and outcome measures, it is difficult to attain a definite conclusion and therefore, additional high-quality randomized controlled trials are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Multivariate combination of magnetization transfer, T2* and B0 orientation to study the myelo-architecture of the in vivo human cortex

    PubMed Central

    Mangeat, G.; Govindarajan, S. T.; Mainero, C.; Cohen-Adad, J.

    2015-01-01

    Recently, T2* imaging at 7 tesla (T) MRI was shown to reveal microstructural features of the cortical myeloarchitecture thanks to an increase in contrast-to-noise ratio. However, several confounds hamper the specificity of T2* measures (iron content, blood vessels, tissues orientation). Another metric, magnetization transfer ratio (MTR), is known to also be sensitive to myelin content and thus would be an excellent complementary measure because its underlying contrast mechanisms are different than that from T2*. The goal of this study was thus to combine MTR and T2* using multivariate statistics in order to gain insights into cortical myelin content. Seven healthy subjects were scanned at 7T and 3T to obtain T2* and MTR data, respectively. A multivariate myelin estimation model (MMEM) was developed, and consists in (i) normalizing T2* and MTR values and (ii) extracting their shared information using independent component analysis (ICA). B0 orientation dependence and cortical thickness were also computed and included in the model. Results showed high correlation between MTR and T2* in the whole cortex (r=0.76, p<10−16), suggesting that both metrics are partly driven by a common source of contrast, here assumed to be the myelin. Average MTR and T2* were respectively 31.0 +/− 0.3% and 32.1 +/− 1.4 ms. Results of the MMEM spatial distribution showed similar trends to that from histological work stained for myelin (r=0.77, p<0.01). Significant right-left differences were detected in the primary motor cortex (p<0.05), the posterior cingulate cortex (p<0.05) and the visual cortex (p<0.05). This study demonstrates that MTR and T2* are highly correlated in the cortex. The combination of MTR, T2*, CT and B0 orientation may be a useful means to study cortical myeloarchitecture with more specificity than using any of the individual methods. The MMEM framework is extendable to other contrasts such as T1 and diffusion MRI. PMID:26095090

  6. Treatment of myofascial trigger points in patients with chronic shoulder pain: a randomized, controlled trial

    PubMed Central

    2011-01-01

    Background Shoulder pain is a common musculoskeletal problem that is often chronic or recurrent. Myofascial trigger points (MTrPs) cause shoulder pain and are prevalent in patients with shoulder pain. However, few studies have focused on MTrP therapy. The aim of this study was to assess the effectiveness of multimodal treatment of MTrPs in patients with chronic shoulder pain. Methods A single-assessor, blinded, randomized, controlled trial was conducted. The intervention group received comprehensive treatment once weekly consisting of manual compression of the MTrPs, manual stretching of the muscles and intermittent cold application with stretching. Patients were instructed to perform muscle-stretching and relaxation exercises at home and received ergonomic recommendations and advice to assume and maintain good posture. The control group remained on the waiting list for 3 months. The Disabilities of Arm, Shoulder and Hand (DASH) questionnaire score (primary outcome), Visual Analogue Scale for Pain (VAS-P), Global Perceived Effect (GPE) scale and the number of muscles with MTrPs were assessed at 6 and 12 weeks in the intervention group and compared with those of a control group. Results Compared with the control group, the intervention group showed significant improvement (P < 0.05) on the DASH after 12 weeks (mean difference, 7.7; 95% confidence interval (95% CI), 1.2 to 14.2), on the VAS-P1 for current pain (mean difference, 13.8; 95% CI, 2.6 to 25.0), on the VAS-P2 for pain in the past 7 days (mean difference, 10.2; 95% CI, 0.7 to 19.7) and VAS-P3 most severe pain in the past 7 days (mean difference, 13.8; 95% CI, 0.8 to 28.4). After 12 weeks, 55% of the patients in the intervention group reported improvement (from slightly improved to completely recovered) versus 14% in the control group. The mean number of muscles with active MTrPs decreased in the intervention group compared with the control group (mean difference, 2.7; 95% CI, 1.2 to 4.2). Conclusions The

  7. PROCESS WATER BUILDING, TRA605. AERIAL TAKEN WHILE SEVERAL PIPE TRENCHES ...

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

    PROCESS WATER BUILDING, TRA-605. AERIAL TAKEN WHILE SEVERAL PIPE TRENCHES REMAINED OPEN. CAMERA FACES EASTERLY. NOTE DUAL PIPES BETWEEN REACTOR BUILDING AND NORTH SIDE OF PROCESS WATER BUILDING. PIPING NEAR WORKING RESERVOIR HEADS FOR RETENTION RESERVOIR. PIPE FROM DEMINERALIZER ENTERS MTR FROM NORTH. SEE ALSO TRENCH FOR COOLANT AIR DUCT AT SOUTH SIDE OF MTR AND LEADING TO FAN HOUSE AND STACK. INL NEGATIVE NO. 2966-A. Unknown Photographer, 7/31/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

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

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

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

  9. MRT fuel element inspection at Dounreay

    SciTech Connect

    Gibson, J.

    1997-08-01

    To ensure that their production and inspection processes are performed in an acceptable manner, ie. auditable and traceable, the MTR Fuel Element Fabrication Plant at Dounreay operates to a documented quality system. This quality system, together with the fuel element manufacturing and inspection operations, has been independently certified to ISO9002-1987, EN29002-1987 and BS5750:Pt2:1987 by Lloyd`s Register Quality Assurance Limited (LRQA). This certification also provides dual accreditation to the relevant German, Dutch and Australian certification bodies. This paper briefly describes the quality system, together with the various inspection stages involved in the manufacture of MTR fuel elements at Dounreay.

  10. Possible Dynamically Gated Conductance along Heme Wires in Bacterial Multiheme Cytochromes

    SciTech Connect

    Smith, Dayle MA; Rosso, Kevin M.

    2014-07-24

    The staggered cross decaheme configuration of electron transfer co-factors in the outer-membrane cytochrome MtrF may serve as a prototype for conformationally-gated multi-heme 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”, suggesting that the protein structure may include a dynamical mechanism for conductance and pathway switching depending on enzymatic functional need. Recent molecular simulations have established the pair-wise electronic couplings, redox potentials, and reorganization energies to predict the maximum conductance along the various heme wire pathways by sequential hopping of a single electron (PNAS (2014)more » 11,611-616). Here, we expand this information with 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 employing ten independent 50-ns simulations at 300 K and 1 atm showed that reduced MtrF is more expanded and explores more conformational space than oxidized MtrF, and that heme reduction leads to increased heme solvent exposure. The slowest mode of collective decaheme motion is 90% similar between the oxidized and reduced states, and consists primarily of inter-heme separation with minor rotational contributions. The frequency of this motion is 1.7×107 s 1 for fully-oxidized and fully-reduced MtrF, respectively, 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

  11. 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

  12. 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

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

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

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

  14. The methionine salvage pathway in Bacillus subtilis

    PubMed Central

    Sekowska, Agnieszka; Danchin, Antoine

    2002-01-01

    Background Polyamine synthesis produces methylthioadenosine, which has to be disposed of. The cell recycles it into methionine through methylthioribose (MTR). Very little was known about MTR recycling for methionine salvage in Bacillus subtilis. Results Using in silico genome analysis and transposon mutagenesis in B. subtilis we have experimentally uncovered the major steps of the dioxygen-dependent methionine salvage pathway, which, although similar to that found in Klebsiella pneumoniae, recruited for its implementation some entirely different proteins. The promoters of the genes have been identified by primer extension, and gene expression was analyzed by Northern blotting and lacZ reporter gene expression. Among the most remarkable discoveries in this pathway is the role of an analog of ribulose diphosphate carboxylase (Rubisco, the plant enzyme used in the Calvin cycle which recovers carbon dioxide from the atmosphere) as a major step in MTR recycling. Conclusions A complete methionine salvage pathway exists in B. subtilis. This pathway is chemically similar to that in K. pneumoniae, but recruited different proteins to this purpose. In particular, a paralogue or Rubisco, MtnW, is used at one of the steps in the pathway. A major observation is that in the absence of MtnW, MTR becomes extremely toxic to the cell, opening an unexpected target for new antimicrobial drugs. In addition to methionine salvage, this pathway protects B. subtilis against dioxygen produced by its natural biotope, the surface of leaves (phylloplane). PMID:12022921

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

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

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

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

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

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

  17. 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...

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

    PubMed

    Seagrave, Jeanclare; Albrecht, Helmut H; Hill, David B; Rogers, Duncan F; Solomon, Gail

    2012-10-31

    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. After IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10-300 μM) 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. 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 μM, 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. 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.

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

    SciTech Connect

    Wang, Yuanmin; Sevinc, Papatya C.; Belchik, Sara M.

    2013-01-22

    We investigate single-cell reduction of toxic Cr(VI) by the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), an important bioremediation process, using Raman spectroscopy and scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX). Our experiments indicate that the toxic and highly soluble Cr(VI) can be efficiently reduced to the less toxic and non-soluble Cr2O3 nanoparticles by MR-1. Cr2O3 is observed to emerge as nanoparticles adsorbed on the cell surface and its chemical nature is identified by EDX imaging and Raman spectroscopy. Co-localization of Cr2O3 and cytochromes by EDX imaging and Raman spectroscopy suggests a terminal reductase role for MR-1more » 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.« less

  20. 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

  1. 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

  2. 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

  3. 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

  4. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Exercises. 154.1055 Section 154... Exercises. (a) A response plan submitted by an owner or operator of an MTR facility must include an exercise program containing both announced and unannounced exercises. The following are the minimum exercise...

  5. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Exercises. 154.1055 Section 154... Exercises. (a) A response plan submitted by an owner or operator of an MTR facility must include an exercise program containing both announced and unannounced exercises. The following are the minimum exercise...

  6. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Exercises. 154.1055 Section 154... Exercises. (a) A response plan submitted by an owner or operator of an MTR facility must include an exercise program containing both announced and unannounced exercises. The following are the minimum exercise...

  7. 33 CFR 154.1055 - Exercises.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Exercises. 154.1055 Section 154... Exercises. (a) A response plan submitted by an owner or operator of an MTR facility must include an exercise program containing both announced and unannounced exercises. The following are the minimum exercise...

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

    PubMed Central

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

    2013-01-01

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

  9. Microstructural Abnormalities Were Found in Brain Gray Matter from Patients with Chronic Myofascial Pain

    PubMed Central

    Xie, Peng; Qin, Bangyong; Song, Ganjun; Zhang, Yi; Cao, Song; Yu, Jin; Wu, Jianjiang; Wang, Jiang; Zhang, Tijiang; Zhang, Xiaoming; Yu, Tian; Zheng, Hong

    2016-01-01

    Myofascial pain, presented as myofascial trigger points (MTrPs)-related pain, is a common, chronic disease involving skeletal muscle, but its underlying mechanisms have been poorly understood. Previous studies have revealed that chronic pain can induce microstructural abnormalities in the cerebral gray matter. However, it remains unclear whether the brain gray matters of patients with chronic MTrPs-related pain undergo alteration. In this study, we employed the Diffusion Kurtosis Imaging (DKI) technique, which is particularly sensitive to brain microstructural perturbation, to monitor the MTrPs-related microstructural alterations in brain gray matter of patients with chronic pain. Our results revealed that, in comparison with the healthy controls, patients with chronic myofascial pain exhibited microstructural abnormalities in the cerebral gray matter and these lesions were mainly distributed in the limbic system and the brain areas involved in the pain matrix. In addition, we showed that microstructural abnormalities in the right anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) had a significant negative correlation with the course of disease and pain intensity. The results of this study demonstrated for the first time that there are microstructural abnormalities in the brain gray matter of patients with MTrPs-related chronic pain. Our findings may provide new insights into the future development of appropriate therapeutic strategies to this disease. PMID:28066193

  10. Professional Pilots Meteorology Training Standards Conference Held in Colorado Springs, Colorado on 13-14 April 1989

    DTIC Science & Technology

    1989-07-01

    precalculus level, which is already a requirement for many college majors. Often the pilot can satisfy the four hours of elective credit required for the minor...with precalculus mathematics courses. Pilots who have taken precalculus mathematics often take four hours of MTR 421, Forecasting Laboratory, to

  11. Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian Tamil Rheumatoid Arthritis patients.

    PubMed

    Muralidharan, Niveditha; Gulati, Reena; Misra, Durga Prasanna; Negi, Vir S

    2018-02-01

    The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.

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

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

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

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

    PubMed Central

    2012-01-01

    Background Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. Methods After IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10–300 μM) 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 μM, 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

  14. An Application of Computerized Axial Tomography (CAT) Technology to Mass Raid Tracking

    DTIC Science & Technology

    1989-08-01

    ESD-TR-89-305 MTR-10542 An Application of Computerized Axial Tomography ( CAT ) Technology to Mass Raid Tracking By John K. Barr August 1989...NO 11. TITLE (Include Security Classification) An Application of Computerized Axial Tomography ( CAT ) Technology to Mass Raid Tracking 12...by block number) Computerized Axial Tomography ( CAT ) Scanner Electronic Support Measures (ESM) Fusion (continued) 19. ABSTRACT (Continue on

  15. Toward Distinguishing Recurrent Tumor From Radiation Necrosis: DWI and MTC in a Gamma Knife–Irradiated Mouse Glioma Model

    SciTech Connect

    Perez-Torres, Carlos J.; Engelbach, John A.; Cates, Jeremy

    Purpose: Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose. Methods and Materials: Two MRI contrasts that are widely used in the clinic were chosen for application to a glioma/radiation-injury model: diffusion weighted imaging, from which the apparent diffusion coefficient (ADC) ismore » obtained, and magnetization transfer contrast, from which the magnetization transfer ratio (MTR) is obtained. These metrics were evaluated longitudinally, first in each lesion type alone–glioma versus irradiation – and then in a combined irradiated glioma model. Results: MTR was found to be consistently decreased in all lesions compared to nonlesion brain tissue (contralateral hemisphere), with limited specificity between lesion types. In contrast, ADC, though less sensitive to the presence of pathology, was increased in radiation injury and decreased in tumors. In the irradiated glioma model, ADC also increased immediately after irradiation, but decreased as the tumor regrew. Conclusions: ADC is a better metric than MTR for differentiating glioma from radiation injury. However, MTR was more sensitive to both tumor and radiation injury than ADC, suggesting a possible role in detecting lesions that do not enhance strongly on T1-weighted images.« less

  16. 78 FR 42492 - Certain Frozen Warmwater Shrimp From India: Final Results of Antidumping Duty Administrative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-16

    ... 3.49 Kalyan Aqua & Marine Exp. India Pvt. Ltd 3.49 Kalyanee Marine 3.49 Kanch Ghar 3.49 Kay Kay... Pvt. Ltd 3.49 MSC Marine Exporters 3.49 MSRDR Exports 3.49 MTR Foods 3.49 N.C. John & Sons (P) Ltd 3...

  17. 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

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

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

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

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

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

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

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

    EPA Science Inventory

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

  1. 41 CFR 302-17.5 - Definitions and discussion of terms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... (See § 302-17.8(d).) (i) Marginal tax rate (MTR). The tax rate (for example, 33 percent) applicable to a specific increment of income. The Federal, Puerto Rico, and State marginal tax rates to be used in...) for instructions on local marginal tax rate determinations.) (j) Combined marginal tax rate (CMTR). A...

  2. Emergence of high level azithromycin-resistant Neisseria gonorrhoeae strain isolated in Argentina.

    PubMed

    Galarza, Patricia G; Alcalá, Belén; Salcedo, Celia; Canigia, Liliana Fernández; Buscemi, Luis; Pagano, Irene; Oviedo, Claudia; Vázquez, Julio A

    2009-12-01

    One Neisseria gonorrhoeae strains highly resistant to azithromycin AzHLR (MIC >2048 mg/L) was isolated in Argentina in 2001 and it has been characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) as ST696, suggesting a different event to other isolates in Europe. Neither, mtrR mutations or presence of mef gene were detected.

  3. Catalog of experimental projects for a fissioning plasma reactor

    NASA Technical Reports Server (NTRS)

    Lanzo, C. D.

    1973-01-01

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

  4. ETRMTR MECHANICAL SERVICES BUILDING, TRA653, INTERIOR. CAMERA IS INSIDE MEN'S ...

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

    ETR-MTR MECHANICAL SERVICES BUILDING, TRA-653, INTERIOR. CAMERA IS INSIDE MEN'S LAVATORY AND SHOWER FACING SOUTHEAST. SHOWER AND TOILET STALLS ARE IN PLACE. ROUND COMMUNAL SINK AT LEFT. INL NEGATIVE NO. 57-3652. K. Mansfield, Photographer, 7/22/1957 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  5. ETRMTR MECHANICAL SERVICES BUILDING, TRA653. CAMERA FACING NORTHWEST AS BUILDING ...

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

    ETR-MTR MECHANICAL SERVICES BUILDING, TRA-653. CAMERA FACING NORTHWEST AS BUILDING WAS NEARLY COMPLETE. INL NEGATIVE NO. 57-3653. K. Mansfield, Photographer, 7/22/1957 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  6. Trusted Network Interpretation of the Trusted Computer System Evaluation Criteria. Version 1.

    DTIC Science & Technology

    1987-07-01

    for Secure Computer Systema, MTR-3153, The MITRE Corporation, Bedford, MA, June 1975. 1 See, for example, M. D. Abrams and H. J. Podell , Tutorial...References References Abrams, M. D. and H. J. Podell , Tutorial: Computer and Network Security, IEEE Com- puter Society Press, 1987. Addendum to the

  7. Design Principles and Guidelines for Security

    DTIC Science & Technology

    2007-11-21

    Padula , Secure Computer Systems: Unified Exposition and Multics Interpretation. Electronic Systems Division, USAF. ESD-TR-75-306, MTR-2997 Rev.1...Hanscom AFB, MA. March 1976 [7] David Elliott Bell. “Looking Back at the Bell-La Padula Model,” Proc. Annual Computer Security Applications Conference

  8. Effect of Latent Myofascial Trigger Points on Strength Measurements of the Upper Trapezius: A Case-Controlled Trial

    PubMed Central

    Anshul

    2011-01-01

    ABSTRACT Purpose: The purpose of this article was to determine whether strength is altered in the upper trapezius in the presence of latent myofascial trigger points (MTrP). Methods: This study was case controlled and used convenience sampling. The sample recruited was homogeneous with respect to age, sex, height, and body mass. Participants were assessed for the presence of latent MTrP in the upper trapezius and placed into two groups: an experimental group that had latent MTrP in the upper trapezius and a control group that did not. Eighteen women (mean age 21.4 y, SD 1.89; mean height 156.9 cm, SD 4.03; and mean body mass 51.7 kg, SD 5.84) made up the experimental group, and 19 women (mean age 20.3 y, SD 1.86; mean height 158.6 cm, SD 3.14; and mean body mass 53.2 kg, SD 5.17) made up the control group. We obtained strength measurements of the non-dominant arm using a handheld dynamometer and compared them between the two groups. Results: The difference in the strength measurements between the two groups was not statistically significant (p=0.59). Conclusions: The presence of latent MTrPs may not affect the strength of the upper trapezius. PMID:22942517

  9. Neurophysiological and clinical effects of dry needling in patients with upper trapezius myofascial trigger points.

    PubMed

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

    2017-01-01

    Dry needling (DN) is a widely used in treatment of myofascial trigger points (MTrPs). The purpose of this pretest-posttest clinical trial was to investigate the neurophysiological and clinical effects of DN in patients with MTrPs. A sample of 20 patients (3 man, 17 women; mean age 31.7 ± 10.8) with upper trapezius MTrPs received one session of deep DN. The outcomes of neuromuscular junction response (NMJR), sympathetic skin response (SSR), pain intensity (PI) and pressure pain threshold (PPT) were measured at baseline and immediately after DN. There were significant improvements in SSR latency and amplitude, pain, and PPT after DN. The NMJR decreased and returned to normal after DN. A single session of DN to the active upper trapezius MTrP was effective in improving pain, PPT, NMJR, and SSR in patients with myofascial trigger points. Further studies are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Postneedling soreness after deep dry needling of a latent myofascial trigger point in the upper trapezius muscle: Characteristics, sex differences and associated factors.

