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Sample records for del gen mthfr

  1. Acantholachesilla gen. n. (Psocodea:'Psocoptera': Lachesillidae: Eolachesillinae: Graphocaeciliini) from Valle del Cauca, Colombia.

    PubMed

    Aldrete, Alfonso N García; Manchola, Oscar Fernando Saenz; Obando, Ranulfo González

    2014-06-25

    Acantholachesilla saltoensis gen. et sp. n. is described from Valle del Cauca, Colombia, in the Lachesillidae, tribe Graphocaeciliini (Eolachesillinae). The genus is related to Dagualachesilla and Dagualachesilloides that occur in the same area, differing from them in the male clunial projection, phallosome, and female subgenital plate and gonapophyses.

  2. Genetic Variation of Methylenetetrahydrofolate Reductase (MTHFR) and Thymidylate Synthase (TS) Genes Is Associated with Idiopathic Recurrent Implantation Failure

    PubMed Central

    Shim, Sung Han; Lee, Yubin; Kim, Ji Hyang; Jeon, Young Joo; Ko, Jung Jae; Lee, Woo Sik; Kim, Nam Keun

    2016-01-01

    The one-carbon metabolism pathway disorder was important role in successful pregnancy. The MTHFR and TS protein were crucial factor in one-carbon metabolism. To investigate the association between recurrent implantation failure (RIF) and enzymes in the one-carbon metabolism pathway. A total of 120 women diagnosed with RIF and 125 control subjects were genotyped for MTHFR 677C>T, 1298A>C, TSER 2R/3R and TS 1494del/ins by a polymerase chain reaction-restriction fragment length polymorphism assay. According to the gene-gene combination analysis, the MTHFR 677/MTHFR 1298 (TT/AA) and MTHFR 677/TS 1494 (TT/6bp6bp) genetic combinations were associated with relatively higher risks [adjusted odds ratio (AOR), 2.764; 95% CI, 1.065–7.174; P = 0.037 and AOR, 3.186; 95% CI, 1.241–8.178; P = 0.016] in RIF patients compared to the CC/AA (MTHFR 677/MTHFR 1298) and TT/6bp6bp (MTHFR 677/TS 1494) combinations, respectively. The results suggested that the combined MTHFR 677/MTHFR 1298 genotype might be associated with increased risk of RIF. To the best of our knowledge, this study is the first to elucidate the potential association of MTHFR, TS and TSER polymorphisms with RIF risk in Korean patients. PMID:27560137

  3. MTHFR — EDRN Public Portal

    Cancer.gov

    The MTHFR gene product catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. This gene is involved in susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia.

  4. Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

    SciTech Connect

    Wlodarczyk, Bogdan J. Zhu, Huiping; Finnell, Richard H.

    2014-02-15

    Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr{sup +/−} × Mthfr{sup +/−} matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr{sup +/+} × Mthfr{sup +/−}, Mthfr{sup +/−} × Mthfr{sup +/−} and Mthfr{sup −/−} × {sup Mthfr+/−}) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype

  5. Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

    PubMed Central

    Wlodarczyk, Bogdan J.; Zhu, Huiping; Finnell, Richard H.

    2014-01-01

    Background In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity vary widely and depend on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results When the dams in Mthfr+/− x Mthfr+/− matings were treated with 7.2mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr+/+ x Mthfr+/−, Mthfr+/− x Mthfr+/− and Mthfr−/− x Mthfr+/−) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote x wild-type versus wild-type x nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. PMID:24384392

  6. Methylenetetrahydrofolate reductase (MTHFR) deficiency enhances resistance against cytomegalovirus infection.

    PubMed

    Fodil-Cornu, N; Kozij, N; Wu, Q; Rozen, R; Vidal, S M

    2009-10-01

    Folates provide one-carbon units for nucleotide synthesis and methylation reactions. A common polymorphism in the MTHFR gene (677C --> T) results in reduced enzymatic activity, and is associated with an increased risk for neural tube defects and cardiovascular disease. The high prevalence of this polymorphism suggests that it may have experienced a selective advantage under environmental pressure, possibly an infectious agent. To test the hypothesis that methylenetetrahydrofolate reductase (MTHFR) genotype influences the outcome of infectious disease, we examined the response of Mthfr-deficient mice against mouse cytomegalovirus (MCMV) infection. Acute MCMV infection of Mthfr(-/-) mice resulted in early control of cytokine secretion, decreased viral titer and preservation of spleen immune cells, in contrast to Mthfr wild-type littermates. The phenotype was abolished in MTHFR transgenic mice carrying an extra copy of the gene. Infection of primary fibroblasts with MCMV showed a decrease in viral replication and in the number of productively infected cells in Mthfr(+/-) fibroblasts compared with wild-type cells. These results indicate that Mthfr deficiency protects against MCMV infection in vivo and in vitro, suggesting that human genetic variants may provide an advantage in the host response against certain pathogens.

  7. Hyperhomocysteinaemia, low folate concentrations and MTHFR C677T mutation in abdominal aortic aneurysm.

    PubMed

    Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Liu, Bing; Wang, Junpeng; Shao, Yang; Zhang, Zhishen; Liu, Chengwei; Hu, Haidi; Zhang, Jian; Xin, Shijie

    2014-05-01

    Hintergrund: Homocystein (Hcy) wurde mit dem Bauchaortenaneurysma (AAA) in Verbindung gebracht. Allerdings wurde der Zusammenhang von Hcy, Vitamin B12 und Folsäure bei Patienten mit AAA bislang nicht in unserer Population untersucht. Patienten und Methoden: 463 Patienten mit einem AAA wurden in die Studie eingeschlossen. 463 Probanden waren nach Alter und Geschlecht mit den Patienten abgestimmt. Wir untersuchten bei allen den Plasmaspiegel von Hcy, Vitamin B12, Folsäure und die Verteilung der C677T Methylentetrahydrofolat Reduktase (MTHFR) Gen-Mutation. Ergebnisse: Die mittlere Plasma- Hcy Konzentrationen waren bei Patienten mit AAA im Vergleich zur Kontrollgruppe signifikant höher (18,37 ± 6,97 vs 12,89 ± 4,08 umol/l, P < 0,001). Die Häufigkeit des homozygoten (TT) Genotyps der MTHFR C677T Mutation war bei Patienten mit AAA signifikant höher als in der Kontrollgruppe (19,4 % vs 11,9 %, P = 0,002). Nüchtern Hcy korrelierte negativ mit Folsäure (AAA: r = - 0,311, P < 0,01; Kontrolle: r = - 0,348, P < 0,01). Die Aneurysmen waren signifikant größer (p < 0,001) bei Patienten mit Hyperhomocysteinämie als bei Patienten mit normalen Hcy Plasmaspiegel. Die Größe des AAA korrelierte linear mit dem Plasma- Hcy Spiegel (r = 0,286, p < 0,001). Schlussfolgerungen: Serum Folsäuremangel und Hyperhomocysteinämie waren mit einem erhöhten Risiko von AAA assoziiert. Der homozygote (TT) Genotyp des MTHFR Genmutation kann ein entscheidender erblicher Risikofaktor für AAA sein.

  8. Role of methylenetetrahydrofolate reductase gene (MTHFR) 677C>T polymorphism in pediatric cerebrovascular disorders.

    PubMed

    Alsayouf, Hamza; Zamel, Khaled M; Heyer, Geoffrey L; Khuhro, A Latif; Kahwash, Samir B; de los Reyes, Emily C

    2011-03-01

    Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation (MTHFR TT) has been linked to an increased risk for stroke, coronary artery disease, and migraine headaches. The authors analyzed the potential link between MTHFR 677C>T homozygosity and childhood stroke. A true association might facilitate screening, recurrence risk stratification, and treatment in patients with cerebrovascular disease. They performed a retrospective chart review of children tested for the MTHFR 677C>/T mutation; 533 patients underwent MTHFR testing, and 8% were homozygous for the MTHFR 677C>T mutation. There was no difference in the cohort compared with the prevalence in the general population. This suggests that the MTHFR 677 C>T polymorphism played a minimal role or no role in stroke risk. However, the data suggest that the MTHFR TT genotype may influence migraine susceptibility in children because there was a higher proportion of migraine patients (28.6%) with the MTHFR TT homozygous genotype.

  9. Increased MTHFR promoter methylation in mothers of Down syndrome individuals.

    PubMed

    Coppedè, Fabio; Denaro, Maria; Tannorella, Pierpaola; Migliore, Lucia

    2016-05-01

    Despite that advanced maternal age at conception represents the major risk factor for the birth of a child with Down syndrome (DS), most of DS babies are born from women aging less than 35 years. Studies performed in peripheral lymphocytes of those women revealed several markers of global genome instability, including an increased frequency of micronuclei, shorter telomeres and impaired global DNA methylation. Furthermore, young mothers of DS individuals (MDS) are at increased risk to develop dementia later in life, suggesting that they might be "biologically older" than mothers of euploid babies of similar age. Mutations in folate pathway genes, and particularly in the methylenetetrahydrofolate reductase (MTHFR) one, have been often associated with maternal risk for a DS birth as well as with risk of dementia in the elderly. Recent studies pointed out that also changes in MTHFR methylation levels can contribute to human disease, but nothing is known about MTHFR methylation in MDS tissues. We investigated MTHFR promoter methylation in DNA extracted from perypheral lymphocytes of 40 MDS and 44 matched control women that coinceived their children before 35 years of age, observing a significantly increased MTHFR promoter methylation in the first group (33.3 ± 8.1% vs. 28.3 ± 5.8%; p=0.001). In addition, the frequency of micronucleated lymphocytes was available from the women included in the study, was higher in MDS than control mothers (16.1 ± 8.6‰ vs. 10.5 ± 4.3‰; p=0.0004), and correlated with MTHFR promoter methylation levels (r=0.33; p=0.006). Present data suggest that MTHFR epimutations are likely to contribute to the increased genomic instability observed in cells from MDS, and could play a role in the risk of birth of a child with DS as well as in the onset of age related diseases in those women.

  10. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    PubMed

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  11. B-vitamins, methylenetetrahydrofolate reductase (MTHFR) and hypertension.

    PubMed

    Ward, Mary; Wilson, Carol P; Strain, J J; Horigan, Geraldine; Scott, John M; McNulty, Helene

    2011-07-01

    Hypertension is a leading risk factor for cardiovascular disease (CVD) and stroke. A common polymorphism in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR), previously identified as the main genetic determinant of elevated homocysteine concentration and also recognized as a risk factor for CVD, appears to be independently associated with hypertension. The B-vitamin riboflavin is required as a cofactor by MTHFR and recent evidence suggests it may have a role in modulating blood pressure, specifically in those with the homozygous mutant MTHFR 677 TT genotype. If studies confirm that this genetic predisposition to hypertension is correctable by low-dose riboflavin, the findings could have important implications for the management of hypertension given that the frequency of this polymorphism ranges from 3 to 32 % worldwide.

  12. Sex-dependent behavioral effects of Mthfr deficiency and neonatal GABA potentiation in mice.

    PubMed

    Levav-Rabkin, Tamar; Blumkin, Elinor; Galron, Dalia; Golan, Hava M

    2011-01-20

    The methylenetetrahydrofolate reductase (Mthfr) gene and/or abnormal homocysteine-folate metabolism are associated with increased risk for birth defects and neuropsychiatric diseases. In addition, disturbances of the GABAergic system in the brain as well as Mthfr polymorphism are associated with neurodevelopmental disorders such as schizophrenia and autism. In the present study we performed behavioral phenotyping of male and female Mthfr mice (wild type and their heterozygous littermates). The present study addresses two main questions: (1) genetic susceptibility, as examined by effects of Mthfr deficiency on behavior (Experiment 1) and (2) possible gene-drug interactions as expressed by behavioral phenotyping of Mthfr-deficient mice neonatally exposed to the GABA potentiating drug GVG (Experiment 2). Newborn development was slightly influenced by Mthfr genotype per se (Experiment 1); however the gene-drug interaction similarly affected reflex development in both male and female offspring (Experiment 2). Hyperactivity was demonstrated in Mthfr heterozygous male mice (Experiment 1) and due to GVG treatment in both Wt and Mthfr+/- male and female mice (Experiment 2). The gene-environment interaction did not affect anxiety-related behavior of male mice (Experiment 2). In female mice, gene-treatment interactions abolished the reduced anxiety observed due to GVG treatment and Mthfr genotype (Experiment 2). Finally, recognition memory of adult mice was impaired due to genotype, treatment and the gene-treatment combination in a sex-independent manner (Experiment 2). Overall, Mthfr deficiency and/or GABA potentiation differentially affect a spectrum of behaviors in male and female mice. This study is the first to describe behavioral phenotypes due to Mthfr genotype, GVG treatment and the interaction between these two factors. The behavioral outcomes suggest that Mthfr deficiency modulates the effects of GABA potentiating drugs. These findings suggest that future treatment

  13. Stability of DNA methylation patterns in mouse spermatogonia under conditions of MTHFR deficiency and methionine supplementation.

    PubMed

    Garner, Justine L; Niles, Kirsten M; McGraw, Serge; Yeh, Jonathan R; Cushnie, Duncan W; Hermo, Louis; Nagano, Makoto C; Trasler, Jacquetta M

    2013-11-01

    Little is known about the conditions contributing to the stability of DNA methylation patterns in male germ cells. Altered folate pathway enzyme activity and methyl donor supply are two clinically significant factors that can affect the methylation of DNA. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key folate pathway enzyme involved in providing methyl groups from dietary folate for DNA methylation. Mice heterozygous for a targeted mutation in the Mthfr gene (Mthfr(+/-)) are a good model for humans homozygous for the MTHFR 677C>T polymorphism, which is found in 10% of the population and is associated with decreased MTHFR activity and infertility. High-dose folic acid is administered as an empirical treatment for male infertility. Here, we examined MTHFR expression in developing male germ cells and evaluated DNA methylation patterns and effects of a range of methionine concentrations in spermatogonia from Mthfr(+/-) as compared to wild-type, Mthfr(+/+) mice. MTHFR was expressed in prospermatogonia and spermatogonia at times of DNA methylation acquisition in the male germline; its expression was also found in early spermatocytes and Sertoli cells. DNA methylation patterns were similar at imprinted genes and intergenic sites across chromosome 9 in neonatal Mthfr(+/+) and Mthfr(+/-) spermatogonia. Using spermatogonia from Mthfr(+/+) and Mthfr(+/-) mice in the spermatogonial stem cell (SSC) culture system, we examined the stability of DNA methylation patterns and determined effects of low or high methionine concentrations. No differences were detected between early and late passages, suggesting that DNA methylation patterns are generally stable in culture. Twenty-fold normal concentrations of methionine resulted in an overall increase in the levels of DNA methylation across chromosome 9, suggesting that DNA methylation can be perturbed in culture. Mthfr(+/-) cells showed a significantly increased variance of DNA methylation at multiple loci across chromosome

  14. MTHFR Gene C677T Polymorphism in Autism Spectrum Disorders

    PubMed Central

    Oztop, Didem Behice; Ozkul, Yusuf

    2014-01-01

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

  15. MTHFR Gene Polymorphism-Mutations and Air Pollution as Risk Factors for Breast Cancer

    PubMed Central

    Gonzales, Mildred C.; Yu, Pojui; Shiao, S. Pamela K.

    2017-01-01

    Background The methylenetetrahydrofolate reductase gene (MTHFR) is one of the most investigated genes associated with breast cancer for its role in epigenetic pathways. Objectives The objectives of this metaprediction study were to examine the polymorphism-mutation risk subtypes of MTHFR and air pollution as contributing factors for breast cancer. Methods For triangulation purposes in metapredictive analyses, we used a recursive partition tree, nonlinear association curve fit, and heat maps for data visualization, in addition to the conventional comparison procedure and pooled analyses. Results We included 36,683 breast cancer cases and 40,689 controls across 82 studies for MTHFR 677 and 23,252 cases and 27,094 controls across 50 studies for MTHFR 1298. MTHFR 677 TT was a risk genotype for breast cancer (p = .0004) and in the East Asian subgroup (p = .005). On global maps, the most polymorphism-mutations on MTHFR 677 TT were found in the Middle East, Europe, Asia, and the Americas, whereas the most mutations on MTHFR 1298 CC were located in Europe and the Middle East for the control group. The geographic information system maps further revealed that MTHFR 677 TT mutations yielded a higher risk of breast cancer for Australia, East Asia, the Middle East, South Europe, Morocco, and the Americas and that MTHFR 1298 CC mutations yielded a higher risk in Asia, the Middle East, South Europe, and South America. Metapredictive analysis revealed that air pollution level was significantly associated with MTHFR 677 TT polymorphism-mutation genotype. Discussion We present the most comprehensive analyses to date of MTHFR polymorphism-mutations and breast cancer risk. Future nursing studies are needed to investigate the health impact on breast cancer of epigenetics and air pollution across populations. PMID:28114181

  16. 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.

  17. Increased resistance to malaria in mice with methylenetetrahydrofolate reductase (Mthfr) deficiency suggests a mechanism for selection of the MTHFR 677C>T (c.665C>T) variant.

    PubMed

    Meadows, Danielle N; Pyzik, Michal; Wu, Qing; Torre, Sabrina; Gros, Philippe; Vidal, Silvia M; Rozen, Rima

    2014-05-01

    The polymorphism 677C>T (NM_005957.4:c.665C>T/p.Ala222Val, rs1801133:C>T) in methylenetetrahydrofolate reductase (MTHFR) results in mild enzymatic deficiency and increased risk for several complex traits including adverse reproductive outcomes, birth defects, and heart disease. Despite these deleterious effects, homozygosity is high (5%-15%) in many populations, and among the highest in Mediterranean regions, where malaria was historically endemic and may have conferred a selective advantage for other mutations. We infected Mthfr-deficient (Mthfr(+) (/-) ) and MTHFR overexpressing (MTHFR(Tg) ) mice with Plasmodium berghei ANKA to induce cerebral malaria. Mthfr(+/-) mice survived longer (P < 0.02, log-rank test), and MTHFR(Tg) mice died earlier (P < 0.05, log-rank test) after infection compared with wild-type littermates. Flow cytometry revealed increased lymphocyte populations and increased CCR4(+) NK cells in spleen of Mthfr(+) (/-) mice; MTHFR(Tg) animals had decreased numbers of these NK cells. Interferon-γ and interleukin-10 immunoreactive proteins were increased and decreased, respectively, in brain of Mthfr(+/-) mice compared with wild-type. We suggest that mild MTHFR deficiency protects against malarial infection and that this phenomenon may have led to the high frequency of the 677C>T/c.665C>T variant in human populations.

  18. MTHFR C677T, MTHFR A1298C, and OPG A163G Polymorphisms in Mexican Patients with Rheumatoid Arthritis and Osteoporosis

    PubMed Central

    Brambila-Tapia, Aniel Jessica Leticia; Durán-González, Jorge; Sandoval-Ramírez, Lucila; Mena, Juan Pablo; Salazar-Páramo, Mario; Gámez-Nava, Jorge Iván; González-López, Laura; Lazalde-Medina B, Brissia; Dávalos, Nory Omayra; Peralta-Leal, Valeria; del Mercado, Mónica Vázquez; Beltrán-Miranda, Claudia Patricia; Dávalos, Ingrid Patricia

    2012-01-01

    MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism in osteoprotegerin (OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation. PMID:22377704

  19. Genetic Analysis of BDNF, GNB3, MTHFR, ACE and APOE Variants in Major and Recurrent Depressive Disorders in Russia

    PubMed Central

    Bondarenko, EA; Shadrina, MI; Grishkina, MN; Druzhkova, TA; Akzhigitov, RG; Gulyaeva, NV; Guekht, AB; Slominsky, PA

    2016-01-01

    This study was conducted to explore the possibility of association between the single-nucleotide polymorphisms rs6264 of BDNF, rs5443 of GNB3, and rs1801133 of MTHFR; the In/Del polymorphism of ACE; and the ε2 allele of APOE and major depressive disorder (MDD) and recurrent depressive disorder (RDD) in an East Slavic population. Generalized multifactor dimensionality reduction (GMDR) method was applied to detect gene-gene interactions. One hundred fifty patients with RDD (101 females and 49 males) and 208 patients with MDD (115 females and 93 males) were included in the study. The comparison group consisted of 200 unrelated individuals. There was no significant difference in genotype distributions or allele frequencies between the controls and any of the diagnostic groups. Nevertheless, the frequency of the G allele of rs1801133 of MTHFR was higher in the RDD group and the frequency of the C allele of rs6264 of BDNF was higher in the MDD group. The difference between the controls and specific disease groups almost reached statistical significance (P = 0.08). A GMDR did not reveal optimal two- and three-dimensional models with significant prediction accuracies (P ˃ 0.05) for the MDD or RDD groups. PMID:27994504

  20. Thermolabile MTHFR genotype and retinal vascular occlusive disease

    PubMed Central

    Cahill, M; Karabatzaki, M; Donoghue, C; Meleady, R; Mynett-Johnson, L; Mooney, D; Graham, I; Whitehead, A; Shields, D

    2001-01-01

    BACKGROUND—Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined.
METHODS—A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined.
RESULTS—87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients.
CONCLUSIONS—The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.

 PMID:11133719

  1. Retinal Ganglion Cell Loss and Mild Vasculopathy in Methylene Tetrahydrofolate Reductase (Mthfr)-Deficient Mice: A Model of Mild Hyperhomocysteinemia

    PubMed Central

    Markand, Shanu; Saul, Alan; Roon, Penny; Prasad, Puttur; Martin, Pamela; Rozen, Rima; Ganapathy, Vadivel; Smith, Sylvia B.

    2015-01-01

    Purpose. Methylenetetrahydrofolate reductase (Mthfr) is a key enzyme in homocysteine-methionine metabolism. We investigated Mthfr expression in retina and asked whether mild hyperhomocysteinemia, due to Mthfr deficiency, alters retinal neurovascular structure and function. Methods. Expression of Mthfr was investigated at the gene and protein level using quantitative (q) RT-PCR, in situ hybridization, immunoblotting, and immunohistochemistry (IHC). The Mthfr+/+ and Mthfr+/− mice were subjected to comprehensive evaluation using ERG, funduscopy, fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), HPLC, and morphometric and IHC analysis of glial fibrillary acidic protein (GFAP) at 8 to 24 weeks. Results. Gene and protein analyses disclosed widespread retinal expression of Mthfr. Electroretinography (ERG) revealed a significant decrease in positive scotopic threshold response in retinas of Mthfr+/− mice at 24 weeks. Fundus examination in mice from both groups was normal; FA revealed areas of focal vascular leakage in 20% of Mthfr+/− mice at 12 to 16 weeks and 60% by 24 weeks. The SD-OCT revealed a significant decrease in nerve fiber layer (NFL) thickness at 24 weeks in Mthfr+/− compared to Mthfr+/+ mice. There was a 2-fold elevation in retinal hcy at 24 weeks in Mthfr+/− mice by HPLC and IHC. Morphometric analysis revealed an approximately 20% reduction in cells in the ganglion cell layer of Mthfr+/− mice at 24 weeks. The IHC indicated significantly increased GFAP labeling suggestive of Müller cell activation. Conclusions. Mildly hyperhomocysteinemic Mthfr+/− mice demonstrate reduced ganglion cell function, thinner NFL, and mild vasculopathy by 24 weeks. The retinal phenotype is similar to that of hyperhomocysteinemic mice with deficiency of cystathionine-β-synthase (Cbs) reported earlier. The data support the hypothesis that hyperhomocysteinemia may be causative in certain retinal neurovasculopathies. PMID:25766590

  2. Genetic variants in 3'-UTRs of methylenetetrahydrofolate reductase (MTHFR) predict colorectal cancer susceptibility in Koreans.

    PubMed

    Jeon, Young Joo; Kim, Jong Woo; Park, Hye Mi; Kim, Jung O; Jang, Hyo Geun; Oh, Jisu; Hwang, Seong Gyu; Kwon, Sung Won; Oh, Doyeun; Kim, Nam Keun

    2015-06-05

    Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) play important roles in tumor development, progression, and metastasis. Moreover, recent studies have reported that a number of 3'-UTR polymorphisms potentially bind to specific microRNAs in a variety of cancers. The aim of this study was to investigate the association of four MTHFR polymorphisms, 2572C>A [rs4846049], 4869C>G [rs1537514], 5488C>T [rs3737967], and 6685T>C [rs4846048] with colorectal cancer (CRC) in Koreans. A total of 850 participants (450 CRC patients and 400 controls) were enrolled in the study. The genotyping of MTHFR 3'-UTR polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis or TaqMan allelic discrimination assay. We found that MTHFR 2572C>A, 4869C>G, and 5488C>T genotypes were substantially associated with CRC susceptibility. Of the potentially susceptible polymorphisms, MTHFR 2572C>A was associated with increased homocysteine and decreased folate levels in the plasma based on MTHFR 677CC. Our study provides the evidences for 3'-UTR variants in MTHFR gene as potential biomarkers for use in CRC prevention.

  3. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility to ischemic stroke: a meta-analysis.

    PubMed

    Li, Pingping; Qin, Chao

    2014-02-10

    Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007; Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are inconsistent. To investigate the possible associations between the MTHFR gene polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case-control studies associated with MTHFR gene C667T involving 2223 cases and 2936 controls were included. Heterogeneity among studies was evaluated with I(2) and Egger's test and an inverted funnel plot was used to assess publication bias. Odds ratio (OR) was observed to identify the associations. Statistically significant association with ischemic stroke was identified for allele T polymorphism of MTHFR [fixed-effects OR=1.28, 95% confidence interval (95% CI): 1.17-1.40, P<0.00001] and marginally significant association was detected with genotype CT of MTHFR (fixed-effects OR=1.13, 95% CI: 1.01-127, P=0.04) and genotype TT of MTHFR (fixed-effects OR=1.43, 95% CI: 1.20-1.70, P<0.001). The results suggested that the MTHFR C667T genetic polymorphism was significantly associated with increased risk of ischemic stroke.