    PubMed

    Martín-Pintado-Zugasti, Aitor; Rodríguez-Fernández, Ángel Luis; Fernandez-Carnero, Josue

    2016-04-27

    Postneedling soreness is considered the most frequent secondary effect associated to dry needling. A detailed description of postneedling soreness characteristics has not been previously reported. (1) to assess the intensity and duration of postneedling soreness and tenderness after deep dry needling of a trapezius latent myofascial trigger point (MTrP), (2) to evaluate the possible differences in postneedling soreness between sexes and (3) to analyze the influence on postneedling soreness of factors involved in the dry needling process. Sixty healthy subjects (30 men, 30 women) with latent MTrPs in the upper trapezius muscle received a dry needling intervention in the MTrP. Pain and pressure pain threshold (PPT) were assessed during a 72 hours follow-up period. Repeated measures analysis of covariance showed a significant effect for time in pain and in PPT. An interaction between sex and time in pain was obtained: women exhibited higher intensity in postneedling pain than men. The pain during needling and the number of needle insertions significantly correlated with postneedling soreness. Soreness and hyperalgesia are present in all subjects after dry needling of a latent MTrP in the upper trapezius muscle. Women exhibited higher intensity of postneedling soreness than men.

  11. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Response Plans for Animal Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  12. 33 CFR 154.1210 - Purpose and applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Response Plans for Animal Fats and Vegetable Oils Facilities § 154.1210 Purpose and applicability. (a) The requirements of this... fats or vegetable oils including— (1) A fixed MTR facility capable of transferring oil in bulk, to or...

  13. 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

  14. 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 ...

  15. 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 ...

  16. FAST CHOPPER DETECTOR HOUSE, TRA665. SECOND FLOOR ADDITION: PLAN, SECTIONS ...

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

    FAST CHOPPER DETECTOR HOUSE, TRA-665. SECOND FLOOR ADDITION: PLAN, SECTIONS AND DETAILS AS ADDED TO THE EXISTING CHOPPER HOUSE IN 1962. F.C. TORKELSON 842-MTR-665-S-3, 4/1962. INL INDEX NO. 531-0665-60-851-150997, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

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

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

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

  18. 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

  19. 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

  20. '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...

  1. 33 CFR 154.1016 - Facility classification by COTP.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Facility classification by COTP... Facilities § 154.1016 Facility classification by COTP. (a) The COTP may upgrade the classification of: (1) An...) The COTP may downgrade, the classification of: (1) An MTR facility specified in § 154.1015(c) to a...

  2. High bit rate mass data storage device

    NASA Technical Reports Server (NTRS)

    1973-01-01

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

  3. Polymorphisms of 5,10-methylenetetrahydrofolate reductase and thymidylate synthase, dietary folate intake, and the risk of leukemia in adults.

    PubMed

    Liu, Ping; Zhang, Min; Xie, Xing; Jin, Jie; Holman, C D'Arcy J

    2016-03-01

    The 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are critical enzymes in folate metabolism. Previous studies have reported conflicting results on the associations between MTHFR/TS polymorphisms and adult leukemia risk, which may due to the lack of information on folate intake. We investigated the risks of adult leukemia with genetic polymorphisms of folate metabolic enzymes (MTHFR C677T, A1298C, and TS) and evaluated if the associations varied by dietary folate intake from a multicenter case-control study conducted in Chinese. This study comprised 442 incident adult leukemia cases and 442 outpatient controls, individually matched to cases by gender, birth quinquennium, and study site. Genotypes were determined by a polymerase chain reaction (PCR) or PCR-based restriction fragment length polymorphism assay. Dietary folate intake was assessed by face-to-face interviews using a validated food-frequency questionnaire. The MTHFR 677TT genotype conferred a significant higher risk of leukemia in males than in females and exhibited an increased risk of acute myeloid leukemia (AML) but a decreased risk of acute lymphoblastic leukemia (ALL). The MTHFR 1298AC genotype appeared to decrease the risks of leukemia in both genders, in AML and ALL. Stratified analysis by dietary folate intake showed the increased risks of leukemia with the MTHFR 677TT and TS 2R3R/2R2R genotypes were only significant in individuals with low folate intake. A significant interaction between TS polymorphism and dietary folate intake was observed (P = 0.03). This study suggests that dietary folate intake and gender may modify the associations between MTHFR/TS polymorphisms and adult leukemia risk.

  4. Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) are associated with susceptibility to adult acute myeloid leukemia in a Chinese population.

    PubMed

    Huang, Lulu; Deng, Donghong; Peng, Zhigang; Ye, Fanghui; Xiao, Qiang; Zhang, Bing; Ye, Bingbing; Mo, Zengnan; Yang, Xiaobo; Liu, Zhenfang

    2015-06-01

    Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in the metabolism of folate. Since acute myeloid leukemia (AML) is characterized by rapidly proliferating tissues that have a high requirement for DNA synthesis, it is possible that the presence of MTHFR polymorphisms could be linked to the multifactorial process of AML development. We evaluated the role of MTHFR C677T and A1298C polymorphisms in a case-control study comprising 98 AML patients and 2016 healthy controls in a Southern Chinese population. We further conducted a sub-study restricted to individuals who neither smoked nor drank alcohol (70 AML patients and 160 healthy controls). MTHFR polymorphisms in the patient and control groups were evaluated by SNaP shot genotype techniques and Illumina BeadChip, respectively. Logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). The MTHFR 1298AC genotype and the 677CC/1298AC haplotype were significantly associated with a decreased risk of AML compared with the AA genotype and 677CC/1298AA haplotype (OR=0.60, 95% CI: 0.38-0.95, P=0.03; OR=0.49, 95% CI: 0.27-0.90, P=0.02, respectively). In addition, the 677TT genotype was significantly associated with an increased risk of AML compared with the AA genotype only in non-smokers and non-drinkers (OR=4.78; 95% CI=1.38-16.61, P=0.01). The results might suggest that MTHFR polymorphisms are significantly associated with AML risk. In addition, the role of MTHFR genetic susceptibility could be greater among non-smokers and non-drinkers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Methotrexate toxicity and efficacy during the consolidation phase in paediatric acute lymphoblastic leukaemia and MTHFR polymorphisms as pharmacogenetic determinants.

    PubMed

    D'Angelo, Velia; Ramaglia, Maria; Iannotta, Adriana; Crisci, Stefania; Indolfi, Paolo; Francese, Matteo; Affinita, Maria Carmen; Pecoraro, Giulia; Napolitano, Addolorata; Fusco, Claudia; Oreste, Matilde; Indolfi, Cristiana; Casale, Fiorina

    2011-11-01

    Folate-metabolizing single-nucleotide polymorphisms (SNPs) are emerging as important pharmacogenetic prognostic determinants of the response to chemotherapy. With high doses of methotrexate (MTX) in the consolidation phase, methylenetetrahydrofolate reductase (MTHFR) polymorphisms could be potential modulators of the therapeutic response to antifolate chemotherapeutics in identifying a possible correlation with the outcome. This study aims to analyse the potential role of the MTHFR C677T and A1298C genetic variants in modulating the clinical toxicity and efficacy of high doses of MTX in a cohort of paediatric ALL patients (n = 151) treated with AIEOP protocols. This work includes DNA extraction by slides and RFLP-PCR. The first observation relative to early toxicities (haematological and non-haematological), after the first doses of MTX in all protocols, was an association between the 677T and 1298C carriers and global toxicity. We found that in the 2 g/m(2) MTX group, patients harbouring 677TT homozygously exhibited a substantial 12-fold risk of developing toxicity. In this study, we demonstrate that the MTHFR 677TT variant is associated with an increased risk of relapse when compared to other genotypes. The Kaplan-Meier analysis showed that the 677TT variant had a lower 7-year DFS(disease-free survival) probability compared to the 677C carrier genotype (log-rank test P = 0.003) and OS (overall survival) and also confirms the lower probability of survival for patients with the 677TT variant (log-rank test, P = 0.006). Our study provides further evidence of the critical role played by folate pathway enzymes in the outcome of ALL, possibly through the interference of MTX.

  6. Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE).

    PubMed

    Amigou, Alicia; Rudant, Jérémie; Orsi, Laurent; Goujon-Bellec, Stéphanie; Leverger, Guy; Baruchel, André; Bertrand, Yves; Nelken, Brigitte; Plat, Geneviève; Michel, Gérard; Haouy, Stéphanie; Chastagner, Pascal; Ducassou, Stéphane; Rialland, Xavier; Hémon, Denis; Clavel, Jacqueline

    2012-08-01

    Fetal folate deficiency may increase the risk of subsequent childhood acute leukemia (AL), since folates are required for DNA methylation, synthesis, and repair, but the literature remains scarce. This study tested the hypothesis that maternal folic acid supplementation before or during pregnancy reduces AL risk, accounting for the SNPs rs1801133 (C677T) and rs1801131 (A1298C) in MTHFR and rs1801394 (A66G) and rs1532268 (C524T) in MTRR, assumed to modify folate metabolism. The nationwide registry-based case-control study, ESCALE, carried out in 2003-2004, included 764 AL cases and 1,681 controls frequency matched with the cases on age and gender. Information on folic acid supplementation was obtained by standardized telephone interview. The genotypes were obtained using high-throughput platforms and imputation for untyped polymorphisms. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. AL was significantly inversely associated with maternal folic acid supplementation before and during pregnancy (OR = 0.4; 95 % confidence interval: [0.3-0.6]). MTHFR and MTRR genetic polymorphisms were not associated with AL. However, AL was positively associated with homozygosity for any of the MTHFR polymorphisms and carriership of both MTRR variant alleles (OR = 1.6 [0.9-3.1]). No interaction was observed between MTHFR, MTRR, and maternal folate supplementation. The study findings support the hypothesis that maternal folic acid supplementation may reduce the risk of childhood AL. The findings also suggest that the genotype homozygous for any of the MTHFR variants and carrying both MTRR variants could be a risk factor for AL.

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

    PubMed Central

    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

    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

  8. Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans.

    PubMed

    Kohlmeier, Martin; da Costa, Kerry-Ann; Fischer, Leslie M; Zeisel, Steven H

    2005-11-01

    Choline is a required nutrient, and some humans deplete quickly when fed a low-choline diet, whereas others do not. Endogenous choline synthesis can spare some of the dietary requirement and requires one-carbon groups derived from folate metabolism. We examined whether major genetic variants of folate metabolism modify susceptibility of humans to choline deficiency. Fifty-four adult men and women were fed diets containing adequate choline and folate, followed by a diet containing almost no choline, with or without added folate, until they were clinically judged to be choline-deficient, or for up to 42 days. Criteria for clinical choline deficiency were a more than five times increase in serum creatine kinase activity or a >28% increase of liver fat after consuming the low-choline diet that resolved when choline was returned to the diet. Choline deficiency was observed in more than half of the participants, usually within less than a month. Individuals who were carriers of the very common 5,10-methylenetetrahydrofolate dehydrogenase-1958A gene allele were more likely than noncarriers to develop signs of choline deficiency (odds ratio, 7.0; 95% confidence interval, 2.0-25; P < 0.01) on the low-choline diet unless they were also treated with a folic acid supplement. The effects of the C677T and A1298C polymorphisms of the 5,10-methylene tetrahydrofolate reductase gene and the A80C polymorphism of the reduced folate carrier 1 gene were not statistically significant. The most remarkable finding was the strong association in premenopausal women of the 5,10-methylenetetrahydrofolate dehydrogenase-1958A gene allele polymorphism with 15 times increased susceptibility to developing organ dysfunction on a low-choline diet.

  9. Hyperhomocysteinaemia, methylenetetrahydrofolate reductase polymorphism and risk of coronary artery disease.

    PubMed

    Kerkeni, Mohsen; Addad, Faouzi; Chauffert, Maryline; Myara, Anne; Gerhardt, Marie; Chevenne, Didier; Trivin, François; Farhat, Mohamed Ben; Miled, Abdelhedi; Maaroufi, Khira

    2006-05-01

    Hyperhomocysteinaemia is an independent, graded risk factor for coronary artery disease (CAD). The methylenetetrahydrofolate reductase (MTHFR) polymorphism is associated with hyperhomcysteinaemia and may therefore influence individual susceptibility to CAD. We have investigated this risk factor in a Tunisian Arab population. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect the C677T and A1298C variants of the MTHFR gene in 100 patients with CAD and 120 healthy controls. The severity of CAD was expressed as the number of affected vessels. Plasma total homocysteine (tHcy) concentration was determined using a direct chemiluminescence assay. MTHFR CC, CT and TT genotype frequencies in the CAD group were significantly different from those observed in the control group (49%, 35% and 16% versus 48.3%, 45.8% and 5.8%, respectively; P = 0.031). However, MTHFR AA, AC and CC genotypes frequencies in the CAD group were not significantly different from the control group ( P = 0.568). Patients with CAD showed higher plasma tHcy concentrations than patients without CAD (15.86 +/- 8.63 micromol/L versus 11.90 +/- 3.25 micromol/L, P < 0.001). There was no association between the MTHFR polymorphisms and the number of stenosed vessels. Patients with the MTHFR TT genotype had higher plasma tHcy, serum creatinine, cholesterol and triglyceride concentrations than patients with the MTHFR CC genotype. The C677T polymorphism of the MTHFR gene is associated with hyperhomocysteinaemia, lipid dysregulation and the presence of CAD in this Tunisian Arab population.

  10. Relationship of MTHFR gene polymorphisms with renal and cardiac disease

    PubMed Central

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

    2015-01-01

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

  11. Meta-Prediction of MTHFR Gene Polymorphisms and Air Pollution on the Risk of Hypertensive Disorders in Pregnancy Worldwide.

    PubMed

    Yang, Ya-Ling; Yang, Hsiao-Ling; Shiao, S Pamela K

    2018-02-13

    Hypertensive disorders in pregnancy (HDP) are devastating health hazards for both women and children. Both methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms and air pollution can affect health status and result in increased risk of HDP for women. The major objective of this study was to investigate the effect of MTHFR polymorphisms, air pollution, and their interaction on the risk of HDP by using meta-predictive analytics. We searched various databases comprehensively to access all available studies conducted for various ethnic populations from countries worldwide, from 1997 to 2017. Seventy-one studies with 8064 cases and 13,232 controls for MTHFR C677T and 11 studies with 1425 cases and 1859 controls for MTHFR A1298C were included. MTHFR C677T homozygous TT (risk ratio (RR) = 1.28, p < 0.0001) and CT plus TT (RR = 1.07, p = 0.0002) were the risk genotypes, while wild-type CC played a protective role (RR = 0.94, p = 0.0017) for HDP. The meta-predictive analysis found that the percentage of MTHFR C677T TT plus CT ( p = 0.044) and CT ( p = 0.043) genotypes in the HDP case group were significantly increased with elevated levels of air pollution worldwide. Additionally, in countries with higher air pollution levels, the pregnant women with wild-type CC MTHFR 677 had a protection effect against HDP ( p = 0.014), whereas, the homozygous TT of MTHFR C677T polymorphism was a risk genotype for developing HDP. Air pollution level is an environmental factor interacting with increased MTHFR C677T polymorphisms, impacting the susceptibility of HDP for women.

  12. Meta-Prediction of MTHFR Gene Polymorphisms and Air Pollution on the Risk of Hypertensive Disorders in Pregnancy Worldwide

    PubMed Central

    Yang, Ya-Ling; Yang, Hsiao-Ling; Shiao, S. Pamela K.

    2018-01-01

    Hypertensive disorders in pregnancy (HDP) are devastating health hazards for both women and children. Both methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and air pollution can affect health status and result in increased risk of HDP for women. The major objective of this study was to investigate the effect of MTHFR polymorphisms, air pollution, and their interaction on the risk of HDP by using meta-predictive analytics. We searched various databases comprehensively to access all available studies conducted for various ethnic populations from countries worldwide, from 1997 to 2017. Seventy-one studies with 8064 cases and 13,232 controls for MTHFR C677T and 11 studies with 1425 cases and 1859 controls for MTHFR A1298C were included. MTHFR C677T homozygous TT (risk ratio (RR) = 1.28, p < 0.0001) and CT plus TT (RR = 1.07, p = 0.0002) were the risk genotypes, while wild-type CC played a protective role (RR = 0.94, p = 0.0017) for HDP. The meta-predictive analysis found that the percentage of MTHFR C677T TT plus CT (p = 0.044) and CT (p = 0.043) genotypes in the HDP case group were significantly increased with elevated levels of air pollution worldwide. Additionally, in countries with higher air pollution levels, the pregnant women with wild-type CC MTHFR 677 had a protection effect against HDP (p = 0.014), whereas, the homozygous TT of MTHFR C677T polymorphism was a risk genotype for developing HDP. Air pollution level is an environmental factor interacting with increased MTHFR C677T polymorphisms, impacting the susceptibility of HDP for women. PMID:29438331

  13. Assessment of the patellofemoral cartilage: Correlation of knee pain score with magnetic resonance cartilage grading and magnetization transfer ratio asymmetry of glycosaminoglycan chemical exchange saturation transfer.

    PubMed

    Lee, Young Han; Yang, Jaemoon; Jeong, Ha-Kyu; Suh, Jin-Suck

    2017-01-01

    Biochemical imaging of glycosaminoglycan chemical exchange saturation transfer (gagCEST) could predict the depletion of glycosaminoglycans (GAG) in early osteoarthritis. The purpose of this study was to evaluate the relationship between the magnetization transfer ratio asymmetry (MTR asym ) of gagCEST images and visual analog scale (VAS) pain scores in the knee joint. This retrospective study was approved by the institutional review board. A phantom study was performed using hyaluronic acid to validate the MTR asym values of gagCEST images. Knee magnetic resonance (MR) images of 22 patients (male, 9; female, 13; mean age, 50.3years; age range; 25-79years) with knee pain were included in this study. The MR imaging (MRI) protocol involved standard knee MRI as well as gagCEST imaging, which allowed region-of-interest analyses of the patellar facet and femoral trochlea. The MTR asym at 1.0ppm was calculated at each region. The cartilages of the patellar facets and femoral trochlea were graded according to the Outerbridge classification system. Data regarding the VAS scores of knee pain were collected from the electronic medical records of the patients. Statistical analysis was performed using Spearman's correlation. The results of the phantom study revealed excellent correlation between the MTR asym values and the concentration of GAGs (r=0.961; p=0.003). The cartilage grades on the MR images showed significant negative correlation with the MTR asym values in the patellar facet and femoral trochlea (r=-0.460; p=0.031 and r=-0.543; p=0.009, respectively). The VAS pain scores showed significant negative correlation with the MTR asym values in the patellar facet and femoral trochlea (r=-0.435; p=0.043 and r=-0.671; p=0.001, respectively). The pain scores were associated with the morphological and biochemical changes in articular cartilages visualized on knee MR images. The biochemical changes, visualized in terms of the MTR asym values of the gagCEST images, exhibited

  14. A multimodal MRI approach to identify and characterize microstructural brain changes in neuropsychiatric systemic lupus erythematosus.

    PubMed

    Ercan, Ece; Ingo, Carson; Tritanon, Oranan; Magro-Checa, Cesar; Smith, Alex; Smith, Seth; Huizinga, Tom; van Buchem, Mark A; Ronen, Itamar

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and results in neurological and psychiatric (NP) symptoms in up to 40% of the patients. To date, the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) poses a challenge due to the lack of neuroradiological gold standards. In this study, we aimed to better localize and characterize normal appearing white matter (NAWM) changes in NPSLE by combining data from two quantitative MRI techniques, diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI). 9 active NPSLE patients (37 ± 13 years, all females), 9 SLE patients without NP symptoms (44 ± 11 years, all females), and 14 healthy controls (HC) (40 ± 9 years, all females) were included in the study. MTI, DTI and fluid attenuated inversion recovery (FLAIR) images were collected from all subjects on a 3 T MRI scanner. Magnetization transfer ratio (MTR), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) maps and white matter lesion maps based on the FLAIR images were created for each subject. MTR and DTI data were then co-analyzed using tract-based spatial statistics and a cumulative lesion map to exclude lesions. Significantly lower MTR and FA and significantly higher AD, RD and MD were found in NPSLE compared to HC in NAWM regions. The differences in DTI measures and in MTR, however, were only moderately co-localized. Additionally, significant differences in DTI measures, but not in MTR, were found between NPSLE and SLE patients, suggesting that the underlying microstructural changes detected by MD are linked to the onset of NPSLE. The co-analysis of the anatomical distribution of MTI and DTI measures can potentially improve the diagnosis of NPSLE and contribute to the understanding of the underlying microstructural damage.