  4. MTHFR homozygous mutation and additional risk factors for cerebral infarction in a large Italian family.

    PubMed

    Del Balzo, Francesca; Spalice, Alberto; Perla, Massimo; Properzi, Enrico; Iannetti, Paola

    2009-01-01

    Several cases with cerebral infarctions associated with the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) have been reported. Given the large number of asymptomatic individuals with the MTHFR mutation, additional risk factors for cerebral infarction should be considered. This study describes a large family with the MTHFR mutation and a combination of heterozygous factor V Leiden mutations and different additional exogenous and endogenous thrombogenic risk factors. Psychomotor retardation and a left fronto-insular infarct associated with the MTHFR mutation together with diminished factor VII and low level of protein C was documented in the first patient. In the second patient, generalized epilepsy and a malacic area in the right nucleus lenticularis was associated with the MTHFR mutation and a low level of protein C. In the third patient, right hemiparesis and a left fronto-temporal porencephalic cyst were documented, together with the MTHFR mutation and hyperhomocysteinemia. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of infants with cerebral infarctions associated with the MTHFR mutation and of their related family members.

  5. MTHFR C677 T gene polymorphism in lymphoproliferative diseases.

    PubMed

    Deligezer, Ugur; Akisik, Ebru E; Yaman, Fulya; Erten, Nilgün; Dalay, Nejat

    2006-01-01

    Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, has been implicated in cancer risk. In the present study we used a melting curve analysis to investigate the association of the common MTHFR C677 T polymorphism with lymphoproliferative diseases. Patients (n=117) were compared with age- and sex-matched control subjects (n=154). Our results indicate that the 677 T variant occurred less frequently in patients (26%) than in the control group (33.7%; P=0.05). Investigation of the variant allele (677 T) frequency in the subgroups with Hodgkin's lymphoma (HL) and B-cell neoplasms (BCNs) revealed that this difference was a result of the significantly lower distribution of the variant allele in patients with HL (20.5%; P=0.01). This was accompanied by a significantly higher frequency of the homozygote normal genotype (677CC) among the patients with HL. In patients with BCNs the distribution of the variant allele (30.3%) was comparable to that in the control group (P=0.47). However, the difference between HL (20.5%) and BCNs (30.3%) did not reach statistical significance (P=0.09). Our results suggest that the distribution of the C677 T polymorphism may vary among lymphoproliferative diseases.

  6. MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

    PubMed Central

    Umerez, Maitane; Gutierrez-Camino, Ángela; Muñoz-Maldonado, Carmen; Martin-Guerrero, Idoia; Garcia-Orad, Africa

    2017-01-01

    Methotrexate (MTX) is an important component in the therapy used to treat childhood acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme for MTX pharmacokinetics. Two single-nucleotide polymorphisms in MTHFR gene, C677T and A1298C, affecting MTHFR activity, have been widely studied as potential markers of MTX toxicity and/or outcome in pediatric ALL. In this review, we show that the majority of published reports do not find association or present opposite effect. Therefore, MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL. The efforts should be focused on other genes, such as transporter genes or microRNA-related genes. PMID:28392709

  7. MTHFR Gene Mutations: A Potential Marker of Late-Onset Alzheimer's Disease?

    PubMed

    Román, Gustavo C

    2015-01-01

    Recent epigenome-wide association studies have confirmed the importance of epigenetic effects mediated by DNA methylation in late-onset Alzheimer's disease (LOAD). Metabolic folate pathways and methyl donor reactions facilitated by B-group vitamins may be critical in the pathogenesis of LOAD. Methylenetetrahydrofolate reductase (MTHFR) gene mutations were studied in consecutive Alzheimer's Disease & Memory Clinic patients up to December 2014. DNA analyses of MTHFR-C667T and - A1298C homozygous and heterozygous polymorphisms in 93 consecutive elderly patients revealed high prevalence of MTHFR mutations (92.5%). Findings require confirmation in a larger series, but MTHFR mutations may become a LOAD marker, opening novel possibilities for prevention and treatment.

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

    PubMed

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

    2015-02-01

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

  9. Pregnancy-associated osteoporosis with a heterozygous deactivating LDL receptor-related protein 5 (LRP5) mutation and a homozygous methylenetetrahydrofolate reductase (MTHFR) polymorphism.

    PubMed

    Cook, Fiona J; Mumm, Steven; Whyte, Michael P; Wenkert, Deborah

    2014-04-01

    Pregnancy-associated osteoporosis (PAO) is a rare, idiopathic disorder that usually presents with vertebral compression fractures (VCFs) within 6 months of a first pregnancy and delivery. Spontaneous improvement is typical. There is no known genetic basis for PAO. A 26-year-old primagravida with a neonatal history of unilateral blindness attributable to hyperplastic primary vitreous sustained postpartum VCFs consistent with PAO. Her low bone mineral density (BMD) seemed to respond to vitamin D and calcium therapy, with no fractures after her next successful pregnancy. Investigation of subsequent fetal losses revealed homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated both with fetal loss and with osteoporosis (OP). Because her neonatal unilateral blindness and OP were suggestive of loss-of-function mutation(s) in the gene that encodes LDL receptor-related protein 5 (LRP5), LRP5 exon and splice site sequencing was also performed. This revealed a unique heterozygous 12-bp deletion in exon 21 (c.4454_4465del, p.1485_1488del SSSS) in the patient, her mother and sons, but not her father or brother. Her mother had a normal BMD, no history of fractures, PAO, ophthalmopathy, or fetal loss. Her two sons had no ophthalmopathy and no skeletal issues. Her osteoporotic father (with a family history of blindness) and brother had low BMDs first documented at ages ∼40 and 32 years, respectively. Serum biochemical and bone turnover studies were unremarkable in all subjects. We postulate that our patient's heterozygous LRP5 mutation together with her homozygous MTHFR polymorphism likely predisposed her to low peak BMD. However, OP did not cosegregate in her family with the LRP5 mutation, the homozygous MTHFR polymorphism, or even the combination of the two, implicating additional genetic or nongenetic factors in her PAO. Nevertheless, exploration for potential genetic contributions to PAO may explain part of the pathogenesis of this

  10. Variants in maternal COMT and MTHFR genes and risk of neural tube defects in offspring.

    PubMed

    Liu, Jufen; Zhang, Yali; Jin, Lei; Li, Guoxing; Wang, Linlin; Bao, Yanping; Fu, Yunting; Li, Zhiwen; Zhang, Le; Ye, Rongwei; Ren, Aiguo

    2015-04-01

    Methylenetetrahydrofolate reductase (MTHFR) C677T and catechol-O-Methyltransferase (COMT) G158A are associated with a risk of neural tube defects (NTDs) in offspring. This study examined the effect of a MTHFR × COMT interaction on the risk of NTDs in a Chinese population with a high prevalence of NTDs. A total of 576 fetuses or newborns with NTDs and 594 controls were genotyped for MTHFRrs1801133, MTHFRrs1801131, and COMTrs4680 and COMTrs737865. Information on maternal sociodemographic characteristics, reproductive history, and related behavior was collected through face-to-face interviews. Possible interactions between genetic variants of MTHFR and COMT were examined. MTHFR C677T homozygous TT was associated with an elevated risk of total NTDs (odds ratio [OR] = 1.37, 95 % confidence interval [CI] = 0.93-2.03) and of anencephaly (OR = 1.67, 95 % CI = 0.98-2.84) compared with the CC genotype. There was a COMT rs737865 CC × MTHFR rs1801133 TT interaction for total NTDs (OR = 3.02, 95 % CI = 1.00-9.14) and for anencephaly (OR = 3.39, 95 % CI = 0.94-12.18). No interaction was found between COMT rs4680 AA/AG and MTHFR CT/TT genotypes for total NTDs or any subtype of NTD. The interaction of COMT rs737865 and MTHFR C677T was associated with an increased risk of NTDs, especially anencephaly, in a Chinese population with a high prevalence of NTDs.

  11. Insights on the structural perturbations in human MTHFR Ala222Val mutant by protein modeling and molecular dynamics.

    PubMed

    Abhinand, P A; Shaikh, Faraz; Bhakat, Soumendranath; Radadiya, Ashish; Bhaskar, L V K S; Shah, Anamik; Ragunath, P K

    2016-01-01

    Methylenetetrahydrofolate reductase (MTHFR) protein catalyzes the only biochemical reaction which produces methyltetrahydrofolate, the active form of folic acid essential for several molecular functions. The Ala222Val polymorphism of human MTHFR encodes a thermolabile protein associated with increased risk of neural tube defects and cardiovascular disease. Experimental studies have shown that the mutation does not affect the kinetic properties of MTHFR, but inactivates the protein by increasing flavin adenine dinucleotide (FAD) loss. The lack of completely solved crystal structure of MTHFR is an impediment in understanding the structural perturbations caused by the Ala222Val mutation; computational modeling provides a suitable alternative. The three-dimensional structure of human MTHFR protein was obtained through homology modeling, by taking the MTHFR structures from Escherichia coli and Thermus thermophilus as templates. Subsequently, the modeled structure was docked with FAD using Glide, which revealed a very good binding affinity, authenticated by a Glide XP score of -10.3983 (kcal mol(-1)). The MTHFR was mutated by changing Alanine 222 to Valine. The wild-type MTHFR-FAD complex and the Ala222Val mutant MTHFR-FAD complex were subjected to molecular dynamics simulation over 50 ns period. The average difference in backbone root mean square deviation (RMSD) between wild and mutant variant was found to be ~.11 Å. The greater degree of fluctuations in the mutant protein translates to increased conformational stability as a result of mutation. The FAD-binding ability of the mutant MTHFR was also found to be significantly lowered as a result of decreased protein grip caused by increased conformational flexibility. The study provides insights into the Ala222Val mutation of human MTHFR that induces major conformational changes in the tertiary structure, causing a significant reduction in the FAD-binding affinity.

  12. Folate metabolism gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with ADHD in myelomeningocele patients.

    PubMed

    Spellicy, Catherine J; Northrup, Hope; Fletcher, Jack M; Cirino, Paul T; Dennis, Maureen; Morrison, Alanna C; Martinez, Carla A; Au, Kit Sing

    2012-01-01

    The objective of this study was to examine the relation between the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and behaviors related to attention- deficit/hyperactivity disorder (ADHD) in individuals with myelomeningocele. The rationale for the study was twofold: folate metabolizing genes, (e.g. MTHFR), are important not only in the etiology of neural tube defects but are also critical to cognitive function; and individuals with myelomeningocele have an elevated incidence of ADHD. Here, we tested 478 individuals with myelomeningocele for attention-deficit hyperactivity disorder behavior using the Swanson Nolan Achenbach Pelham-IV ADHD rating scale. Myelomeningocele participants in this group for whom DNAs were available were genotyped for seven single nucleotide polymorphisms (SNPs) in the MTHFR gene. The SNPs were evaluated for an association with manifestation of the ADHD phenotype in children with myelomeningocele. The data show that 28.7% of myelomeningocele participants exhibit rating scale elevations consistent with ADHD; of these 70.1% had scores consistent with the predominantly inattentive subtype. In addition, we also show a positive association between the SNP rs4846049 in the 3'-untranslated region of the MTHFR gene and the attention-deficit hyperactivity disorder phenotype in myelomeningocele participants. These results lend further support to the finding that behavior related to ADHD is more prevalent in patients with myelomeningocele than in the general population. These data also indicate the potential importance of the MTHFR gene in the etiology of the ADHD phenotype.

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

    PubMed

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

    2015-02-01

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

  14. Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis.

    PubMed

    Xiao, Wen-Lin; Wu, Min; Shi, Bing

    2006-11-01

    It's clear that environmental factors play a role in the aetiology of orofacial clefting (OFC) and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo. Periconceptional folic acid supplementation may reduce the risk of OFC. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methylenetetrahydrofolate, the predominant circulating form of folic acid. To determine the effect of MTHFR gene mutation on murine embryonic palatal mesenchymal (MEPM) cells and the interaction with folic acid supplement, we used RNAi study in the primary cultures of MEPM cells. The cells of MTHFR gene silencing grew slower and the apoptosis cell number was more than the cells of control. Supplement with 20 microg/ml folic acid was the best to preventing teratogenic effect of MTHFR gene silencing. By flow cytometry analysis of cell cycle, results were shown that the MEPM cells were retarded in G(0)/G(1) after MTHFR gene silencing. While using 20 microg/ml folic acid supplements could make cell transit the G(1)/S restriction point and the cells growth was close to normal level.

  15. C677T (RS1801133 ) MTHFR gene polymorphism frequency in a colombian population

    PubMed Central

    Gómez-Gutierrez, Alberto; Gómez, Piedad Elena; Casas-Gomez, Maria Consuelo; Briceño, Ignacio

    2015-01-01

    Introduction: Abnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy. Objective: To establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals. Methods: Data from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics®). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed. Results: Microarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001). Conclusions: Results for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies. PMID:26309343

  16. Variants in MTHFR gene and neural tube defects susceptibility in China.

    PubMed

    Wang, Yongxin; Liu, Yuan; Ji, Wenyu; Qin, Hu; Wu, Hao; Xu, Danshu; Turtuohut, Tukebai; Wang, Zengliang

    2015-08-01

    Neural tube defect (NTD) is a severe congenital birth abnormalities involving incomplete neural tube closure. 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene plays key role in folate cycle and methylation cycle, which could affect the DNA synthesis, repair and methylation. In this study, we aim to investigate the correlation between MTHFR polymorphisms and NTD-affected pregnancy. There were 444 participants involved in our study. Tag-SNPs were identified in HapMap Databases. Blood samples were collected from all subjects to further extract the genomic DNAs by TaqMan Blood DNA kits. We also carried out a meta-analysis based on previous published studies to further examine the association between MTHFR polymorphisms and NTD. In case-control study analysis, two SNPs were identified to be associated with NTD risk. The 677 C > T genetic variant was correlated with increased risk of NTD-affected pregnancy. However, the 1298 A > C polymorphism was shown to lower the risk of NTD-affected pregnancy. The protective role of 1298 A > C polymorphisms was further supported by the result of meta-analysis. Our study revealed that the SNPs of 677C > T and 1298A > C in MTHFR were associated with NTD-affected pregnancy, in which 677C > T was a risk factor and in contrast 1298A > C was protective factor against NTD. Our results of meta-analysis also revealed the 1298A > C MTHFR polymorphism play protective role in NTD.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Evaluation of High Resolution Melting for MTHFR C677T Genotyping in Congenital Heart Disease

    PubMed Central

    Yue, Shuying; Zhang, Kun; Wang, Hui; Dong, Rui; Yang, Xiaomeng; Liu, Yi; Ma, Yanhui

    2016-01-01

    Background High resolution melting (HRM) is a simple, flexible and low-cost mutation screening technique. The methylenetetrahydrofolate reductase (MTHFR) gene encoding a critical enzyme, potentially affects susceptibility to some congenital defects like congenital heart disease (CHD). We evaluate the performance of HRM for genotyping of the MTHFR gene C677T locus in CHD cases and healthy controls of Chinese Han population. Methods A total of 315 blood samples from 147 CHD patients (male72, female 75) and 168 healthy controls (male 92, female 76) were enrolled in the study. HRM was utilized to genotype MTHFR C677T locus of all the samples. The results were compared to that of PCR-RFLP and Sanger sequencing. The association of the MTHFR C677T genotypes and the risk of CHD was analyzed using odds ratio with their 95% confidence interval (CIs) from unconditional logistic regression. Results All the samples were successfully genotyped by HRM within 1 hour and 30 minutes while at least 6 hours were needed for PCR-RFLP and sequencing. The genotypes of MTHFR C677T CC, CT, and TT were 9.52%, 49.66%, and 40.82% in CHD group but 29.17%, 50% and 20.83% in control group, which were identical using both methods of HRM and PCR-RFLP, demonstrating the sensitivity and specificity of HRM were all 100%. Conclusion MTHFR C677T is a potential risk factor for CHD in our local residents of Shandong province in China. HRM is a fast, sensitive, specific and reliable method for clinical application of genotyping. PMID:26990189

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

    PubMed

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

    2015-04-27

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

  20. Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice

    PubMed Central

    Cui, Xuezhi; Navneet, Soumya; Wang, Jing; Roon, Penny; Chen, Wei; Xian, Ming; Smith, Sylvia B.

    2017-01-01

    Purpose Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/−]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/−]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also. Methods Retinas isolated from wild-type (WT), Mthfr+/−, and Cbs+/− mice (12 and 22 weeks) were analyzed for methylene tetrahydrofolate reductase (MTHFR), cystathionine-β-synthase (CBS), and cystathionase (CTH) RNA/protein levels. Retinas were evaluated for levels of reduced:oxidized GSH (GSH:GSSG), Slc7a11 (xCT), taurine, taurine transporter (TAUT), and H2S. Results Aside from decreased CBS RNA/protein levels in Cbs+/− retinas, there were minimal alterations in remethylation/transsulfuration pathways in the two mutant mice strains. Glutathione and taurine levels in Mthfr+/− and Cbs+/− retinas were similar to WT, which may be due to robust levels of xCT and TAUT in mutant retinas. Interestingly, levels of H2S were markedly increased in retinas of Mthfr+/− and Cbs+/− mice compared with WT. Conclusions Ganglion cell loss and vasculopathy observed in Mthfr+/− and Cbs+/− mouse retinas may be milder than expected, not because of compensatory increases of enzymes in remethylation/transsulfuration pathways, but because downstream transsulfuration pathway products GSH, taurine, and H2S are maintained at robust levels. Elevation of H2S is particularly intriguing owing to neuroprotective properties reported for this gasotransmitter. PMID:28384716

  1. Increased risk of the abdominal aortic aneurysm in carriers of the MTHFR 677T allele.

    PubMed

    Strauss, Ewa; Waliszewski, Krzysztof; Gabriel, Marcin; Zapalski, Stanisław; Pawlak, Andrzej L

    2003-01-01

    Abdominal aortic aneurysm (AAA) presents itself as a progressive dilation of the abdominal aorta, leading--if untreated--to rupture. It is a common disease of the elderly, with a complex etiology. Several genetic, biochemical and environmental factors are recognized as relevant for the pathogenesis of AAA. We determined the polymorphism of the MTHFR (methylenetetrahydrofolate reductase) gene within the fourth exon (C677T) in 63 patients with AAA and compared it to that in 75 subjects of the population sample. The frequencies of the C/C, C/T and T/T genotypes were 65%, 27%, and 8% in the population sample and 33%, 60%, and 6% in the patients. This corresponds to a 4.4-fold greater risk of AAA in subjects who have the 677C/T variant of MTHFR, as compared with those who are 677C/C (p < 0.0001; 95% CI=2.11-9.34). The frequency of allele MTHFR 677T in patients (0.37) was higher than in the population sample (0.21; p < 0.007). This association between the common allele of the MTHFR gene--MTHFR 677T--and the development of AAA suggests that elevated homocysteine (Hcy) may disturb the function of the aortic wall. The disturbance may involve enhancement of elastin degradation, the process enhanced by mild hyperhomocysteinemia in minipigs. The magnitude of this effect, which refers to the AAA patients unselected for familial occurrence, indicates that the disturbance of aortic wall physiology caused by the presence of the MTHFR 677T allele is greater than the effect of the earlier described allele disequilibrium at the polymorphic alleles of the PAI1 (plasminogen activator inhibitor 1) gene seen only in familial cases of AAA.

  2. Renal cell carcinoma risk is associated with the interactions of APOE, VHL and MTHFR gene polymorphisms

    PubMed Central

    Lv, Cai; Bai, Zhiming; Liu, Zhenxiang; Luo, Pengcheng; Zhang, Jie

    2015-01-01

    Objective: The study was designed to explore the association of renal cell carcinoma (RCC) with VHL (rs779805), MTHFR (rs1801133) and APOE (rs8106822 and rs405509) polymorphisms, investigate the interactions among the single nucleotide polymorphisms (SNPs), and explore roles of the interactions in the pathogenesis of RCC in Chinese Han population. Methods: 81 RCC patients and 80 healthy controls were included in the study. Polymerase chain reaction (PCR) and direct sequencing methods were used in the analysis on the genotypes of APOE, VHL and MTHFR gene polymorphisms. Multifactor dimensionality reduction (MDR) method was adopted to conduct gene-gene interaction analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to evaluate the correlation between gene-gene interactions and RCC risk. Results: Significant correlations were found between RCC risk and 3 SNPs (rs8106822, rs779805 and rs1801133). Genotype AA and allele A of APOE rs8106822 were significantly associated with RCC susceptibility (OR=2.65, 95% CI=1.05-6.69). Meanwhile, we found that the frequencies of genotype GG and allele G were much higher in case group, compared with controls (P<0.05 for both) and they appeared to be risk factors for RCC (OR=2.90, 95% CI=1.22-6.87; OR=1.78, 95% CI=1.14-2.27). While, allele T of MTHFR rs1801133 could decrease the risk of RCC (OR=0.62, 95% CI=0.40-0.97). MDR analysis showed that gene-gene interactions among APOE, VHL and MTHFR SNPs were closely related with RCC susceptibility. Conclusion: APOE, VHL and MTHFR gene polymorphisms were related to the risk of RCC. The interactions among APOE, VHL and MTHFR genes could increase the risk of RCC. PMID:26191297

  3. Meta-Prediction of MTHFR Gene Polymorphism Mutations and Associated Risk for Colorectal Cancer

    PubMed Central

    Yu, C. H.

    2016-01-01

    The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most investigated of the genes associated with chronic human diseases because of its associations with hyperhomocysteinemia and toxicity. It has been proposed as a prototype gene for the prevention of colorectal cancer (CRC). The major objectives of this meta-analysis were to examine the polymorphism-mutation patterns of MTHFR and their associations with risk for CRC as well as potential contributing factors for mutations and disease risks. This analysis included 33,626 CRC cases and 48,688 controls across 92 studies for MTHFR 677 and 16,367 cases and 24,874 controls across 54 studies for MTHFR 1298, comprising data for various racial and ethnic groups, both genders, and multiple cancer sites. MTHFR 677 homozygous TT genotype was protective (p < .05) for CRC for all included populations; however, with heterogeneity across various racial–ethnic groups and opposing findings, it was a risk genotype for the subgroup of Hispanics (p < .01). Additional countries for which subgroup analyses resulted in 677 TT as a risk genotype included Turkey, Romania, Croatia, Hungary, Portugal, Mexico, Brazil, U.S. Hawai’i, Taiwan, India, and Egypt. Countries with the highest mutation rates and risks for both MTHFR 677 and 1298 genotypes are presented using global maps to visualize the grouping patterns. Meta-predictive analyses revealed that air pollution levels were associated with gene polymorphisms for both genotypes. Future nursing research should be conducted to develop proactive measures to protect populations in cities where air pollution causes more deaths. PMID:26858257

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

    PubMed

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

    2014-10-31

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

  5. Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population

    PubMed Central

    Yakub, Mohsin; Moti, Naushad; Parveen, Siddiqa; Chaudhry, Bushra; Azam, Iqbal; Iqbal, Mohammad Perwaiz

    2012-01-01

    Background Hyperhomocysteinemia (>15 µmol/L) is highly prevalent in South Asian populations including Pakistan. In order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes - methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-β-synthase (CBS; T833C/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with nutritional and environmental factors in a Pakistani population. Methodology/Principal Findings In a cross-sectional survey, 872 healthy adults (355 males and 517 females; age 18–60 years) were recruited from a low-income urban population in Karachi. Fasting venous blood was obtained and assessed for plasma/serum homocysteine; folate, vitamin B12, pyridoxal phosphate and blood lead. DNA was isolated and genotyping was performed by PCR-RFLP (restriction-fragment-length- polymorphism) based assays. The average changes in homocysteine levels for MTHFR 677CT and TT genotypes were positive [β(SE β), 2.01(0.63) and 16.19(1.8) µmol/L, respectively]. Contrary to MTHFR C677T polymorphism, the average changes in plasma homocysteine levels for MS 2756AG and GG variants were negative [β(SE β), −0.56(0.58) and −0.83(0.99) µmol/L, respectively]. The average change occurring for CBS 844ins68 heterozygous genotype (ancestral/insertion) was −1.88(0.81) µmol/L. The combined effect of MTHFR C677T, MS A2756G and CBS 844ins68 genotypes for plasma homocysteine levels was additive (p value <0.001). Odds of having hyperhomocysteinemia with MTHFR 677TT genotype was 10-fold compared to MTHFR 677CC genotype [OR (95%CI); 10.17(3.6–28.67)]. Protective effect towards hyperhomocysteinemia was observed with heterozygous (ancestral/insertion) genotype of CBS 844ins68 compared to homozygous ancestral type [OR (95% CI); 0.58 (0.34–0.99)]. Individuals with MTHFR 677CT or TT genotypes were at a greater risk of hyperhomocysteinemia in

  6. A founder mutation causing a severe methylenetetrahydrofolate reductase (MTHFR) deficiency in Bukharian Jews.

    PubMed

    Ben-Shachar, Shay; Zvi, Tal; Rolfs, Arndt; Breda Klobus, Andrea; Yaron, Yuval; Bar-Shira, Anat; Orr-Urtreger, Avi

    2012-11-01

    Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. A novel homozygous MTHFR c.474A>T (p.G158G) mutation was detected in two unrelated children of Jewish Bukharian origin. This mutation generates an abnormal splicing and early termination codon. A carrier frequency of 1:39 (5/196) was determined among unrelated healthy Bukharian Jews. Given the disease severity and allele frequency, a population screening for individuals of this ancestry is warranted in order to allow prenatal, or preimplantation diagnosis.

  7. A study on the correlation between MTHFR promoter methylation and diabetic nephropathy

    PubMed Central

    Yang, Xiao-Hui; Cao, Ren-Fang; Yu, Yang; Sui, Miao; Zhang, Tao; Xu, Jing-Yi; Wang, Xiao-Mei

    2016-01-01

    Objective: In order to observe the relationship between MTHFR promoter and DN, the determinations on MTHFR promoter methylation level and expression of HCY from DN patients have been carried out. Methods: According to the Diabetes diagnosis and classification standard from WHO in 1999, 85 patients with DM diagnosed by Endocrinology and 30 healthy participants from our medical examination center were chosen as control specimen to study in this paper. All this specimen were divided into A, B, C and D four groups , which are corresponding simple diabetes mellitus group (SDM), early diabetic nephropathy group (EDN), clinical diabetic nephropathy group (CDN) and normal control group. And then, all common materials and clinical experiments data have been collected respectively. (1) Extracted the peripheral blood DNA of each group and determinate the methylation status of MTHFR gene promoter by PCR (MSP). (2) Determinated the serum HCY protein expression of each group. Results: (1) The MTHFR promoter methylation of SDM and diabetic nephropathy group are wear off comparied with normal control group. And MTHFR promoter was in demethylation state in normal control group, a slightly weak in SDN, a obviously weak in early diabetic nephropathy group; the MTHFR promoter was in methylation state in clinical diabetic nephropathy group. (2) The HCY protein of simple diabetes mellitus group, early diabetic nephropathy group and clinical diabetic nephropathy group are Pitch with normal control group. HCY protein level of each group are as 7.41±1.61 umol/L, 10.34±2.89 umol/L, 10.95±5.89 umol/L and 13.03±6.14 umol/L corresponding normal control group, simple diabetes mellitus group, early diabetic nephropathy group and clinical diabetic nephropathy group. And there is no statistical significance about the differences among four groups. Conclusion: The demethylation state of MTHFR promoter was obviously weaker in clinical diabetic nephropathy group than in SDM. The level of serum

  8. Isolated renal vein thrombosis associated with MTHFR-1298 and PAI-1 4G gene mutations.

    PubMed

    Cinemre, Hakan; Bilir, Cemil; Akdemir, Nermin

    2010-12-01

    Isolated renal vein thrombosis is very rare without the presence of nephrotic syndrome. It is more common in the newborns and infants. Whereas major risk factors in adults are the procoagulant states such as protein C or S deficiency, factor V Leiden mutation, primary or secondary antiphospholipid syndrome, severe hypothyroidism, and trauma. Here, we report a case of isolated renal vein thrombosis associated with MTHFR-1298 and PAI-1 4G gene mutations. It should be noted that the presence of MTHFR-1298 and PAI-1 4G gene mutations together might be one of the examples of genetic mutation combinations that increase the likelihood of a thrombotic event.

  9. Risk of colorectal cancer associated with the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in the Kashmiri population.

    PubMed

    Sameer, A S; Shah, Z A; Nissar, S; Mudassar, S; Siddiqi, M A

    2011-06-21

    Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C→T and 1298 A→C, have been shown to impact various diseases, including cancer. The 677 C→T polymorphism has been widely investigated in different cancers and has been implicated as a risk factor for the development of various cancers. We investigated MTHFR C677T genotype frequency in colorectal cancer cases in the Kashmiri population and correlated this information with the known clinicopathological characters of colorectal cancer, in a case-control study. Eighty-six colorectal cancer cases were studied for MTHFR C677T polymorphism, compared to 160 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of MTHFR in our ethnic Kashmir population, i.e., CC, CT and TT, to be 68.6, 20.9 and 10.4% among colorectal cancer cases and 75.6, 16.9 and 7.5% among the general control population, respectively. There was a significant association between the MTHFR TT genotype and colorectal cancer in the higher age group. We conclude that the MTHFR C677T polymorphism slightly increases the risk for colorectal cancer development in our ethnic Kashmir population.

  10. The association of the MTHFR C677T polymorphism with inflammatory bowel diseases in the Israeli Jewish population

    PubMed Central

    Karban, Amir; Feldman, Tzah; Waterman, Matti; Leiba, Ronit; Efrati, Edna

    2016-01-01

    Abstract MTHFR C677T is a common gene polymorphism that has been shown to be associated with hyperhomocysteinemia. Studies on the role of MTHFR in inflammatory bowel diseases (IBD) have yielded conflicting results, perhaps due in part to genetic heterogeneity. The prevalence of the MTHFR C677T variant allele varies according to Jewish subpopulations: Ashkenazi vs non-Ashkenazi. The aim of this study was to examine the association between MTHFR C677T genotype and IBD in the different Jewish populations. DNA samples were assessed for the presence of the MTHFR C677T variant allele in 445 Jewish Israeli IBD patients: 338 with Crohn's disease [CD] (214 Ashkenazi and 124 non-Ashkenazi Jews) and 107 with ulcerative colitis [UC] (73 Ashkenazi and 34 non-Ashkenazi Jews), and in 347 healthy controls: 173 Ashkenazi and 174 Non-Ashkenazi Jews. Possible genotype–phenotype associations were investigated. We showed a significantly higher frequency of MTHFR 677T variant genotypes in non-Ashkenazi CD patients: Odds ratio of 1.86 for heterozygotes (CT) and 2.89 for homozygotes (TT) compared to non-Ashkenazi healthy controls. No significant association was found for UC in non-Ashkenazi patients or for CD or UC in Ashkenazi patients. Our findings suggest that the MTHFR 677T variant may contribute to the risk of CD in non-Ashkenazi but not Ashkenazi Jews. This may result from genetic heterogeneity and highlights the complexity of the genetic etiology of IBD. PMID:28002332

  11. Association of MTHFR C677T polymorphism with loneliness but not depression in cognitively normal elderly males.

    PubMed

    Lan, Wen-Hsuan; Yang, Albert C; Hwang, Jen-Ping; Hong, Chen-Jee; Liou, Ying-Jay; Yeh, Heng-Liang; Liu, Mu-En; Tsai, Shih-Jen

    2012-07-11

    Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is involved in folate and homocysteine metabolism, and has been associated with geriatric disorders, including dementia and late-life depression. The present work aimed to investigate the effect of MTHFR C677T polymorphism on the presence of depression and loneliness in cognitively normal male subjects. A total of 323 cognitively normal male subjects were included in this study (mean age=80.6; SD=5.3). Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Analysis of variance (ANOVA) was used to test the between MTHFR genotype difference in depression and loneliness. Multiple regression was used to test the effect of MTHFR polymorphism on the loneliness, controlling for age, education, cognitive function, and depression. ANOVA showed a significant between-genotype difference in loneliness scores (P=0.015), and post hoc comparisons showed that subjects with C/C genotype had significantly higher loneliness ratings, compared to those with C/T or T/T genotype. Regression analysis indicated that the effect of MTHFR polymorphism on loneliness was independent of age, education, cognitive function, and depression. Our findings suggest that MTHFR C677T polymorphism may be linked more to loneliness than depression in the cognitively normal elderly males, and may be implicated in the pathophysiology of late-life depression in relation to MTHFR genes.

  12. Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency.

    PubMed

    Li, Wen-Xing; Dai, Shao-Xing; Zheng, Jun-Juan; Liu, Jia-Qian; Huang, Jing-Fei

    2015-08-10

    Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28-75 were enrolled in this study from September 2005-December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk.

  13. Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency

    PubMed Central

    Li, Wen-Xing; Dai, Shao-Xing; Zheng, Jun-Juan; Liu, Jia-Qian; Huang, Jing-Fei

    2015-01-01

    Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28–75 were enrolled in this study from September 2005–December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk. PMID:26266420

  14. Population- and Family-Based Studies Associate the "MTHFR" Gene with Idiopathic Autism in Simplex Families

    ERIC Educational Resources Information Center

    Liu, Xudong; Solehdin, Fatima; Cohen, Ira L.; Gonzalez, Maripaz G.; Jenkins, Edmund C.; Lewis, M. E. Suzanne; Holden, Jeanette J. A.

    2011-01-01

    Two methylenetetrahydrofolate reductase gene ("MTHFR") functional polymorphisms were studied in 205 North American simplex (SPX) and 307 multiplex (MPX) families having one or more children with an autism spectrum disorder. Case-control comparisons revealed a significantly higher frequency of the low-activity 677T allele, higher prevalence of the…

  15. Thrombosis Related ABO, F5, MTHFR, and FGG Gene Polymorphisms in Morbidly Obese Patients

    PubMed Central

    Kupcinskiene, Kristina; Murnikovaite, Martyna; Varkalaite, Greta; Juzenas, Simonas; Trepenaitis, Darius; Petereit, Ruta; Maleckas, Almantas

    2016-01-01

    Objective. Obesity is a well-known risk factor for thrombotic complications. The aim of the present study was to determine the frequency of thrombosis related ABO, F5, MTHFR, and FGG gene polymorphisms in morbidly obese patients and compare them with the group of nonobese individuals. Methods. Gene polymorphisms were analyzed in 320 morbidly obese patients (BMI > 40 kg/m2) and 303 control individuals (BMI < 30 kg/m2) of European descent. ABO C>T (rs505922), F5 C>G (rs6427196), MTHFR C>T (rs1801133), and FGG C>T (rs6536024) SNPs were genotyped by RT-PCR. Results. We observed a tendency for MTHFR rs1801133 TT genotype to be linked with morbid obesity when compared to CC genotype; however, the difference did not reach the significant P value (OR 1.84, 95% CI 0.83–4.05, P = 0.129). Overall, the genotypes and alleles of rs505922, rs6427196, rs1801133, and rs6536024 SNPs had similar distribution between morbidly obese and nonobese control individuals. Distribution of height and weight means among individuals carrying different rs505922, rs6427196, rs1801133, and rs6536024 genotypes did not differ significantly. Conclusions. Gene polymorphisms ABO C>T (rs505922), F5 C>G (rs6427196), MTHFR C>T (rs1801133), and FGG C>T (rs6536024) were not associated with height, weight, or morbid obesity among European subjects. PMID:27999448

  16. Dietary consumption of B vitamins, maternal MTHFR polymorphisms and risk for spontaneous abortion

    PubMed Central

    Rodríguez-Guillén, María del Rosario; Torres-Sánchez, Luisa; Chen, Jia; Galván-Portillo, Marcia; Silva-Zolezzi, Irma; Blanco-Muñoz, Julia; Hernández-Valero, María A.; López-Carrillo, Lizbeth

    2010-01-01

    Objective To asses he association between intake of folate and B vitamins and the incidence of spontaneous abortion (SA) according to the maternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms (677 C>T and 1298 A>C). Material and Methods We conducted a nested case-control study within a perinatal cohort of women recruited in the state of Morelos, Mexico. Twenty-three women with SA were compared to 74 women whose pregnancy survived beyond week 20th. Intake of folate and B vitamins respectively, was estimated using a validated food frequency questionnaire. Maternal MTHFR polymorphisms were determined by PCR-RFLP and serum homocysteine levels by HPLC. Results Carriers of MTHFR 677TT and 1298AC genotypes respectively showed an increased risk of SA (OR 677TT vs. CC/CT=5.0; 95% CI: 1.2, 20.9 and OR 1298 AC vs. AA=5.5; 95% CI: 1.1, 26.6). Conclusions Our results support the role of MTHFR polymorphisms as a risk factor for SA, regardless of dietary intake of B vitamins. PMID:19180309

  17. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.

    PubMed

    Yasar, Ali; Gunduz, Kamer; Onur, Ece; Calkan, Mehmet

    2012-01-01

    The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.

  18. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases.

    PubMed

    Liew, Siaw-Cheok; Gupta, Esha Das

    2015-01-01

    The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with various diseases (vascular, cancers, neurology, diabetes, psoriasis, etc) with the epidemiology of the polymorphism of the C677T that varies dependent on the geography and ethnicity. The 5,10-Methylenetetrahydrofolate reductase (MTHFR) locus is mapped on chromosome 1 at the end of the short arm (1p36.6). This enzyme is important for the folate metabolism which is an integral process for cell metabolism in the DNA, RNA and protein methylation. The mutation of the MTHFR gene which causes the C677T polymorphism is located at exon 4 which results in the conversion of valine to alanine at codon 222, a common polymorphism that reduces the activity of this enzyme. The homozygous mutated subjects have higher homocysteine levels while the heterozygous mutated subjects have mildly raised homocysteine levels compared with the normal, non-mutated controls. Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education. This literature review therefore focuses on the recent evidence-based reports on the associations of the MTHFR C677T polymorphism and the various diseases globally.

  19. Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Alzheimer Disease Risk: a Meta-Analysis.

    PubMed

    Rai, Vandana

    2017-03-01

    Methylenetetrahydrofolate reductase (MTHFR) is key enzyme of folate/homocysteine pathway. Case control association studies on MTHFR C677T polymorphism and Alzheimer's disease (AD) have been repeatedly performed over the last two decades, but the results are inconclusive. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for AD. Forty-one studies were identified by a search of PubMed, Google Scholar, Elsevier, and Springer Link databases, up to January 2015. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effect model or random effect model. The subgroup analyses based on ethnicity were performed. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C OR = 1.29, 95 % CI = 1.07-1.56, p = 0.003; for TT + CT vs CC OR = 1.29, 95 % CI = 1.19-1.40, p = 0.0004; for TT vs CC OR = 1.31, 95 % CI = 1.16-1.48, p = 0.001; for CT vs CC OR = 1.24, 95 % CI = 1.13-1.35, p < 0.004; and for TT vs CT + CC OR = 1.13, 95 % CI = 1.00-1.28, p = 0.02). Results of present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD.

  20. Gene-specific DNA methylation of DNMT3B and MTHFR and colorectal adenoma risk.

    PubMed

    Ho, Vikki; Ashbury, Janet E; Taylor, Sherryl; Vanner, Stephen; King, Will D

    2015-12-01

    DNA methyltransferase 3B (DNMT3B) and methylenetetrahydrofolate reductase (MTHFR) are genes which encode enzymes critical to one-carbon metabolism. Polymorphisms in these genes have been implicated in colorectal cancer etiology; however, epigenetic modifications such as gene-specific DNA methylation also affect gene expression. DNA methylation of DNMT3B and MTHFR was quantified in blood leukocytes using Sequenom EpiTYPER® among 272 participants undergoing a screening colonoscopy. DNA methylation was quantified in 66 and 28CpG sites of DNMT3B and MTHFR respectively, and conceptualized using two approaches. First, measures representing average methylation across all CpG sites were created. Second, unsupervised principal component (PC) analysis was used to identify summary variables representing methylation around the transcription start site and in the gene-coding area for both DNMT3B and MTHFR. Logistic regression was used to compare methylation levels between participants diagnosed with colorectal adenoma(s) versus those with a normal colonoscopy via the estimation of odds ratios (ORs) and 95% confidence intervals (95% CIs) for the risk of colorectal adenomas. No association was observed between average DNA methylation of either DNMT3B or MTHFR and colorectal adenoma risk. For DNMT3B, increasing DNA methylation of CpG sites in the gene-coding area was associated with a higher risk of colorectal adenomas (OR=1.34; 95% CI: 1.01-1.79 per SD). This research provides preliminary evidence that methylation of DNMT3B may have functional significance with respect to colorectal adenomas, precursors to the vast majority of colorectal cancers.

  1. Effect of MTHFR polymorphisms on hyperhomocysteinemia in levodopa-treated Parkinsonian patients.

    PubMed

    Caccamo, D; Gorgone, G; Currò, M; Parisi, G; Di Iorio, W; Menichetti, C; Belcastro, V; Parnetti, L; Rossi, A; Pisani, F; Ientile, R; Calabresi, P

    2007-01-01

    High plasma homocysteine levels have been observed in Parkinson's disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with L-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 L-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 +/- 5.7 vs. 11.7 +/- 2.7 micromol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0-5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 +/- 4.9 micromol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 +/- 1.6 micromol/l; OR = 0.19, CI = 0.06-0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 +/- 3.6 micromol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.

  2. Epistasis between COMT and MTHFR in maternal-fetal dyads increases risk for preeclampsia.

    PubMed

    Hill, Lori D; York, Timothy P; Kusanovic, Juan P; Gomez, Ricardo; Eaves, Lindon J; Romero, Roberto; Strauss, Jerome F

    2011-01-31

    Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1α, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C → T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor "T" allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia

  3. The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency

    PubMed Central

    Spellicy, Catherine J.; Kosten, Thomas R.; Hamon, Sara C.; Harding, Mark J.; Nielsen, David A.

    2013-01-01

    Objective: Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Methods: Sixty-seven cocaine-dependent patients were stabilized on methadone for 2 weeks and then randomized into disulfiram (250 mg/day, N = 32) and placebo groups (N = 35) for 10 weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10 weeks of the study (N = 56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. Results: The CT or TT MTHFR genotype group (N = 32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p = 0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N = 24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81–69% (p = 0.007). Conclusion: This study indicates that a patient’s MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence. Clinical Trial: Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630. PMID:23335901

  4. Using GenBank.

    PubMed

    Sayers, Eric W; Karsch-Mizrachi, Ilene

    2016-01-01

    GenBank(®) is a comprehensive database of publicly available DNA sequences for 300,000 named organisms, more than 110,000 within the embryophyta, obtained through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Daily data exchange with the European Nucleotide Archive (ENA) in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system that integrates data from the major DNA and protein sequence databases with taxonomy, genome, mapping, protein structure and domain information, as well as the biomedical journal literature in PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. GenBank usage scenarios ranging from local analyses of the data available via FTP to online analyses supported by the NCBI web-based tools are discussed. To access GenBank and its related retrieval and analysis services, go to the NCBI home page at www.ncbi.nlm.nih.gov .

  5. GenBank

    PubMed Central

    Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.

    2016-01-01

    GenBank® (www.ncbi.nlm.nih.gov/genbank/) is a comprehensive database that contains publicly available nucleotide sequences for over 340 000 formally described species. Recent developments include a new starting page for submitters, a shift toward using accession.version identifiers rather than GI numbers, a wizard for submitting 16S rRNA sequences, and an Identical Protein Report to address growing issues of data redundancy. GenBank organizes the sequence data received from individual laboratories and large-scale sequencing projects into 18 divisions, and GenBank staff assign unique accession.version identifiers upon data receipt. Most submitters use the web-based BankIt or standalone Sequin programs. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the nuccore, nucest, and nucgss databases of the Entrez retrieval system, which integrates these records with a variety of other data including taxonomy nodes, genomes, protein structures, and biomedical journal literature in PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. PMID:26590407

  6. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2008-01-01

    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 260 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.

  7. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Sayers, Eric W

    2011-01-01

    GenBank® is a comprehensive database that contains publicly available nucleotide sequences for more than 380,000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system that integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.

  8. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Sayers, Eric W

    2010-01-01

    GenBank is a comprehensive database that contains publicly available nucleotide sequences for more than 300,000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bi-monthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI homepage: www.ncbi.nlm.nih.gov.

  9. Using GenBank.

    PubMed

    Wheeler, David

    2007-01-01

    GenBank(R) is a comprehensive database of publicly available DNA sequences for more than 205,000 named organisms and for more than 60,000 within the embryophyta, obtained through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Daily data exchange with the European Molecular Biology Laboratory (EMBL) in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases with taxonomy, genome, mapping, protein structure, and domain information and the biomedical journal literature through PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available through FTP. GenBank usage scenarios ranging from local analyses of the data available through FTP to online analyses supported by the NCBI Web-based tools are discussed. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov.

  10. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2007-01-01

    GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 240 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage (www.ncbi.nlm.nih.gov).

  11. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2006-01-01

    GenBank (R) is a comprehensive database that contains publicly available DNA sequences for more than 205 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the Web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at www.ncbi.nlm.nih.gov.

  12. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Sayers, Eric W

    2009-01-01

    GenBank is a comprehensive database that contains publicly available nucleotide sequences for more than 300,000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank(R) staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the National Center for Biotechnology Information (NCBI) Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov.

  13. GenBank.

    PubMed

    Benson, Dennis A; Karsch-Mizrachi, Ilene; Lipman, David J; Ostell, James; Wheeler, David L

    2005-01-01

    GenBank is a comprehensive database that contains publicly available DNA sequences for more than 165,000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan helps to ensure worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov.

  14. Regulation of Folate-Mediated One-Carbon Metabolism by Glycine N-Methyltransferase (GNMT) and Methylenetetrahydrofolate Reductase (MTHFR).

    PubMed

    Wang, Yi-Cheng; Wu, Ming-Tsung; Lin, Yan-Jun; Tang, Feng-Yao; Ko, Hsin-An; Chiang, En-Pei

    2015-01-01

    Folate-mediated one-carbon metabolism is an important therapeutic target of human diseases. We extensively investigated how gene-nutrient interactions may modulate human cancer risk in 2 major folate metabolic genes, MTHFR and GNMT. The biochemical impacts of MTHFR and GNMT on methyl group supply, global DNA methylation, nucleotide biosynthesis, DNA damage, and partitioning of the folate dependent 1-carbon group were carefully studied. The distinct model systems used included: EB virus-transformed lymphoblasts expressing human MTHFR polymorphic genotypes; liver-derived GNMT-null cell-lines with and without GNMT overexpression; and HepG2 cells with stabilized inhibition of MTHFR using shRNA, GNMT wildtype, heterozygotous (GNMT(het)) and knockout (GNMT(nul)) mice. We discovered that the MTHFR TT genotype significantly reduces folate-dependent remethylation under folate restriction, but it assists purine synthesis when folate is adequate. The advantage of de novo purine synthesis found in the MTHFR TT genotype may account for the protective effect of MTHFR in human hematological malignancies. GNMT affects transmethylation kinetics and S-adenosylmethionine (adoMet) synthesis, and facilitates the conservation of methyl groups by limiting homocysteine remethylation fluxes. Restoring GNMT assists methylfolate-dependent reactions and ameliorates the consequences of folate depletion. GNMT expression in vivo improves folate retention and bioavailability in the liver. Loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. The systematic series of studies gives new insights into the underlying mechanisms by which MTHFR and GNMT may participate in human tumor prevention.

  15. Gender-Specific Effect of Mthfr Genotype and Neonatal Vigabatrin Interaction on Synaptic Proteins in Mouse Cortex

    PubMed Central

    Blumkin, Elinor; Levav-Rabkin, Tamar; Melamed, Osnat; Galron, Dalia; Golan, Hava M

    2011-01-01

    The enzyme methylenetetrahydrofolate reductase (MTHFR) is a part of the homocysteine and folate metabolic pathways, affecting the methylations of DNA, RNA, and proteins. Mthfr deficiency was reported as a risk factor for neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. Neonatal disruption of the GABAergic system is also associated with behavioral outcomes. The interaction between the epigenetic influence of Mthfr deficiency and neonatal exposure to the GABA potentiating drug vigabatrin (GVG) in mice has been shown to have gender-dependent effects on mice anxiety and to have memory impairment effects in a gender-independent manner. Here we show that Mthfr deficiency interacts with neonatal GABA potentiation to alter social behavior in female, but not male, mice. This impairment was associated with a gender-dependent enhancement of proteins implicated in excitatory synapse plasticity in the female cortex. Reelin and fragile X mental retardation 1 protein (FMRP) levels and membrane GluR1/GluR2 ratios were elevated in wild-type mice treated neonatally with GVG and in Mthfr+/− mice treated with saline, but not in Mthfr+/− mice treated with GVG, compared with control groups (wild type treated with saline). A minor influence on the levels of these proteins was observed in male mice cortices, possibly due to high basal protein levels. Interaction between gender, genotype, and treatment was also observed in the GABA pathway. In female mice, GABA Aα2/gephyrin ratios were suppressed in all test groups; in male mice, a genotype-specific enhancement of GABA Aα2/gephyrin was observed. The lack of an effect on either reln or Fmr1 transcription suggests post-transcriptional regulation of these genes. Taken together, these findings suggest that Mthfr deficiency may interact with neonatal GABA potentiation in a gender-dependent manner to interrupt synaptic function. This may illustrate a possible mechanism for the epigenetic involvement of Mthfr

  16. Gender-specific effect of Mthfr genotype and neonatal vigabatrin interaction on synaptic proteins in mouse cortex.

    PubMed

    Blumkin, Elinor; Levav-Rabkin, Tamar; Melamed, Osnat; Galron, Dalia; Golan, Hava M

    2011-07-01

    The enzyme methylenetetrahydrofolate reductase (MTHFR) is a part of the homocysteine and folate metabolic pathways, affecting the methylations of DNA, RNA, and proteins. Mthfr deficiency was reported as a risk factor for neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. Neonatal disruption of the GABAergic system is also associated with behavioral outcomes. The interaction between the epigenetic influence of Mthfr deficiency and neonatal exposure to the GABA potentiating drug vigabatrin (GVG) in mice has been shown to have gender-dependent effects on mice anxiety and to have memory impairment effects in a gender-independent manner. Here we show that Mthfr deficiency interacts with neonatal GABA potentiation to alter social behavior in female, but not male, mice. This impairment was associated with a gender-dependent enhancement of proteins implicated in excitatory synapse plasticity in the female cortex. Reelin and fragile X mental retardation 1 protein (FMRP) levels and membrane GluR1/GluR2 ratios were elevated in wild-type mice treated neonatally with GVG and in Mthfr+/- mice treated with saline, but not in Mthfr+/- mice treated with GVG, compared with control groups (wild type treated with saline). A minor influence on the levels of these proteins was observed in male mice cortices, possibly due to high basal protein levels. Interaction between gender, genotype, and treatment was also observed in the GABA pathway. In female mice, GABA Aα2/gephyrin ratios were suppressed in all test groups; in male mice, a genotype-specific enhancement of GABA Aα2/gephyrin was observed. The lack of an effect on either reln or Fmr1 transcription suggests post-transcriptional regulation of these genes. Taken together, these findings suggest that Mthfr deficiency may interact with neonatal GABA potentiation in a gender-dependent manner to interrupt synaptic function. This may illustrate a possible mechanism for the epigenetic involvement of Mthfr

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

    PubMed Central

    Weiwei, Zheng; Liping, Chen; Dequan, Li

    2014-01-01

    Objective: we conducted a case-control study to investigate the association between dietary folate, vitamin B6 and vitamin B12 intake, MTHFR and MTR genotype, and breast cancer risk. Methods: Genotyping for MTHFR C677T and A1298C and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. The intake of folate, vitamin B6 and vitamin B12 were calculated by each food item from questionnaire. Results: Subjects with breast cancer tended to have more first-degree relatives (χ2=30.77, P<0.001) and have high intake of folate (t=2.42, P=0.008) and Vitamin B6 (t=2.94, P=0.002). Compared to the reference group, women with MTHFR 677 TT genotype and T allele had a significantly increased risk of breast cancer, with ORs (95%CI) of 1.8(1.08-2.27) and 1.39(1.02-1.92), respectively. For those who had folate intake<450 ug/day, MTHFR 667TT genotype was associated with a higher risk of breast cancer (OR=2.45, 95% CI=1.09-5.82, P=0.02). Similarly, subjects with Vitamin B6 intake<0.84 mg/day and MTHFR 667T allele genotype was correlated with a marginally increased risk of breast cancer. A significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer (P for interaction was 0.025). Conclusion: This case-control study found a significant association between MTHFR C667T polymorphism, folate intake and vitamin B6 and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer. PMID:24639841

  18. MTHFR Functional Polymorphism C677T and Genomic Instability in the Etiology of Idiopathic Autism in Simplex Families. Revision

    DTIC Science & Technology

    2013-10-01

    leads to increase global DNA hypomethylation and consequently results in increased generation of de novo CNVs bringing about a higher risk for...association of of MTHFR 677T allele with increased level of global hypomethylation; and 3) the association of level of global hypomethylation with increased...MTHFR 677T allele leads to increase global DNA hypomethylation and consequently results in increased generation of de novo CNVs bringing about a

  19. Regulación del flujo sanguíneo uterino. II. Funciones de estrógeno y receptores estrogénicos α/β en acciones genómicas y no-genómicas del endotelio uterino *

    PubMed Central

    Mayra, Pastore R.; Rosalina, Villalón L.; López, Gladys; Iruretagoyena, Jesús; Magness, Ronald

    2015-01-01

    Resumen El embarazo está marcado por cambios y adaptaciones cardiovasculares que son importantes para el crecimiento y mantenimiento de la placenta y el feto. Durante este periodo, las adaptaciones vasculares uterinas manifiestan cambios clasificados como de corto o largo plazo los cuales están relacionados con adaptaciones vasodilatadoras, angiogénicas o de remodelación. El estrógeno y los receptores estrogénicos clásicos (REs), RE-α y RE-β, han demostrado ser parcialmente responsables por facilitar el incremento dramático en el fluido sanguíneo uterino necesario durante el embarazo. En ésta revisión bibliográfica se discuten la base estructural para la diversidad y selectividad funcional de los REs por el estrógeno, el papel de los REs sobre los efectos genómicos y no-genómicos en células endoteliales de arterias uterinas (CEAU). Estos temas integran el conocimiento científico sobre la regulación molecular de CEAU para mantener el incremento fisiológico en la perfusión útero-placentaria observada durante un embarazo normal. PMID:26113751

  20. GenBank

    PubMed Central

    Benson, Dennis A.; Cavanaugh, Mark; Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.