  15. Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: A randomized, placebo-controlled clinical trial

    PubMed Central

    Moraska, Albert F.; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P.; Schmiege, Sarah J.; Mann, J. Douglas

    2014-01-01

    Objective Myofascial trigger points (MTrPs) are focal disruptions in skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type headache (TTH). The present study applied massage focused on MTrPs of subjects with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache pain. Methods Fifty-six subjects with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over six weeks, or to wait-list. Trigger point release (TPR) massage focused on MTrPs in cervical musculature. Headache pain (frequency, intensity and duration) was recorded in a daily headache diary. Additional outcome measures included self-report of perceived clinical change in headache pain and pressure-pain threshold (PPT) at MTrPs in the upper trapezius and sub-occipital muscles. Results From diary recordings, group differences across time were detected in headache frequency (p=0.026), but not for intensity or duration. Post hoc analysis indicated headache frequency decreased from baseline for both massage (p<0.0003) and placebo (p=0.013), but no difference was detected between massage and placebo. Subject report of perceived clinical change was a greater reduction in headache pain for massage than placebo or wait-list groups (p=0.002). PPT improved in all muscles tested for massage only (all p's<0.002). Discussion Two findings from this study are apparent: 1) MTrPs are important components in the treatment of TTH, and 2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on headache that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention. PMID:25329141

  16. Reduction of myocardial ischemia-reperfusion injury by mechanical tissue resuscitation using sub-atmospheric pressure.

    PubMed

    Argenta, Louis C; Morykwas, Michael J; Mays, Jennifer J; Thompson, Edreca A; Hammon, John W; Jordan, James E

    2010-03-01

    Reperfusion-induced injury after myocardial infarction is associated with a well-defined sequence of early and late cardiomyocyte death. Most present attempts to ameliorate this sequence focus on a single facet of the complex process in an attempt to salvage cardiomyocytes. We examined, as proof of concept, the effects of mechanical tissue resuscitation (MTR) with controlled negative pressure on myocardial injury following acute myocardial infarction. Anesthetized swine were subjected to 75 minutes of left coronary artery occlusion and three hours of reperfusion. Animals were assigned to one of three groups: (A) untreated control; treatment of involved myocardium for 180 minutes of MTR with (B) -50 mmHg, or (C) -125 mmHg. All three groups were subjected to equivalent ischemic stress. Treatment of the ischemic area with MTR for 180 minutes significantly (p < 0.001) reduced infarct size (area of necrosis/area at risk) in both treatment groups compared to control: 9.3 +/- 1.8% (-50 mmHg) and 11.9 +/- 1.2% (-125 mmHg) versus 26.4 +/- 2.1% (control). Total area of cell death was reduced by 65% with -50 mmHg treatment and 55% in the -125 mmHg group. Treatment of ischemic myocardium with MTR, for a controlled period of time during reperfusion, successfully reduced the extent of myocardial death after acute myocardial infarction. These data provide evidence that MTR using subatmospheric pressure may be a simple, efficacious, nonpharmacological, mechanical strategy for decreasing cardiomyocyte death following myocardial infarction, which can be delivered in the operating room.

  17. Quantitative Ultrasound Using Texture Analysis of Myofascial Pain Syndrome in the Trapezius.

    PubMed

    Kumbhare, Dinesh A; Ahmed, Sara; Behr, Michael G; Noseworthy, Michael D

    2018-01-01

    Objective-The objective of this study is to assess the discriminative ability of textural analyses to assist in the differentiation of the myofascial trigger point (MTrP) region from normal regions of skeletal muscle. Also, to measure the ability to reliably differentiate between three clinically relevant groups: healthy asymptomatic, latent MTrPs, and active MTrP. Methods-18 and 19 patients were identified with having active and latent MTrPs in the trapezius muscle, respectively. We included 24 healthy volunteers. Images were obtained by research personnel, who were blinded with respect to the clinical status of the study participant. Histograms provided first-order parameters associated with image grayscale. Haralick, Galloway, and histogram-related features were used in texture analysis. Blob analysis was conducted on the regions of interest (ROIs). Principal component analysis (PCA) was performed followed by multivariate analysis of variance (MANOVA) to determine the statistical significance of the features. Results-92 texture features were analyzed for factorability using Bartlett's test of sphericity, which was significant. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.94. PCA demonstrated rotated eigenvalues of the first eight components (each comprised of multiple texture features) explained 94.92% of the cumulative variance in the ultrasound image characteristics. The 24 features identified by PCA were included in the MANOVA as dependent variables, and the presence of a latent or active MTrP or healthy muscle were independent variables. Conclusion-Texture analysis techniques can discriminate between the three clinically relevant groups.

  18. SciTech Connect

    Yoshikatsu, Yuki; Ishida, Yo-ichi; Sudo, Haruka

    Nuclear VCP-like 2 (NVL2) is a member of the chaperone-like AAA-ATPase family and is involved in the biosynthesis of 60S ribosomal subunits in mammalian cells. We previously showed the interaction of NVL2 with a DExD/H-box RNA helicase MTR4/DOB1, which is a known cofactor for an exoribonuclease complex, the exosome. This finding implicated NVL2 in RNA metabolic processes during ribosome biogenesis. In the present study, we found that a series of mutations within the ATPase domain of NVL2 causes a defect in pre-rRNA processing into mature 28S and 5.8S rRNAs. Co-immunoprecipitation analysis showed that NVL2 was associated with the nuclear exosomemore » complex, which includes RRP6 as a nucleus-specific catalytic subunit. This interaction was prevented by depleting either MTR4 or RRP6, indicating their essential role in mediating this interaction with NVL2. Additionally, knockdown of MPP6, another cofactor for the nuclear exosome, also prevented the interaction by causing MTR4 to dissociate from the nuclear exosome. These results suggest that NVL2 is involved in pre-rRNA processing by associating with the nuclear exosome complex and that MPP6 is required for maintaining the integrity of this rRNA processing complex. - Highlights: • ATPase-deficient mutants of NVL2 have decreased pre-rRNA processing. • NVL2 associates with the nuclear exosome through interactions with MTR4 and RRP6. • MPP6 stabilizes MTR4-RRP6 interaction and allows NVL2 to interact with the complex.« less

  19. In vivo magnetization transfer and diffusion-weighted magnetic resonance imaging detects thrombus composition in a mouse model of deep vein thrombosis.

    PubMed

    Phinikaridou, Alkystis; Andia, Marcelo E; Saha, Prakash; Modarai, Bijan; Smith, Alberto; Botnar, René M

    2013-05-01

    Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; PANOVA<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10(-3) mm(2)/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10(-3) mm(2)/s]). MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention.

  20. Characterization of the periplasmic redox network that sustains the versatile anaerobic metabolism of Shewanella oneidensis MR-1

    PubMed Central

    Alves, Mónica N.; Neto, Sónia E.; Alves, Alexandra S.; Fonseca, Bruno M.; Carrêlo, Afonso; Pacheco, Isabel; Paquete, Catarina M.; Soares, Cláudio M.; Louro, Ricardo O.

    2015-01-01

    The versatile anaerobic metabolism of the Gram-negative bacterium Shewanella oneidensis MR-1 (SOMR-1) relies on a multitude of redox proteins found in its periplasm. Most are multiheme cytochromes that carry electrons to terminal reductases of insoluble electron acceptors located at the cell surface, or bona fide terminal reductases of soluble electron acceptors. In this study, the interaction network of several multiheme cytochromes was explored by a combination of NMR spectroscopy, activity assays followed by UV-visible spectroscopy and comparison of surface electrostatic potentials. From these data the small tetraheme cytochrome (STC) emerges as the main periplasmic redox shuttle in SOMR-1. It accepts electrons from CymA and distributes them to a number of terminal oxidoreductases involved in the respiration of various compounds. STC is also involved in the electron transfer pathway to reduce nitrite by interaction with the octaheme tetrathionate reductase (OTR), but not with cytochrome c nitrite reductase (ccNiR). In the main pathway leading the metal respiration STC pairs with flavocytochrome c (FccA), the other major periplasmic cytochrome, which provides redundancy in this important pathway. The data reveals that the two proteins compete for the binding site at the surface of MtrA, the decaheme cytochrome inserted on the periplasmic side of the MtrCAB–OmcA outer-membrane complex. However, this is not observed for the MtrA homologues. Indeed, neither STC nor FccA interact with MtrD, the best replacement for MtrA, and only STC is able to interact with the decaheme cytochrome DmsE of the outer-membrane complex DmsEFABGH. Overall, these results shown that STC plays a central role in the anaerobic respiratory metabolism of SOMR-1. Nonetheless, the trans-periplasmic electron transfer chain is functionally resilient as a consequence of redundancies that arise from the presence of alternative pathways that bypass/compete with STC. PMID:26175726

  1. Amide proton transfer magnetic resonance imaging of Alzheimer's disease at 3.0 Tesla: a preliminary study.

    PubMed

    Wang, Rui; Li, Sa-Ying; Chen, Min; Zhou, Jin-Yuan; Peng, Dan-Tao; Zhang, Chen; Dai, Yong-Ming

    2015-03-05

    Amide proton transfer (APT) imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging (MRI) in the field of molecular and cellular imaging. The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer's disease (AD) at 3.0 Tesla. Twenty AD patients (9 men and 11 women; age range, 67-83 years) and 20 age-matched normal controls (11 men and 9 women; age range, 63-82 years) underwent APT and traditional MRI examination on a 3.0 Tesla MRI system. The magnetic resonance ratio asymmetry (MTR asym ) values at 3.5 ppm of bilateral hippocampi (Hc), temporal white matter regions, occipital white matter regions, and cerebral peduncles were measured on oblique axial APT images. MTR asym (3.5 ppm) values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test. Controlling for age, partial correlation analysis was used to investigate the associations between mini-mental state examination (MMSE) and the various MRI measures among AD patients. Compared with normal controls, MTR asym (3.5 ppm) values of bilateral Hc were significantly increased in AD patients (right 1.24% ± 0.21% vs. 0.83% ± 0.19%, left 1.18% ± 0.18% vs. 0.80%± 0.17%, t = 3.039, 3.328, P = 0.004, 0.002, respectively). MTR asym (3.5 ppm) values of bilateral Hc were significantly negatively correlated with MMSE (right r = -0.559, P = 0.013; left r = -0.461, P = 0.047). Increased MTR asym (3.5 ppm) values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.

  2. Simultaneous pH-sensitive and oxygen-sensitive MRI of human gliomas at 3 T using multi-echo amine proton chemical exchange saturation transfer spin-and-gradient echo echo-planar imaging (CEST-SAGE-EPI).

    PubMed

    Harris, Robert J; Yao, Jingwen; Chakhoyan, Ararat; Raymond, Catalina; Leu, Kevin; Liau, Linda M; Nghiemphu, Phioanh L; Lai, Albert; Salamon, Noriko; Pope, Whitney B; Cloughesy, Timothy F; Ellingson, Benjamin M

    2018-04-06

    To introduce a new pH-sensitive and oxygen-sensitive MRI technique using amine proton CEST echo spin-and-gradient echo (SAGE) EPI (CEST-SAGE-EPI). pH-weighting was obtained using CEST estimations of magnetization transfer ratio asymmetry (MTR asym ) at 3 ppm, and oxygen-weighting was obtained using R2' measurements. Glutamine concentration, pH, and relaxation rates were varied in phantoms to validate simulations and estimate relaxation rates. The values of MTR asym and R2' in normal-appearing white matter, T 2 hyperintensity, contrast enhancement, and macroscopic necrosis were measured in 47 gliomas. Simulation and phantom results confirmed an increase in MTR asym with decreasing pH. The CEST-SAGE-EPI estimates of R 2 , R2*, and R2' varied linearly with gadolinium diethylenetriamine penta-acetic acid concentration (R 2  = 6.2 mM -1 ·sec -1 and R2* = 6.9 mM -1 ·sec -1 ). The CEST-SAGE-EPI and Carr-Purcell-Meiboom-Gill estimates of R 2 (R 2  = 0.9943) and multi-echo gradient-echo estimates of R2* (R 2  = 0.9727) were highly correlated. T 2 lesions had lower R2' and higher MTR asym compared with normal-appearing white matter, suggesting lower hypoxia and high acidity, whereas contrast-enhancement tumor regions had elevated R2' and MTR asym , indicating high hypoxia and acidity. The CEST-SAGE-EPI technique provides simultaneous pH-sensitive and oxygen-sensitive image contrasts for evaluation of the brain tumor microenvironment. Advantages include fast whole-brain acquisition, in-line B 0 correction, and simultaneous estimation of CEST effects, R 2 , R2*, and R2' at 3 T. © 2018 International Society for Magnetic Resonance in Medicine.

  3. Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: a randomized, placebo-controlled clinical trial.

    PubMed

    Moraska, Albert F; Stenerson, Lea; Butryn, Nathan; Krutsch, Jason P; Schmiege, Sarah J; Mann, John D

    2015-02-01

    Myofascial trigger points (MTrPs) are focal disruptions in the skeletal muscle that can refer pain to the head and reproduce the pain patterns of tension-type HA (TTH). The present study applied massage focused on MTrPs of patients with TTH in a placebo-controlled, clinical trial to assess efficacy on reducing headache (HA) pain. Fifty-six patients with TTH were randomized to receive 12 massage or placebo (detuned ultrasound) sessions over 6 weeks, or to wait-list. Trigger point release massage focused on MTrPs in cervical musculature. HA pain (frequency, intensity, and duration) was recorded in a daily HA diary. Additional outcome measures included self-report of perceived clinical change in HA pain and pressure-pain threshold at MTrPs in the upper trapezius and suboccipital muscles. From diary recordings, group differences across time were detected in HA frequency (P=0.026), but not for intensity or duration. Post hoc analysis indicated that HA frequency decreased from baseline for both massage (P<0.0003) and placebo (P=0.013), but no difference was detected between massage and placebo. Patient report of perceived clinical change was greater reduction in HA pain for massage than placebo or wait-list groups (P=0.002). Pressure-pain threshold improved in all muscles tested for massage only (all P's<0.002). Two findings from this study are apparent: (1) MTrPs are important components in the treatment of TTH, and (2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on HA that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention.

  4. Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis.

    PubMed

    Tur, C; Penny, S; Khaleeli, Z; Altmann, D R; Cipolotti, L; Ron, M; Thompson, A J; Ciccarelli, O

    2011-11-01

    To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55). The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

  5. 5′-Methylthioadenosine Nucleosidase and 5-Methylthioribose Kinase Activities and Ethylene Production during Tomato Fruit Development and Ripening 1

    PubMed Central

    Kushad, Mosbah M.; Richardson, Daryl G.; Ferro, Adolph J.

    1985-01-01

    5′-Methylthioadenosine (MTA) nucleosidase and 5-methylthioribose (MTR) kinase activities were measured in crude extracts of tomato fruits (Lycopersicon esculentum Mill cv Rutgers) during fruit development and ripening. The highest activity of MTA nucleosidase (1.2 nanomoles per milligram protein per minute) was observed in small green fruits. The activity decreased during ripening; at the overripe stage only 6.5% of the peak activity remained. MTR kinase activity was low at the small green stage and increased thereafter until it reached peak activity at the breaker stage (0.7 nanomoles per milligram protein per minute) followed by a sharp decline at the later stages of fruit ripening. 1-Amino-cyclopropane-1-carboxylic acid (ACC) levels peaked at the red stage, while ethylene reached its highest level at the light-red stage. Several analogs of MTA and MTR were tested as both enzyme and ethylene inhibitors. Of the MTA analogs examined for their ability to inhibit MTA nucleosidase, 5′-chloroformycin reduced enzyme activity 89%, whereas 5′-chloroadenosine, 5′-isobutylthioadenosine, 5′-isopropylthioadenosine, and 5′-ethylthioadenosine inhibited the reaction with MTA by about 40%. 5′-Chloroformycin and 5′-chloroadenosine inhibited ethylene production over a period of 24 hours by about 64 and 42%, respectively. Other analogs of MTA were not effective inhibitors of ethylene production, whereas aminoethoxyvinylglycine showed a 34% inhibition over the same period of time. Of the MTR analogs tested, 5-isobutylthioribose was the most effective inhibitor of both MTR-kinase (41%) and ethylene production (35%). PMID:16664444

  6. Comparison of radiography and ultrasonography for the diagnosis of osteochondritis dissecans in the equine femoropatellar joint.

    PubMed

    Bourzac, C; Alexander, K; Rossier, Y; Laverty, S

    2009-09-01

    Osteochondritis dissecans (OCD) lesions of the femoropatellar (FP) joint are diagnosed routinely by radiography, but lesions located in the trochlear groove or without accompanying subchondral bone changes can be difficult to visualise. Ultrasonography allows evaluation of articular cartilage and subchondral bone in the FPjoint. To document the radiographic and ultrasonographic appearance of OCD lesions in the equine FP joint, grade ultrasonographic lesions and compare their accuracy in the diagnosis of these lesions. The medical records of all horses diagnosed with FP OCD between 1995 and 2006 were assessed. Inclusion criteria included availability of both radiographic and ultrasonographic images. Lesion characteristics were evaluated in each trochlear ridge and trochlear groove. For assessment of the accuracy (sensitivity and specificity) of both imaging techniques in the diagnosis of OCD, only cases with an arthroscopic or necropsy examination were studied. Twenty-one horses were included. OCD lesions were diagnosed by radiography (30/32 joints) and ultrasound (32/32 joints). The lateral trochlear ridge (LTR, 91%) and the medial trochlear ridge (MTR, 17%) were involved on radiography. The localisation on ultrasound examination was similar (97% LTR, 25% MTR). All but one lesion seen on radiography were also detected with ultrasound; 2 LTR and 3 MTR lesions, not seen on radiography were diagnosed by ultrasound and confirmed at arthroscopy or necropsy. The specificity was 100% regardless of the site and imaging procedure except for the distal third of the MTR (94% for ultrasound). The sensitivity varied, depending on lesion site. Ultrasonography is a valuable diagnostic tool to diagnose OCD lesions in the FP joint and more sensitive than radiography for lesions affecting the MTR of the distal femur. Ultrasound should be considered as a useful adjunct to radiography for diagnosing equine FP OCD, especially in cases of high clinical suspicion but equivocal

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

    PubMed Central

    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

    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

  8. In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with (18)F-PBR111 PET.

    PubMed

    Colasanti, Alessandro; Guo, Qi; Muhlert, Nils; Giannetti, Paolo; Onega, Mayca; Newbould, Rexford D; Ciccarelli, Olga; Rison, Stuart; Thomas, Charlotte; Nicholas, Richard; Muraro, Paolo A; Malik, Omar; Owen, David R; Piccini, Paola; Gunn, Roger N; Rabiner, Eugenii A; Matthews, Paul M

    2014-07-01

    PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune

  9. In Vitro Activity of Delafloxacin against Clinical Neisseria gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance.

    PubMed

    Soge, Olusegun O; Salipante, Stephen J; No, David; Duffy, Erin; Roberts, Marilyn C

    2016-05-01

    We evaluated the in vitro activity of delafloxacin against a panel of 117 Neisseria gonorrhoeae strains, including 110 clinical isolates collected from 2012 to 2015 and seven reference strains, compared with the activities of seven antimicrobials currently or previously recommended for treatment of gonorrhea. We examined the potential for delafloxacin to select for resistant mutants in ciprofloxacin-susceptible and ciprofloxacin-resistant N. gonorrhoeae We characterized mutations in the gyrA, gyrB, parC, and parE genes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) by PCR and sequencing and by whole-genome sequencing. The MIC50, MIC90, and MIC ranges of delafloxacin were 0.06 μg/ml, 0.125 μg/ml, and ≤0.001 to 0.25 μg/ml, respectively. The frequency of spontaneous mutation ranged from 10(-7) to <10(-9) The multistep delafloxacin resistance selection of 30 daily passages resulted in stable resistant mutants. There was no obvious cross-resistance to nonfluoroquinolone comparator antimicrobials. A mutant with reduced susceptibility to ciprofloxacin (MIC, 0.25 μg/ml) obtained from the ciprofloxacin-susceptible parental strain had a novel Ser91Tyr alteration in the gyrA gene. We also identified new mutations in the gyrA and/or parC and parE genes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) of two mutant strains with elevated delafloxacin MICs of 1 μg/ml. Although delafloxacin exhibited potent in vitro activity against N. gonorrhoeae isolates and reference strains with diverse antimicrobial resistance profiles and demonstrated a low tendency to select for spontaneous mutants, it is important to establish the correlation between these excellent in vitro data and treatment outcomes through appropriate randomized controlled clinical trials. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. A drain current model for amorphous InGaZnO thin film transistors considering temperature effects

    NASA Astrophysics Data System (ADS)

    Cai, M. X.; Yao, R. H.