    2017-01-01

    GenBank® (www.ncbi.nlm.nih.gov/genbank/) is a comprehensive database that contains publicly available nucleotide sequences for 370 000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or the NCBI Submission Portal. GenBank staff assign accession numbers upon data receipt. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Nucleotide database, which links to related information such as taxonomy, genomes, protein sequences and structures, and biomedical journal literature in PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. Recent updates include changes to policies regarding sequence identifiers, an improved 16S submission wizard, targeted loci studies, the ability to submit methylation and BioNano mapping files, and a database of anti-microbial resistance genes. PMID:27899564

  1. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and promoter methylation in cervical oncogenic lesions and cancer.

    PubMed

    Botezatu, Anca; Socolov, Demetra; Iancu, Iulia V; Huica, Irina; Plesa, Adriana; Ungureanu, Carmen; Anton, Gabriela

    2013-04-01

    The aim of this study was to investigate the role of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and MTHFR methylation pattern in cervical lesions development among women from Romania, a country with high prevalence of human papillomavirus (HPV) cervical infections. To achieve this goal, blood samples and cervical cytology specimens (n = 77)/tumour tissue specimens (n = 23) were investigated. As control, blood and negative cytological smears (n = 50) were used. A statistically significant association was found between T allele of C677T polymorphism and cervical lesions, heterozygote women presenting a threefold increased risk (normal/cervical lesions and tumours: wild homozygote 34/41 (0.68/0.41), heterozygote 14/51 (0.28/0.51), mutant homozygote 2/8 (0.04/0.08); OR = 3.081, P = 0.0035). Using χ square test for the control group, the HPV-negative and HPV-positive patients with cervix lesions, a significant correlation between viral infection and T allele of C677T polymorphism (P = 0.0287) was found. The MTHFR promoter was methylated in all HGSIL and tumour samples, significant differences being noted between HPV-positive samples, control group and cases of cervical dysplastic lesions without HPV DNA (P < 0. 0001) and between samples from patients with high-risk (hr)HPV versus low-risk (lr)HPV (P = 0.0026). No correlations between polymorphisms and methylation were observed. In Romania, individuals carrying T allele are susceptible for cervical lesions. MTHFR promoter methylation is associated with cervical severity lesions and with hrHPV.

  2. Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition.

    PubMed

    McAuley, E; McNulty, H; Hughes, C; Strain, J J; Ward, M

    2016-08-01

    Clinical deficiency of the B-vitamin riboflavin (vitamin B2) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with the MTHFR C677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with the MTHFR 677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5-13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required.

  3. 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

  4. DNA promoter methylation in breast tumors: no association with genetic polymorphisms in MTHFR and MTR.

    PubMed

    Tao, Meng Hua; Shields, Peter G; Nie, Jing; Marian, Catalin; Ambrosone, Christine B; McCann, Susan E; Platek, Mary; Krishnan, Shiva S; Xie, Bin; Edge, Stephen B; Winston, Janet; Vito, Dominica; Trevisan, Maurizio; Freudenheim, Jo L

    2009-03-01

    Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in the one-carbon metabolism, may alter DNA methylation levels and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata-defined by promoter methylation status for each of three genes, E-cadherin, p16, and RAR-beta2 in breast cancer; in addition, we evaluated case-case comparisons of the likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real-time methylation-specific PCRs for 803 paraffin-embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios and 95% confidence intervals. We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, estrogen receptor status, folate intake, and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E-cadherin, p16, and RAR-beta2 genes in breast cancer.

  5. Alcohol consumption and genetic variation in MTHFR and MTR in relation to breast cancer risk

    PubMed Central

    Platek, Mary E.; Shields, Peter G.; Marian, Catalin; McCann, Susan E.; Bonner, Matthew R.; Nie, Jing; Ambrosone, Christine B.; Millen, Amy E.; Ochs-Balcom, Heather M.; Quick, Sylvia K.; Trevisan, Maurizio; Russell, Marcia; Nochajski, Thomas H.; Edge, Stephen B.; Freudenheim, Jo L.

    2010-01-01

    It has been hypothesized that effects of alcohol consumption on one-carbon metabolism may explain, in part, the association of alcohol consumption with breast cancer risk. The methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferease (MTR) genes express key enzymes in this pathway. We investigated the association of polymorphisms in MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) with breast cancer risk and their interaction with alcohol consumption in a case-control study, the Western New York Exposures and Breast Cancer (WEB) study. Cases (n=1063) were women with primary, incident breast cancer and controls (n= 1890) were frequency matched to cases on age and race. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression. We found no association of MTHFR or MTR genotype with risk of breast cancer. In the original case control study, there was a nonsignificant increased odds of breast cancer among women with higher lifetime drinking. In the current study, there was no evidence of an interaction of genotype and alcohol in premenopausal women. However, among postmenopausal women there was an increase in breast cancer risk for women who were homozygote TT for MTHFR C677T and had high lifetime alcohol intake (≥1161.84 ounces) (OR=1.92, CI=1.13–3.28) and for those who had a high number of drinks per drinking day (> 1.91 drinks/day) (OR=1.80, CI=1.03–3.28) compared to nondrinkers who were homozygote CC. Our findings indicate that among postmenopausal women, increased breast cancer risk with alcohol consumption may be as a result of effects on one-carbon metabolism. PMID:19706843

  6. DNA promoter methylation in breast tumors: No association with genetic polymorphisms in MTHFR and MTR

    PubMed Central

    Tao, Meng Hua; Shields, Peter G.; Nie, Jing; Marian, Catalin; Ambrosone, Christine B.; McCann, Susan E.; Platek, Mary; Krishnan, Shiva S.; Xie, Bin; Edge, Stephen B.; Winston, Janet; Vito, Dominica; Trevisan, Maurizio; Freudenheim, Jo L.

    2013-01-01

    Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in one-carbon metabolism, may alter DNA methylation levels, and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata defined by promoter methylation status for each of three genes, E- cadherin, p16, and RAR-β2 in breast cancer; in addition, we evaluated case-case comparisons of likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real time methylation-specific PCRs for 803 paraffin embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios (OR) and 95% confidence intervals (CI). We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, ER status, folate intake and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E- cadherin, p16, and RAR-β2 genes in breast cancer. PMID:19240236

  7. Association of MTHFR (C677T) Gene Polymorphism With Breast Cancer in North India

    PubMed Central

    Waseem, Mohammad; Hussain, Syed Rizwan; Kumar, Shashank; Serajuddin, Mohammad; Mahdi, Farzana; Sonkar, Satyendra Kumar; Bansal, Cherry; Ahmad, Mohammad Kaleem

    2016-01-01

    BACKGROUND Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population. MATERIALS AND METHODS Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. RESULTS The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P = 0.007 and P = 0.005, respectively) between the control and the case subjects. CONCLUSION This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women. PMID:27721657

  8. Screening of polymorphisms for MTHFR and DHFR genes in spina bifida children and their mothers

    NASA Astrophysics Data System (ADS)

    Husna, M. Z.; Endom, I.; Ibrahim, S.; Selvi, N. Amaramalar; Fakhrurazi, H.; Htwe, R. Ohnmar; Kanehaswari, Y.; Halim, A. R. Abdul; Wong, S. W.; Subashini, K.; Syahira, O. Nur; Aishah, S.

    2013-11-01

    Mechanism underlying the beneficial effect of folic acid supplementation in reducing the risk of neural tube defect is still not well understood. Current evidences show the involvement of folic acid metabolic gene's polymorphism as contributing factors that regulate this pathway. Therefore, the objective of this research was to determine the presence of C677T polymorphism for methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR-19 bp deletion) genes between mother-children pairs of case and control. With the approval of UKMMC ethic committee, genomic DNA was extracted from one hundred and forty consented bloods. Polymerase chain reaction (PCR), PCR-RFLP (Restriction Fragment Length Polymorphism) and sequencing were employed to verify each nucleotide change. Our result shows that mutant MTHFR and DHFR alleles are present in all Malaysian sub-ethnic groups, case and control. Even though mutant MTHFR are found to be slightly higher in the case groups, 75% of the affected child is a non carrier for this allele and 62.5% of the mothers with an affected child are genotypically normal. For DHFR, almost all (87.5-100%) investigated samples are a carrier or having a double DHFR deletion be it a case or control pairs. However, strong maternal inheritance shown by the deleted allele might be due to a cascade effect of lacks of folate consumption or maternal uniparental disomy. In conclusion, the use of MTHFR and DHFR as markers in determining the risk of having spina bifida baby is uninformative and plays a small indirect role as the genetic causes of spina bifida. Therefore, spina bifida remains etiologically unknown polygenic and quantitative developmental trait whereby the searches for positive genetic marker need to be continued.

  9. 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

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

    PubMed

    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; Orozco, Lorena

    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.

  11. Comparison of the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in depressed versus nondepressed patients.

    PubMed

    Lizer, Mitsi H; Bogdan, Renee L; Kidd, Robert S

    2011-11-01

    Numerous studies have found an association between low serum folate levels and incidence of depression. Folic acid supplementation has been successfully used as an adjunct to treat depression in these patients. However, some individuals have a genetic deficiency in the methylene tetrahydrofolate reductase (MTHFR) gene that limits conversion of folic acid to its biologically active form, L-methylfolate. Several studies have identified a higher frequency of genetic variations in the MTHFR gene in depressed patients than in nondepressed controls. This study evaluated the frequency of the most common genetic variation MTHFR C667T in a group of depressed U.S. Caucasians and compared results with those of a control group of nondepressed U.S. Caucasians. Subjects were recruited from a psychiatric practice, an ambulatory care clinic, and the community. Informed consent and a cheek swab sample were obtained from each subject for analysis using real-time polymerase chain reaction (PCR). Allele and genotype frequencies were compared using Pearson X2 analysis. Complete data were obtained for 156 subjects. No significant differences were found in frequency of the MTHFR C667T T allele (0.415 vs 0.365; p=0.408) or the MTHFR C667T TT genotype (20.7% vs 17.6%; p=0.619) between the depressed and non-depressed controls, respectively. Therefore, use of L-methylfolate without an additional indication of need does not appear to be warranted in this group of U.S. Caucasians. Some patients may benefit from L-methylfolate, but an evidence-based approach, such as MTHFR genotyping, should be used to identify these specific patients. Additional research is also needed to confirm the benefit of L-methylfolate in specific patient populations (e.g., MTHFR TT genotype).

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

    PubMed

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

    2014-07-01

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

  13. The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case-control studies.

    PubMed

    Tang, Min; Wang, Shang-Qian; Liu, Bian-Jiang; Cao, Qiang; Li, Bing-Jie; Li, Peng-Chao; Li, Yong-Fei; Qin, Chao; Zhang, Wei

    2014-07-01

    Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, which is essential for DNA synthesis and methylation. Genetic variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR, ultimately confer increased susceptibility to cancer. As the most extensively studied polymorphism, MTHFR C677T polymorphism was shown to contribute to cancer susceptibility but the results were inconsistent. The authors performed a meta-analysis including 134 studies (46,207 cases and 69,160 controls) to address the issue. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the association. Overall, a significant elevated risk of cancer was associated with the MTHFR C677T polymorphism in T-allele versus C-allele comparison (OR = 1.06, 95% CI 1.02-1.11, P(heterogeneity) < 0.001), homozygote model (OR = 1.08, 95% CI 1.01-1.17, P(heterogeneity) < 0.001) and dominant model (OR = 1.05, 95% CI 1.00-1.10, P(heterogeneity) < 0.001). In the stratified analyses, significantly increased cancer risks were indicated among Asians in all genetic models except for heterozygote model. Further analysis revealed that C677T was significantly associated with an increased risk of esophageal and stomach cancer. This meta-analysis supports an association between the MTHFR C677T polymorphism and increased risk of esophageal and stomach cancer, especially among Asians. Additionally, more high-quality studies and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of MTHFR C677T in cancer.

  14. Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption

    PubMed Central

    Livrinova, Vesna; Lega, Marija Hadzi; Dimcheva, Anita Hristova; Samardziski, Igor; Isjanovska, Rozalinda

    2015-01-01

    BACKGROUND: Factor V Leiden, Prothrombin and MTHFR gene mutation, could have an influence in pregnancy with adverse outcome Preeclamsia, IUGR and Placental abruption. AIM: The aim of this study is to investigate the presence of above mentioned inherited thrombophilias and its statistical significance, distribution among the complicated and normal pregnancy, and relative risk for carrier of mutation to develop preeclampsia, IUGR and placental abruption. MATERIAL AND METHODS: Prospective cohort study is implemented at University Clinic for Obstetric and Gynecology in Skopje, Republic of Macedonia. The study included 109 delivered patients: 40 with preeclapmsia, 22 with IUGR, 17 with placental abruption and 30 as control group with normal pregnancy. The amount of 3 ml venous blood has been used for detection of these point mutations using ThromboStrip -Opegen, QIAGEN kit manufactured for thrombotic risk. RESULTS: The highest frequency was found: in the group with preeclampsia 35% were MTHFR homozygous, IUGR -MTHFR heterozygous 45%, Placental abruption- 52.9% MTHFR heterozygous, and in the control group without thrombophilia 56.7%. There were combined thrombophilia in 3 patients. There aren`t statistical significance in presence of thrombophilia among groups (p > 0.05). Statistical significance (p < 0.05) was found between carriers of MTHFR homozygous in preeclampsia and group with placental abruption and control group. Relative risk in IUGR group for MTHFR homozygous was 5.54 (1.37MTHFR homozygous could increase the risk for development of IUGR and mutation of Factor V Leiden for placental abruption. Further investigations with more patients are warranted. PMID:27275292

  15. Quantification of gene-specific methylation of DNMT3B and MTHFR using sequenom EpiTYPER®.

    PubMed

    Ho, Vikki; Ashbury, Janet E; Taylor, Sherryl; Vanner, Stephen; King, Will D

    2016-03-01

    Among 272 patients undergoing a screening colonoscopy, DNA methylation of DNMT3B and MTHFR, genes encoding enzymes critical to one-carbon metabolism, was quantified in blood leukocytes using Sequenom EpiTYPER®. DNA methylation was quantified in 66 and 28 CpG sites of DNMT3B and MTHFR respectively, and conceptualized using two approaches. First, measures representing average methylation across all CpG sites were created. Second, unsupervised principal component (PC) analysis was used as a pattern derivation and data-reduction approach, to develop two summary variables (PC1 and PC2). These two summary variables represented methylation around the transcription start site (PC1) and in the gene-coding area (PC2) for both DNMT3B and MTHFR. The data contained in this article presents the variation of methylation levels for individual CpG sites within the DNMT3B and MTHFR genes and possible correlations uncovered using PC analysis. The data are related to the research article "Gene-specific DNA methylation of DNMT3B and MTHFR and colorectal adenoma risk" in Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis.

  16. A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of Manipur, India.

    PubMed

    Singh, Huidrom Suraj; Salam, Kabita; Saraswathy, Kallur Nava

    2014-01-01

    Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (P > 0.05). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (P > 0.05). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41-5.01, P > 0.05). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers.

  17. Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico.

    PubMed

    Ruiz-Argüelles, Guillermo J; Coconi-Linares, Lucia Nancy; Garcés-Eisele, Javier; Reyes-Núñez, Virginia

    2007-10-01

    Methylenetetrahydrofolate reductase (MTHFR) has two common variants with reduced activity due to polymorphisms at nucleotides 677 and 1298. Both affect folate metabolism and thus remethylation of homocysteine, but are also thought to affect nucleotide synthesis and DNA methylation. Methotrexate (MTX), which interrupts folate metabolism, is used in the treatment of a variety of diseases including acute lymphoblastic leukemia (ALL), but exerts in some patients toxic effects on fast dividing tissues such as mucosal epithelia. The enhanced toxicity may be due to cooperative effects between MTX and MTHFR variants. Accordingly, it has been reported that carrying the 677T allele of the MTHFR is a risk factor for MTX-associated mucositis. As in the Mexican population, which is characterized by a high prevalence of the 677T MTHFR variant, several of its commonly associated defects have not been observed, we investigated the relationship between MTX toxicity and the 677T allele. Out of 28 patients with ALL (CC: 2, CT: 10, TT: 16), 16 had episodes of MTX-associated mucositis (CC: 0, CT: 6, TT: 10). Neither at the gene level nor at the genotype level was a significant association with mucositis found. It may be postulated that the risk of higher MTX toxicity in patients with decreased MTHFR activity could be neutralized by the normally folate rich diet in Mexico.

  18. GenBank

    PubMed Central

    Burks, Christian; Cinkosky, Michael J.; Fischer, William M.; Gilna, Paul; Hayden, Jamie E.-D.; Keen, Gifford M.; Kelly, Michael; Kristofferson, David; Lawrence, Julie

    1992-01-01

    The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 85,000,000 nucleotides in 67,000 entries from a total of 3,000 organisms. The input stream of data coming into the database is primarily as direct submissions from the scientific community on electronic media, with little or no data being keyboarded from the printed page by the databank staff. The data are maintained in a relational database management system and are made available in flatfile form through on-line access, and through various network and off-line computer-readable media. The data are also distributed in relational form through satellite copies at a number of institutions in the U.S. and elsewhere. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service. PMID:1598235

  19. Altered protein phosphatase 2A methylation and Tau phosphorylation in the young and aged brain of methylenetetrahydrofolate reductase (MTHFR) deficient mice

    PubMed Central

    Sontag, Jean-Marie; Wasek, Brandi; Taleski, Goce; Smith, Josephine; Arning, Erland; Sontag, Estelle; Bottiglieri, Teodoro

    2014-01-01

    Common functional polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, a key enzyme in folate and homocysteine metabolism, influence risk for a variety of complex disorders, including developmental, vascular, and neurological diseases. MTHFR deficiency is associated with elevation of homocysteine levels and alterations in the methylation cycle. Here, using young and aged Mthfr knockout mouse models, we show that mild MTHFR deficiency can lead to brain-region specific impairment of the methylation of Ser/Thr protein phosphatase 2A (PP2A). Relative to wild-type controls, decreased expression levels of PP2A and leucine carboxyl methyltransferase (LCMT1) were primarily observed in the hippocampus and cerebellum, and to a lesser extent in the cortex of young null Mthfr−/− and aged heterozygous Mthfr+/− mice. A marked down regulation of LCMT1 correlated with the loss of PP2A/Bα holoenzymes. Dietary folate deficiency significantly decreased LCMT1, methylated PP2A and PP2A/Bα levels in all brain regions examined from aged Mthfr+/+ mice, and further exacerbated the regional effects of MTHFR deficiency in aged Mthfr+/− mice. In turn, the down regulation of PP2A/Bα was associated with enhanced phosphorylation of Tau, a neuropathological hallmark of Alzheimer’s disease (AD). Our findings identify hypomethylation of PP2A enzymes, which are major CNS phosphatases, as a novel mechanism by which MTHFR deficiency and Mthfr gene-diet interactions could lead to disruption of neuronal homeostasis, and increase the risk for a variety of neuropsychiatric disorders, including age-related diseases like sporadic AD. PMID:25202269

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

    PubMed

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

    2013-04-01

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

  1. 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.

  2. Adaptive developmental plasticity in methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism limits its frequency in South Indians.

    PubMed

    Naushad, Shaik Mohammad; Krishnaprasad, Chintakindi; Devi, Akella Radha Rama

    2014-05-01

    Methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism shows considerable heterogeneity in its distribution in humans worldwide. The current study was conducted to investigate whether this polymorphism exhibited adaptive developmental plasticity in the control of the TT-genotype frequency. We screened 1,818 South Indian subjects (895 males and 923 females) for MTHFR C677T polymorphism using PCR-restriction fragment length polymorphism approach. MTHFR 677T-allele frequency in males and females was 9.1 and 11.0%, respectively. Compared to females, males had lower frequency of TT-genotype [odds ratio 0.31, 95% confidence interval (CI) 0.08-1.01]. The frequency of MTHFR 677T-allele was highest in the age group of 20-40 years and it gradually decreased from 40-60 to 60-80 years (P trend<0.0001). MTHFR 677TT-genotype was associated with 7.02-folds (95% CI: 2.12-25.63, P<0.0001) cumulative risk for recurrent pregnancy loss (RPL), neural tube defects (NTDs) and deep vein thrombosis (DVT). Linear regression model suggested that male gender exhibited increased homocysteine levels by 9.35 μmol/L while each MTHFR 677T-allele contributed to 4.63 μmol/L increase in homocysteine. Plasma homocysteine showed inverse correlation with dietary folate (r=-0.17, P<0.0001), B2 (r=-0.14, P<0.0001) and B6 (r=-0.07, P=0.03). Examination of the spontaneously aborted fetuses (n=35) showed no significant association of fetal genotype on its in utero viability. From the current study, it was concluded that C677T seemed to have acquired adaptive developmental plasticity among South Indians due to environmental influences thus contributing to hyperhomocysteinemia and its associated complications such as RPL, NTDs, DVT, etc.

  3. Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node-positive breast cancer patients

    PubMed Central

    Suner, Ali; Buyukhatipoglu, Hakan; Aktas, Gokmen; Kus, Tulay; Ulasli, Mustafa; Oztuzcu, Serdar; Kalender, Mehmet Emin; Sevinc, Alper; Kul, Seval; Camci, Celaletdin

    2016-01-01

    Purpose The aim of this study is to clarify the relationship between recurrence risk of breast cancer and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms. Patients and methods Breast cancer patients who had undergone surgery in Gaziantep University Oncology Hospital between June 2005 and June 2012 were followed-up and retrospectively enrolled in this study. Blood samples were collected from all patients to assess MTHFR C677T polymorphisms. Stage according to tumor–node–metastasis system, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, grade of disease, menopausal status, and administered chemotherapy or hormonal therapy were recorded. Effects of these parameters on recurrence risk were evaluated using univariate analysis and multivariate binary logistic regression model. Results Association of MTHFR C677T polymorphisms with recurrence risk was evaluated in 298 patients whose median age was 47 years (range: 21–79 years). In all patients, age (odds ratio [OR] =0.953, P=0.005) and N3 lymph node status (OR =6.293, P=0.001) were found to affect the recurrence risk. While MTHFR homozygote genotype did not have an effect on recurrence risk in all patients, increased risk was observed in lymph node-positive subgroup (OR =4.271; 95% CI 1.515–12.023; P=0.006). Adjusting for age, tumor size (T), and node status (N), MTHFR homozygote genotype had more statistically significant risk for recurrence (OR =3.255; 95% CI 1.047–10.125; P=0.041). Conclusion MTHFR TT genotype was found to be associated with increased recurrence risk in patients with lymph node-positive breast cancer. PMID:27672331

  4. Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis.

    PubMed

    Wu, Shuai; Han, Yan; Hu, Qiang; Zhang, Xiaojie; Cui, Guangcheng; Li, Zezhi; Guan, Yangtai

    2017-05-01

    Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR = 1.43, 95 % CI 1.12-1.83, P = 0.004) and MTHFR 677 C>T mutation (OR = 1.43, 95 % CI 1.08-1.90, P = 0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P < 0.05). Subgroup analysis by country indicated that the MTHFR 677 C>T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.

  5. The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia

    PubMed Central

    Thomsen, Liv Cecilie V.; McCarthy, Nina S.; Melton, Phillip E.; Cadby, Gemma; Austgulen, Rigmor; Nygård, Ottar K.; Johnson, Matthew P.; Brennecke, Shaun; Moses, Eric K.; Bjørge, Line; Iversen, Ann-Charlotte

    2017-01-01

    Objective: Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia. Methods: We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n = 1006) and nonpreeclamptic controls (n = 816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genome-wide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model. Results: The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53–0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case–control cohort (P = 0.68, odds ratio 1.05, 95% confidence interval 0.83–1.32, minor allele frequency = 0.15). Conclusion: MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a

  6. 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

  7. Genetic and epigenetic variation in the DNMT3B and MTHFR genes and colorectal adenoma risk.

    PubMed

    Ho, Vikki; Ashbury, Janet E; Taylor, Sherryl; Vanner, Stephen; King, Will D

    2016-05-01

    Polymorphisms in DNMT3B and MTHFR have been implicated in cancer etiology; however, it is increasingly clear that gene-specific DNA methylation also affects gene expression. A cross-sectional study (N = 272) investigated the main and joint effects of polymorphisms and DNA methylation in DNMT3B and MTHFR on colorectal adenoma risk. Polymorphisms examined included DNMT3B c.-6-1045G > T, and MTHFR c.665C > T and c.1286A > C. DNA methylation of 66 and 28 CpG sites in DNMT3B and MTHFR, respectively, was quantified in blood leukocytes using Sequenom EpiTYPER®. DNA methylation was conceptualized using two approaches: (1) average methylation and (2) unsupervised principal component analysis to identify variables that represented methylation around the transcription start site and the gene coding area of both genes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with the main and joint effects of polymorphisms and DNA methylation. DNA methyltransferase 3B (DNMT3B) TT versus GG/GT genotypes was associated with increased colorectal adenoma risk (OR = 2.12; 95% CI: 1.03-4.34). In addition, increasing DNA methylation in the gene-coding area of DNMT3B was associated with higher risk of colorectal adenomas (OR = 1.34; 95% CI: 1.01-1.79 per SD). In joint effect analyses, synergistic effects were observed among those with both the DNMT3B TT genotype and higher DNMT3B methylation levels compared to those with GT/GG genotypes and lower methylation levels (OR = 4.19; 95% CI: 1.45-12.13 for average methylation; OR = 4.26; 95%CI: 1.31-13.87 for methylation in the transcription start site). This research provides novel evidence that genetic and epigenetic variations contribute to colorectal adenoma risk, precursor to the majority of colorectal cancer (CRC).

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

    PubMed Central

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

    2014-01-01

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

  9. Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data.

    PubMed

    Yoshimi, Akira; Aleksic, Branko; Kawamura, Yukiko; Takahashi, Nagahide; Yamada, Shinnosuke; Usui, Hinako; Saito, Shinichi; Ito, Yoshihito; Iwata, Nakao; Inada, Toshiya; Noda, Yukihiro; Yamada, Kiyofumi; Ozaki, Norio

    2010-12-01

    Methylenetetrahydrofolate reductase (MTHFR) is a critical molecule for single-carbon transfer reactions. Recent evidence suggests that polymorphisms of MTHFR are related to neural tube deficits and the pathogenesis of schizophrenia. While several studies have demonstrated associations between the gene encoding the MTHFR (MTHFR) polymorphisms and schizophrenia, these studies lack consistency. Therefore, we conducted a gene-wide association study (patients with schizophrenia = 696, control subjects = 747) and performed imputation analysis. Additionally, we performed meta-analysis on currently available data from 18 studies for two common functional polymorphisms (rs1801131 and rs1801133). There were no significant associations with schizophrenia in the single marker analysis for the seven tagging SNPs of MTHFR. In the haplotypic analysis, a nominally significant association was observed between the haplotypes, which included four SNPs (rs1801133, rs17421511, rs17037396, and rs9651118) and the schizophrenic patients. Additionally, the imputation analysis demonstrated there were several associated markers on the MTHFR chromosomal region. However, confirmatory analyses of three tagging SNPs (rs1801133, rs17037396, and rs9651118) and the top SNP (rs17421511) for the imputation results (patients with schizophrenia = 797, control subjects = 1025) failed to replicate the haplotypic analysis and the imputation results. These findings suggest that MTHFR polymorphisms are unlikely to be related to the development of schizophrenia in the Japanese population. However, since our meta-analysis results demonstrated strong support for association of rs1801133 with schizophrenia, further replication studies based on a gene-wide approach need to be considered.

  10. Associations of MTHFR C677T and MTRR A66G Gene Polymorphisms with Metabolic Syndrome: A Case-Control Study in Northern China

    PubMed Central

    Yang, Boyi; Fan, Shujun; Zhi, Xueyuan; Wang, Da; Li, Yongfang; Wang, Yinuo; Wang, Yanxun; Wei, Jian; Zheng, Quanmei; Sun, Guifan

    2014-01-01

    Prior evidence indicates that homocysteine plays a role in the development of metabolic syndrome (MetS). Methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms are common genetic determinants of homocysteine levels. To investigate the associations of the MTHFR C677T and MTRR A66G polymorphisms with MetS, 692 Chinese Han subjects with MetS and 878 controls were recruited. The component traits of MetS and the MTHFR C677T and MTRR A66G genotypes were determined. A significant association was observed between the MTHFR 677T allele and increased risk of MetS, high fasting blood glucose, high waist circumference, and increasing number of MetS components. The MTRR A66G polymorphism was associated with an increased risk of MetS when combined with the MTHFR 677TT genotype, although there was no association found between MetS and MTRR A66G alone. Furthermore, the MTRR 66GG genotype was associated with high fasting blood glucose and triglycerides. Our data suggest that the MTHFR 677T allele may contribute to an increased risk of MetS in the northern Chinese Han population. The MTRR A66G polymorphism is not associated with MetS. However, it may exacerbate the effect of the MTHFR C677T variant alone. Further large prospective population-based studies are required to confirm our findings. PMID:25429430

  11. HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women.

    PubMed

    Batschauer, Anna P; Cruz, Nathalia G; Oliveira, Vanessa C; Coelho, Fernanda F; Santos, Izabela R; Alves, Michelle T; Fernandes, Ana P; Carvalho, Maria G; Gomes, Karina B

    2011-11-01

    Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival.

  12. Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura

    PubMed Central

    Roecklein, Kathryn A.; Scher, Ann I.; Smith, Albert; Harris, Tamara; Eiriksdottir, Gudny; Garcia, Melissa; Gudnason, Villi; Launer, Lenore J.

    2014-01-01

    Aims The C677T variant in the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include Methionine synthase (MTR; EC 2.1.1.13), and Methionine synthase reductase (MTRR; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR, MTR, and MTRR. Methods Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache (n=367), migraine without aura (n=85), migraine with aura (n=167), and no headache (n=1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNPs and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing Results Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing. Conclusions These results suggest that MTRR variants may protect against migraine with aura in an older population. PMID:23430981

  13. 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.

  14. Association of Polymorphisms in BDNF, MTHFR, and Genes Involved in the Dopaminergic Pathway with Memory in a Healthy Chinese Population

    ERIC Educational Resources Information Center

    Yeh, Ting-Kuang; Hu, Chung-Yi; Yeh, Ting-Chi; Lin, Pei-Jung; Wu, Chung-Hsin; Lee, Po-Lei; Chang, Chun-Yen

    2012-01-01

    The contribution of genetic factors to the memory is widely acknowledged. Research suggests that these factors include genes involved in the dopaminergic pathway, as well as the genes for brain-derived neurotrophic factor (BDNF) and methylenetetrahydrofolate reductase (MTHFR). The activity of the products of these genes is affected by single…

  15. 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.

  16. Association of the MTHFR C677T (rs1801133) polymorphism with idiopathic male infertility in a local Pakistani population

    PubMed Central

    Ismail, M; Azhar Beg, M; Shabbir, A; Rashid Kayani, A; Kaukab Raja, G

    2016-01-01

    Abstract The present study determined an association between idiopathic sperm disorders in a local Pakistani infertile male population and the MTHFR C677T polymorphism. After ruling out non genetic factors, a total of 437 idiopathic infertile men including 57 azoospermic, 66 oligospermic, 44 asthenozoospermic, 29 teratozoospermic, 20 oligoasthenospermic and 221 infertile normospermic men were recruited. Furthermore, 218 normospermic fertile men, who had two children (or more) were included as controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine MTHFR C677T (rs1801133) polymorphism. A significant association of the minor MTHFR 677T allele with male infertility was observed (p <0.05). In addition, men with MTHFR 677 CT and TT genotypes were at a greater risk [odds ratio (OR): 1.81, 95% confidence interval (95% CI): 1.17-2.80, p = 0.008 and OR: 9.24, 95% CI: 1.20-70.92, p = 0.032, respectively] of infertility. All the subgroups of male infertility (azoospermic, oligospermic, asthenospermic, oligoasthenoteratospermic (OAT) and normospermic infertile) had significantly (p <0.05) higher frequencies of CT and TT genotypes when compared to fertile men. The combined genotypes (CT + TT) were also found significantly (OR: 2.01, 95% CI: 1.31-3.08, p <0.001) associated with male infertility. The results suggest that the polymorphism might be a factor of male infertility in the Pakistani population. PMID:27785408

  17. MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis.

    PubMed

    Inanir, Ahmet; Yigit, Serbulent; Tural, Sengul; Cecen, Osman; Yildirim, Eren

    2013-01-01

    Osteoarthritis is a degenerative joint disorder resulting in destruction of articular cartilage, osteophyte formation, and subchondral bone sclerosis. In recent years, numerous genetic factors have been identified and implicated in osteoarthritis. The aim of the current study was to examine the influence of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) variations on the risk of osteoarthritis. Genomic DNA is obtained from 421 persons (221 patients with osteoarthritis and 200 healthy controls). ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. The MTHFR C677T mutation was analyzed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) methods. We found significant difference between the groups with respect to both ACE and MTHFR genotype distributions (p< 0.001, p< 0.001 respectively). Our study suggests that ACE gene DD genotype and MTHFR gene CC genotype could be used as genetic markers in osteoarthritis in Turkish study populations.

  18. 5,10-Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) gene polymorphisms and adult meningioma risk.

    PubMed

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

    2013-11-01

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

  19. Prevalence of MTHFR C677T Polymorphism in North Indian Mothers Having Babies with Trisomy 21 Down Syndrome

    ERIC Educational Resources Information Center

    Kohli, Utkarsh; Arora, Sadhna; Kabra, Madhulika; Ramakrishnan, Lakshmy; Gulati, Sheffali; Pandey, Ravindra

    2008-01-01

    Recent studies have evaluated possible links between polymorphisms in maternal folate metabolism genes and Down syndrome. Some of these studies show a significantly increased prevalence of the C677T polymorphism of the 5,10-methylene tetrahydrofolate reductase (NADPH) gene (MTHFR) among mothers who have had babies with Down syndrome. This study…

  20. Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus.

    PubMed

    Zhou, Tian-Biao; Drummen, Gregor P C; Jiang, Zong-Pei; Li, Hong-Yan

    2015-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme that regulates nucleotide synthesis and DNA methylation. The MTHFR C677T gene polymorphism (rs1801133), a C → T transition at nucleotide 677 in exon 4, is a common gene variant of MTHFR and has been implicated in diabetic nephropathy, albeit with inconsistent results. Here, we performed a meta-analysis to assess the common effect size of this polymorphism on DN susceptibility. Case-control studies on the association of the MTHFR C677T gene polymorphism with DN risk were retrieved from databases up to August 1, 2013, and eligible studies were recruited into the meta-analysis and further analyzed. Of 132 studies, 33 were identified as suitable for this analysis. The results showed that T allele and TT genotype were distinctly associated with DN susceptibility in the overall population and Asians, and might be a risk factor in Caucasians and Africans (T allele: Overall population: p < 0.00001, Asians: p = 0.0002, Caucasians: p = 0.02, Africans: p < 0.00001; TT genotype: Overall population: p < 0.00001, Asians: p = 0.0003, Caucasians: p = 0.008, Africans: p = 0.0003). Furthermore, the analysis suggested that the CC genotype might play a protective role against DN onset in patients with type 2 diabetes for the overall population, Asians, Caucasian and Africans. However, due to the limited sample size in the African population, these results should be interpreted with care. In conclusion, the MTHFR C677T T allele or TT genotype might be a significant genetic molecular marker to determine the risk of DN in patients with type 2 diabetes and help to develop suitable disease prevention and management strategies.

  1. Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to depression in Asian population: a systematic meta-analysis.

    PubMed

    Rai, V

    2014-01-01

    Genetic association studies on MTHFR C677 T polymorphism and depression have been repeatedly performed over the last two decades and results are generally inconsistent. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for depression in Asian population. The author performed a meta-analysis and pooled data from individual case-control studies that examined the association between C677T polymorphism and depression (meta-analysis: 13 studies, 1,120 cases and 1,688 controls).The pooled Odd Ratios (OR) were estimated by both fixed effects and random effects models. Overall, there was an association between MTHFR C677T polymorphism and increased risk of depression under five genetic models (OR T vs. C=1.44, 95% CI= 1.56-1.78, P=0.001; OR TT vs. CC= 1.78, 95% CI 1.17– 2.69, P=0.006; OR CT vs CC=1.102, 95% CI=0.91-1.32,P=0.31; OR TT vs. CT+CC=1.73, 95% CI= 0.87-3.41, P=0.11; OR TT+CT vs. CC=1.26, 95% CI=0.96-1.64, P=0.08). Sensitivity analysis suggested exclusion of any single study did not alter the overall pooled Ors. In conclusion results of present meta-analysis supports that there is a significant association between MTHFR C677T polymorphism and depression risk, and MTHFR 677T allele contributes to increased risk of depression in Asian individuals.

  2. Role of 677C→T polymorphism a single substitution in methylenetetrahydrofolate reductase (MTHFR) gene in North Indian infertile men.

    PubMed

    Naqvi, Hena; Hussain, Syed Rizwan; Ahmad, Mohammad Kaleem; Mahdi, Farzana; Jaiswar, Shyam Pyari; Shankhwar, Satya Narayain; Mahdi, Abbas Ali

    2014-02-01

    Failure or severe difficulty in conceiving a child is surprisingly common, worldwide problem. Half of these cases are due to male factors with defects in sperm (1 in 15 men) being the single most common cause. Also about 60-75 % of male infertility cases are idiopathic, since the molecular mechanisms underlying the defects remain unknown. DNA methylation is crucial for spermatogenesis and high methylenetetrahydrofolate reductase (MTHFR) activity in adult testis than other organs in mouse, signifies its critical role in spermatogenesis. According to recent findings there is a correlation of epigenetic regulation of several imprinted genes with disturbed spermatogenesis and fertility. Consequently any change in the MTHFR gene sequence can modify the spermatogenesis including transmission of infertility to the carriers. The aim of the study is to analyze the distribution of the single nucleotide polymorphism C677T in the MTHFR gene in 637 North Indian infertile patients and 364 fertile North Indian men as controls by using PCR-RFLP technique and Chi Square test for statistical analysis. The average MTHFR 677CC, 677CT, 677TT genotype frequencies of total infertile men were 70.17, 24.17, 5.65 % in infertile men and 75.27, 21.7, 2.74 % in controls, respectively. The average frequency of the MTHFR 677T allele was 17.73 % in infertile men as compared to 13.59 % in controls. The statistical difference was significant. Disease risk was found 2.27-folds increased in patients who were carrying T allele. We found an association of C677T polymorphism with male infertility and that it may be a genetic risk factor for male infertility in North Indian population.

  3. Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population.

    PubMed

    Jiang, Wei; Xu, Jun; Lu, Xiao-Jie; Sun, Yang

    2016-09-01

    Depression is a worldwide public health issue, and its prevalence increases each year. Although a number of studies have been conducted on the association between MTHFR C677T polymorphism and depression in China, this association remains elusive and controversial. To clarify the impact of MTHFR C677T polymorphism on the risk of depression, a meta-analysis was performed in the Chinese population. Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine through May 5, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 13 case-control studies including 1895 patients and 1913 controls were involved in this meta-analysis. Overall, T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of depression in the Chinese population (T vs. C: OR = 1.52, 95% CI = 1.24-1.85; TT + CT vs. CC: OR = 1.64, 95% CI = 1.16-2.30; TT vs. CC: OR = 2.19, 95% CI = 1.49-3.24; TT vs. CC + CT: OR = 1.80, 95% CI = 1.31-2.46). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies, in hospital-based studies, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. In conclusion, this meta-analysis suggests that MTHFR C677T polymorphism is associated with depression in the Chinese population, but these associations vary in different geographic locations.

  4. C677T and A1298C Polymorphisms of MTHFR Gene and Their Relation to Homocysteine Levels in Turner Syndrome

    PubMed Central

    Oliveira, Kelly C.; Verreschi, Ieda T.N.; Sugawara, Eduardo K.; Silva, Vanessa C.; Galera, Bianca B.; Galera, Marcial Francis; Bianco, Bianca

    2012-01-01

    Aims: To determine the frequency of C677T and A1298C polymorphisms of the MTHFR gene and correlate them with homocysteine serum levels in patients with Turner syndrome (TS) and controls. Methods: This case–control study included 78 women with TS and a control group of 372 healthy individuals without personal or family history of cardiovascular disease and cancer. C677T (rs1801133) and A1298C (rs1801131) polymorphisms were detected by polymerase chain reaction–restriction fragment-length polymorphism and the TaqMan system, respectively. Homocysteine serum levels were determined by high-performance liquid chromatography. The results were analyzed statistically, and p<0.05 was considered to represent a significant difference. Results: The homocysteine levels change was 13.9+3.3 nM in patients with TS and 8.8+3.2 nM in the control group. No significant difference between groups was found (p=0.348). Single-marker analysis revealed no association between MTHFR C677T polymorphism and TS when genotype (p=0.063) or allelic (p=0.277) distribution was considered. Regarding MTHFR A1298C polymorphism, a statistical difference was found between the TS group and the control group, for both genotype (p<0.0001) and allele (p<0.0001) distribution. Haplotype analysis of 2 MTHFR polymorphisms identified 2 haplotypes—CC and TC—associated with TS (p<0.001 and p=0.0165, respectively). However, homocysteine levels were not higher in patients with haplotype risk. Conclusion: The results suggest that the C677T and A1298C polymorphisms of the MTHFR gene are not related to homocysteine levels in Brazilian patients with TS, despite the differential distribution of the mutated allele C (A1298C) in these patients. Further studies are needed to investigate the possible genetic interaction with homocysteine levels in TS. PMID:22283972

  5. A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy

    PubMed Central

    Luo, Shasha; Wang, Furu; Shi, Chao; Wu, Zhifeng

    2016-01-01

    Aims: To shed light on the conflicting findings of the association between the methylenetetrahydrofolate reductase gene (MTHFR) 677C/T polymorphism and the risk of diabetic retinopathy (DR), a meta-analysis was conducted. Methods: A predefined search was performed on 1747 DR cases and 3146 controls from 18 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the sizes of overall and stratification effects of the MTHFR 677C/T polymorphism on the risk of DR, as appropriate. Results: Risks were evaluated by odds ratios (OR) with 95% confidence intervals (95% CI). We found a significant association between the MTHFR 677C/T polymorphism and the risk of DR for each genetic model (recessive model: OR = 1.67; 95% CI: 1.19–2.40 and dominant model: OR = 1.71; 95% CI: 1.28–2.28; respectively). In stratified analysis; we further found that the Asian group with both types of diabetes mellitus (DM) showed a significant association with genetic models (recessive model: OR = 2.16; 95% CI: 1.75–2.60 and dominant model: OR = 1.98; 95% CI: 1.42–2.76; respectively). Conclusions: Our study suggested that the MTHFR 677C/T polymorphism may contribute to DR development, especially in Asian populations. Prospective and additional genome-wide association studies (GWAS) are needed to clarify the real role of the MTHFR gene in determining susceptibility to DR. PMID:27517946

  6. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and age at onset of schizophrenia: no consistent evidence for an association in the Nordic population.

    PubMed

    Saetre, Peter; Grove, Jakob; Børglum, Anders D; Mors, Ole; Werge, Thomas; Andreassen, Ole A; Vares, Maria; Agartz, Ingrid; Terenius, Lars; Jönsson, Erik G

    2012-12-01

    Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in metabolic pathways of importance for nucleotide synthesis and methylation of DNA, membranes, proteins and lipids. The MTHFR gene includes a common polymorphism (rs1801133 or C677T), which is associated with enzyme activity. The T-allele of the C677T polymorphism has been associated with earlier age at onset of schizophrenia in a Scandinavian population, although no association was found in replication attempts in other populations. Extending the study to five Nordic samples consisting of 2,198 patients with schizophrenia, including the original Scandinavian samples, there was no significant association between MTHFR C677T polymorphism and age at onset in schizophrenia. The present results do not suggest that the investigated MTHFR polymorphism has any significant influence on age at onset of schizophrenia in the Nordic population.

  7. TrafficGen Architecture Document

    DTIC Science & Technology

    2016-01-01

    v 1. Overview of TrafficGen Application 1 2. Modules 2 3. User Interface 3 3.1 Top-Level MVC Classes 3 3.1.1 TrafficGenView 3 3.1.2...release; distribution unlimited. 3 A key design concept in use here is the model-view-controller ( MVC ) pattern. In general, the MVC design pattern...and easier to manage. MVC facilitates reuse by reducing and formalizing coupling between model components and the user interface. The same TrafficGen

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

    PubMed

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

    2006-12-11

    Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.

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

    PubMed

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

    2012-11-01

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

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

    PubMed Central

    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

    2016-01-01

    Abstract 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. PMID:28031756

  11. MTHFR C677T polymorphism and recurrent early pregnancy loss risk in north Indian population.

    PubMed

    Nair, Rohini R; Khanna, Anuradha; Singh, Kiran

    2012-02-01

    Recurrent early pregnancy loss (REPL) is a multifactorial disorder as both genetic and environmental factors contribute to the development of disease. Folate metabolism is an important mechanism to ensure proper fetal growth. Hyperhomocysteinemia leads to a number of disorders and REPL is one of them. In a case-control study DNA from 106 cases with the history of 3 or more REPL and 140 healthy fertile controls with successful pregnancy outcomes were genotyped for C677T single-nucleotide polymorphism (SNP) of the MTHFR (methylenetetrahydrofolate reductase) gene through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), which was further confirmed by sequencing. Allele frequencies of REPL cases were compared with healthy controls and a statistically significant association was found between REPL and the mutant T allele (χ² = 8.786, odds ratio [OR] = 2.20, 95% confidence interval [CI] = 1.323-3.9658, P = .003). The genotype frequencies of SNP C677T also differ significantly between these 2 groups (χ² = 8.237, P = .016). The OR for heterozygous CT in the REPL versus controls is 1.9591 (95% CI = 1.0285-3.7318, P = .04). The OR for TT homozygous is 6.3009 (95% CI = 1.2065, P = .02). Combined odds ratio of CT and TT against the control has been calculated as 2.2194 (95% CI = 1.2029-4.0952, P = .02) which is also significant. Thus the present study clearly indicates that homozygosity and heterozygosity for the MTHFR C677T polymorphism confer a 6.3009- and 1.9591-fold increased risk of idiopathic REPL, respectively.

  12. The methylenetetrahydrofolate reductase (MTHFR) 677 C>T polymorphism increases the risk of developing chronic myeloid leukemia-a case-control study.

    PubMed

    Bănescu, Claudia; Iancu, Mihaela; Trifa, Adrian P; Macarie, Ioan; Dima, Delia; Dobreanu, Minodora

    2015-04-01

    The methylenetetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C polymorphisms are associated with variations in folate levels, a phenomenon linked to the development of various malignancies. The aim of this study was to investigate the influence of the 677 C>T and 1298 A>C polymorphisms in the MTHFR gene on the risk of developing chronic myeloid leukemia (CML). Our study included 151 patients with CML and 305 controls. The MTHFR 677 C>T and 1298 A>C polymorphisms were investigated by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR techniques. The CT and TT genotypes of the MTHFR 677 C>T polymorphism were associated with an increased risk of developing CML (odds ratio (OR) = 1.556, 95% confidence interval (CI) = 1.017-2.381, p value = 0.041, and OR = 1.897, 95% CI = 1.046-3.44, p value = 0.035, respectively). No association was observed between the prognostic factors (blasts, basophils, additional chromosomal abnormalities, EUTOS score, Sokal and Hasford risk groups) and the MTHFR 677 C>T and 1298 A>C variant genotypes in CML patients. Our study shows that the MTHFR 677 C>T polymorphism is significantly associated with the risk of CML in Romanian patients.

  13. MTHFR c.677C>T Inhibits Cell Proliferation and Decreases Prostate Cancer Susceptibility in the Han Chinese Population in Shanghai

    PubMed Central

    Wu, Jun-Long; Zhou, Shu-Xian; Zhao, Rui; Zhang, Xuan; Chang, Kun; Gu, Cheng-Yuan; Gan, Hua-Lei; Dai, Bo; Zhu, Yao; Zhang, Hai-Liang; Shi, Guo-Hai; Qu, Yuan-Yuan; Zhao, Jian-Yuan; Ye, Ding-Wei

    2016-01-01

    Methylenetetrahydrofolate reductase (MTHFR) c.677C>T and c.1298A>C variants were known to be associated with prostate cancer (PCa) risk with conflicting results, because of MTHFR and nutrient status interaction in the prostate development. In this large-scale, hospital-based, case-control study of 1817 PCa cases and 2026 cancer-free controls, we aimed to clarify the association between these two MTHFR variants and PCa risk in Shanghai and to explore the underlying molecular mechanisms. We found that both the heterozygous CT (adjusted OR = 0.78, 95% CI: 0.67–0.92) and the homozygous TT genotypes (adjusted OR = 0.68, 95% CI: 0.55–0.83) of c.677C>T were associated with a significantly decreased risk of PCa compared with homozygous wild-type CC genotype, respectively, using multivariate logistic regression. Furthermore, we confirmed that MTHFR c.677T allele was related to an increased serum homocysteine level in the Han Chinese population in Shanghai. In the cultured PCa cell lines, we observed that MTHFR c.677T could elevate the cellular homocysteine level and cause DNA damage, thus increasing cell apoptosis and finally inhibiting cell proliferation. In conclusion, MTHFR c.677T was a protective factor of PCa risk in ethnic Han Chinese males by inducing DNA damage and cell apoptosis. PMID:27819322

  14. Prevalence of hyperhomocysteinemia and the MTHFR C677T polymorphism in patients with arterial and venous thrombosis from North Western Russia.