    2018-03-01

    Temperature dependent electrical characteristics of amorphous InGaZnO (a-IGZO) thin film transistors (TFTs) are investigated considering the percolation and multiple trapping and release (MTR) conduction mechanisms. Carrier-density and temperature dependent carrier mobility in a-IGZO is derived with the Boltzmann transport equation, which is affected by potential barriers above the conduction band edge with Gaussian-like distributions. The free and trapped charge densities in the channel are calculated with Fermi-Dirac statistics, and the field effective mobility of a-IGZO TFTs is then deduced based on the MTR theory. Temperature dependent drain current model for a-IGZO TFTs is finally derived with the obtained low field mobility and free charge density, which is applicable to both non-degenerate and degenerate conductions. This physical-based model is verified by available experiment results at various temperatures.

  11. Modeling and characterization of the low frequency noise behavior for amorphous InGaZnO thin film transistors in the subthreshold region

    NASA Astrophysics Data System (ADS)

    Cai, Minxi; Yao, Ruohe

    2017-10-01

    An analytical model of the low-frequency noise (LFN) for amorphous InGaZnO (a-IGZO) thin film transistors (TFTs) in the subthreshold region is developed. For a-IGZO TFTs, relations between the device noise and the subgap defects are characterized based on the dominant multiple trapping and release (MTR) mechanism. The LFN is considered to be contributed from trapping/detrapping of carriers both into the border traps and the subgap density of states (DOS). It is revealed that the LFN behavior of a-IGZO TFTs in the subthreshold region is significantly influenced by the distribution of tail states, where MTR process prevails. The 1/f α (with α < 1) spectrum of the drain current noise is also related to the characteristic temperature of the tail states. The new method is introduced to calculate the LFN of devices by extracting the LFN-related DOS parameters from the current-voltage characteristics.

  12. The effect of inflammation-related lifestyle exposures and interactions with gene variants on long interspersed nuclear element-1 DNA methylation.

    PubMed

    Gogna, Priyanka; O'Sullivan, Dylan E; King, Will D

    2018-06-11

    To examine the relationship between inflammation-related lifestyle factors and long interspersed nuclear element-1 (LINE-1) DNA methylation, and test for interaction by gene variants involved in one-carbon metabolism. The study population consisted of 280 individuals undergoing colonoscopy screening. Multivariable linear regression was employed to examine associations of physical activity, BMI and NSAID use with LINE-1 DNA methylation and interactions with MTR and MTHFR gene variants. The highest quartile of physical activity compared with the lowest was associated with higher LINE-1 DNA methylation (p = 0.005). Long-term NSAID use and a normal BMI were associated with increased LINE-1 DNA methylation among individuals with the variant MTR allele (p = 0.02; p = 0.03). This study provides evidence that inflammation-related exposures may influence LINE-1 DNA methylation.

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

    SciTech Connect

    Richardson, David J.; Edwards, Marcus; White, Gaye F.

    2012-06-01

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

  14. Polarization loss correction derived from hydrogen local-resistance measurement in low Pt-loaded polymer-electrolyte fuel cells

    DOE PAGES

    Freiberg, Anna T. S.; Tucker, Michael C.; Weber, Adam Z.

    2017-04-12

    The reduction of platinum-loading on the cathode side of polymer-electrolyte fuel cells leads to a poorly understood increase in mass-transport resistance (MTR) at high current densities. This local resistance was measured using a facile hydrogen-pump technique with dilute active gases for membrane-electrode assemblies with catalyst layers of varying platinum-loading (0.03-0.40 mgPt/cm²). Furthermore, polarization curves in H 2/air were measured and corrected for the overpotential caused by the increased MTR for low loadings on the air side due to the reduced concentration of reactant gas at the catalyst surface. The difference in performance after correction for all resistances including the MTRmore » is minor, suggesting its origin to be diffusive in nature, and proving the meaningfulness of the facile hydrogen-pump technique for the characterization of the cathode catalyst layer under defined operation conditions.« less

  15. Final Environmental Assessment for Proposed Airspace Changes for Paradise East and Paradise West Military Operations Areas (MOAs) at Mountain Home Air Force Base (MHAFB) Idaho

    DTIC Science & Technology

    2010-03-29

    IR FO R C E\\ 32 99 91 AI R SP A C E EA \\G IS \\M X D \\F IG U R E- A LT ER N AT IV E A. M X D M KO U BE K...basis. BO I \\\\O W L\\ PR O J\\ M O U N TA IN H O M EA IR FO R C E\\ 32 99 91 AI R SP A C E EA \\G IS \\M X D \\F IG U R E- A LT ER N AT IV E B. M X D M KO...MTR. MTR segments are identified and charted as either IR routes (IFR) or VR routes

  16. 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

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

    SciTech Connect

    Ball, G.; Pond, R.; Hanan, N.

    1995-02-01

    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.

  18. Changes in masseter muscle trigger points following strain-counterstrain or neuro-muscular technique.

    PubMed

    Ibáñez-García, Jordi; Alburquerque-Sendín, Francisco; Rodríguez-Blanco, Cleofás; Girao, Didac; Atienza-Meseguer, Albert; Planella-Abella, Sergi; Fernández-de-Las Peñas, César

    2009-01-01

    The aim of this study was to compare the immediate effects, on pressure pain sensitivity and active mouth opening, following the application of neuromuscular or strain/counter-strain technique in latent myofascial trigger points (MTrPs) in the masseter muscle. Seventy-one subjects, 34 men and 37 women, aged 20-65 years old, participated in this study. Subjects underwent a screening process to establish the presence of MTrPs in the masseter muscle. Subjects were divided randomly into three groups: group A which was treated with a neuromuscular intervention, group B treated with the strain/counter-strain technique, and group C as control group. Each treatment group received a weekly treatment session during 3 consecutive weeks. Outcomes measures were pressure pain thresholds (PPTs), active mouth opening and local pain (visual analogue scale, VAS) elicited by the application of 2.5kg/cm(2) of pressure over the MTrP. They were captured at baseline and 1 week after discharge by an assessor blinded to the treatment allocation of the subject. The ANOVA found a significant groupxtime interaction (F=25.3; p<0.001) for changes in PPT, changes in active mouth opening (F=10.5; p<0.001), and local pain evoked by 2.5kg/cm(2) of pressure (F=10.1; p<0.001). Within-group effect sizes were large (d>1) for PPT and mouth opening, and moderate for local pain (d<0.7, 0.5) in both intervention groups; but small (d<0.2) for the control group in all outcomes. No significant differences between both intervention groups were found for any outcome (p>0.8). Our results suggest that neuromuscular or strain/counter-strain technique might be employed in the management of latent MTrPs in the masseter muscle.

  19. Mission Connect Mild TBI Translational Research Consortium

    DTIC Science & Technology

    2013-08-01

    year 2 and 3 annual progress report we completed the morphometric and the diffusion tensor imaging (DTI) in cortical impact injury with and without...and morphometric measures. Response to EAB feedback: No concerns were expressed by the External Advisory Board about the MRI core. Manuscript...automatic analysis of morphometry, DTI, and MTR for both humans and rodents.  Completed morphometric and DTI analysis in traumatically injured animals

  20. Wet needling of myofascial trigger points in abdominal muscles for treatment of primary dysmenorrhoea.

    PubMed

    Huang, Qiang-Min; Liu, Lin

    2014-08-01

    To evaluate the effect of wet needling (related to acupuncture) and home stretching exercises on myofascial trigger points (MTrPs) in abdominal muscles for the treatment of dysmenorrhoea. The effect of wet needing of MTrPs in abdominal muscles, supplemented by home stretching exercises, was observed in 65 patients with moderate and severe primary dysmenorrhoea. The MTrPs in the abdominal region were localised and repeatedly needled with lidocaine injection. Menstrual pain was evaluated with a Visual Analogue Scale (VAS) score after every treatment, with the final evaluation made at a 1-year follow-up. Treatment was stopped when the VAS pain score reduced to ≤3. Symptoms scores were analysed with one-way analysis of variance. The mean VAS pain score before treatment was 7.49±1.16. After a single wet needling session, 41 patients had a reduction in their VAS pain score to <3 during their following menstrual cycle, with a mean of 1.63±0.49. Twenty-four patients who needed two treatments showed a reduction in menstrual pain scores to 0.58±0.50. After 1 year, the mean VAS pain score among all patients was 0.28±0.45, with a response rate of 100%. Primary dysmenorrhoea was significantly reduced 1 year after wet needling to MTrPs in the abdominal region and home stretching exercises, justifying further research with controlled trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

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

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

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

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

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

  3. Computer Security Models

    DTIC Science & Technology

    1984-09-01

    Verification Technique for a Class of Security Kernels," International Symposium on Programming , Lecture Notes in Computer Science 137, Springer-Verlag, New York...September 1984 MTR9S31 " J. K. Millen Computer Security C. M. Cerniglia Models * 0 Ne c - ¢- C. S• ~CONTRACT SPONSOR OUSDRE/C31 & ESO/ALEE...ABSTRACT The purpose of this report is to provide a basis for evaluating security models in the context of secure computer system development

  4. 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

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

    DTIC Science & Technology

    2011-09-20

    significantly alter the regulation of the mtrCDE operon and result in increased resistance to anti- microbials. IMPORTANCE Gonorrhea is the second most...causative agent of the sexually trans-mitted infection gonorrhea , is a Gram-negative diplococcus and is strictly a human pathogen. Clinical isolates of N...produced in response to experimental human gonorrhea . J. Infect. Dis. 172:186 –191. 34. Schmidt KA, et al. 2001. Experimental gonococcal urethritis and

  6. Evolution of the methodological quality of controlled clinical trials for myofascial trigger point treatments for the period 1978-2015: A systematic review.

    PubMed

    Stoop, Rahel; Clijsen, Ron; Leoni, Diego; Soldini, Emiliano; Castellini, Greta; Redaelli, Valentina; Barbero, Marco

    2017-08-01

    The methodological quality of controlled clinical trials (CCTs) of physiotherapeutic treatment modalities for myofascial trigger points (MTrP) has not been investigated yet. To detect the methodological quality of CCTs for physiotherapy treatments of MTrPs and demonstrating the possible increase over time. Systematic review. A systematic search was conducted in two databases, Physiotherapy Evidence Database (PEDro) and Medicine Medical Literature Analysis and Retrieval System online (MEDLINE), using the same keywords and selection procedure corresponding to pre-defined inclusion criteria. The methodological quality, assessed by the 11-item PEDro scale, served as outcome measure. The CCTs had to compare at least two interventions, where one intervention had to lay within the scope of physiotherapy. Participants had to be diagnosed with myofascial pain syndrome or trigger points (active or latent). A total of n = 230 studies was analysed. The cervico-thoracic region was the most frequently treated body part (n = 143). Electrophysical agent applications was the most frequent intervention. The average methodological quality reached 5.5 on the PEDro scale. A total of n = 6 studies scored the value of 9. The average PEDro score increased by 0.7 points per decade between 1978 and 2015. The average PEDro score of CCTs for MTrP treatments does not reach the cut-off of 6 proposed for moderate to high methodological quality. Nevertheless, a promising trend towards an increase of the average methodological quality of CCTs for MTrPs was recorded. More high-quality CCT studies with thorough research procedures are recommended to enhance methodological quality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. A close relationship between verbal memory and SN/VTA integrity in young and older adults.

    PubMed

    Düzel, Sandra; Schütze, Hartmut; Stallforth, Sabine; Kaufmann, Jörn; Bodammer, Nils; Bunzeck, Nico; Münte, Thomas F; Lindenberger, Ulman; Heinze, Hans-Jochen; Düzel, Emrah

    2008-11-01

    Age-related dysfunction in dopaminergic neuromodulation is assumed to contribute to age-associated memory impairment. However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults. We investigated this relationship in a cross-sectional study including data from the hippocampus and frontal white matter (FWM) and also assessing working memory span and attention. In groups of young and older adults matched for the variance of their age distribution, gender and body mass index, we observed a robust positive correlation between Magnetization Transfer Ratio (MTR)--a measure of structural integrity--of the SN/VTA and FWM with verbal learning and memory performance among older adults, while there was a negative correlation in the young. Two additional imaging parameters, anisotropy of diffusion and diffusion coefficient, suggested that in older adults FWM changes reflected vascular pathology while SN/VTA changes pointed towards neuronal loss and loss of water content. The negative correlation in the young possibly reflected maturational changes. Multiple regression analyses indicated that in both young and older adults, SN/VTA MTR explained more variance of verbal learning and memory than FWM MTR or hippocampal MTR, and contributed less to explaining variance of working memory span. Together these findings indicate that structural integrity in the SN/VTA has a relatively selective impact on verbal learning and memory and undergoes specific changes from young adulthood to older age that qualitatively differ from changes in the FWM and hippocampus.

  8. The New Zealand Major Trauma Registry: the foundation for a data-driven approach in a contemporary trauma system.

    PubMed

    Isles, Siobhan; Christey, Grant; Civil, Ian; Hicks, Peter

    2017-10-06

    To describe the development of the New Zealand Major Trauma Registry (NZ-MTR) and the initial experiences of its use. The background to the development of the NZ-MTR was reviewed and the processes undertaken to implement a single-instance of a web-based national registry described. A national minimum dataset was defined and utilised. Key structures to support the Registry such as a data governance group were established. The NZ-MTR was successfully implemented and is the foundation for a new, data-driven model of quality improvement. In its first year of operation over 1,300 patients were entered into the Registry although coverage is not yet universal. Overall incidence is 40.8 major trauma cases/100,000 population. The incidence in the Māori population was 69/100,000 compared with 31/100,000 in the non-Māori population. Case fatality rate was 9%. Three age peaks were observed at 20-24 years, 50-59 years and above 85 years. Road traffic crashes accounted for 50% of all caseload. A significant proportion of major trauma patients (21%) were transferred to one or more hospitals before reaching a definitive care facility. Despite the challenges working across multiple jurisdictions, initiation of a single-instance web-based registry has been achieved. The NZ-MTR enables New Zealand to have a national view of trauma treatment and outcomes for the first time. It will inform quality improvement and injury prevention initiatives and potentially decrease the burden of injury on all New Zealanders.

  9. Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis.

    PubMed

    Pardini, Matteo; Sudre, Carole H; Prados, Ferran; Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Samson, Rebecca S; van de Pavert, Steven H; Cardoso, M Jorge; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

    2016-11-01

    To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm 3 ) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. SciTech Connect

    Hiraishi, Nobuhiro; Ishida, Yo-ichi; Nagahama, Masami, E-mail: nagahama@my-pharm.ac.jp

    Nuclear VCP-like 2 (NVL2) is a chaperone-like nucleolar ATPase of the AAA (ATPase associated with diverse cellular activities) family, which exhibits a high level of amino acid sequence similarity with the cytosolic AAA-ATPase VCP/p97. These proteins generally act on macromolecular complexes to stimulate energy-dependent release of their constituents. We previously showed that NVL2 interacts with RNA processing/degradation machinery containing an RNA helicase MTR4/DOB1 and an exonuclease complex, nuclear exosome, and involved in the biogenesis of 60S ribosomal subunits. These observations implicate NVL2 as a remodeling factor for the MTR4-exosome complex during the maturation of pre-ribosomal particles. Here, we used amore » proteomic screen and identified a WD repeat-containing protein 74 (WDR74) as a factor that specifically dissociates from this complex depending on the ATPase activity of NVL2. WDR74 shows weak amino acid sequence similarity with the yeast ribosome biogenesis protein Nsa1 and is co-localized with NVL2 in the nucleolus. Knockdown of WDR74 decreases 60S ribosome levels. Taken together, our results suggest that WDR74 is a novel regulatory protein of the MTR4-exsosome complex whose interaction is regulated by NVL2 and is involved in ribosome biogenesis. - Highlights: • WDR74 accumulates in MTR4-exosome complex upon expression of dominant-negative NVL2. • WDR74 is co-localized with NVL2 in the nucleolus. • WDR74, along with NVL2, is involved in the synthesis of 60S ribosomal subunits.« less

  11. ADVANCED HEAT TRANSFER TEST FACILITY, TRA666A. ELEVATIONS. ROOF FRAMING PLAN. ...

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

    ADVANCED HEAT TRANSFER TEST FACILITY, TRA-666A. ELEVATIONS. ROOF FRAMING PLAN. CONCRETE BLOCK SIDING. SLOPED ROOF. ROLL-UP DOOR. AIR INTAKE ENCLOSURE ON NORTH SIDE. F.C. TORKELSON 842-MTR-666-A5, 8/1966. INL INDEX NO. 531-0666-00-851-152258, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

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

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

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

  13. Quantification of in vivo pH-weighted amide proton transfer (APT) MRI in acute ischemic stroke

    NASA Astrophysics Data System (ADS)

    Zhou, Iris Y.; Igarashi, Takahiro; Guo, Yingkun; Sun, Phillip Z.

    2015-03-01

    Amide proton transfer (APT) imaging is a specific form of chemical exchange saturation transfer (CEST) MRI that probes the pH-dependent amide proton exchange.The endogenous APT MRI is sensitive to tissue acidosis, which may complement the commonly used perfusion and diffusion scans for characterizing heterogeneous ischemic tissue damage. Whereas the saturation transfer asymmetry analysis (MTRasym) may reasonably compensate for direct RF saturation, in vivo MTRasym is however, susceptible to an intrinsically asymmetric shift (MTR'asym). Specifically, the reference scan for the endogenous APT MRI is 7 ppm upfield from that of the label scan, and subjects to concomitant RF irradiation effects, including nuclear overhauser effect (NOE)-mediated saturation transfer and semisolid macromolecular magnetization transfer. As such, the commonly used asymmetry analysis could not fully compensate for such slightly asymmetric concomitant RF irradiation effects, and MTRasym has to be delineated in order to properly characterize the pH-weighted APT MRI contrast. Given that there is very little change in relaxation time immediately after ischemia and the concomitant RF irradiation effects only minimally depends on pH, the APT contrast can be obtained as the difference of MTRasym between the normal and ischemic regions. Thereby, the endogenous amide proton concentration and exchange rate can be solved using a dual 2-pool model, and the in vivo MTR'asym can be calculated by subtracting the solved APT contrast from asymmetry analysis (i.e., MTR'asym =MTRasym-APTR). In addition, MTR'asym can be quantified using the classical 2-pool exchange model. In sum, our study delineated the conventional in vivo pH-sensitive MTRasym contrast so that pHspecific contrast can be obtained for imaging ischemic tissue acidosis.

  14. Gonococcal Resistance to β-Lactams and Tetracycline Involves Mutation in Loop 3 of the Porin Encoded at the penB Locus

    PubMed Central

    Gill, M. J.; Simjee, S.; Al-Hattawi, K.; Robertson, B. D.; Easmon, C. S. F.; Ison, C. A.