    PubMed

    Shmeleva, Veronika M; Kapustin, Sergey I; Papayan, Ludmila P; Sobczyńska-Malefora, Agata; Harrington, Dominic J; Savidge, Geoffrey F

    2003-01-01

    Conflicting data from Western European and USA population studies led us to investigate hyperhomocysteinemia (HHcy), the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms and thrombotic disease in North Western Russia. Plasma total homocysteine (tHcy) levels, MTHFR C677T genotype, selected life style determinants and haemostatic factor activity were determined in patients with arterial (n = 33), venous (n = 40), arterial + venous (n = 11) thrombosis and healthy controls (n = 30). We found raised median tHcy levels in all patient groups vs. controls (p < 0.05), with odds ratios (95% CI) for vascular disease among patients with HHcy (defined as > 15 micromol/l) of 3.9 (0.6 - 14.3), 4.8 (1.2 - 18.8) and 15.8 (2.8 - 87.3) respectively. tHcy levels were a function of MTHFR C677T genotype, and all patients with tHcy levels > 30 micromol/l had the MTHFR C677T homozygous substitution. Elevated tHcy levels (p < 0.05) were identified in smokers and coffee drinkers, with the degree of elevation dependent on MTHFR C677T genotype. Of the studied haemostatic parameters increased factor VIII activity and vWF antigen and activity was observed in HHcy subjects. We conclude that HHcy and MTHFR C677T genotype are positively associated with arterial and venous thrombotic disease in the population of North Western Russia.

  15. 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

  16. Genetic risk factors for arterial ischemic stroke in children: a possible MTHFR and eNOS gene-gene interplay?

    PubMed

    Djordjevic, Valentina; Stankovic, Marija; Brankovic-Sreckovic, Vesna; Rakicevic, Ljiljana; Radojkovic, Dragica

    2009-07-01

    In order to investigate the influence of genetic factors in childhood stroke, we compared the distributions of mutations/ polymorphisms affecting hemostasis and/or endothelial function (factor V [FV] Leiden, factor II [FII] G20210A, methylenetetrahydrofolate reductase [MTHFR] C677T, angiotensin-converting enzyme [ACE] insertion/deletion [ID], and endothelial nitric oxide synthase [eNOS] G894T) among children with stroke and controls. A total number of 26 children with arterial ischemic stroke and a control group of 50 healthy children were included in the study. No statistically significant differences in allelic and genotypic distribution were detected in comparisons between groups. However, when combined genotypes were analyzed, statistical significance was observed for the association of MTHFR CT and eNOS TT gene variants. The results of our study suggest that this genotype combination represents a risk factor of 7.2 (P = .017) for arterial ischemic stroke in children.

  17. Life-threatening methylenetetrahydrofolate reductase (MTHFR) deficiency with extremely early onset: characterization of two novel mutations in compound heterozygous patients.

    PubMed

    Forges, Thierry; Chery, Céline; Audonnet, Sandra; Feillet, François; Gueant, Jean-Louis

    2010-06-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzymatic component of the folate cycle, converting 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine into methionine. Severe MTHFR deficiency is a rare recessive disease leading to major hyperhomocysteinemia, homocystinuria, and progressive neurological distress within the two first decades of life. More than 50 mutations have been reported so far in affected patients but only a few cases with very early onset of symptoms during the first weeks have been described, most of them showing a particular severe clinical course. We detected two novel mutations by direct sequencing of MTHFR in compound heterozygous patients with extremely low or undetectable enzyme activity; one of them had clinical onset during the first week of life and fatal issue at the age of six weeks. Prenatal diagnosis of his sibling allowed for early treatment with B vitamins and betaine and a favorable outcome. One of these mutations (c.523G>A) led to an Ala>Thr transition in the catalytic domain of the enzyme, the other (c.1166G>A) induced alternative splicing of exon 7 at the junction of the catalytic and regulatory domains. Both parents carried only one of these mutations and presented with moderate and intermediate hyperhomocysteinemia, respectively, without neurological symptoms. Severe MTHFR deficiency thus has to be taken into consideration when investigating neurological distress even in the newborn, regarding the need for an earliest possible treatment. Characterization of the relatives further allows for preventive measure to limit the risks of chronic hyperhomocysteinemia.

  18. Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

    PubMed Central

    Traylor, Matthew; Adib-Samii, Poneh; Thijs, Vincent; Sudlow, Cathie; Rothwell, Peter M.; Boncoraglio, Giorgio; Dichgans, Martin; Meschia, James; Maguire, Jane; Levi, Christopher; Rost, Natalia S.; Rosand, Jonathan; Hassan, Ahamad; Bevan, Steve; Markus, Hugh S.

    2016-01-01

    Background and Purpose— Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels–associated genetic variant MTHFR C677T for association with magnetic resonance imaging–confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. Methods— We included 1359 magnetic resonance imaging–confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. Results— MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). Conclusions— MTHFR C677T was associated with magnetic resonance imaging–confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes. PMID:26839351

  19. MTHFR Functional Polymorphism C677T and Genomic Instability in the Etiology of Idiopathic Autism in Simplex Families

    DTIC Science & Technology

    2014-12-01

    AWARD NUMBER: W81XWH-12-1-0298 TITLE: MTHFR Functional Polymorphism C677T and Genomic Instability in the Etiology of Idiopathic Autism in... Autism in Simplex Families 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0298 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Xudong Liu, PhD 5d...DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Autism Spectrum Disorder (ASD

  20. Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development.

    PubMed

    Zara-Lopes, T; Gimenez-Martins, A P A; Nascimento-Filho, C H V; Castanhole-Nunes, M M U; Galbiatti-Dias, A L S; Padovani-Júnior, J A; Maniglia, J V; Francisco, J L E; Pavarino, E C; Goloni-Bertollo, E M

    2016-05-09

    Folate metabolism is essential for DNA synthesis and repair. Alterations in genes that participate in folate metabolism can be associated with several types of malignant neoplasms, including thyroid and breast cancer. In the present case-control study, we examined the association between methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) and methionine synthase (MTR A2756G, rs1805087) polymorphisms and risk for thyroid and breast cancer. Polymerase chain reaction-restriction fragment length technique was used to determine the specific genotypes in the genes of interest. Statistical analysis was performed by multiple logistic regression test. We found an association between MTHFR C677T polymorphism and risks to both thyroid (OR = 2.50; 95%CI = 1.15-5.46; P = 0.02) and breast cancer (OR = 2.53; 95%CI = 1.08-5.93; P = 0.03). Tobacco consumption and high body mass index were also associated with thyroid cancer. In addition, increased age (≥50 years) and alcohol consumption were found to be associated with breast cancer. Our results indicated that MTHFR C677T is significantly associated with thyroid and breast cancer risks. Thus, these factors may be used as potential prognostic markers for thyroid and breast cancers.

  1. Functional variants in CYP1B1, KRAS and MTHFR genes are associated with shorter telomere length in postmenopausal women.

    PubMed

    Cerne, Jasmina Z; Pohar-Perme, Maja; Cerkovnik, Petra; Gersak, Ksenija; Novakovic, Srdjan

    2015-07-01

    Estrogens and antioxidants indirectly alleviate telomere attrition. However, available clinical data on the association between hormone exposure and telomere length are inconclusive. In the present study, we examined the effects of exogenous estrogen use and of some genetic factors implicated in estrogen metabolism and oxidative stress response on mean leukocyte telomere length. We studied 259 postmenopausal women. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695), MnSOD (rs4880), KRAS (rs61764370), and MTHFR (rs1801133 and rs1801131) polymorphisms. Mean leukocyte telomere length was measured using a quantitative real-time PCR assay. In multivariate analysis we found no association between oral contraceptives or hormone replacement therapy (HRT) and mean leukocyte telomere length. The presence of variant alleles in CYP1B1, KRAS and MTHFR genes was statistically significantly associated with shorter mean leukocyte telomere length. Further, the data provided evidence for the effect modification of the association between HRT and mean leukocyte telomere length by the CYP1B1, KRAS and MTHFR genotypes. Our findings suggest that functionally relevant genetic variants within estrogen and folate metabolic pathways may influence telomere length. We propose these genetic factors should be taken into consideration when interpreting associations between hormone exposure and telomere length.

  2. Preferential transmission of the MTHFR 677 T allele to infants with Down syndrome: implications for a survival advantage.

    PubMed

    Hobbs, Charlotte A; Cleves, Mario A; Lauer, Ronald M; Burns, Trudy L; James, S Jill

    2002-11-15

    We have examined the transmission frequencies of the methylenetetrahydrofolate reductase (MTHFR) 677 T and C alleles from heterozygous parents to children with Down syndrome (trisomy 21) in 202 Caucasian families. Our results indicated that the MTHFR 677T allele was transmitted to children with Down syndrome at a significantly higher rate than would be expected based on Mendelian inheritance patterns, and the C allele was transmitted at a significantly lower rate (P < 0.009). Transmission frequencies were also examined independently for maternally and paternally transmitted alleles to assess potential parent-of-origin effects. Because the vast majority of conceptions with trisomy 21 end in pregnancy loss, we questioned whether the observed preferential transmission of the T allele to this population of liveborn infants with Down syndrome could reflect a survival advantage. A plausible biochemical interpretation of these results is presented based on a maternal-fetal MTHFR 677T allele interaction in the context of the constitutive overexpression of three copies of the cystathionine beta synthase gene in the trisomy 21 fetus. Published 2002 Wiley-Liss, Inc.

  3. Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies

    PubMed Central

    Zou, Peng; Ji, Guixiang; Gu, Aihua; Zhao, Peng

    2012-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs. Methods An electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis. Results A significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR  = 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR  = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR  = 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR  = 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls. Conclusion The results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted. PMID:23056169

  4. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to diabetic nephropathy in Chinese type 2 diabetic patients: a meta-analysis.

    PubMed

    Chang, Wei-wei; Zhang, Liu; Yao, Ying-shui; Su, Hong; Jin, Yue-long; Chen, Yan

    2013-08-01

    The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and diabetic nephropathy (DN) or diabetes mellitus (DM) risk has been widely reported, but the results are still debatable. To investigate the role of MTHFR C677T polymorphism on DM or DN, 13 separate studies in the Chinese population on the relation between MTHFR C677T polymorphism and DM or DN were analyzed by a meta-analysis. Five genetic models were used to estimate the association between MTHFR C677T polymorphism and the risk of DM or DN. Overall, our meta-analysis for DN versus healthy controls produced significant results for all genetic contrasts except for the co-dominant model (allele contrast: OR = 2.24, 95%CI: 1.88-2.65, p < 0.00001, Pheterogeneity = 0.49). However, the meta-analysis for DM versus healthy controls produced non-significant results for all contrasts (allele contrast: OR = 1.12, 95%CI: 0.92-1.35, p = 0.25, Pheterogeneity = 0.07). In addition, the meta-analysis for DM versus DN produced significant results for all contrasts (allele contrast: OR = 1.88, 95%CI: 1.65-2.15, p < 0.00001, Pheterogeneity = 0.83). The current meta-analysis suggested that MTHFR C677T polymorphism might influence DN risk, but not for DM in the Chinese population.

  5. Methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphism is associated with antipsychotic-induced weight gain in first-episode schizophrenia.

    PubMed

    Srisawat, Umarat; Reynolds, Gavin P; Zhang, Zhi Jun; Zhang, Xiang Rong; Arranz, Belen; San, Luis; Dalton, Caroline F

    2014-03-01

    Genetic variants of the methylenetetrahydrofolate reductase (MTHFR) gene involved in homocysteine metabolism may be important predictors of antipsychotic drug-induced weight gain (AIWG). We tested whether two functional MTHFR polymorphisms are related to AIWG. Weight gain was studied in two cohorts of first-episode, initially drug-naive schizophrenia patients; Chinese Han (n = 182) and Spanish Caucasians (n = 72) receiving antipsychotics for 10 wk and 3 months respectively. Blood DNA was genotyped for 677C/T and 1298A/C MTHFR polymorphisms. Patients with the 677 CC genotype had a significantly greater increase in BMI compared to T-allele carriers in both Chinese (p = 0.012) and Spanish (p = 0.017) samples. The 677C/T MTHFR polymorphism showed an additive effect, but no significant interaction, with the -759C/T HTR2C polymorphism previously associated with AIWG. These results suggest that the 677C/T MTHFR polymorphism might, along with the -759C/T HTR2C polymorphism and other genetic factors, provide a useful marker for the important and limiting side effect of AIWG.

  6. The effect of MTHFR C677T polymorphism on type 2 diabetes mellitus with vascular complications in Chinese Han population: a meta-analysis.

    PubMed

    Zhang, Dan; Zhou, Yijun; Han, Lingling; Ji, Hongmei; Li, Jia

    2014-01-01

    Methylenetetrahydrofolate reductase plays an important role in folate metabolism. Individuals who are type 2 diabetes mellitus have greatest risk for the development of vascular complications. The results of studies which assessed the association between MTHFR C677T polymorphism and T2DM with vascular complications were inconsistent in the Chinese Han population. The purpose of this meta-analysis was to assess the associations between MTHFR C677T polymorphism and T2DM with vascular complications in the Chinese Han population. We collected all relevant articles on MTHFR C677T polymorphisms and T2DM with vascular complications in the Chinese Han population in multiple electronic databases which were searched to December 2013. Fixed-effects and random-effects meta-analyses were performed to assess the odds ratios (ORs). Stratified Analysis, sensitivity Analysis and publication bias were examined. A total of 1984 diabetic patients with vascular complications and 1703 single diabetic patients were found in meta-analysis. There was a significant association between MTHFR C677T polymorphisms and T2DM with vascular complications under recessive genetic model, dominant genetic model, homozygous genetic model, heterozygous genetic model and allele comparison. Sensitivity analysis indicated that the overall result was dependable. Our meta-analysis suggests the MTHFR C677T polymorphisms is associated with T2DM with vascular complications in the Chinese Han population.

  7. 25 Years of GenBank

    MedlinePlus

    ... of this page please turn Javascript on. Unique DNA database has helped advance scientific discoveries worldwide Since ... GenBank? Basically, GenBank is the biggest database of DNA in the world. Deoxyribonucleic acid (DNA) is the ...

  8. Introduction to GenCade

    DTIC Science & Technology

    2012-10-01

    16-18 October 2012 5 GenCade Conceptual Processes: Coastal Sediment Dynamics Flood shoal ~150,000 m3/yr D50 = 0.27 (W) 0.38 (E) Moriches...offset • LMOVY 0.0 Leftward shoreline displacement velocity • D50 0.33 Grain size diameter in millimeters • BERMHT 2 Average berm height • DCLOS 8

  9. FutureGen Project Report

    SciTech Connect

    Cabe, Jim; Elliott, Mike

    2010-09-30

    This report summarizes the comprehensive siting, permitting, engineering, design, and costing activities completed by the FutureGen Industrial Alliance, the Department of Energy, and associated supporting subcontractors to develop a first of a kind near zero emissions integrated gasification combined cycle power plant and carbon capture and storage project (IGCC-CCS). With the goal to design, build, and reliably operate the first IGCC-CCS facility, FutureGen would have been the lowest emitting pulverized coal power plant in the world, while providing a timely and relevant basis for coal combustion power plants deploying carbon capture in the future. The content of this report summarizes key findings and results of applicable project evaluations; modeling, design, and engineering assessments; cost estimate reports; and schedule and risk mitigation from initiation of the FutureGen project through final flow sheet analyses including capital and operating reports completed under DOE award DE-FE0000587. This project report necessarily builds upon previously completed siting, design, and development work executed under DOE award DE-FC26- 06NT4207 which included the siting process; environmental permitting, compliance, and mitigation under the National Environmental Policy Act; and development of conceptual and design basis documentation for the FutureGen plant. For completeness, the report includes as attachments the siting and design basis documents, as well as the source documentation for the following: • Site evaluation and selection process and environmental characterization • Underground Injection Control (UIC) Permit Application including well design and subsurface modeling • FutureGen IGCC-CCS Design Basis Document • Process evaluations and technology selection via Illinois Clean Coal Review Board Technical Report • Process flow diagrams and heat/material balance for slurry-fed gasifier configuration • Process flow diagrams and heat/material balance

  10. High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short-term memory impairment in offspring.

    PubMed

    Bahous, Renata H; Jadavji, Nafisa M; Deng, Liyuan; Cosín-Tomás, Marta; Lu, Jessica; Malysheva, Olga; Leung, Kit-Yi; Ho, Ming-Kai; Pallàs, Mercè; Kaliman, Perla; Greene, Nicholas DE; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

    2017-01-09

    Methylenetetrahydrofolate reductase (MTHFR) generates methyltetrahydrofolate for methylation reactions. Severe MTHFR deficiency results in homocystinuria and neurologic impairment. Mild MTHFR deficiency (677C>T polymorphism) increases risk for complex traits, including neuropsychiatric disorders. Although low dietary folate impacts brain development, recent concerns have focused on high folate intake following food fortification and increased vitamin use. Our goal was to determine whether high dietary folate during pregnancy affects brain development in murine offspring. Female mice were placed on control diet (CD) or folic acid-supplemented diet (FASD) throughout mating, pregnancy and lactation. Three-week-old male pups were evaluated for motor and cognitive function. Tissues from E17.5 embryos, pups and dams were collected for choline/methyl metabolite measurements, immunoblotting or gene expression of relevant enzymes. Brains were examined for morphology of hippocampus and cortex.Pups of FASD mothers displayed short-term memory impairment, decreased hippocampal size and decreased thickness of the dentate gyrus. MTHFR protein levels were reduced in FASD pup livers, with lower concentrations of phosphocholine and glycerophosphocholine in liver and hippocampus, respectively. FASD pup brains showed evidence of altered acetylcholine availability and Dnmt3a mRNA was reduced in cortex and hippocampus. E17.5 embryos and placentas from FASD dams were smaller. MTHFR protein and mRNA were reduced in embryonic liver, with lower concentrations of choline, betaine and phosphocholine. Embryonic brain displayed altered development of cortical layers. In summary, high folate intake during pregnancy leads to pseudo-MTHFR 3 deficiency, disturbed choline/methyl metabolism, embryonic growth delay and memory impairment in offspring. These findings highlight the unintended negative consequences of supplemental folic acid.

  11. MTHFR (C677T) polymorphism and PR (PROGINS) mutation as genetic factors for preterm delivery, fetal death and low birth weight: A Northeast Indian population based study

    PubMed Central

    Tiwari, Diptika; Bose, Purabi Deka; Das, Somdatta; Das, Chandana Ray; Datta, Ratul; Bose, Sujoy

    2015-01-01

    Preterm delivery (PTD) is one of the most significant contributors to neonatal mortality, morbidity, and long-term adverse consequences for health; with highest prevalence reported from India. The incidence of PTD is alarmingly very high in Northeast India. The objective of the present study is to evaluate the associative role of MTHFR gene polymorphism and progesterone receptor (PR) gene mutation (PROGINS) in susceptibility to PTD, negative pregnancy outcome and low birth weights (LBW) in Northeast Indian population. Methods A total of 209 PTD cases {extreme preterm (< 28 weeks of gestation, n = 22), very preterm (28–32 weeks of gestation, n = 43) and moderate preterm (32–37 weeks of gestation, n = 144) and 194 term delivery cases were studied for MTHFR C677T polymorphism and PR (PROGINS) gene mutation. Statistical analysis was performed using SPSS software. Results Distribution of MTHFR and PR mutation was higher in PTD cases. Presence of MTHFR C677T polymorphism was significantly associated and resulted in the increased risk of PTD (p < 0.001), negative pregnancy outcome (p < 0.001) and LBW (p = 0.001); more significantly in extreme and very preterm cases. Presence of PR mutation (PROGINS) also resulted in increased risk of PTD and negative pregnancy outcome; but importantly was found to increase the risk of LBW significantly in case of very preterm (p < 0.001) and moderately preterm (p < 0.001) delivery cases. Conclusions Both MTHFR C677T polymorphism and PR (PROGINS) mutation are evident genetic risk factors associated with the susceptibility of PTD, negative pregnancy outcome and LBW. MTHFR C677T may be used as a prognostic marker to stratify subpopulation of pregnancy cases predisposed to PTD; thereby controlling the risks associated with PTD. PMID:25709895

  12. Glutamatergic synapse protein composition of wild-type mice is sensitive to in utero MTHFR genotype and the timing of neonatal vigabatrin exposure.

    PubMed

    Zuckerman, Chava; Blumkin, Elinor; Melamed, Osnat; Golan, Hava M

    2015-10-01

    The enzyme methylenetetrahydrofolate-reductase (MTHFR) is part of the homocysteine and folate metabolic pathways. In utero, Mthfr-deficient environment has been reported as a risk factor for neurodevelopmental disorders such as autism and neural tube defects. Neonatal disruption of the GABAergic system is also associated with behavioral outcomes. The interaction between Mthfr deficiency and neonatal exposure to the GABA-potentiating drug vigabatrin (GVG) in mice alters anxiety, memory, and social behavior in a gender-dependent manner. In addition, a gender-dependent enhancement of proteins implicated in excitatory synapse plasticity in the cerebral cortex was shown. Here we show that in utero MTHFR deficiency is sufficient to alter the levels of glutamate receptor subunits GluR1, GluR2, and NR2B in the cerebral cortex and hippocampus of adult offspring with a WT genotype. In addition, FMRP1, CAMKII α and γ, and NLG1 levels in WT offspring were vulnerable to the in utero genotype. These effects depend on brain region and the cellular compartment tested. The effect of in utero MTHFR deficiency varies with the age of neonatal GVG exposure to modify GluR1, NR2A, reelin, CAMKII α, and NLG1 levels. These changes in molecular composition of the glutamatergic synapse were associated with increased anxiety-like behavior. Complex, multifactorial disorders of the nervous system show significant association with several genetic and environmental factors. Our data exemplify the contribution of an in utero MTHFR-deficient environment and early exposure to an antiepileptic drug to the basal composition of the glutamatergic synapses. The robust effect is expected to alter synapse function and plasticity and the cortico-hippocampal circuitry.

  13. MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis.

    PubMed

    Nikzad, Hossein; Karimian, Mohammad; Sareban, Kobra; Khoshsokhan, Maryam; Hosseinzadeh Colagar, Abasalt

    2015-11-01

    Methylenetetrahydrofolate reductase (MTHFR) functions as a main regulatory enzyme in folate metabolism. The association of MTHFR gene Ala222Val polymorphism with male infertility in an Iranian population was investigated by undertaking a meta-analysis and in-silico approach. A genetic association study included 497 men; 242 had unexplained infertility and 255 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism was used for genotyping MTHFR-Ala222Val. OpenMeta[Analyst] software was used to conduct the analysis; 22 studies were identified by searching PubMed and the currently reported genetic association study. A novel in-silico approach was used to analyse the effects of Ala222Val substitution on the structure of mRNA and protein. Genetic association study revealed a significant association of MTHFR-222Val/Val genotype with oligozoospermia (OR 2.32; 95% CI, 1.12 to 4.78; P = 0.0451) and azoospermia (OR 2.59; 95% CI 1.09 to 6.17; P = 0.0314). Meta-analysis for allelic, dominant and codominant models showed a significant association between Ala222Val polymorphism and the risk of male infertility (P < 0.001). In silico-analysis showed MTHFR-Ala222Val affects enzyme structure and could also change the mRNA properties (P = 0.1641; P < 0.2 is significant). The meta-analysis suggested significant association of MTHFR-Ala222Val with risk of male infertility, especially in Asian populations.

  14. Summary of CPAS Gen II Parachute Analysis

    NASA Technical Reports Server (NTRS)

    Morris, Aaron L.; Bledsoe, Kristin J.; Fraire, Usbaldo, Jr.; Moore, James W.; Olson, Leah M.; Ray, Eric

    2011-01-01

    The Orion spacecraft is currently under development by NASA and Lockheed Martin. Like Apollo, Orion will use a series of parachutes to slow its descent and splashdown safely. The Orion parachute system, known as the CEV Parachute Assembly System (CPAS), is being designed by NASA, the Engineering and Science Contract Group (ESCG), and Airborne Systems. The first generation (Gen I) of CPAS testing consisted of thirteen tests and was executed in the 2007-2008 timeframe. The Gen I tests provided an initial understanding of the CPAS parachutes. Knowledge gained from Gen I testing was used to plan the second generation of testing (Gen II). Gen II consisted of six tests: three singleparachute tests, designated as Main Development Tests, and three Cluster Development Tests. Gen II required a more thorough investigation into parachute performance than Gen I. Higher fidelity instrumentation, enhanced analysis methods and tools, and advanced test techniques were developed. The results of the Gen II test series are being incorporated into the CPAS design. Further testing and refinement of the design and model of parachute performance will occur during the upcoming third generation of testing (Gen III). This paper will provide an overview of the developments in CPAS analysis following the end of Gen I, including descriptions of new tools and techniques as well as overviews of the Gen II tests.

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

    PubMed

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

    2012-04-01

    Few prospective studies have examined the associations between blood levels of folate, in conjunction with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and colorectal cancer. We evaluated the associations between plasma folate, MTHFR C677T, and A1298C, and colorectal cancer in three large prospective studies: the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physicians' Health Study. A total of 602 incident cases were identified and individually matched to controls who provided blood specimens. We used conditional logistic regression to calculate the relative risk (RR) and 95% confidence interval (95% CI) and then pooled the estimates using a random effects model. We found a lower risk of colorectal cancer among participants with low plasma folate levels: compared with the lowest quartile, RRs (95% CIs) for each successively higher quartile of plasma folate levels were 1.55 (1.14-2.11), 1.37 (1.00-1.88), and 1.47 (1.07-2.01; P for trend = 0.10). For the MTHFR polymorphisms, RRs (95% CIs) were 0.62 (0.44-0.90) for 677TT versus CC/CT and 0.68 (0.31-1.51) for 1298CC versus AC/AA, and these lower-risk genotypes were associated with lower circulating plasma folate levels. When we partitioned the variation in plasma folate levels, variation due to folate intake was not positively associated with colorectal cancer risk. We found that low plasma folate levels were associated with lower risk of colorectal cancer. The reasons underlying a lower risk of colorectal cancer with low plasma folate levels require elucidation because plasma folate levels can reflect dietary intake, genetic influences, and other factors.

  16. Role of MTHFR C677T gene polymorphism in the susceptibility of schizophrenia: An updated meta-analysis.

    PubMed

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

    2016-04-01

    Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate/homocysteine metabolic pathway. C677T polymorphism of MTHFR gene was reported as risk factor for congenital defects, metabolic and neuropsychiatric disorders. Numerous case-control studies investigated C677T polymorphism as risk factor for schizophrenia but results of these studies were contradictory. To draw a conclusion, a meta-analysis of all available case-control studies was performed. PubMed, Google Scholar, Springer Link and Elsevier databases were searched for eligible case-control studies. Pooled odds ratio with 95%CI was used as an association measure and all statistical analyses were performed by Open Meta-Analyst and MIX software. Total 38 studies with 10,069 cases and 13,372 controls were included in the present meta-analysis. Results of meta-analysis showed significant associated between C677T polymorphism and risk of schizophrenia (ORTvsC=1.18, 95%CI=1.10-1.27, p=<0.001; ORCTvsCC=1.10, 95%CI=1.04-1.17, p=<0.001; ORTTvsCC=1.40, 95%CI=1.20-1.64, p=<0.001; ORTT+CTvsCC=1.19, 95%CI=1.09-1.30, p=<0.001). We also performed subgroup and sensitivity analyses. Subgroup analysis was done according to ethnicity and significant association was found between C677T polymorphism and risk of schizophrenia in all three ethnic populations-African (OR=2.51; 95%CI=1.86-3.40; p=<0.001), Asian (OR=1.21; 95%CI=1.10-1.33; p=<0.001) and Caucasian (OR=1.07; 95%CI=1.01-1.14; p=0.01). In conclusion the results of the present meta-analysis suggested that the MTHFR C677T polymorphism is a risk factor for schizophrenia.

  17. The MTHFR 677C-->T polymorphism and behaviors in children with autism: exploratory genotype-phenotype correlations.

    PubMed

    Goin-Kochel, Robin P; Porter, Anne E; Peters, Sarika U; Shinawi, Marwan; Sahoo, Trilochan; Beaudet, Arthur L

    2009-04-01

    New evidence suggests that autism may be associated with (a) varied behavioral responses to folate therapy and (b) metabolic anomalies, including those in folate metabolism, that contribute to hypomethylation of DNA. We hypothesized that children with autism who are homozygous for the MTHFR 677 T allele (TT) and, to a lesser extent those with the CT variant, would exhibit more behavioral problems and/or more severe problematic behaviors than homozygous wild-type (CC) individuals because of difficulties in effectively converting 5,10-MTHF to 5-MTHF. Data from the Autism Genetic Resource Exchange (AGRE) collection were analyzed for all children who met strict criteria for autism per the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) and who had been genotyped for the 677 C to T MTHFR polymorphism (n=147). Chi-square tests, logistic regression, and one-way ANOVAs were used to determine whether differences existed among MTHFR genotypes for specific behaviors on the ADI-R and indices for level of functioning. Exploratory results indicated four behaviors from the ADI-R that were more common and problematic (95% CI) among those with at least one copy of the T allele as compared to homozygous wild-type individuals: direct gaze, current complex body movements, a history of self-injurious behavior, and current overactivity (ORs=2.72, 2.33, 2.12, 2.47, respectively). No differences existed among genotypes for level of functioning as measured with the Peabody Picture Vocabulary Test-Third Edition, Ravens Colored Progressive Matrices, or the Vineland Adaptive Behavior Scales. Findings call for further investigation of the relationship between folate metabolism and problem behaviors among children with autism.

  18. Coenzyme Q10, hyperhomocysteinemia and MTHFR C677T polymorphism in levodopa-treated Parkinson's disease patients.

    PubMed

    Gorgone, Gaetano; Currò, Monica; Ferlazzo, Nadia; Parisi, Giulia; Parnetti, Lucilla; Belcastro, Vincenzo; Tambasco, Nicola; Rossi, Aroldo; Pisani, Francesco; Calabresi, Paolo; Ientile, Riccardo; Caccamo, Daniela

    2012-03-01

    There is evidence that increased homocysteine (Hcy) levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects. Homocysteine neurotoxicity mainly relies on redox state alterations. The present work was aimed at investigating the relationships between plasma Hcy concentrations and percent content of oxidized versus total Coenzyme Q10 (%CoQ10) in 60 PD patients and 82 healthy subjects. Both groups were screened for plasma levels of Hcy, vitamin B12, folate, %CoQ10 and C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism. The MTHFR TT677 mutated genotype was found more frequently in patients than in controls (p = 0.01). In a multivariate analysis, Hcy levels and %CoQ10 were associated with the case/control category (p < 0.0001), MTHFR genotype (p < 0.0001) and their interaction term (p = 0.0015), even after adjusting for age, sex, folate and vitamin B12. Patients carrying the TT677 genotype exhibited the highest values of Hcy and %CoQ10 (p < 0.0001). Structural equation modelling evidenced that the TT677 genotype and levodopa daily dose were independently and directly correlated with Hcy (p < 0.0001, and p = 0.003, respectively), which, in turn, showed a significant correlation (p < 0.0001) with the %CoQ10 in PD patients. Our results suggest that increased Hcy levels act as mediator of the systemic oxidative stress occurring in PD, and %CoQ10 determination might be regarded as a predictor of toxic Hcy effects.

  19. The C677T variant in MTHFR modulates associations between blood-based and cerebrospinal fluid biomarkers of neurodegeneration

    PubMed Central

    Roussotte, Florence F.; Narr, Katherine L.; Small, Gary W.

    2016-01-01

    The C677T functional variant in the methylene-tetrahydrofolate reductase (MTHFR) gene results in reduced enzymatic activity and elevated blood levels of homocysteine. Plasma levels of apolipoprotein E (ApoE) are negatively correlated with cerebral amyloid burden, but plasma homocysteine concentrations are associated with increased amyloid-β (Aβ) deposition in the brain. Here, we sought to determine whether associations between low plasma ApoE levels and elevated in-vivo amyloid burden were modulated by carrying the C677T variant. We tested this hypothesis in a large sample of elderly participants from the Alzheimer’s Disease Neuroimaging Initiative. We used general linear models to examine associations between plasma homocysteine concentrations, circulating ApoE levels, cerebrospinal fluid concentrations of Aβ, and their modulation by MTHFR and ApoE genotype. Age, sex, and dementia status were included as covariates in all analyses. Higher circulating levels of ApoE predicted increased cerebrospinal fluid concentrations of Aβ, indicating lower in-vivo burden, in C-allele carriers, but not in homozygotes at the C677T variant, who showed significant elevations in plasma homocysteine levels. This modulation by the MTHFR genotype did not remain significant after controlling for ApoE genotype. In T-homozygotes who do not carry the ApoE-ε4 allele, the relationship between low plasma ApoE levels and an increased risk of dementia is likely obscured by the presence of elevated plasma homocysteine. This report suggests the value of genotyping patients at the C677T functional variant when using plasma ApoE levels as a preclinical biomarker for Alzheimer’s disease. PMID:27380243

  20. Association of OGG1 and MTHFR polymorphisms with age-related cataract: A systematic review and meta-analysis

    PubMed Central

    Liu, Yizhi

    2017-01-01

    Purpose To discern and confirm genetic biomarkers that help identify populations at high risk for age-related cataract (ARC). Methods A literature search was performed in the PubMed, Web of Science and China National Knowledge Internet databases for genetic association studies published before June 26, 2016 regarding ARC susceptibility. All genetic polymorphisms reported were systematically reviewed, followed by extraction of candidate genes/loci with sufficient genotype data in ≥3 studies for the meta-analysis. A random/fixed-effects model was used to calculate the pooled odds ratios and 95% confidence intervals to evaluate the associations considering multiple genetic models. Sensitivity analysis was also performed. Results A total of 144 polymorphisms in 36 genes were reported in the 61 previous genetic association studies. Thereby, three polymorphisms of two genes (8-oxoguanine DNA glycosylase-1 [OGG1]; methylenetetrahydrofolate reductase NADPH [MTHFR]) in eight studies were included in the meta-analysis. Regarding the OGG1-rs1052133, the GG (OR = 1.925; 95%CI, 1.181–3.136; p = 0.009) and CG (OR = 1.384; 95%CI, 1.171–1.636; p<0.001) genotypes indicated higher risk of ARC. For the MTHFR gene, the CC+TT genotype of rs1801133 might be protective (OR, 0.838; 95%CI, 0.710–0.989; p = 0.036), whereas the AA+CC genotype of rs1801131 indicated increased risk for the mixed subtype (OR = 1.517; 95%CI, 1.113–2.067; p = 0.008). Conclusions Polymorphisms of OGG1 and MTHFR genes are associated with ARC susceptibility and may help identify populations at high risk for ARC. PMID:28253266

  1. Association of MTHFR, SLC19A1 Genetic Polymorphism, Serum Folate, Vitamin B12 and Hcy Status with Cognitive Functions in Chinese Adults

    PubMed Central

    Cai, Can; Xiao, Rong; Van Halm-Lutterodt, Nicholas; Zhen, Jie; Huang, Xiaochen; Xu, Yao; Chen, Shuying; Yuan, Linhong

    2016-01-01

    Background/Aim: Studies have indicated a relationship between either gene polymorphism or in vivo B vitamins’ nutritional status with cognition in the elderly. However, the combined effects of MTHFR and SLC19A1gene polymorphism with serum folate and vitamin B12 levels on cognition in Chinese adult population remain unclear. Methods: Demographic information of 426 Chinese adults aged from 55 to 90 were collected by a well designed self-administered questionnaire. The Montreal Cognitive Assessment test was utilized to evaluate the cognition status of the participants. MTHFR and SLC19A1 genotyping was analyzed using polymerase chain reaction-ligase detection reaction (PCR- LDR) method. Serum folate, vitamin B12 and homocysteine (Hcy) levels were detected by commercial assay kits. Pearson’s correlation was used for data analyses and statistical significance was set at p < 0.05. Results: Serum Hcylevels demonstrated a negative correlation with serum folate (r = −0.301) and vitamin B12 (r = −0.292) levels. The negative correlation found between serum Hcy levels and attention ability was observed in all 426 studied subjects (r = −0.122). Subjects with MTHFR 677 T/T and 1298 A/A genotypes demonstrated a higher serum Hcy levels (p < 0.05). Carriers of MTHFR (1298 A/C + C/C and 1793 G/A) and SLC19A1 80 G/G genotypes showed lower abstraction and delayed memory ability, respectively (p < 0.05). Subjects with MTHFR 1793 G/A genotype along with low serum folate concentration demonstrated the lowest name and orientation abilities. The effects of MTHFR 1793 G/A genotype on cognitive performance were dependent on the status of serum vitamin B12. Conclusion: Cognition of adults was associated with MTHFR, SLC19A1 gene polymorphism and serum Hcy levels. This study clearly establishes a combined effect of MTHFR gene polymorphism and serum B vitamins levels on cognition in Chinese adults. PMID:27783031

  2. Human genetic selection on the MTHFR 677C>T polymorphism

    PubMed Central

    Mayor-Olea, Álvaro; Callejón, Gonzalo; Palomares, Arturo R; Jiménez, Ana J; Gaitán, María Jesús; Rodríguez, Alfonso; Ruiz, Maximiliano; Reyes-Engel, Armando

    2008-01-01

    Background The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA). Methods A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman® probes. A section of our population (n = 276) born in 1980–1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period. Results An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980–1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98. Conclusion Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations. PMID:19040733

  3. Meta-analysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity

    PubMed Central

    Fisher, Mark C.; Cronstein, Bruce N.

    2008-01-01

    Objective Methotrexate is an effective therapy for Rheumatoid Arthritis (RA) but is also associated with toxicity. Pharmacogenetics is the systematic evaluation of the role of genetic differences in the efficacy and toxicity of therapeutic interventions. Because the results of small pharmacogenetic studies are often misleading, we undertook a meta-analysis of published studies to determine the role of polymorphisms in the therapeutic efficacy and toxicity of methotrexate. Methods A search of PUBMED produced 55 publications which were then reviewed for relevance to methotrexate toxicity and efficacy in patients with RA. To ensure that no studies were missed, each polymorphism found was then entered as an independent search string and all results were again reviewed. Results Only 2 polymorphisms (C677T and A1298C in methylenetetrahydrofolate reductase, MTHFR, total: 8 studies) relevant to methotrexate metabolism and efficacy had sufficient data to perform a meta-analysis of their association with toxicity; there was no polymorphism with sufficient data to perform a meta-analysis of efficacy. In a fixed effects model, the C677T polymorphism was associated with increased toxicity (OR 1.71, CI 1.32 – 2.21, p<0.001). The A1298C polymorphism was not associated with increased toxicity (OR 1.12, CI 0.79 – 1.6, p=0.626). Conclusions As pharmacogenetics evolves, more data are needed to assess the role of various polymorphisms for drug efficacy and toxicity. These results illustrate the paucity of reliable pharmacogenetic data on a commonly used anti-rheumatic drug and the potential role of pharmacogenetics in tailoring drug therapy for an individual patient. PMID:19208607

  4. Mutation and association analysis of GEN1 in breast cancer susceptibility

    PubMed Central

    Turnbull, Clare; Hines, Sarah; Renwick, Anthony; Hughes, Deborah; Pernet, David; Elliott, Anna; Seal, Sheila; Warren-Perry, Margaret; Evans, D. Gareth; Eccles, Diana; Stratton, Michael R.

    2013-01-01

    GEN1 was recently identified as a key Holliday junction resolvase involved in homologous recombination. Somatic truncating GEN1 mutations have been reported in two breast cancers. Together these data led to the proposition that GEN1 is a breast cancer predisposition gene. In this article we have formally investigated this hypothesis. We performed full-gene mutational analysis of GEN1 in 176 BRCA1/2-negative familial breast cancer samples and 159 controls. We genotyped six SNPs tagging the 30 common variants in the transcribed region of GEN1 in 3,750 breast cancer cases and 4,907 controls. Mutation analysis revealed one truncating variant, c.2515_2519del-AAGTT, which was present in 4% of cases and 4% of controls. We identified control individuals homozygous for the deletion, demonstrating that the last 69 amino acids of GEN1 are dispensable for its function. We identified 17 other variants, but their frequency did not significantly differ between cases and controls. Analysis of 3,750 breast cancer cases and 4,907 controls demonstrated no evidence of significant association with breast cancer for six SNPs tagging the 30 common GEN1 variants. These data indicate that although it also plays a key role in double-strand DNA break repair, GEN1 does not make an appreciable contribution to breast cancer susceptibility by acting as a high- or intermediate-penetrance breast cancer predisposition gene like BRCA1, BRCA2, CHEK2, ATM, BRIP1 and PALB2 and that common GEN1 variants do not act as low-penetrance susceptibility alleles analogous to SNPs in FGFR2. Furthermore, our analyses demonstrate the importance of undertaking appropriate genetic investigations, typically full gene screening in cases and controls together with large-scale case–control association analyses, to evaluate the contribution of genes to cancer susceptibility. PMID:20512659

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

    PubMed

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

    2008-03-01

    We tested whether the polymorphisms of the methylenetetrahydrofolate reductase gene, MTHFR C677T and A1298C, the methionine synthase gene, MTR A2756G, the methionine synthase reductase gene, MTRR A66G, and the thymidylate synthase gene, TYMS 2R-->3R, involved in folate and methionine metabolism, altered the risk for multiple myeloma (MM). Genomic DNA from 123MM patients and 188 controls was analysed by polymerase chain reaction and restriction digestion for the polymorphism analyses. The frequency of the MTR 2756 AG plus GG genotype was higher in patients than in controls (39.8% versus 23.4%, P=0.001). Individual carriers of the variant allele G had a 2.31 (95% CI: 1.38-3.87)-fold increased risk for MM compared with others. In contrast, similar frequencies of the MTHFR, the MTRR and the TYMS genotypes were seen in patients and controls. These results suggest, for the first time, a role for the MTR A2756G polymorphism in MM risk in our country, but should be confirmed by large-scale epidemiological studies with patients and controls age matched.

  6. Folate supplementation, MTHFR gene polymorphism and neural tube defects: a community based case control study in North India.

    PubMed

    Deb, Roumi; Arora, Jyoti; Meitei, Sanjenbam Yaiphaba; Gupta, Sangeeta; Verma, Vanita; Saraswathy, Kallur Nava; Saran, Sunil; Kalla, Aloke Kumar

    2011-09-01

    The present study analyses the potential role of MTHFR gene polymorphism, folate supplementation and dietary pattern among the mothers of NTD neonates and controls in heterogeneous populations of North India, with the special focus on their ethnic labels. Results indicated significant increased risk for neural tube defects with respect to low folic acid supplementation and vegetarian diet in univariate and multivariate analyses. There was no significant difference in the genotypic or allelic distribution of MTHFR C677T polymorphism, however, high frequency of CT genotype, as observed, among controls suggests heterozygous advantage probably due to supplementary folate. Among the two communities, Muslim NTD mothers had higher TT genotype showing increased risk for neural tube defects (adjusted OR: 12.9; 95% CI: 1.21-136.8) and lower folic acid supplementation (adjusted OR: 3.5; 95% CI: 1.18-10.22). Whereas, marginal increased risk for NTDs with vegetarian diet was observed among Hindus. Cultural and ethnic variation in the risk factors for neural tube defects is highlighted in the study.

  7. The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia

    PubMed Central

    Trifonova, E.A.; Eremina, E.R.; Urnov, F.D.; Stepanov, V.A.

    2012-01-01

    The structure of the haplotypes and linkage disequilibrium (LD) of the methylenetetrahydrofolate reductase gene (MTHFR) in 9 population groups from Northern Eurasia and populations of the international HapMap project was investigated in the present study. The data suggest that the architecture of LD in the human genome is largely determined by the evolutionary history of populations; however, the results of phylogenetic and haplotype analyses seems to suggest that in fact there may be a common “old” mechanism for the formation of certain patterns of LD. Variability in the structure of LD and the level of diversity of MTHFRhaplotypes cause a certain set of tagSNPs with an established prognostic significance for each population. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: namely, the association of interpopulation differences in the patterns of LD with structures possessing a genetic susceptibility to complex diseases, and the functional significance of the pleiotropicMTHFR gene effect. Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics. PMID:22708063

  8. MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

    PubMed

    Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

    2015-08-06

    Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory

  9. The 844ins68 cystathionine beta-synthase and C677T MTHFR gene polymorphism and the vaso-occlusive event risk in sickle cell disease

    PubMed Central

    Alves Jacob, Maza; da Cunha Bastos, Celso; Regina Bonini-Domingos, Claudia

    2011-01-01

    Introduction Sickle cell disease (SCD) is an inflammatory condition with an increase in the adhesion of sickled erythrocytes, and it is a potential cause of vaso-occlusive episodes, an event related to clinical manifestations, morbidity and mortality. The cystathionine beta-synthase enzyme gene (CBS) and the methylenetetrahydrofolate reductase enzyme gene (MTHFR) are risk factors for thromboembolic disorders. This study evaluated the frequency of the 844ins68 CBS and C677T MTHFR gene polymorphisms and their possibility to be risk factors for vaso-occlusive crises. Material and methods In total 91 blood samples from SCD patients were studied by PCR-RFLP and PCR-allele-specific, for the SCD genotype confirmation and polymorphism identification. Results The presence of clinical manifestations related to vaso-occlusive crises were more frequent among patients with the Hb SS genotype (p = 0.007). The CBS enzyme gene was three times more frequent (p = 0.011) among patients with vaso-occlusive complications. The MTHFR gene mutation frequency showed no increased risk for vaso-occlusive crises in SCD patients (p = 0.193). The interaction between the two polymorphisms was evaluated in 12.08% of the SCD patients and doubled the vaso-occlusive disease risk (relative risk: 2.16). Conclusions We conclude that the presence of 844ins68 CBS and C677T MTHFR gene polymorphism was a risk factor for vaso-occlusive episodes in the SCD patients evaluated. PMID:22291740

  10. Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population

    PubMed Central

    Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

    2015-01-01

    Abstract The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population. A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group). Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model. Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population. PMID:26717388

  11. The 677C>T mutation of the MTHFR gene increases the risk of venous thromboembolism in Koreans and a meta-analysis from Asian population.

    PubMed

    Jang, Moon Ju; Jeon, Young Joo; Choi, Won-Il; Choi, Yi Seul; Kim, Su Yeoun; Chong, So Young; Oh, Doyeun; Kim, Nam Keun

    2013-06-01

    The frequency of methylenetetrahydrofolate reductase (MTHFR) mutations varies between racial and ethnic groups, and there are also conflicting data regarding MTHFR gene mutations in Asian patients with venous thromboembolism (VTE). The aim of this study was to examine the association between common MTHFR gene mutations (677C>T and 1298A>C) and risk of VTE in Koreans. This study was a retrospective case-control study. We enrolled 203 patients with VTE and 403 controls. For the 677C>T polymorphism, there was no difference in the frequency of the CT genotype and TT genotype between the patients with VTE and the controls. However, in the recessive analysis (CC + CT vs TT), the frequency of the TT genotype was significantly higher in VTE than in controls (odds ratio = 1.700; 95% confidence interval = 1.108-2.607, P = .015). In conclusion, the TT genotype of MTHFR 677C>T increases the risk of VTE in Koreans. This finding was supported by meta-analysis of previous Asian studies.

  12. Association between MTHFR C677T Polymorphism and Risk of Acute Lymphoblastic Leukemia: A Meta-Analysis Based on 51 Case-Control Studies

    PubMed Central

    Li, Su-yi; Ye, Jie-yu; Liang, En-yu; Zhou, Li-xia; Yang, Mo

    2015-01-01

    Background Studies and systematic reviews have reached inconsistent conclusions on the role of 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T in acute lymphoblastic leukemia (ALL) risk. Material/Methods The present meta-analysis comprising of 51 case-control studies, including 7892 cases and 14 280 controls was performed to reevaluate the association between MTHFR C677T polymorphism and ALL risk. Results Statistical differences were found in the dominant model (TT+CT vs. CC, odd ratio (OR)=0.89, 95% CI, 0.79–1.00, P=0.04) and the CT vs. CC (OR=0.89, 95% CI, 0.80–1.00, P=0.05), but not in the allele contrast model (T vs. C, OR=0.92, 95% CI, 0.84–1.01, P=0.08), additive model (TT vs. CC, OR=0.87, 95% CI, 0.73–1.05, P=0.15), or recessive model (TT vs. CT+CC, OR=0.94, 95% CI, 0.81–1.10, P=0.44) in overall populations. In the subgroup analyses stratified by age (children and adults) and ethnicity (Asian and Caucasian), no significant associations between MTHFR C677T polymorphism and ALL risk were observed. Conclusions The current study found no sufficient evidence of a protective role of MTHFR C677T polymorphism in ALL susceptibility. PMID:25761797

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Association of MTHFR C677T and A1298C polymorphisms with oral cancer susceptibility: evidence from a meta-analysis

    PubMed Central

    Jiang, Sui; Xu, Jin-Dong; Zhuo, Zhen-Jian; Hua, Zhu-Ming

    2017-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is a central enzyme involved in folate metabolism and plays an important role in DNA synthesis and methylation. Several studies have been conducted to illustrate the associations between MTHFR C677T and A1298C polymorphisms with oral cancer susceptibility; however, the results are inconsistent. Therefore, we conducted an updated meta-analysis to obtain a more reliable estimation of the associations. We retrieved eligible studies from PubMed, EMBASE, and CBM databases through September 2016. Ultimately, pooled analyses involved 10 studies with 1443 cases and 1640 controls for the C677T polymorphism, as well as five studies with 973 cases and 1024 controls for the A1298C polymorphism. Risk estimates were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). Pooled results indicated that neither C677T nor A1298C polymorphism was associated with oral cancer susceptibility. However, a borderline significant association was detected between MTHFR C677T polymorphism and a decreased oral cancer risk (homozygous model: OR=0.71, 95% CI=0.50–1.00) in hospital-based studies. Our results suggested that MTHFR C677T and A1298C polymorphisms might not be associated with oral cancer risk. However, more evidence is needed to further confirm these findings in the future. PMID:28138253

  15. MTHFR C677T polymorphism and breast, ovarian cancer risk: a meta-analysis of 19,260 patients and 26,364 controls

    PubMed Central

    He, Lilin; Shen, Yongxiang

    2017-01-01

    Objective Previous studies have found that many gene variations can be detected in both breast cancer and ovarian cancer, which is beneficial for the elaboration of the molecular origin of breast and ovarian cancer. Furthermore, many studies have explored the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with the risk of breast cancer and/or ovarian cancer; however, the results remained inconclusive. Therefore, this study conducted a systematic review and meta-analysis to evaluate the association between MTHFR C677T polymorphism and the risk of breast and ovarian cancer. Materials and methods A total of 50 studies with 19,260 cases and 26,364 controls including 39 studies for breast cancer and 8 studies for ovarian cancer were identified on searching through PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP). Allele model, dominant model, recessive model, homozygous model, and co-dominant model were applied to evaluate the association of MTHFR C677T polymorphism with breast cancer and/or ovarian cancer risk. Moreover, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between MTHFR C677T polymorphism and breast and ovarian cancer risk. Results A significantly increased breast cancer risk was observed in the overall analysis (for C vs T, OR =1.19, CI: 1.12–1.28, P<0.05; for CC vs TT, OR =1.20, CI: 1.10–1.23, P<0.05; for (CT+CC) vs TT, OR =1.19, CI: 1.11–1.27, P<0.05; for CC vs (CT+TT), OR =1.19, CI: 1.79–1.95, P<0.05), while no significantly increased ovarian cancer risk was detected. In the subgroup analysis based on ethnicity, a significant association of breast cancer and/or ovarian cancer risk with MTHFR C677T polymorphism was observed in Asians. Interestingly, there was no significant association between MTHFR C677T polymorphism and ovarian cancer risk in

  16. Sodium arsenite alters cell cycle and MTHFR, MT1/2, and c-Myc protein levels in MCF-7 cells

    SciTech Connect

    Ruiz-Ramos, Ruben; Lopez-Carrillo, Lizbeth; Albores, Arnulfo; Hernandez-Ramirez, Raul U.; Cebrian, Mariano E.