    1998-01-01

    penB is a chromosomal mutation that confers resistance to β-lactams and tetracyclines and reduced susceptibility to quinolones in Neisseria gonorrhoeae. It is linked to the porin gene (por) and requires the increased expression of an efflux pump due to mtr. Transformation of a susceptible gonococcus (strain H1) with chromosomal DNA from strain FA140 (penA mtr penB; porin serovar IB1) and conjugal transfer of a β-lactamase-expressing plasmid was used to produce isogenic strains for determination of equilibrium periplasmic penicillin concentrations by the method of Zimmermann and Rosselet (W. Zimmermann and A. Rosselet, Antimicrob. Agents Chemother. 12:368–372, 1977). In transformants with the Mtr and PenB phenotypes, equilibrium concentrations of penicillin were reduced. DNA sequence analysis of por from isogenic penB and penB+ transformants revealed 14 sequence differences; nine of these differences resulted in amino acid changes. Three amino acid changes were found in the putative gonococcal equivalent of the pore-constricting loop 3 of Escherichia coli OmpF. Two of these changes (Gly-101–Ala-102→Asp-Asp) result in an increased negative charge at this position in por loop 3. PCR products comprising the complete por gene from strain FA140 were transformed into strain H1-2 (penA mtr; porin serovar IB-3), with the resulting transformants having the antibiotic susceptibility phenotype associated with penB. penB-like mutations were found in loop 3 of clinical isolates of gonococci with chromosomally mediated resistance to penicillin. We conclude that penB is a mutation in loop 3 of por that reduces porin permeability to hydrophilic antibiotics and plays an important role in the development of chromosomally mediated resistance to penicillin and tetracycline in gonococci. PMID:9797206

  15. Analysis of Material Distribution from NSC San Diego to Local Customers.

    DTIC Science & Technology

    1981-09-01

    local customers, especially the Naval Air Rework Facility (NARY) at NASNI. This thesis offers a general discussion and documentation of the~- D 2...improved post-consolidation support to its local customers, especially the Naval Air Rework Facility (NARF) at NASNI. This thesis offers a general...Turned In To Store MTR Mandatory Turn-in Repairable NAB Naval Amphibious Base NC Not Carried NCA National City Annex NARF Naval Air Rework Facility

  16. REACTOR SERVICE BUILDING, TRA635, CONTEXTUAL VIEW DURING CONSTRUCTION. CAMERA IS ...

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

    REACTOR SERVICE BUILDING, TRA-635, CONTEXTUAL VIEW DURING CONSTRUCTION. CAMERA IS ATOP MTR BUILDING AND LOOKING SOUTHERLY. FOUNDATION AND DRAINS ARE UNDER CONSTRUCTION. THE BUILDING WILL BUTT AGAINST CHARGING FACE OF PLUG STORAGE BUILDING. HOT CELL BUILDING, TRA-632, IS UNDER CONSTRUCTION AT TOP CENTER OF VIEW. INL NEGATIVE NO. 8518. Unknown Photographer, 8/25/1953 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  17. Picosecond Optical Electronics

    DTIC Science & Technology

    1988-08-01

    Optoelecironics, New York: Springer-Verlag, 1987 65. J. Archer, "Millimeter Wavelength Frequency Multipliers", IEEE MTr, Vol. 29, No. 6, June * 1981. 66. R. Majidi ...337-339. I 74. R. Majidi -Ahy et al., "Electrooptic Sampling Measurement of Coplanar Waveguide (Coupled Slot Line) Modes", Elect. Lett., Vol. 23, No...24, Nov. 1987, pp. 1262-1263. 1 75. R. Majidi -Ahy et al., "Electrooptic Sampling Measurement of Dispersion Characteristics of Slot line and Coplanar

  18. Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury.

    PubMed

    Tu, Tsang-Wei; Lescher, Jacob D; Williams, Rashida A; Jikaria, Neekita; Turtzo, L Christine; Frank, Joseph A

    2017-01-01

    Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the

  19. Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury

    PubMed Central

    Lescher, Jacob D.; Williams, Rashida A.; Jikaria, Neekita; Turtzo, L. Christine; Frank, Joseph A.

    2017-01-01

    Abstract Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate

  20. Toward the Use of an Upper Ontology for U.S. Government and U.S. Military Domains: An Evaluation

    DTIC Science & Technology

    2004-09-01

    applications outpace other government applications, but this state of affairs is changing with the advent of eGov [48]. Recently, the Defense Advanced...DOCUMENTNUMBER MTR 04B0000063 MITRE TECHNICAL REPORT Toward the Use of an Upper Ontology for U.S. Government and U.S. Military Domains: An...construed as an official Government position, policy, or decision, unless designated by other documentation. Approved for public release (04-0603

  1. Sulfur-Mediated Electron Shuttling Sustains Microbial Long-Distance Extracellular Electron Transfer with the Aid of Metallic Iron Sulfides.

    PubMed

    Kondo, Katsuhito; Okamoto, Akihiro; Hashimoto, Kazuhito; Nakamura, Ryuhei

    2015-07-07

    In addition to serving as an energy source for microbial growth, iron sulfides are proposed to act as naturally occurring electrical wires that mediate long-distance extracellular electron transfer (EET) and bridge spatially discrete redox environments. These hypothetical EET reactions stand on the abilities of microbes to use the interfacial electrochemistry of metallic/semiconductive iron sulfides to maintain metabolisms; however, the mechanisms of these phenomena remain unexplored. To obtain insight into EET to iron sulfides, we monitored EET at the interface between Shewanella oneidensis MR-1 cells and biomineralized iron sulfides in an electrochemical cell. Respiratory current steeply increased with the concomitant formation of poorly crystalline mackinawite (FeS) minerals, indicating that S. oneidensis has the ability to exploit extracellularly formed metallic FeS for long-distance EET. Deletion of major proteins of the metal-reduction (Mtr) pathway (OmcA, MtrC, CymA, and PilD) caused only subtle effects on the EET efficiency, a finding that sharply contrasts the majority of studies that report that the Mtr pathway is indispensable for the reduction of metal oxides and electrodes. The gene expression analyses of polysulfide and thiosulfate reductase suggest the existence of a sulfur-mediated electron-shuttling mechanism by which HS(-) ions and water-soluble polysulfides (HS(n)(-), where n ≥ 2) generated in the periplasmic space deliver electrons from cellular metabolic processes to cell surface-associated FeS. The finding of this Mtr-independent pathway indicates that polysulfide reductases complement the function of outer-membrane cytochromes in EET reactions and, thus, significantly expand the number of microbial species potentially capable of long-distance EET in sulfur-rich anoxic environments.

  2. FAST CHOPPER BUILDING, TRA665, INTERIOR. LOWER (DETECTOR) LEVEL. NOTE BRICKEDIN ...

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

    FAST CHOPPER BUILDING, TRA-665, INTERIOR. LOWER (DETECTOR) LEVEL. NOTE BRICKED-IN WINDOW ON MTR SIDE. USED FOR STORAGE OF LEAD BRICKS AFTER EXPERIMENTAL NEUTRON INSTRUMENTS WERE REMOVED. SIGN SAYS "IN-PROCESS LEAD SOURCE STORAGE." INL NEGATIVE NO. HD-42-2. Mike Crane, Photographer, 3/2004 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

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

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

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

  4. 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

  5. GAMMA FACILITY, TRA611, INTERIOR. WITH HELP OF OVERHEAD CHAIN AND ...

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

    GAMMA FACILITY, TRA-611, INTERIOR. WITH HELP OF OVERHEAD CHAIN AND HOOK, SCIENTIST GUIDES METAL CONTAINER (HOLDING POTATOES, IN THIS CASE) INTO RECEIVING "COLUMN" IN THE GAMMA CANAL. NOTE OTHER COLUMNS AT RIGHT AND LEFT WALLS OF CANAL. NEAR BOTTOM OF CANAL, SPENT MTR FUEL WILL IRRADIATE POTATOES. INL NEGATIVE NO. 56-439. R.G. Larsen, Photographer, 2/8/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  6. Phylogeography and genetic structure of the oriental river prawn Macrobrachium nipponense (Crustacea: Decapoda: Palaemonidae) in East Asia

    PubMed Central

    Chu, Ta-Jen; Lee, Ying-Chou

    2017-01-01

    The oriental river prawn (Macrobrachium nipponense) is mainly distributed in East Asia. The phylogeography, population genetic structure and historical demography of this species in the East Asia were examined by using partial sequences of the cytochrome oxidase subunit I (COI) and 16S rRNA in mitochondrial DNA. Ten populations that included 239 individuals were collected from Taiwan (Shihmen Reservoir, SMR, Mingte Reservoir, MTR and Chengching Lake Reservoir, CLR), mainland China (Taihu Lake, TLC, Min River, MRC, Jiulong River, JRC and Shenzhen Reservoir, SRC), Japan (Biwa Lake, BLJ and Kasumigaura Lake, KLJ) and Korea (Han River, HRK). The nucleotide diversity (π) of all individuals was 0.01134, with values ranging from 0.0089 (BLJ, Japan) to 0.01425 (MTR, Taiwan). A total of 83 haplotypes were obtained, and the haplotypes were divided into 2 main lineages: lineage A included the specimens from BLJ, KLJ, CLR, MTR, TLC, MRC and JRC, and lineage B comprised the ones from HRK, SRC, SMR, MTR, TLC, MRC and JRC. Lineage A could be further divided two sub-lineages (A1 and A2). Individuals of lineage A2 were only from TLC. Demographic expansion was observed in each lineage, starting within the second-to-latest interglacial period for lineage A and within the last glacial period for lineage B. All FST values among the ten populations were significantly different, except for the values between MRC and JRC, and SMR and SRC. The phylogeography and genetic structure of M. nipponense in East Asia might be influenced by Pleistocene glacial cycles, lake isolation and human introduction. The possible dispersal routes of M. nipponense in the East Asia were also discussed. PMID:28267807

  7. Molecular, dynamic, and structural origin of inhomogeneous magnetization transfer in lipid membranes.

    PubMed

    Swanson, Scott D; Malyarenko, Dariya I; Fabiilli, Mario L; Welsh, Robert C; Nielsen, Jon-Fredrik; Srinivasan, Ashok

    2017-03-01

    To elucidate the dynamic, structural, and molecular properties that create inhomogeneous magnetization transfer (ihMT) contrast. Amphiphilic lipids, lamellar phospholipids with cholesterol, and bovine spinal cord (BSC) specimens were examined along with nonlipid systems. Magnetization transfer (MT), enhanced MT (eMT, obtained with double-sided radiofrequency saturation), ihMT (MT - eMT), and dipolar relaxation, T 1D , were measured at 2.0 and 11.7 T. The amplitude of ihMT ratio (ihMTR) is positively correlated with T 1D values. Both ihMTR and T 1D increase with increasing temperature in BSC white matter and in phospholipids and decrease with temperature in other lipids. Changes in ihMTR with temperature arise primarily from alterations in MT rather than eMT. Spectral width of MT, eMT, and ihMT increases with increasing carbon chain length. Concerted motions of phospholipids in white matter decrease proton spin diffusion leading to increased proton T 1D times and increased ihMT amplitudes, consistent with decoupling of Zeeman and dipolar spin reservoirs. Molecular specificity and dynamic sensitivity of ihMT contrast make it a suitable candidate for probing myelin membrane disorders. Magn Reson Med 77:1318-1328, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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

    PubMed

    McGarvey, Daniel J; Johnston, John M

    2013-04-01

    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.

  9. Structure of frequency-interacting RNA helicase from Neurospora crassa reveals high flexibility in a domain critical for circadian rhythm and RNA surveillance.

    PubMed

    Morales, Yalemi; Olsen, Keith J; Bulcher, Jacqueline M; Johnson, Sean J

    2018-01-01

    The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH results in an ATP binding site that is undisturbed by crystal contacts and adopts a conformation consistent with nucleotide binding and hydrolysis. Strikingly, this new FRH structure adopts an arch domain conformation that is dramatically altered from previous structures. Comparison of the existing FRH structures reveals conserved hinge points that appear to facilitate arch motion. Regions in the arch have been previously shown to mediate a variety of protein-protein interactions critical for RNA surveillance and circadian clock functions. The conformational changes highlighted in the FRH structures provide a platform for investigating the relationship between arch dynamics and Mtr4/FRH function.

  10. Dissolution of Material and Test reactor Fuel in an H-Canyon Dissolver

    SciTech Connect

    Daniel, W. E.; Rudisill, T. S.; O'Rourke, P. E.

    2017-01-26

    In an amended record of decision for the management of spent nuclear fuel (SNF) at the Savannah River Site, the US Department of Energy has authorized the dissolution and recovery of U from 1000 bundles of Al-clad SNF. The SNF is fuel from domestic and foreign research reactors and is typically referred to as Material Test Reactor (MTR) fuel. Bundles of MTR fuel containing assemblies fabricated from U-Al alloys (or other U compounds) are currently dissolved using a Hg-catalyzed HNO3 flowsheet. Since the development of the existing flowsheet, improved experimental methods have been developed to more accurately characterize the offgasmore » composition and generation rate during laboratory dissolutions. Recently, these new techniques were successfully used to develop a flowsheet for the dissolution of High Flux Isotope Reactor (HFIR) fuel. Using the data from the HFIR dissolution flowsheet development and necessary laboratory experiments, the Savannah River National Laboratory (SRNL) was requested to define flowsheet conditions for the dissolution of MTR fuels. With improved offgas characterization techniques, SRNL will be able define the number of bundles of fuel which can be charged to an H-Canyon dissolver with much less conservatism.« less

  11. Imaging outcomes for trials of remyelination in multiple sclerosis

    PubMed Central

    Mallik, Shahrukh; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Miller, David H

    2014-01-01

    Trials of potential neuroreparative agents are becoming more important in the spectrum of multiple sclerosis research. Appropriate imaging outcomes are required that are feasible from a time and practicality point of view, as well as being sensitive and specific to myelin, while also being reproducible and clinically meaningful. Conventional MRI sequences have limited specificity for myelination. We evaluate the imaging modalities which are potentially more specific to myelin content in vivo, such as magnetisation transfer ratio (MTR), restricted proton fraction f (from quantitative magnetisation transfer measurements), myelin water fraction and diffusion tensor imaging (DTI) metrics, in addition to positron emission tomography (PET) imaging. Although most imaging applications to date have focused on the brain, we also consider measures with the potential to detect remyelination in the spinal cord and in the optic nerve. At present, MTR and DTI measures probably offer the most realistic and feasible outcome measures for such trials, especially in the brain. However, no one measure currently demonstrates sufficiently high sensitivity or specificity to myelin, or correlation with clinical features, and it should be useful to employ more than one outcome to maximise understanding and interpretation of findings with these sequences. PET may be less feasible for current and near-future trials, but is a promising technique because of its specificity. In the optic nerve, visual evoked potentials can indicate demyelination and should be correlated with an imaging outcome (such as optic nerve MTR), as well as clinical measures. PMID:24769473

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

    PubMed

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

    2012-02-01

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

  13. Single Tablet Regimen Usage and Efficacy in the Treatment of HIV Infection in Australia

    PubMed Central

    Armstrong, B.; Chan, D. J.; Stewart, M. J.; Fagan, D.; Smith, D.

    2015-01-01

    Single tablet regimens (STRs) for HIV infection improve patient satisfaction, quality of life, medication adherence, and virological suppression compared to multitablet regimens (MTRs). This is the first study assessing STR uptake and durability in Australia. This retrospective audit of all patients receiving an STR (n = 299) at a large Sydney HIV clinic (January 2012–December 2013) assessed patient demographics, treatment prior to STR, HIV RNA load and CD4 during MTR and STR dosing, and reasons for STR switch. 206 patients switched from previous antiretroviral treatment to an STR, of which 88% switched from an MTR. Reasons for switching included desire to simplify treatment (57%), reduced side effects or toxicity (18%), and cost-saving for the patient. There was no switching for virological failure. Compared to when on an MTR, patients switching to an STR had significantly lower HIV RNA counts (p < 0.001) and significantly higher CD4 counts (p < 0.001). The discontinuation rate from STR was very low and all patients who switched to an STR maintained virological suppression throughout the study duration, although the study is limited by the absence of a control group. PMID:26550490

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

    PubMed

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

    2014-11-01

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Contribution of l-theanine to the formation of 2,5-dimethylpyrazine, a key roasted peanutty flavor in Oolong tea during manufacturing processes.

    PubMed

    Guo, Xiangyang; Song, Chuankui; Ho, Chi-Tang; Wan, Xiaochun

    2018-10-15

    l-Theanine, the most abundant amino acid in tea, is widely believed to be associated with the tea taste, however, its contribution to the formation of tea aroma is still unknown. Volatiles were determined and nitrogen-containing compounds formed during manufacturing processes were quantified. Lower levels of total sugar and l-theanine were detected in the Oolong tea product undergoing full fire processing (FFOT) suggesting that l-theanine probably involved in the volatile formation during manufacturing processes. Methylpyrazine and 2,5-dimethylpyrazine, two newly formed compounds in FFOT, together with other volatiles were successfully detected in a model thermal reaction of d-glucose and l-theanine (GT-MTR) but not detectable in thermal reactions with single d-glucose (G-MTR) or l-theanine (T-MTR). The concentration of 2,5-dimethylpyrazine increased significantly by adding additional l-theanine to 2nd roasted tea. Our study demonstrated that l-theanine, at least partly, contributed to the formation of 2,5-dimethylpyrazine, a key roasted peanutty flavor in Oolong tea. Copyright © 2018. Published by Elsevier Ltd.

  16. Hydraulic parameters estimation by using an approach based on vertical electrical soundings (VES) in the semi-arid Khanasser valley region, Syria

    NASA Astrophysics Data System (ADS)

    Asfahani, Jamal

    2016-05-01

    A new alternative approach based on using Vertical electrical sounding (VES) technique is proposed for computing the hydraulic conductivity K of an aquifer. The approach takes only the salinity of the groundwater into consideration. VES measurements in the locations, where available water samples exist, are required in such an approach, in order to calibrate and establish empirical relationships between transverse resistance Dar-Zarrouck TR parameter and modified transverse resistance MTR, and between MTR and transmissivity T. Those relationships are thereafter used to extrapolate the transmissivity even in the VES points where no water samples exist. This approach is tested and practiced in the Khanasser valley, Northern Syria, where the hydraulic conductivity of the Quaternary aquifer is computed. An acceptable agreement is found between the hydraulic conductivity values obtained by the proposed approach and those obtained by the pumping test which range between 0.864 and 8.64 m/day (10-5 and 10-4 m/s). The Quaternary aquifer transmissivity of the Khanasser Valley, has been characterized by using this approach and by adapting the MTR parameter. The transmissivity varies between a minimum of 79 m2/day and a maximum of 814 m2/day, with an average of 283 m2/day and a standard deviation of 145 m2/day. The easy and inexpensive approach proposed in this paper can be applied in other semi arid regions.

  17. Motor network efficiency and disability in multiple sclerosis

    PubMed Central

    Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Liu, Zheng; Samson, Rebecca S.; Altmann, Daniel R.; Ron, Maria A.; Wheeler-Kingshott, Claudia A.M.; Miller, David H.; Chard, Declan T.

    2015-01-01

    Objective: To develop a composite MRI-based measure of motor network integrity, and determine if it explains disability better than conventional MRI measures in patients with multiple sclerosis (MS). Methods: Tract density imaging and constrained spherical deconvolution tractography were used to identify motor network connections in 22 controls. Fractional anisotropy (FA), magnetization transfer ratio (MTR), and normalized volume were computed in each tract in 71 people with relapse onset MS. Principal component analysis was used to distill the FA, MTR, and tract volume data into a single metric for each tract, which in turn was used to compute a composite measure of motor network efficiency (composite NE) using graph theory. Associations were investigated between the Expanded Disability Status Scale (EDSS) and the following MRI measures: composite motor NE, NE calculated using FA alone, FA averaged in the combined motor network tracts, brain T2 lesion volume, brain parenchymal fraction, normal-appearing white matter MTR, and cervical cord cross-sectional area. Results: In univariable analysis, composite motor NE explained 58% of the variation in EDSS in the whole MS group, more than twice that of the other MRI measures investigated. In a multivariable regression model, only composite NE and disease duration were independently associated with EDSS. Conclusions: A composite MRI measure of motor NE was able to predict disability substantially better than conventional non-network-based MRI measures. PMID:26320199

  18. Short-Term Effects of Kinesio Taping and Cross Taping Application in the Treatment of Latent Upper Trapezius Trigger Points: A Prospective, Single-Blind, Randomized, Sham-Controlled Trial

    PubMed Central

    Słupska, Lucyna; Paprocka-Borowicz, Małgorzata; Taradaj, Jakub; Bidzińska, Gabriela; Marczyński, Daniel; Cynarska, Aleksandra; Rosińczuk, Joanna

    2015-01-01

    Kinesio taping (KT) may be a new treatment in patients with myofascial trigger points (MTrPs). A new method available for taping practitioners is cross taping (CT). The main objective was to determine how CT, KT, and medical adhesive tape (sham group) affect the subjective assessment of resting bioelectrical activity and pain of the upper trapezius muscle (UT) in patients with MTrPs. 105 volunteers were recruited to participate. The primary outcome was resting bioelectrical activity of UT muscle as assessed by surface electromyography (sEMG) in each group and pain intensity on a visual analog scale (VAS). Assessments were collected before and after intervention and after the 24-hours follow-up. No significant differences were observed in bioelectrical activity of UT between pre-, post-, and follow-up results. In three groups patients had significantly lower pain VAS score after the intervention (CT—p < 0.001, KT—p < 0.001, and sham—p < 0.01). The Kruskal-Wallis ANOVA showed no significant differences in almost all measurements between groups. The application of all three types of tapes does not influence the resting bioelectrical activity of UT muscle and may not lead to a reduction in muscle tone in the case of MTrPs. PMID:26491458

  19. An examination of the effects of mountaintop removal coal mining on respiratory symptoms and COPD using propensity scores.

    PubMed

    Hendryx, Michael; Luo, Juhua

    2015-01-01

    Previous research on public health consequences of mountaintop removal (MTR) coal mining has been limited by the observational nature of the data. The current study used propensity scores, a method designed to overcome this limitation, to draw more confident causal inferences about mining effects on respiratory health using non-experimental data. These data come from a health survey of 682 adults residing in two rural areas of Virginia, USA characterized by the presence or absence of MTR mining. Persons with a history of occupational exposure as coal miners were excluded. Nine covariates including age, sex, current and former smoking, overweight, obesity, high school education, college education, and exposure to coal as a home-heating source were selected to estimate propensity scores. Propensity scores were tested for balance and then used as weights to create quasi-experimental exposed and unexposed groups. Results indicated that persons in the mountaintop mining group had significantly (p < 0.0001) elevated prevalence of respiratory symptoms and chronic obstructive pulmonary disease. The results suggest that impaired respiratory health results from exposure to MTR environments and not from other risks.

  20. Linking land use with pesticides in Dutch surface waters.

    PubMed

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

    2012-01-01

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

  1. Protocol: Testing the Relevance of Acupuncture Theory in the Treatment of Myofascial Pain in the Upper Trapezius Muscle.

    PubMed

    Elsdon, Dale S; Spanswick, Selina; Zaslawski, Chris; Meier, Peter C

    2017-01-01

    A protocol for a prospective single-blind parallel four-arm randomized placebo-controlled trial with repeated measures was designed to test the effects of various acupuncture methods compared with sham. Eighty self-selected participants with myofascial pain in the upper trapezius muscle were randomized into four groups. Group 1 received acupuncture to a myofascial trigger point (MTrP) in the upper trapezius. Group 2 received acupuncture to the MTrP in addition to relevant distal points. Group 3 received acupuncture to the relevant distal points only. Group 4 received a sham treatment to both the MTrP and distal points using a deactivated acupuncture laser device. Treatment was applied four times within 2 weeks with outcomes measured throughout the trial and at 2 weeks and 4 weeks posttreatment. Outcome measurements were a 100-mm visual analog pain scale, SF-36, pressure pain threshold, Neck Disability Index, the Upper Extremity Functional Index, lateral flexion in the neck, McGill Pain Questionnaire, Massachusetts General Hospital Acupuncture Sensation Scale, Working Alliance Inventory (short form), and the Credibility Expectance Questionnaire. Two-way analysis of variance (ANOVA) with repeated measures were used to assess the differences between groups. Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

  2. Assessment of MRI parameters as imaging biomarkers for radiation necrosis in the rat brain.

    PubMed

    Wang, Silun; Tryggestad, Erik; Zhou, Tingting; Armour, Michael; Wen, Zhibo; Fu, De-Xue; Ford, Eric; van Zijl, Peter C M; Zhou, Jinyuan

    2012-07-01

    Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T(1), T(2), apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 × 10 mm(2)) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at ~25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T(1), T(2), MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T(1), T(2), MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Molecular MRI differentiation between primary central nervous system lymphomas and high-grade gliomas using endogenous protein-based amide proton transfer MR imaging at 3 Tesla

    PubMed Central

    Jiang, Shanshan; Yu, Hao; Wang, Xianlong; Lu, Shilong; Li, Yufa; Feng, Lyujin; Zhang, Yi; Heo, Hye-Young; Lee, Dong-Hoon; Zhou, Jinyuan; Wen, Zhibo

    2015-01-01

    Objectives To show the ability of using the amide-proton-transfer-weighted (APTW) MRI signals as imaging biomarkers to differentiate primary central-nervous-system lymphomas (PCNSLs) from high-grade gliomas (HGGs). Methods Eleven patients with lymphomas and 21 patients with HGGs were examined. Magnetization-transfer (MT) spectra over an offset range of ±6 ppm and the conventional MT ratio (MTR) at 15.6 ppm were acquired. The APTW signals, total chemical-exchange-saturation-transfer signal (integral between 0 and 5 ppm, CESTtotal), and MTR signal were obtained and compared between PCNSLs and HGGs. The diagnostic performance was assessed with the receiver-operating-characteristic-curve analysis. Results The PCNSLs usually showed more homogeneous APTW hyperintensity (spatially compared to the normal brain tissue) than the HGGs. The APTWmax, APTWmax-min, and CESTtotal signal intensities were significantly lower (P < 0.05, 0.001, and 0.05, respectively), while the APTWmin and MTR were significantly higher (both P < 0.01) in PCNSL lesions than in HGG lesions. The APTW values in peritumoral oedema were significantly lower for PCNSLs than for HGGs (P < 0.01). APTWmax-min had the highest area under the receiver-operating-characteristic curve (0.963) and accuracy (94.1%) in differentiating PCNSLs from HGGs. Conclusions The protein-based APTW signal would be a valuable MRI biomarker by which to identify PCNSLs and HGGs presurgically. PMID:25925361

  4. Respiration of metal (hydr)oxides by Shewanella and Geobacter: a key role for multihaem c-type cytochromes

    PubMed Central

    Shi, Liang; Squier, Thomas C; Zachara, John M; Fredrickson, James K

    2007-01-01

    Dissimilatory reduction of metal (e.g. Fe, Mn) (hydr)oxides represents a challenge for microorganisms, as their cell envelopes are impermeable to metal (hydr)oxides that are poorly soluble in water. To overcome this physical barrier, the Gram-negative bacteria Shewanella oneidensis MR-1 and Geobacter sulfurreducens have developed electron transfer (ET) strategies that require multihaem c-type cytochromes (c-Cyts). In S. oneidensis MR-1, multihaem c-Cyts CymA and MtrA are believed to transfer electrons from the inner membrane quinone/quinol pool through the periplasm to the outer membrane. The type II secretion system of S. oneidensis MR-1 has been implicated in the reduction of metal (hydr)oxides, most likely by translocating decahaem c-Cyts MtrC and OmcA across outer membrane to the surface of bacterial cells where they form a protein complex. The extracellular MtrC and OmcA can directly reduce solid metal (hydr)oxides. Likewise, outer membrane multihaem c-Cyts OmcE and OmcS of G. sulfurreducens are suggested to transfer electrons from outer membrane to type IV pili that are hypothesized to relay the electrons to solid metal (hydr)oxides. Thus, multihaem c-Cyts play critical roles in S. oneidensis MR-1- and G. sulfurreducens-mediated dissimilatory reduction of solid metal (hydr)oxides by facilitating ET across the bacterial cell envelope. PMID:17581116

  5. Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenous leukemia.

    PubMed

    Robien, Kim; Bigler, Jeannette; Yasui, Yutaka; Potter, John D; Martin, Paul; Storb, Rainer; Ulrich, Cornelia M

    2006-09-01

    Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) play key roles in intracellular folate metabolism. Polymorphisms in these enzymes have been shown to modify toxicity of methotrexate (MTX) after hematopoietic cell transplantation. In this study, we evaluated the risk of acute graft-versus-host disease (GVHD) associated with genetic variation in recipient and donor MTHFR and TS genotypes to assess whether genotype alters the efficacy of MTX in acute GVHD prophylaxis. Data on the transplantation course were abstracted from medical records for 304 adults who received allogeneic hematopoietic cell transplants. MTHFR (C677T and A1298C) and TS (enhancer-region 28-base pair repeat, TSER, and 1494del6) genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Multivariable logistic regression was used to assess the associations between genotypes and risk of acute GVHD. Compared with recipients with the wild-type MTHFR 677CC genotype, those with the variant 677T allele showed a decreased risk of detectable acute GVHD (677CT: odds ratio, 0.8; 95% confidence interval, 0.4-1.6; 677TT: odds ratio, 0.4; 95% confidence interval, 0.2-0.8; P for trend = .01). The variant MTHFR 1298C allele in recipients was associated with an increased risk of acute GVHD compared with the wild-type MTHFR 1298AA genotype (1298AC: odds ratio, 2.0; 95% confidence interval, 1.1-3.9; 1298CC: odds ratio, 3.6; 95% confidence interval, 1.0-12.7; P for trend < .01). No association with risk of acute GVHD was observed for donor MTHFR genotypes or for recipient or donor TS genotypes, with the exception of an increase in acute GVHD among recipients whose donors had the TSER 3R/2R genotype (odds ratio, 3.0; 95% confidence interval, 1.3-7.2). These findings indicate that host, but not donor, MTHFR genotypes modify the risk of acute GVHD in recipients receiving MTX, in a manner consistent with our previously reported associations

  6. Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children.

    PubMed

    Sadananda Adiga, M N; Chandy, S; Ramachandra, N; Appaji, L; Aruna Kumari, B S; Ramaswamy, G; Savithri, H S; Krishnamoorthy, L

    2010-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. Genetic polymorphisms of this enzyme have been shown to impact several diseases, including cancer. Leukemias are malignancies arising from rapidly proliferating hematopoietic cells having great requirement of DNA synthesis. This case-control study was undertaken to analyze the association of the MTHFR gene polymorphisms 677 C"T and 1298 A"C and the risk of acute lymphoblastic leukemia in children. Eighty-six patients aged below 15 years with a confirmed diagnosis of acute lymphoblastic leukemia (ALL) and 99 matched controls were taken for this study. Analysis of the polymorphisms was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Frequency of MTHFR 677 CC and CT were 85.9% and 14.1% in the controls, and 84.9% and 15.1% in the cases. The 'T' allele frequency was 7% and 7.5% in cases and controls respectively. The frequency of MTHFR 1298 AA, AC, and CC were 28.3%, 55.6% and 16.1% for controls and 23.3%, 59.3% and 17.4% for cases respectively. The 'C' allele frequency for 1298 A-->C was 43.9% and 47% respectively for controls and cases. The odds ratio (OR) for C677T was 1.08 (95% CI 0.48-2.45, p = 0.851) and OR for A1298C was 1.29 (95% CI 0.65-2.29, p = 0.46) and OR for 1298 CC was 1.31 (95% CI 0.53-3.26, p = 0.56). The OR for the combined heterozygous status (677 CT and 1298 AC) was 1.94 (95% CI 0.58-6.52, p = 0.286). The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C-->T and 1298 A-->C gene polymorphisms and risk of ALL, which may be due to the small sample size.

  7. High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

    PubMed Central

    Mouawad, Charbel; Haddad, Katia; Hamoui, Samar; Azar, Albert; Fajloun, Ziad; Makdissy, Nehman

    2015-01-01

    Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI-1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles “Del” and “4G”. The frequencies of the Del and 4G alleles were found to be 0.98 and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively. Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-γ and TNF-α contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations

  8. Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

    PubMed

    Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

    2018-03-15

    Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and

  9. Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?

    PubMed

    Hoang, Phuong Thu Vu; Ambroise, Jérôme; Dekairelle, Anne-France; Durant, Jean-François; Butoescu, Valentina; Chi, Vu Luan Dang; Huynh, Nghia; Nguyen, Tan Binh; Robert, Annie; Vermylen, Christiane; Gala, Jean-Luc

    2015-03-01

    Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model. The prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤ 3), those with a high MGRS (≥ 4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months). Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of

  10. Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?

    PubMed Central

    Vu Hoang, Phuong Thu; Ambroise, Jérôme; Dekairelle, Anne-France; Durant, Jean-François; Butoescu, Valentina; Dang Chi, Vu Luan; Huynh, Nghia; Nguyen, Tan Binh; Robert, Annie; Vermylen, Christiane; Gala, Jean-Luc

    2015-01-01

    Aims Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model. Results The prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤3), those with a high MGRS (≥4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months). Conclusion Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the

  11. High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin.

    PubMed

    AlBacha, Jeanne d'Arc; Khoury, Mira; Mouawad, Charbel; Haddad, Katia; Hamoui, Samar; Azar, Albert; Fajloun, Ziad; Makdissy, Nehman

    2015-01-01

    Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI-1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles "Del" and "4G". The frequencies of the Del and 4G alleles were found to be 0.98 and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively. Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-γ and TNF-α contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations (Del/4G

  12. The presence of PAI-1 4G/5G and ACE DD genotypes increases the risk of early-stage AVF thrombosis in hemodialysis patients.

    PubMed

    Güngör, Yahya; Kayataş, Mansur; Yıldız, Gürsel; Özdemir, Öztürk; Candan, Ferhan

    2011-01-01

    In this study, we investigated the relationship between early arteriovenous fistula (AVF) thrombosis with angiotensin-converting enzyme (ACE) gene and thrombophilic factor gene polymorphisms. Thirty-five patients who suffered from three or more fistula thrombosis episodes in the early period after AVF operation and 33 control patients with no history of thrombosis for at least 3 years were enrolled in this study. Factor V G1691A Leiden, factor V H1299R (R2), prothrombin G20210A, factor XIIIV34L, β-fibrinogen-455 G-A, glycoprotein IIIa L33P human platelet antigens (HPA-1), methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C gene polymorphisms were similar in both groups (p > 0.05). Plasminogen activator inhibitor 1 (PAI-1) 4G/5G genotype in the study group and 4G/4G genotype in the control group were significantly higher (p = 0.014). No significant difference was detected in terms of the 5G/5G genotype. With regard to the ACE gene polymorphism, the control group showed more ID genotype (19/33, 57.6%), whereas the study group showed more DD genotype (17/35, 48.6%). II genotype was similar in both groups (x(2) = 7.40, p = 0.025). The rate of ACE inhibitor-angiotensin II receptor blockers use was 5/35 in the study group (14.3%) and 5/33 in the control group (15.2%). Individuals with PAI-1 4G/5G genotype showed 5.03 times more risk of thrombosis when compared with 4G/4G and 5G/5G genotypes [p = 0.008, OR = 5.03, 95% confidence interval (1.44:17.64)]. Individuals with ACE DD genotype showed 4.25 times more risk of thrombosis when compared with II and ID [p = 0.008, OR = 4.25, 95% confidence interval (1.404:12.83)]. PAI-1 4G/5G and ACE DD genotypes are associated with increased risk for early AVF thrombosis.

  13. Systematic review and meta-analysis of the associations between maternal methylenetetrahydrofolate reductase polymorphisms and preterm delivery.

    PubMed

    Fang, Qiwen; Jiang, Yixuan; Liu, Zhenqiu; Zhang, Zhijie; Zhang, Tiejun

    2018-04-01

    To date, reported associations between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and preterm delivery are conflicting. The present meta-analysis summarized the existing evidence and evaluated these associations. Eligible studies were retrieved from Medline (PubMed), EMBASE, the Chinese Biomedical Literature Database and the Cochrane Library. We calculated pooled odds ratios (ORs) and 95% confidence interval (CIs) within five genetic models using either random-effects or fixed-effects models dependent on study heterogeneity. Potential publication bias was assessed using a Begg's test. Sensitivity analysis was performed to evaluate the stability of the results. Thirteen studies involving 4816 mothers who experienced preterm delivery and 34 506 normal controls were finally included. Significant associations between MTHFR C677T polymorphism and the risk of preterm delivery were detected overall (OR T/C  = 1.34, 95% CI 1.12-1.61; OR TT/CC  = 1.60, 95% CI 1.21-2.11; OR CT/CC  = 1.33, 95% CI 1.07-1.65; OR TT/(CC + CT)  = 1.41, 95% CI 1.11-1.78; OR (TT + CT)/CC  = 1.36, 95% CI 1.11-1.66) and in an Asian population (OR T/C  = 1.80, 95% CI 1.24-2.62; OR TT/CC  = 2.13, 95% CI 1.27-3.57; OR CT/CC  = 1.93, 95% CI 1.37-2.71; OR (TT + CT)/CC  = 2.03, 95% CI 1.49-2.77). Negative associations of the A1298C polymorphism were only observed among Asian pregnant women (OR C/A  = 0.66, 95% CI 0.50-0.88; OR CC/AA  = 0.10, 95% CI 0.02-0.53; OR CC/(AA + AC)  = 0.11, 95% CI 0.02-0.57; OR (CC + AC)/AA  = 0.68, 95% CI 0.49-0.94). MTHFR 677 T may play a significant role in regard to the risk of preterm delivery, especially in the Asian population. © 2018 Japan Society of Obstetrics and Gynecology.

  14. Polymorphisms in folate-metabolizing enzymes and response to 5-fluorouracil among patients with stage II or III rectal cancer (INT-0144; SWOG 9304).

    PubMed

    Ulrich, Cornelia M; Rankin, Cathryn; Toriola, Adetunji T; Makar, Karen W; Altug-Teber, Özge; Benedetti, Jacqueline K; Holmes, Rebecca S; Smalley, Stephen R; Blanke, Charles D; Lenz, Heinz-Josef

    2014-11-01

    Recurrence and toxicity occur commonly among patients with rectal cancer who are treated with 5-fluorouracil (5-FU). The authors hypothesized that genetic variation in folate-metabolizing genes could play a role in interindividual variability. The objective of the current study was to evaluate the associations between genetic variants in folate-metabolizing genes and clinical outcomes among patients with rectal cancer treated with 5-FU. The authors investigated 8 functionally significant polymorphisms in 6 genes (methylenetetrahydrofolate reductase [MTHFR] [C677T, A1298C], SLC19A1 [G80A], SHMT1 [C1420T], dihydrofolate reductase [DHFR] [Del19bp], TS 1494del,and TSER) involved in folate metabolism in 745 patients with TNM stage II or III rectal cancer enrolled in a phase 3 adjuvant clinical trial of 3 regimens of 5-FU and radiotherapy (INT-0144 and SWOG 9304). There were no statistically significant associations noted between polymorphisms in any of the genes and overall survival, disease-free survival (DFS), and toxicity in the overall analyses. Nevertheless, there was a trend toward worse DFS among patients with the variant allele of MTHFR C677T compared with wild-type, particularly in treatment arm 2, in which patients with the MTHFR C677T TT genotype had worse overall survival (hazards ratio, 1.76; 95% confidence interval, 1.06-2.93 [P = .03]) and DFS (hazards ratio, 1.84; 95% confidence interval, 1.12-3.03 [P = .02]) compared with those with homozygous wild-type. In addition, there was a trend toward reduced hematological toxicity among patients with variants of SLC19A1 G80A in treatment arm 1 (P for trend, .06) and reduced esophagitis/stomatitis noted among patients with variants of TSER in treatment arm 3 (P for trend, .06). Genetic variability in folate-metabolizing enzymes was found to be associated only to a limited degree with clinical outcomes among patients with rectal cancer treated with 5-FU. © 2014 American Cancer Society.

  15. PREVAIL: Predicting Recovery through Estimation and Visualization of Active and Incident Lesions.

    PubMed

    Dworkin, Jordan D; Sweeney, Elizabeth M; Schindler, Matthew K; Chahin, Salim; Reich, Daniel S; Shinohara, Russell T

    2016-01-01

    The goal of this study was to develop a model that integrates imaging and clinical information observed at lesion incidence for predicting the recovery of white matter lesions in multiple sclerosis (MS) patients. Demographic, clinical, and magnetic resonance imaging (MRI) data were obtained from 60 subjects with MS as part of a natural history study at the National Institute of Neurological Disorders and Stroke. A total of 401 lesions met the inclusion criteria and were used in the study. Imaging features were extracted from the intensity-normalized T1-weighted (T1w) and T2-weighted sequences as well as magnetization transfer ratio (MTR) sequence acquired at lesion incidence. T1w and MTR signatures were also extracted from images acquired one-year post-incidence. Imaging features were integrated with clinical and demographic data observed at lesion incidence to create statistical prediction models for long-term damage within the lesion. The performance of the T1w and MTR predictions was assessed in two ways: first, the predictive accuracy was measured quantitatively using leave-one-lesion-out cross-validated (CV) mean-squared predictive error. Then, to assess the prediction performance from the perspective of expert clinicians, three board-certified MS clinicians were asked to individually score how similar the CV model-predicted one-year appearance was to the true one-year appearance for a random sample of 100 lesions. The cross-validated root-mean-square predictive error was 0.95 for normalized T1w and 0.064 for MTR, compared to the estimated measurement errors of 0.48 and 0.078 respectively. The three expert raters agreed that T1w and MTR predictions closely resembled the true one-year follow-up appearance of the lesions in both degree and pattern of recovery within lesions. This study demonstrates that by using only information from a single visit at incidence, we can predict how a new lesion will recover using relatively simple statistical techniques. The

  16. Connection between nitrogen and manganese cycles revealed by transcriptomic analysis in Shewanella algae C6G3

    NASA Astrophysics Data System (ADS)

    Michotey, V.; Aigle, A.; Armougom, F.; Mejean, V.; Guasco, S.; Bonin, P.

    2016-02-01

    In sedimentary systems, the repartition of terminal electron-accepting molecules is often stratified on a permanent or seasonal basis. Just below to oxic zone, the suboxic one is characterized by high concentrations of oxidized inorganic compounds such as nitrate, manganese oxides (MnIII/IV) and iron oxides that are in close vicinity. Several studies have reported unexpected anaerobic nitrite/nitrate production at the expense of ammonium mediated by MnIII/IV, however this transient processes is difficult to discern and poorly understood. In the frame of this study, genes organization of nitrate and MnIII/IV respiration was investigated in S.algae. Additional genes were identified in S. algae compare to S. oneidensis: genes coding for nitrate and nitrite reductase (napA-a and nrfA-2) and an OMC protein (mtrH). In contrast to S. oneidensis, an anaerobic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during growth with MnIII/IV, concomitantly with expression of nitrate/nitrite reductase genes (napA, nrfA, nrfA-2). Among the hypothesis explaining this data, the potential putative expression of unidentified gene able to perform ammonium oxidation was not observed on the global transcriptional level, however several signs of oxidative stress were detected and the existence of a secondary reaction generated by a putative oxidative s could not be excluded. Another option could be the action of reverse reaction by an enzyme such as NrfA or NrfA-2 due to the electron flow equilibrium. Whatever the electron acceptor (Nitrate/ MnIII/IV), the unexpected expression level of of omcA, mtrF, mtrH, mtrC was observed and peaked at the end of the exponential phase. Different expression patterns of the omc genes were observed depending on electron acceptor and growth phase. Only mtrF-2 gene was specifically expressed in Mn(III/IV) condition. Nitrate and Mn(III/IV) respirations seem connected at physiological as well as at transcriptional level

  17. Associations between prenatal, childhood, and adolescent stress and variations in white-matter properties in young men.

    PubMed

    Jensen, Sarah K G; Pangelinan, Melissa; Björnholm, Lassi; Klasnja, Anja; Leemans, Alexander; Drakesmith, Mark; Evans, C J; Barker, Edward D; Paus, Tomáš

    2017-10-21

    Previous studies have shown that both pre- and post-natal adversities, the latter including exposures to stress during childhood and adolescence, explain variation in structural properties of white matter (WM) in the brain. While previous studies have examined effects of independent stress exposures within one developmental period, such as childhood, we examine effects of stress across development using data from a prospective longitudinal study. More specifically, we ask how stressful events during prenatal development, childhood, and adolescence relate to variation in WM properties in early adulthood in young men recruited from a birth cohort. Using data from 393 mother-son pairs from a community-based birth cohort from England (Avon Longitudinal Study of Parents and Children), we examined how stressful life events relate to variation in different structural properties of WM in the corpus callosum and across the whole brain in early adulthood in men aged 18-21 years. We distinguish between stress occurring during three developmental periods: a) prenatal maternal stress, b) postnatal stress within the first four years of life, c) stress during adolescence (age 12-16 years). To obtain a comprehensive quantification of variation in WM, we assess structural properties of WM using four different measures, namely fractional anisotropy (FA), mean diffusivity (MD), magnetization transfer ratio (MTR) and myelin water fraction (MWF). The developmental model shows that prenatal stress is associated with lower MTR and MWF in the genu and/or splenium of the corpus callosum, and with lower MTR in global (lobar) WM. Stress during early childhood is associated with higher MTR in the splenium, and stress during adolescence is associated with higher MTR in the genu and lower MD in the splenium. We see no associations between postnatal stress and variation in global (lobar) WM. The current study found evidence for independent effects of stress on WM properties during distinct

  18. In Vivo Magnetization Transfer and Diffusion-Weighted Magnetic Resonance Imaging Detects Thrombus Composition in a Mouse Model of Deep Vein Thrombosis

    PubMed Central

    Saha, Prakash; Modarai, Bijan; Smith, Alberto; Botnar, René M.

    2014-01-01

    Background Deep vein thrombosis remains a major health problem necessitating accurate diagnosis. Thrombolysis is associated with significant morbidity and is effective only for the treatment of unorganized thrombus. We tested the feasibility of in vivo magnetization transfer (MT) and diffusion-weighted magnetic resonance imaging to detect thrombus organization in a murine model of deep vein thrombosis. Methods and Results Deep vein thrombosis was induced in the inferior vena cava of male BALB/C mice. Magnetic resonance imaging was performed at days 1, 7, 14, 21, and 28 after thrombus induction using MT, diffusion-weighted, inversion-recovery, and T1-mapping protocols. Delayed enhancement and T1 mapping were repeated 2 hours after injection of a fibrin contrast agent. Finally, excised thrombi were used for histology. We found that MT and diffusion-weighted imaging can detect histological changes associated with thrombus aging. MT rate (MTR) maps and percentage of MT rate (%MTR) allowed visualization and quantification of the thrombus protein content, respectively. The %MTR increased with thrombus organization and was significantly higher at days 14, 21, and 28 after thrombus induction (days 1, 7, 14, 21, 28: %MTR=2483±451, 2079±1210, 7029±2490, 10 295±4356, 32 994±25 449; Panova<0.05). There was a significant positive correlation between the %MTR and the histological protein content of the thrombus (r=0.70; P<0.05). The apparent diffusion coefficient was lower in erythrocyte-rich and collagen-rich thrombus (0.72±0.10 and 0.69±0.05 [×10−3 mm2/s]). Thrombus at days 7 and 14 had the highest apparent diffusion coefficient values (0.95±0.09 and 1.10±0.18 [×10−3 mm2/s]). Conclusions MT and diffusion-weighted magnetic resonance imaging sequences are promising for the staging of thrombus composition and could be useful in guiding medical intervention. PMID:23564561

  19. Hepatic Activity and Transcription of Betaine-Homocysteine Methyltransferase, Methionine Synthase, and Cystathionine Synthase in Periparturient Dairy Cows Are Altered to Different Extents by Supply of Methionine and Choline.

    PubMed

    Zhou, Zheng; Garrow, Timothy A; Dong, Xianwen; Luchini, Daniel N; Loor, Juan J

    2017-01-01

    Compared with choline, Met enhances milk yield and feed intake, and elicits a better immuno-metabolic status in periparturient cows. It is unknown whether hepatic activity and transcription of betaine-homocysteine methyltransferase (BHMT), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and cystathionine β-synthase (CBS) are responsive to Met and choline supply. This study sought to characterize hepatic BHMT, MTR, and CBS transcription and activity in response to Met and choline supplementation. Forty multiparous cows were used in a 2 × 2 factorial design from -21 d through 30 d around parturition to assess effects of dietary rumen-protected Met (0% or 0.08% dry matter basis) or rumen-protected choline (0 or 60 g · cow -1 · d -1 ). Liver tissue obtained on days -10, 7, 20, and 30 was used for analyses. Met-supplemented cows had greater methionine adenosyltransferase 1A (MAT1A) (0.38 compared with 0.27; SEM = 0.05; P = 0.02) and phosphatidylethanolamine methyltransferase (PEMT) (0.74 compared with 0.58; SEM = 0.08; P = 0.05) expression. Greater S-adenosylhomocysteine hydrolase (SAHH) (0.93 compared with 0.74; SEM = 0.05; P = 0.01) and CBS (1.16 compared with 1.02; SEM = 0.07; P = 0.04), as well as lower MTR activity (23.4 compared with 29.7 nmol product · h -1 · mg protein -1 ; SEM = 2.9; P = 0.04), also were detected in Met- but not choline-supplemented cows. Although BHMT and MTR expression and BHMT enzyme activity did not change (P > 0.05), MTR enzyme activity was lower in choline-supplemented cows (23.5 compared with 29.6 nmol product · h -1 · mg protein -1 ; SEM = 2.9; P = 0.05). These findings indicate that greater synthesis of phosphatidylcholine and antioxidants contribute to the better performance and immuno-metabolic status in Met-supplemented cows. Failure to generate a comparable amount of endogenous Met from choline could be one reason that choline-fed cows fail to achieve comparable performance and health benefits during the

  20. Improving outcomes for hospital patients with critical bleeding requiring massive transfusion: the Australian and New Zealand Massive Transfusion Registry study methodology.

    PubMed

    Oldroyd, J C; Venardos, K M; Aoki, N J; Zatta, A J; McQuilten, Z K; Phillips, L E; Andrianopoulos, N; Cooper, D J; Cameron, P A; Isbister, J P; Wood, E M

    2016-10-06

    The Australian and New Zealand (ANZ) Massive Transfusion (MT) Registry (MTR) has been established to improve the quality of care of patients with critical bleeding (CB) requiring MT (≥ 5 units red blood cells (RBC) over 4 h). The MTR is providing data to: (1) improve the evidence base for transfusion practice by systematically collecting data on transfusion practice and clinical outcomes; (2) monitor variations in practice and provide an opportunity for benchmarking, and feedback on practice/blood product use; (3) inform blood supply planning, inventory management and development of future clinical trials; and (4) measure and enhance translation of evidence into policy and patient blood management guidelines. The MTR commenced in 2011. At each participating site, all eligible patients aged ≥18 years with CB from any clinical context receiving MT are included using a waived consent model. Patient information and clinical coding, transfusion history, and laboratory test results are extracted for each patient's hospital admission at the episode level. Thirty-two hospitals have enrolled and 3566 MT patients have been identified across Australia and New Zealand between 2011 and 2015. The majority of CB contexts are surgical, followed by trauma and gastrointestinal haemorrhage. Validation studies have verified that the definition of MT used in the registry correctly identifies 94 % of CB events, and that the median time of transfusion for the majority of fresh products is the 'product event issue time' from the hospital blood bank plus 20 min. Data linkage between the MTR and mortality databases in Australia and New Zealand will allow comparisons of risk-adjusted mortality estimates across different bleeding contexts, and between countries. Data extracts will be examined to determine if there are differences in patient outcomes according to transfusion practice. The ratios of blood components (e.g. FFP:RBC) used in different types of critical bleeding will also

  1. HAMLET -Human Model MATROSHKA for Radiation Exposure Determination of Astronauts -Current status and results

    NASA Astrophysics Data System (ADS)

    Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Burmeister, Soenke; Labrenz, Johannes; Hager, Luke; Palfalvi, Jozsef K.; Hajek, Michael; Puchalska, Monika; Sihver, Lembit

    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

  2. Cardiac Chemical Exchange Saturation Transfer MR Imaging Tracking of Cell Survival or Rejection in Mouse Models of Cell Therapy.

    PubMed

    Pumphrey, Ashley L; Ye, Shaojing; Yang, Zhengshi; Simkin, Jennifer; Gensel, John C; Abdel-Latif, Ahmed; Vandsburger, Moriel H

    2017-01-01

    Purpose To examine whether cardiac chemical exchange saturation transfer (CEST) imaging can be serially and noninvasively used to probe cell survival or rejection after intramyocardial implantation in mice. Materials and Methods Experiments were compliant with the National Institutes of Health Guidelines on the Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee. One million C2C12 cells labeled with either europium (Eu) 10-(2-hydroxypropyl)-1,4,7-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) or saline via the hypotonic swelling technique were implanted into the anterior-lateral left ventricular wall in C57BL/6J (allogeneic model, n = 17) and C3H (syngeneic model, n = 13) mice. Imaging (frequency offsets of ±15 parts per million) was performed 1, 10, and 20 days after implantation, with the asymmetrical magnetization transfer ratio (MTR asym ) calculated from image pairs. Histologic examination was performed at the conclusion of imaging. Changes in MTR asym over time and between mice were assessed by using two-way repeated-measures analysis of variance. Results MTR asym was significantly higher in C3H and C57BL/6J mice in grafts of Eu-HP-DO3A-labeled cells (40.2% ± 5.0 vs 37.8% ± 7.0, respectively) compared with surrounding tissue (-0.67% ± 1.7 vs -1.8% ± 5.3, respectively; P < .001) and saline-labeled grafts (-0.4% ± 6.0 vs -1.2% ± 3.6, respectively; P < .001) at day 1. In C3H mice, MTR asym remained increased (31.3% ± 9.2 on day 10, 28.7% ± 5.2 on day 20; P < .001 vs septum) in areas of in Eu-HP-DO3A-labeled cell grafts. In C57BL/6J mice, corresponding MTR asym values (11.3% ± 8.1 on day 10, 5.1% ± 9.4 on day 20; P < .001 vs day 1) were similar to surrounding myocardium by day 20 (P = .409). Histologic findings confirmed cell rejection in C57BL/6J mice. Estimation of graft area was similar with cardiac CEST imaging and histologic examination (R 2 = 0.89). Conclusion Cardiac CEST imaging can be used to image

  3. A dual flip angle 3D bSSFP magnetization transfer-like method to differentiate between recent and old myocardial infarction.

    PubMed

    Germain, Philippe; El Ghannudi, Soraya; Labani, Aissam; Jeung, Mi Y; Gangi, Afshin; Ohlmann, Patrick; Roy, Catherine

    2018-03-01

    Magnetic resonance imaging (MRI) tissue signal is modulated by magnetization transfer (MT) phenomena, intrinsically induced by balanced steady-state free precession (bSSFP) imaging. To investigate the possible value of such a MT-like bSSFP approach in two clinical settings involving focal myocardial lesions highligthed by late gadolinium enhancement (LGE+): edema induced by recent myocardial infarction (MI) and fibrotic scar related to chronic infarction. Population: 48 LGE + patients were studied: 26 with recent MI, 22 with chronic MI. 20 LGE-normal subjects were considered the control group. Field strength/sequence: Navigator-based short axis 3D-bSSFP sequences with 20° and 90° excitation flip angles were acquired (1.5T). Pixel-wise normalized MT Ratio (nMTR) parametric images were calculated according to: nMTR = 100*(S 20 -S 90 *k)/S 20 , with S 20 and S 90 signal intensity in 20° and 90° flip angle images and k = Blood 20 /Blood 90 as a normalization ratio. Statistical tests: analysis of variance (ANOVA), receiver operating characteristic (ROC) analysis. Overall normal myocardial nMTR was 50.2 ± 3.6%. In recent MI, nMTR values were significantly reduced in LGE + regions (-22.3 ± 9.9%, P < 0.0001). In cases of chronic infarct, nMTR was significantly increased in LGE + regions (14.2 ± 11.4%, P < 0.0001). Comparison between observed results and theoretical values obtained with the Freeman-Hill formula showed that most variations observed in MI are related to MT effects instead of relaxation effects. In contrast to LGE imaging, which may show a similar hyperenhancement in recent and old infarctions, nMTR imaging demonstrates an opposite pattern: decreased values for recent infarction and increased values for old infarction, thus allowing to discriminate between these two clinical conditions without gadolinium injection. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:798-808. © 2017 International Society for

  4. 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

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

    2014-01-01

    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. 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. 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/μL, 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/μL, 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

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

    PubMed Central

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

    2014-01-01

    Objective In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. Methods The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher’s exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. Results A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/μL, 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/μL, 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

  6. PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION

    SciTech Connect

    J.G. Wijmans; J.O. Stull

    2001-11-07

    The goal of this project was to develop chemical protective clothing for use by DOE decontamination and decommissioning workers that is sufficiently water vapor permeable to keep the workers cool, thereby enhancing their productivity. This report describes the results of Phase II of a two-phase project to complete development of the novel permselective material and to test protective clothing made from the fabric. In Phase I a novel material incorporating a nonporous hydrophilic polyvinylacohol (PVA) layer, which is water vapor permeable but relatively impermeable to organic vapors, was developed. The results of the Phase I tests showed that the chemicalmore » 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

  7. Magnetic minerals' classification for sources of magnetic anomalies

    NASA Astrophysics Data System (ADS)

    Kletetschka, G.; Wieczorek, M. A.

    2016-12-01

    Our analysis allows interpretation of magnetic anomalies detected in meteorites, on Mars and Moon, and other bodies where the sources of magnetic field can be assumed to be thermoremanent magnetization (Mtr). We show how the specific approach allows reconsideration of the major magnetic carriers on Moon and Mars. Furthermore we are deriving a generalized equation for iron concentration estimate from magnetizations derived from crustal magnetic anomalies on the Moon. There is fundamental linear relation between the magnetic efficiency of thermoremanent magnetization Mtr measured at room temperature and level of the ambient field present at the time of acquisition. We used experimental data for derivation of the empirical constants for paleofield estimate equations. Specific magnetic mineral carriers from single domain (SD) through pseudosingle domain (PSD) to multidomain (MD) states include iron, meteoritic iron, magnetite, maghemite, pyrrhotite, and hematite. The Mtr/Msr is linearly proportional to the product of the magnetizing field and saturation remanence, while the proportionality constant is independent of magnetic mineralogy, domain state, or composition. We show that the level of magnetic paleofield record relates to two types of demagnetizing field that act as a barrier against the domain wall pinning during the magnetic acquisition. The first type of demagnetizing field relates to saturation magnetization constant derived from the distribution of Bohr's magnetons within the crystal lattice. The second type of demagnetizing field originates from the effect of shape of the magnetic minerals. Knowledge of the character of these demagnetizing fields is a prerequisite for paleofield estimates from rocks containing known magnetic mineralogy and magnetic shape anisotropy.

  8. CRISPRi-sRNA: Transcriptional-Translational Regulation of Extracellular Electron Transfer in Shewanella oneidensis.

    PubMed

    Cao, Yingxiu; Li, Xiaofei; Li, Feng; Song, Hao

    2017-09-15

    Extracellular electron transfer (EET) in Shewanella oneidensis MR-1, which is one of the most well-studied exoelectrogens, underlies many microbial electrocatalysis processes, including microbial fuel cells, microbial electrolysis cells, and microbial electrosynthesis. However, regulating the efficiency of EET remains challenging due to the lack of efficient genome regulation tools that regulate gene expression levels in S. oneidensis. Here, we systematically established a transcriptional regulation technology, i.e., clustered regularly interspaced short palindromic repeats interference (CRISPRi), in S. oneidensis MR-1 using green fluorescent protein (GFP) as a reporter. We used this CRISPRi technology to repress the expression levels of target genes, individually and in combination, in the EET pathways (e.g., the MtrCAB pathway and genes affecting the formation of electroactive biofilms in S. oneidensis), which in turn enabled the efficient regulation of EET efficiency. We then established a translational regulation technology, i.e., Hfq-dependent small regulatory RNA (sRNA), in S. oneidensis by repressing the GFP reporter and mtrA, which is a critical gene in the EET pathways in S. oneidensis. To achieve coordinated transcriptional and translational regulation at the genomic level, the CRISPRi and Hfq-dependent sRNA systems were incorporated into a single plasmid harbored in a recombinant S. oneidensis strain, which enabled an even higher efficiency of mtrA gene repression in the EET pathways than that achieved by the CRISPRi and Hfq-dependent sRNA system alone, as exhibited by the reduced electricity output. Overall, we developed a combined CRISPRi-sRNA method that enabled the synergistic transcriptional and translational regulation of target genes in S. oneidensis. This technology involving CRISPRi-sRNA transcriptional-translational regulation of gene expression at the genomic level could be applied to other microorganisms.

  9. Adiposity is associated with structural properties of the adolescent brain.

    PubMed

    Schwartz, Deborah H; Dickie, Erin; Pangelinan, Melissa M; Leonard, Gabriel; Perron, Michel; Pike, G Bruce; Richer, Louis; Veillette, Suzanne; Pausova, Zdenka; Paus, Tomáš

    2014-12-01

    Obesity, a major risk factor for cardiometabolic disease, is associated with variations in a number of structural properties in the adult brain, as assessed with magnetic resonance imaging (MRI). In this study, we investigated the cross-sectional relationship between visceral fat (VF), total body fat (TBF) and three MRI parameters in the brains of typically developing adolescents: (i) T1-weighted (T1W) signal intensity; (ii) T1W signal contrast between white matter (WM) and gray matter (GM); and (iii) magnetization transfer ratio (MTR). In a community-based sample of 970 adolescents (12-18 years old, 466 males), VF was quantified using MRI, and total body fat was measured using a multifrequency bioimpedance. T1W images of the brain were used to determine signal intensity in lobar GM and WM, as well as WM:GM signal contrast. A magnetization transfer (MT) sequence of MT(ON) and MT(OFF) was used to obtain MTR in GM and WM. We found that both larger volumes of VF and more TBF were independently associated with higher signal intensity in WM and higher WM:GM signal contrast, as well as higher MTR in both GM and WM. These relationships were independent of a number of potential confounders, including age, sex, puberty stage, household income and height. Our results suggest that both visceral fat and fat deposited elsewhere in the body are associated independently with structural properties of the adolescent brain. We speculate that these relationships suggest the presence of adiposity-related variations in phospholipid composition of brain lipids. Copyright © 2014. Published by Elsevier Inc.

  10. Multi-Parametric Spinal Cord MRI as Potential Progression Marker in Amyotrophic Lateral Sclerosis

    PubMed Central

    El Mendili, Mohamed-Mounir; Cohen-Adad, Julien; Pelegrini-Issac, Mélanie; Rossignol, Serge; Morizot-Koutlidis, Régine; Marchand-Pauvert, Véronique; Iglesias, Caroline; Sangari, Sina; Katz, Rose; Lehericy, Stéphane; Benali, Habib; Pradat, Pierre-François

    2014-01-01

    Objective To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. Materials and Methods After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. Results At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change. Conclusion Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs. PMID:24755826

  11. Multi-parametric spinal cord MRI as potential progression marker in amyotrophic lateral sclerosis.

    PubMed

    El Mendili, Mohamed-Mounir; Cohen-Adad, Julien; Pelegrini-Issac, Mélanie; Rossignol, Serge; Morizot-Koutlidis, Régine; Marchand-Pauvert, Véronique; Iglesias, Caroline; Sangari, Sina; Katz, Rose; Lehericy, Stéphane; Benali, Habib; Pradat, Pierre-François

    2014-01-01

    To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change. Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.

  12. Maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of recurrent pregnancy loss.

    PubMed

    Sata, F; Yamada, H; Kishi, R; Minakami, H

    2012-10-01

    Epidemiological studies have suggested that the condition of recurrent pregnancy loss (RPL) may be multifactorial, with both genetic predisposition and environmental factors potentially involved in its pathogenesis. The aim of this study is to elucidate the associations between maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of RPL. This case-control study, which involved 116 cases with two or more instances of RPL and 306 fertile controls, was performed in the city of Sapporo, Japan. The associations between eight single nucleotide polymorphisms of folate, alcohol and energy metabolism-related genes [methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), beta-3-adrenergic receptor (ADRB3) and peroxisome proliferator-activated receptor gamma (PPARG)], and RPL were assessed. Without consideration of cigarette smoking or alcohol use, the risk of RPL significantly decreased in women with the MTHFR rs1801133 TT, MTR rs1805087 AG or ALDH2 rs671 AA genotype (P < 0.05). The risk of RPL associated with cigarette smoking and alcohol use decreased significantly in women carrying the MTHFR rs1801133 T allele [odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27-0.95]. Similarly, the risk of RPL significantly decreased in women carrying the MTR rs1805087 G allele (OR, 0.44; 95% CI, 0.23-0.85). Our findings suggest that maternal gene polymorphisms related to folate metabolism may decrease the risk of RPL. Molecular epidemiological studies are needed to unequivocally elucidate the multifactorial effects of both genetic and environmental factors on human fecundity.

  13. Testing of a Transport Cask for Research Reactor Spent Fuel - 13003

    SciTech Connect

    Mourao, Rogerio P.; Leite da Silva, Luiz; Miranda, Carlos A.

    2013-07-01

    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 frommore » 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)« less

  14. Effect of Soft Tissue Techniques on Headache Impact, Disability, and Quality of Life in Migraine Sufferers: A Pilot Study.

    PubMed

    Espí-López, Gemma-Victoria; Ruescas-Nicolau, Maria-Arantzazu; Nova-Redondo, Cristina; Benítez-Martínez, Josep C; Dugailly, Pierre-Michel; Falla, Deborah

    2018-04-30

    To determine the efficacy of suboccipital inhibitory techniques in people with migraine compared with a control treatment based on myofascial trigger point (MTrP) therapy and stretching. A randomized, double-blind controlled pilot trial was conducted. University research laboratory. Forty-six adults diagnosed with migraine with over 6 months duration. Participants were randomized to receive either combined MTrP therapy and stretching (control group) or the control treatment plus suboccipital soft tissue inhibition (experimental group). Treatment was applied on four occasions over 8 weeks (one every 15 days), with a duration of 30 minutes per session in the experimental group and 20 min in the control group. The impact of headache was assessed with the Headache Impact Test (HIT-6), disability by the migraine disability assessment (MIDAS), and quality of life by the Short Form Health Survey (SF-36). Both groups were assessed at baseline and 1 week immediately after the end of treatment. The amount of change of the HIT-6 score and MIDAS scores were significantly different between groups (p < 0.05), although the SF-36 scores were not. The change in the HIT-6 score and MIDAS scores was greater in the experimental group. Both groups showed a reduction on the HIT-6 score (p < 0.001), MIDAS scores (p < 0.05), and SF-36 physical subscale, whereas the SF-36 mental subscale improved only in the experimental group (p < 0.001). Soft tissue techniques based on MTrP therapy and stretching were helpful for improving certain aspects of migraine, such as the impact and disability caused by the headache, and the frequency and intensity of headache; however, when combined with suboccipital soft tissue inhibition, the treatment effect was larger.

  15. White matter hyperintensities and normal-appearing white matter integrity in the aging brain.

    PubMed

    Maniega, Susana Muñoz; Valdés Hernández, Maria C; Clayden, Jonathan D; Royle, Natalie A; Murray, Catherine; Morris, Zoe; Aribisala, Benjamin S; Gow, Alan J; Starr, John M; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

    2015-02-01

    White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

    SciTech Connect

    Wang Silun; Tryggestad, Erik; Zhou Tingting

    Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T{sub 1}, T{sub 2}, apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Methods and Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 Multiplication-Sign 10 mm{sup 2}) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at {approx}25 weeks' postradiation. The MRI signals of necroticmore » cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. Results: ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T{sub 1}, T{sub 2}, MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T{sub 1}, T{sub 2}, MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. Conclusion: ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.« less

  17. Imaging outcomes for trials of remyelination in multiple sclerosis.

    PubMed

    Mallik, Shahrukh; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Miller, David H

    2014-12-01

    Trials of potential neuroreparative agents are becoming more important in the spectrum of multiple sclerosis research. Appropriate imaging outcomes are required that are feasible from a time and practicality point of view, as well as being sensitive and specific to myelin, while also being reproducible and clinically meaningful. Conventional MRI sequences have limited specificity for myelination. We evaluate the imaging modalities which are potentially more specific to myelin content in vivo, such as magnetisation transfer ratio (MTR), restricted proton fraction f (from quantitative magnetisation transfer measurements), myelin water fraction and diffusion tensor imaging (DTI) metrics, in addition to positron emission tomography (PET) imaging. Although most imaging applications to date have focused on the brain, we also consider measures with the potential to detect remyelination in the spinal cord and in the optic nerve. At present, MTR and DTI measures probably offer the most realistic and feasible outcome measures for such trials, especially in the brain. However, no one measure currently demonstrates sufficiently high sensitivity or specificity to myelin, or correlation with clinical features, and it should be useful to employ more than one outcome to maximise understanding and interpretation of findings with these sequences. PET may be less feasible for current and near-future trials, but is a promising technique because of its specificity. In the optic nerve, visual evoked potentials can indicate demyelination and should be correlated with an imaging outcome (such as optic nerve MTR), as well as clinical measures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study.

    PubMed

    Miller, David H; Fox, Robert J; Phillips, J Theodore; Hutchinson, Michael; Havrdova, Eva; Kita, Mariko; Wheeler-Kingshott, Claudia A M; Tozer, Daniel J; MacManus, David G; Yousry, Tarek A; Goodsell, Mary; Yang, Minhua; Zhang, Ray; Viglietta, Vissia; Dawson, Katherine T

    2015-03-17

    To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment. © 2015 American Academy of Neurology.

  19. 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)

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

    2006-12-01

    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.

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

    PubMed Central

    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

    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

  1. Simulations of MATROSHKA experiments at ISS using PHITS

    NASA Astrophysics Data System (ADS)

    Puchalska, Monika; Sihver, L.; Sato, T.; Berger, T.; Reitz, G.

    Concerns about the biological effects of space radiation are increasing rapidly due to the per-spective of long-duration manned missions, both in relation to the International Space Station (ISS) and to manned interplanetary missions to Moon and Mars in the future. As a prepara-tion for these long duration space missions it is important to ensure an excellent capability to evaluate the impact of space radiation on human health in order to secure the safety of the astronauts/cosmonauts and minimize their risks. It is therefore necessary to measure the radi-ation load on the personnel both inside and outside the space vehicles and certify that organ and tissue equivalent doses can be simulated as accurate as possible. In this paper we will present simulations using the three-dimensional Monte Carlo Particle and Heavy Ion Transport code System (PHITS) of long term dose measurements performed with the ESA supported ex-periment MATROSHKA (MTR), which is an anthropomorphic phantom containing over 6000 radiation detectors, mimicking a human head and torso. The MTR experiment, led by the German Aerospace Center (DLR), was launched in January 2004 and has measured the ab-sorbed dose from space radiation both inside and outside the ISS. In this paper preliminary comparisons of measured and calculated dose and organ doses in the MTR located outside the ISS will be presented. The results confirm previous calculations and measurements which indicate that PHITS is a suitable tool for estimations of dose received from cosmic radiation and when performing shielding design studies of spacecraft. Acknowledgement: The research leading to these results has received funding from the Euro-pean Commission in the frame of the FP7 HAMLET project (Project 218817).

  2. Realistic Bomber Training Initiative Supplemental Environmental Impact Statement

    DTIC Science & Technology

    2007-03-01

    mph at the surface and 27 mph at 22 feet AGL; e ) A pull-up maneuver by the B-1B, which may be executed once or twice per sortie- operation, can...avoid resources, where feasible. ( e ) Developing and implementing site-specifi.c mitigation measures, if required. (3) The Air Force will avoid or...form a complete MOA, the LancerMOA. (2) Concerns were expressed about the structw~ e of the proposed MTR, IR 178. The Air Force reduced noise

  3. NUMBER AND TYPE OF OPERATING CYCLES FOR THE FFTF

    SciTech Connect

    Boyd, D. C.

    1969-05-15

    The choice of materials and other vessel design decisions necessary to provide the desired life expectancy for the FTR vessel are partially dependent upon estimates of the number and type of reactor shutdowns and startups which may be anticipated. Current estimates of these so-called "cycles" are given, including scram frequency, experimental outage frequency, standard shutdowns and startups, and rapid controlled shutdowns. Also discussed are abnormal heatup or cooldown, and tentative goals for temperature controls. MTR, ETR, and typical PRTR operating histories are tabulated.

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

    SciTech Connect

    Not Available

    1990-01-01

    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.

  5. Auto-Targeted Neurostimulation Is Not Superior to Placebo in Chronic Low Back Pain: A Fourfold Blind Randomized Clinical Trial.

    PubMed

    Aguilar Ferrándiz, Maria Encarnación; Nijs, Jo; Gidron, Yori; Roussel, Nathalie; Vanderstraeten, Rob; Van Dyck, Dries; Huysmans, Eva; De Kooning, Margot

    2016-07-01

    Myofascial trigger points (MTrPs) are common in people with musculoskeletal pain and may play a role in chronic nonspecific low back pain (CLBP). One of the potential treatments of MTrPs is the Nervomatrix Soleve® auto-targeted neurostimulation device, providing targeted transcutaneous electrical nerve stimulation (TENS) to MTrPs in the lower back muscles. To date, no controlled studies have evaluated the effectiveness of this device for the pain management of this population. To examine whether the Nervomatrix Soleve® auto-targeted neurostimulation device is superior over placebo for the treatment of CLBP. A fourfold-blind randomized controlled trial was conducted. Brussels University Hospital, health care centers and pharmacies around Belgium. Participants with CLBP for at least 3 months were randomly assigned to the experimental (the Nervomatrix Soleve® auto-targeted neurostimulation device providing TENS-stimulation and mechanical pressure) or placebo group (the Nervomatrix Soleve® auto-targeted neurostimulation device providing mechanical pressure alone without current). The treatment protocol in both groups consisted of 6 treatment sessions per patient. Participants were evaluated at baseline prior to the intervention, immediately following treatment, and at one month follow-up. Pain and pain behavior (steps climbed) were assessed as primary outcome measures. Secondary outcome measures were pain functioning, health beliefs, symptoms of central sensitization, pain catastrophizing, and kinesiophobia. In total, 39 participants were included in the study. Participants in both groups improved significantly for pain and functioning, but no significant differences were observed between groups. These improvements were not clinically meaningful for any of the reported measures. The health beliefs changed significantly in both groups (P < 0.05), with superior results at follow-up in the placebo group. The follow-up period is limited to one month. Treatment of MTr

  6. ETR COMPLEX. CAMERA FACING EAST. FROM LEFT TO RIGHT: ETRCRITICAL ...

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

    ETR COMPLEX. CAMERA FACING EAST. FROM LEFT TO RIGHT: ETR-CRITICAL FACILITY BUILDING, ETR CONTROL BUILDING (ATTACHED TO HIGH-BAY ETR), ETR, ONE-STORY SECTION OF ETR BUILDING, ELECTRICAL BUILDING, COOLING TOWER PUMP HOUSE, COOLING TOWER. COMPRESSOR AND HEAT EXCHANGER BUILDING ARE PARTLY IN VIEW ABOVE ETR. DARK-COLORED DUCTS PROCEED FROM GROUND CONNECTION TO ETR WASTE GAS STACK. OTHER STACK IS MTR STACK WITH FAN HOUSE IN FRONT OF IT. RECTANGULAR STRUCTURE NEAR TOP OF VIEW IS SETTLING BASIN. INL NEGATIVE NO. 56-4102. Unknown Photographer, ca. 1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  7. ETR, TRA642. ETR COMPLEX NEARLY COMPLETE. CAMERA FACES NORTHWEST, PROBABLY ...

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

    ETR, TRA-642. ETR COMPLEX NEARLY COMPLETE. CAMERA FACES NORTHWEST, PROBABLY FROM TOP DECK OF COOLING TOWER. SHADOW IS CAST BY COOLING TOWER UNITS OFF LEFT OF VIEW. HIGH-BAY REACTOR BUILDING IS SURROUNDED BY ITS ATTACHED SERVICES: ELECTRICAL (TRA-648), HEAT EXCHANGER (TRA-644 WITH U-SHAPED YARD), AND COMPRESSOR (TRA-643). THE CONTROL BUILDING (TRA-647) ON THE NORTH SIDE IS HIDDEN FROM VIEW. AT UPPER RIGHT IS MTR BUILDING, TRA-603. INL NEGATIVE NO. 56-3798. Jack L. Anderson, Photographer, 11/26/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  8. Changes in pressure pain sensitivity in latent myofascial trigger points in the upper trapezius muscle after a cervical spine manipulation in pain-free subjects.

    PubMed

    Ruiz-Sáez, Mariana; Fernández-de-las-Peñas, César; Blanco, Cleofás Rodríguez; Martínez-Segura, Raquel; García-León, Rafael

    2007-10-01

    This study analyzed the immediate effects on pressure pain threshold (PPT) in latent myofascial trigger points (MTrPs) in the upper trapezius muscle of a single cervical spine manipulation directed at the C3 through C4 level. Seventy-two volunteers (27 men and 46 women; mean age, 31 years; SD, 10 years) participated in this study. Subjects underwent a screening process to establish both the presence of MTrPs in the upper trapezius muscle as described by Simons et al (Myofascial pain and dysfunction: the trigger point manual, vol 2. 3rd ed. Baltimore: Williams & Wilkins, 1999. p. 23-34) and the presence of intervertebral joint dysfunction at the C3 through C4 level by the lateral gliding test for the cervical spine. Subjects were divided randomly into 2 groups: manipulative group, which received a cervical spine manipulation directed at the C3 through C4 level, and a placebo group, which received a sham manual procedure. The outcome measure was the PPT on the MTrP in the upper trapezius muscle ipsilateral to the side of the joint dysfunction, which was assessed pretreatment and 1, 5, and 10 minutes posttreatment by an assessor blinded to the treatment allocation of the subject. The analysis of variance showed a significant effect for time (F = 5.157; P = .02) but not for side (F = 0.234; P = .63). Furthermore, an interaction between group and time was also found (F = 37.240; P < .001). The experimental group showed a trend toward an increase in PPT levels after the manipulative procedure, whereas the control group showed a trend toward a decrease in PPT. Positive within-group effect sizes ranging from medium to small were found in the manipulative group (0.1 MTrPs in the upper trapezius muscle

  9. Management of land use land cover through the application of remote sensing, geographic information systems and simulation

    NASA Astrophysics Data System (ADS)

    Jha, Praveen

    Deforestation and degradation of forest areas, including those in the Protected Areas (PAs), are major concerns in India. There were 2 broad objectives of the study: the technological objective pertained to the development of state-of-art programs that could serve as Decision Support Systems while finalizing plans and policy interventions, while the other objective aimed at generating geo-spatial data in 2 PAs. A part of the Eastern Himalaya biodiversity hotspot, Manas Tiger Reserve (MTR), Assam, India having an area of 2837.12 sq km and an important part of Rajaji-Corbett Tiger Conservation Unit, Rajaji National Park (RNP), Uttarakhand, India, having an area of 820.42 sq km, were taken for the assessment of land use and land cover (LULC) change during 1990--2004. Simulation was undertaken in a smaller area of 1.2 km * 1.2 km right on the fringe of RNP. Three advanced geo-spatial programs---Multi-Algorithm Automation Program (MAAP), Data Automatic Modification Program (DAMP) and Multi-Stage Simulation Program (MUSSIP)---developed by the author were used extensively. Based on the satellite data, MAAP was used for the rapid assessments of LULC of 2004 and 1990; DAMP was used for the spectral modification of the satellite data of the adjacent scenes of 2004 and of 1990; and MUSSIP was used to simulate LULC maps for the future periods (till 2018). These programs produced very high accuracy levels: 91.12% in 2004 and 89.67% in 1990 were obtained for MTR; and 94.87% in 2004 and 94.10% in 1990 were obtained for RNP; 93.40% pixel-to-pixel accuracy and 0.7904 for kappa were achieved for simulation. The annual rate of loss of forests (0.41% in MTR and 1.20% in RNP) and loss of water (1.79% in MTR and 1.69% in RNP) during 1990-2004 is a matter of serious concern. The scenario analysis in the study area for simulation revealed that the deforestation rate of 1.27% per year during 2004--2018 would increase to 2.04% if the human population growth rate is enhanced by 10%. Hence

  10. NATO Planning Guide for the Estimation of CBRN Casualties

    DTIC Science & Technology

    2014-11-01

    for CBRN Defense ( J -8, JRO). The publication of this IDA document does not indicate endorsement by the Department of Defense, nor should the...Vehicle - Closed Windows 4.2 MTR, ACE, CHAPP, 36 M106 A2 4.2, M113 Stationary Vehicle - Open Windows, TruckNan 40 Fan on Fresh Air * Adapted from J ...5. CFHD= ECt50-severe(HD/PC/V) ED50-severe(HD/PC/L) , (4-5) where: 47 Gene E. McClellan, George H. Anno , and Leigh N. Matheson, Consequence

  11. Report to Congress on Sustainable Ranges

    DTIC Science & Technology

    2007-07-01

    B-106 July 2007 Military Training Route Inventory MTR Originating Agency* Scheduling Agency* Effective Times Length ** (NM) SR847 Alpena CRTC/OTM...ANG), 5884 A Street, Alpena MI 49707-8125 DSN 741-3509/3226. Same as Originating Activity 0700-2300 local daily 119 SR867 Alpena CRTC/OTM (ANG...5884 A Street, Alpena MI 49707-8125 DSN 741-3509/3226. Same as Originating Activity 0700-2300 local daily 152 SR871 440 AW/DOO, General Mitchell IAP

  12. European Scientific Notes. Volume 34. Number 5,

    DTIC Science & Technology</