    2009-12-15

    There is limited available information on the effects of arsenic on enzymes participating in the folate cycle. Therefore, our aim was to evaluate the effects of sodium arsenite on the protein levels of methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) and its further relationship with the expression MT1/2 and c-myc in MCF-7 cells. Arsenite treatment (0-10 muM) for 4 h decreased MTHFR levels in a concentration-dependent fashion without significant effects on DHFR. The effects on MTHFR were observed at arsenite concentrations not significantly affecting cell viability. We also observed an increase in S-phase recruitment at all concentrations probed. Lower concentrations (< 5 muM) induced cell proliferation, showing a high proportion of BrdU-stained cells, indicating a higher DNA synthesis rate. However, higher concentrations (>= 5 muM) or longer treatment periods induced apoptosis. Arsenite also induced dose-dependent increases in MT1/2 and c-Myc protein levels. The levels of MTHFR were inversely correlated to MT1/2 and c-Myc overexpression and increased S-phase recruitment. Our findings indicate that breast epithelial cells are responsive to arsenite and suggest that exposure may pose a risk for breast cancer. The reductions in MTHFR protein levels contribute to understand the mechanisms underlying the induction of genes influencing growth regulation, such as c-myc and MT1/2. However, further research is needed to ascertain if the effects here reported following short-time and high-dose exposure are relevant for human populations chronically exposed to low arsenic concentrations.

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

    PubMed

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

    2014-08-01

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

  18. Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia.

    PubMed

    Nishi, Akira; Numata, Shusuke; Tajima, Atsushi; Kinoshita, Makoto; Kikuchi, Kumiko; Shimodera, Shinji; Tomotake, Masahito; Ohi, Kazutaka; Hashimoto, Ryota; Imoto, Issei; Takeda, Masatoshi; Ohmori, Tetsuro

    2014-09-01

    Previous studies suggest that elevated blood homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are risk factors for schizophrenia. However, the effects of gender and MTHFR C677T genotypes on blood homocysteine levels in schizophrenia have not been consistent. We first investigated whether plasma total homocysteine levels were higher in patients with schizophrenia than in controls with stratification by gender and by the MTHFR C677T genotypes in a large cohort (N = 1379). Second, we conducted a meta-analysis of association studies between blood homocysteine levels and schizophrenia separately by gender (N = 4714). Third, we performed a case-control association study between the MTHFR C677T polymorphism and schizophrenia (N = 4998) and conducted a meta-analysis of genetic association studies based on Japanese subjects (N = 10 378). Finally, we assessed the effect of plasma total homocysteine levels on schizophrenia by a mendelian randomization approach. The ANCOVA after adjustment for age demonstrated a significant effect of diagnosis on the plasma total homocysteine levels in all strata, and the subsequent meta-analysis for gender demonstrated elevated blood homocysteine levels in both male and female patients with schizophrenia although antipsychotic medication might influence the outcome. The meta-analysis of the Japanese genetic association studies demonstrated a significant association between the MTHFR C677T polymorphism and schizophrenia. The mendelian randomization analysis in the Japanese populations yielded an OR of 1.15 for schizophrenia per 1-SD increase in plasma total homocysteine. Our study suggests that increased plasma total homocysteine levels may be associated with an increased risk of schizophrenia.

  19. Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer's and Parkinson's diseases.

    PubMed

    Dorszewska, Jolanta; Florczak, Jolanta; Rozycka, Agata; Kempisty, Bartosz; Jaroszewska-Kolecka, Joanna; Chojnacka, Katarzyna; Trzeciak, Wiesław H; Kozubski, Wojciech

    2007-01-01

    Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are accompanied by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo2dG) and alterations in levels of homocysteine (Hcy), methionine (Met), and cysteine (Cys). Hcy may undergo remethylation due to involvement of MTHFR, MTR and MTHFD1 proteins. Present studies are aimed at determination of 8-oxo2dG, Hcy, Met, and Cys in AD and PD patients as well as in control groups, using HPLC/EC/UV, as well as estimation, by restriction analysis, frequency of following gene polymorphisms: MTHFR (C677T, A1298C, G1793A), MTHFD1 (G1958A), and MTR (A2756G). In AD there were significant differences of the levels of only Cys (GG, MTHFR, G1793A) and Met/Hcy (AA, MTHFD1, G1958A) whereas in PD there were more significant differences of the levels of thiols: Hcy [MTHFR: CT (C677T) and GG (G1793A); MTR, AG (A2756G)], Met [MTR, AA (A2756G)], Cys [MTR, AG (A2756G)], and Met/Hcy [MTHFR: CC, CT (C677T) and AA (A1298C), and GG (G1793A); MTHFD1 AA(G1958A); MTR AA(A2756G)]. Significant differences in the levels of Cys/Hcy, MTHFD1 GA (G1958) were varied between AD and PD groups. The results indicate that of the enzymes studied only polymorphisms of folate-dependent enzyme MTHFD1 have pointed to significant differences in intensity of turnover of circulating thiols between AD and PD patients.

  20. MTHFR C677T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d9-choline123

    PubMed Central

    Yan, Jian; Wang, Wei; Gregory, Jesse F; Malysheva, Olga; Brenna, J Thomas; Stabler, Sally P; Allen, Robert H; Caudill, Marie A

    2011-01-01

    Background: Homozygosity for the variant 677T allele in the methylenetetrahydrofolate reductase (MTHFR) gene increases the requirement for folate and may alter the metabolic use of choline. The choline adequate intake is 550 mg/d for men, although the metabolic consequences of consuming extra choline are unclear. Objective: Deuterium-labeled choline (d9-choline) as tracer was used to determine the differential effects of the MTHFR C677T genotype and the effect of various choline intakes on the isotopic enrichment of choline derivatives in folate-compromised men. Design: Mexican American men with the MTHFR 677CC or 677TT genotype consumed a diet providing 300 mg choline/d plus supplemental choline chloride for total choline intakes of 550 (n = 11; 4 with 677CC and 7 with 677TT) or 1100 (n = 12; 4 with 677CC and 8 with 677TT) mg/d for 12 wk. During the last 3 wk, 15% of the total choline intake was provided as d9-choline. Results: Low but measurable enrichments of the choline metabolites were achieved, including that of d3-phosphatidylcholine (d3-PtdCho)—a metabolite produced in the de novo pathway via choline-derived methyl groups. Men with the MTHFR 677TT genotype had a higher urinary enrichment ratio of betaine to choline (P = 0.041), a higher urinary enrichment of sarcosine (P = 0.041), and a greater plasma enrichment ratio of d9-betaine to d9-PtdCho with the 1100 mg choline/d intake (P = 0.033). Conclusion: These data show for the first time in humans that choline itself is a source of methyl groups for de novo PtdCho biosynthesis and indicate that the MTHFR 677TT genotype favors the use of choline as a methyl donor. PMID:21123458

  1. Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts.

    PubMed

    Chevrier, Cécile; Perret, Claire; Bahuau, Michel; Zhu, Huiping; Nelva, Agnès; Herman, Christine; Francannet, Christine; Robert-Gnansia, Elisabeth; Finnell, Richard H; Cordier, Sylvaine

    2007-02-01

    The association between maternal folate intake and risk of nonsyndromic oral clefts has been studied among many populations with conflicting results. The methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate metabolism, and several polymorphisms, including C677T, are common in European populations. Data from a French study (1998-2001) let us investigate the roles of maternal dietary folate intake and the MTHFR polymorphism and their interaction on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only (CP). We used both case-control (164 CL/P, 76 CP, 236 controls; 148, 59, 168 of whom, respectively, had an available genotype) and case-parent (143 CL/P and 56 CP families) study designs and distinguished the role of the child's genotype and maternally mediated effects on risks. This study observed a beneficial effect of mothers' dietary folate intake on their offspring's risk (odds ratio (OR)(< or = 230 microg/day) = ref; for CL/P, OR([230-314 microg/day]) = 0.56, 95% confidence interval = 0.3-0.9, OR(>314 microg/day) = 0.64, 0.4-1.1; for CP, OR([230-314 microg/day]) = 1.15, 0.6-2.2, OR(>314 microg/day) = 0.70, 0.3-1.4). We observed a reduced risk associated with the TT genotype of the child in the case-control analysis (OR(CC) = ref; for CL/P, OR(TT) = 0.54, 0.3-1.1; for CP, OR(TT) = 0.33, 0.1-1.0); this genotype, either fetal or maternal, was not statistically significant in the case-parent analysis. A frequency of TT genotype higher in our control group than previously reported in France can partly explain the risk reduction observed in case-control comparison. Interactions were not statistically significant. Stratified case-parent analysis showed, however, slight heterogeneity in the role of TT genotype according to folate intake. The modest sample size limits this study, which nonetheless provides new estimate of the possible impact of dietary folate intake and MTHFR polymorphism on oral clefts.

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

    PubMed

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

    2004-01-01

    Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate reductase (MTHFR) enzyme activity, owing to genetic polymorphisms andor inadequate folate intake. This study was aimed at investigating the prevalence of C677T and A1298C MTHFR polymorphisms, and their impact on hyperhomocysteinemia in 95 epileptic patients and 98 controls. Double gradient-denaturing gradient gel electrophoresis screening revealed that the frequency of T677 polymorphic allele was similar between cases and controls (46.3% vs 42.3%), whereas that of C1298 allele was significantly higher in patients (30.5% vs 19.4%, p < 0.05). Significant differences between the two groups were also found for the frequencies of genotypes AA1298 (46.3% in cases vs 67.3% in controls, p < 0.01) and AC1298 (46.3% in cases vs 26.6% in controls, p < 0.01). Other genotype frequencies did not show any statistically significant differences. Haplotype frequencies significantly differed between the two groups. The CT677/AC1298 diplotype was significantly more frequent in epileptic patients than in controls (32.6% vs 18.4%, p < 0.05). Patients treated with enzyme-inducing antiepileptic drugs, having this diplotype and concomitant low folate concentration (i.e., < 3.4 nmol/L), exhibited plasma homocysteine levels significantly higher than normal values (27.1 +/- 2.44 micromol/L, p < 0.001). This increase, however, was lower than that observed in folate-deficient patients with diplotype TT677/AA1298 (41.3 +/- 3.41 micromol/L, p < 0.001). Indeed, these two diplotypes could be regarded as risk factors for hyperhomocysteinemia. Conversely, we found that the CC677/AA1298 diplotype was significantly more frequent in controls (p < 0.01), suggesting a protective role. Our study suggests that both C677T and A1298C MTHFR polymorphisms should be examined when assessing genetic risk factors of hyperhomocysteinemia in epilepsy.

  3. Genetic polymorphism of MTHFR C677T and premature coronary artery disease susceptibility: A meta-analysis.

    PubMed

    Hou, Xiaowen; Chen, Xin; Shi, Jingpu

    2015-07-01

    The association between 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and premature coronary artery disease (PCAD) is controversial. To explore a more precise estimation of the association, a meta-analysis was conducted in the present study. The relevant studies were identified by searching PubMed, EMBASE, the Web of Science, Cochrane Collaboration Database, Chinese National Knowledge Infrastructure, Wanfang Database and China Biological Medicine up to November, 2014. The meta-analysis was performed by STATA 11. 21 studies with a total of 6912 subjects, including 2972 PCAD patients and 3940 controls. The pooled analysis showed that MTHFR C677T gene polymorphism was probably associated with PCAD (CT vs. CC: OR=1.13, 95% CI=1.01-1.27; dominant model: OR=1.16, 95% CI=1.04-1.29; recessive model: OR=1.19, 95% CI=1.00-1.40; allele analysis: OR=1.17, 95% CI=1.01-1.34). Subgroup analysis by plasma homocysteine concentration showed a significant association in the homocysteine >15μmol/L subgroup (CT vs. CC: OR=1.44, 95% CI=1.10-1.88; TT vs. CC: OR=2.51, 95% CI=1.12-5.63; dominant model: OR=1.51, 95% CI=1.16-1.96; recessive model: OR=2.33, 95% CI=1.05-5.20; allele analysis: OR=1.48, 95% CI=1.18-1.87). Subgroup analysis by continent displayed a significant association among the Asian population (CT vs. CC: OR=1.51, 95% CI=1.23-1.86; TT vs. CC: OR=2.81, 95% CI=1.87-4.23; dominant model: OR=1.65, 95% CI=1.35-2.01; recessive model: OR=2.22, 95% CI=1.53-3.21; allele analysis: OR=1.61, 95% CI=1.37-1.89). The statistical stability and reliability was demonstrated by sensitivity analysis and publication bias outcomes. In conclusion, the meta-analysis suggests that MTHFR C677T gene polymorphism may be associated with PCAD.

  4. The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women.

    PubMed

    Tong, Seo-Yun; Lee, Jong-Min; Song, Eun-Seop; Lee, Kwang-Beom; Kim, Mi-Kyung; Yun, Young Mi; Lee, Jae-Kwan; Son, Sung-Kyong; Lee, Jung-Pil; Kim, Jae-Hoon; Hur, Soo-Young; Kwon, Yong-Il

    2010-01-01

    The purpose of the study was to investigate the association between cervical cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve SNPs were identified in MTHFR, MTR, and MTRR in the 927 case-control samples, which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440 normal controls. The frequencies of the genotypes and haplotypes were assessed in the controls, CINs, and cervical cancers. Individual carriers of the variant allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes. However, no significant association was found between most other variants and cervical cancer risk. The results also identified an increased CIN1 risk in carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio, 1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer in Korean women. In addition, there was no significant association of MTHFR haplotypes with risk of CIN2/3 and cervical cancer.

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

    PubMed

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

    2011-12-01

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

  6. Plasminogen activator inhibitor-1 4G/5G and the MTHFR 677C/T polymorphisms and susceptibility to polycystic ovary syndrome: a meta-analysis.

    PubMed

    Lee, Young Ho; Song, Gwan Gyu

    2014-04-01

    The aim of this study was to explore whether the plasminogen activator inhibitor-1 (PAI-1) 4G/5G and the methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS). Meta-analyses were conducted to determine the association between the PAI-1 4G/5G and MTHFR 677C/T polymorphisms and PCOS using: (1) allele contrast (2) homozygote contrast, (3) recessive, and (4) dominant models. For meta-analysis, nine studies of the PAI-1 4G/5G polymorphism with 2384 subjects (PCOS, 1615; controls, 769) and eight studies of the MTHFR 677C/T polymorphism with 1270 study subjects were included. Meta-analysis of all study subjects showed no association between PCOS and the PAI-1 4G allele (OR=0.949, 95% CI=0.671-1.343, p=0.767). Stratification by ethnicity, however, indicated a significant association between the PAI-1 4G allele and PCOS in Turkish and Asian populations (OR=0.776, 95% CI=0.602-0.999, p=0.049; OR=1.749, 95% CI=1.297-2.359, p=2.5×10(-5) respectively). In addition, meta-analysis indicated an association between PCOS and the PAI-1 4G4G+4G5G genotype in Europeans (OR=1.406, 95% CI=1.025-1.928, p=0.035). However, meta-analysis of all study subjects showed no association between PCOS and the MTHFR 677T allele (OR=0.998, 95% CI=0.762-1.307, p=0.989), including Europeans (OR=0.806, 95% CI=0.610-1.063, p=0.126). Meta-analysis showed no association between PCOS and the MTHFR 677C/T polymorphism using homozygote contrast, and recessive and dominant models. In conclusion, meta-analysis suggests the PAI-1 4G/5G polymorphism is associated with susceptibility to PCOS in European, Turkish, and Asian populations, but the MTHFR 677C/T polymorphism is not associated with susceptibility to PCOS in Europeans.

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

    PubMed

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

    2014-01-01

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

  8. Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val and susceptibility to ovary cancer: a systematic review and meta-analysis.

    PubMed

    Pan, Xinwei; Lu, Yan; Long, Ying; Yao, Desheng

    2014-03-01

    Many studies have reported the role of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val polymorphism with ovary cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR Ala222Val polymorphism and ovary cancer risk. A total of 8 studies including 3,723 cases and 4,001 controls were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, no significant association between ovary cancer risk and MTHFR Ala222Val polymorphism was found in all genetic models [codominant model: OR = 0.980, 95% CI = 0.756-1.270, P h = 0.088, P = 0.877; dominant model: OR = 1.022, 95% CI = 0.864-1.208, P h = 0.033, P = 0.803; recessive model: OR = 1.050, 95% CI = 0.803-1.373, P h = 0.032, P = 0.723; allele comparison model: OR = 1.028, 95% CI = 0.898-1.178, P h = 0.012, P = 0.685]. In the stratified analysis by ethnicity, no evidence of any associations of this polymorphism with ovary cancer was found in the Caucasian populations. Our meta-analysis supports that the MTHFR Ala222Val polymorphism is not contributed to the risk of ovary cancer from currently available evidence.

  9. Additive Interaction of MTHFR C677T and MTRR A66G Polymorphisms with Being Overweight/Obesity on the Risk of Type 2 Diabetes

    PubMed Central

    Zhi, Xueyuan; Yang, Boyi; Fan, Shujun; Li, Yongfang; He, Miao; Wang, Da; Wang, Yanxun; Wei, Jian; Zheng, Quanmei; Sun, Guifan

    2016-01-01

    Although both methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms have been associated with type 2 diabetes (T2D), their interactions with being overweight/obesity on T2D risk remain unclear. To evaluate the associations of the two polymorphisms with T2D and their interactions with being overweight/obesity on T2D risk, a case-control study of 180 T2D patients and 350 healthy controls was conducted in northern China. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). After adjustments for age and gender, borderline significant associations of the MTHFR C677T and MTRR A66G polymorphisms with T2D were observed under recessive (OR = 1.43, 95% CI: 0.98–2.10) and dominant (OR = 1.43, 95% CI: 1.00–2.06) models, respectively. There was a significant interaction between the MTHFR 677TT genotype and being overweight/obesity on T2D risk (AP = 0.404, 95% CI: 0.047–0.761), in addition to the MTRR 66AG/GG genotypes (RERI = 1.703, 95% CI: 0.401–3.004; AP = 0.528, 95% CI: 0.223–0.834). Our findings suggest that individuals with the MTHFR 677TT or MTRR 66AG/GG genotypes are more susceptible to the detrimental effect of being overweight/obesity on T2D. Further large-scale studies are still needed to confirm our findings. PMID:27983710

  10. Aberrant DNA Methylation of P16, MGMT, and hMLH1 Genes in Combination with MTHFR C677T Genetic Polymorphism in gastric cancer

    PubMed Central

    Song, Binbin; Ai, Jiang; Kong, Xianghong; Liu, Dexin; Li, Jun

    2013-01-01

    Objective: We aimed to explore the association of P16, MGMT and HMLH1 with gastric cancer and their relation with Methylenetetrahydrofolate reductase (MTHFR). Methods: 322 gastric patients who were confirmed with pathological diagnosis were included in our study. Aberrant DNA methylation of P16, MGMT and HMLH1 and polymorphisms of MTHFR C677T and A1298C were detected using PCR-RFLP. Results: The proportions of DNA hypermethylation in P16, MGMT and hMLH1 genes in gastric cancer tissues were 75.2% (242/322), 27.6% (89/322) and 5.3% (17/322), respectively. In the remote normal-appearing tissues, 29.5% (95/322) and 16.1%(52/322) showed hypermethylation in P16 and MGMT genes, respectively. We found a significantly higher proportion of DNA hypermethylation of P16 in patients with N1 TNM stage in cancer tissues and remote normal-appearing tissues (P<0.05). Similarly, we found DNA hypermethylation of MGMT had significantly higher proportion in N1 and M1 TNM stage (P<0.05). Individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues [OR (95% CI)=4.27(1.76-7.84)], and a significant risk was also found in those carrying MTHFR 677CT/TT genotype [OR (95% CI)= 3.27(1.21-4.77)]. Conclusion: We found the aberrant hypermethylation of cancer-related genes, such as P16, MGMT and HMLH1, could be predictive biomarkers for detection of gastric cancer. PMID:24550949

  11. Haplotypes of the MTHFR gene are associated with an increased risk of breast cancer in a Han Chinese population in Gansu province.

    PubMed

    Song, Ailing; Zhao, Lei; Li, Yumin; Wu, Li; Li, Yu; Liu, Xiaokang; Lan, Shen

    2016-07-01

    Elevated homocysteine levels are a risk factor for breast cancer, although the mechanism underlying this effect is unknown. Genome-wide association studies were used to systematically identify genetic variants which were significantly associated with the circulating homocysteine concentration. To examine the role of homocysteine-related variants in the occurrence of breast cancer, we investigated the association between these variants and breast cancer in a Han Chinese population. Five variants of genome-wide significant homocysteine-related genes were selected for the analysis in a case-control study, with a total of 487 patients with breast cancer and 605 controls. We found that none of the studied polymorphisms were related to the altered breast cancer risk. In the haplotypic analysis, the 5,10-methylenetetrahydrofolate reductase (MTHFR) haplotypes rs12085006A/rs1999594G/rs1801133C (OR = 3.44, 95% CI = 1.58-7.50, P = 0.0019) and rs12085006A/rs1999594G/rs1801133T (OR = 16.21, 95% CI = 2.19- 120.32, P = 0.0065) were significantly associated with an increased breast cancer risk when compared with the wild-type haplotype. Both of the risky MTHFR haplotypes were correlated with decreased MTHFR gene expression and elevated homocysteine concentrations, indicating a genetic component for hyperhomocysteinemia. The MTHFR haplotypes reconstructed with homocysteine-related variants were associated with the occurrence of breast cancer. This finding further emphasizes the importance of homocysteine metabolism genes in breast carcinogenesis and highlights the interplay of diet, genetics, and human cancers. © 2016 IUBMB Life, 68(7):526-534, 2016.

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

    PubMed Central

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

    2014-01-01

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

  13. [Allele polymorphism analysis in coagulation factors F2, F5 and folate metabolism gene MTHFR by using microchip-based multiplex real time PCR].

    PubMed

    Bogdanov, K V; Nikitin, M M; Slyadnev, M N

    2015-01-01

    Single nucleotide polymorphism (SNP) genotyping methods are widely used for the detection of hereditary thrombophilias caused by genetic defects in the coagulation system. The hereditary thrombophilias are frequently associated with higher incidences of point mutations in hemostasis (F2 20210G>A, F5 1691G>A) and folate metabolism (MTHFR 677C>Т, MTHFR 1298A>C) genes. Moreover, the combination of gene abnormalities in F2 or/and MTHFR with F5 Leiden mutation leads to increased risk of developing thrombosis. Thus, simultaneous detection of the multiple gene mutations in a sample has important clinical relevance. The microchip-based multiplex real time PCR for estimation of allele specific polymorphism in hemostatic and folate metabolism genes presented here has a high efficiency and may be used for laboratory diagnosis. The optimized protocol for estimation of 4 different types of genetic polymorphisms allowed PCR to be performed with minimal quantity of DNA template and PCR reagents including Taq polymerase and a short-term thermocycling.

  14. Incidence Assessment of MTHFR C677T and A1298C Polymorphisms in Iranian Non-syndromic Cleft Lip and/or Palate Patients

    PubMed Central

    Ebadifar, Asghar; Ameli, Nazila; Khorramkhorshid, Hamid Reza; Salehi Zeinabadi4, Mehdi; Kamali, Kourosh; Khoshbakht, Tayyebeh

    2015-01-01

    Background and aims. The aim of the present study is to determine the incidence of MTHFR C677 T and A1298C muta-tions in Iranian patients with cleft lip and/or cleft palate. Materials and methods. We screened 61 Iranian patients with cleft lip and/or cleft palate for mutations in the two alleles of MTHFR gene associated with cleft lip and/or palate: A1298C and C677T, using Polymerase Chain Reaction following by RFLP. Results. The 677T and 1298C homozygote genotypes showed a frequency of 36.1% and 11.4%, respectively. Combined genotype frequencies in newborns having oral clefts showed that the highest genotype was 677TT/1298AA (22.9%) and 677TT/1298CC genotypes were not observed. Conclusion. The results showed that 65.6% of all patients had at least one T mutant allele in C677T and 58.9% C mutant allele for A1298C. According to the frequencies of homozygosity of mutant alleles, it could be said that MTHFR genotype of 677TT shows a greater role in having oral clefts. PMID:26236436

  15. Synergistic Effect of the MTHFR C677T and EPHX2 G860A Polymorphism on the Increased Risk of Ischemic Stroke in Chinese Type 2 Diabetic Patients

    PubMed Central

    Ma, Liang; Kong, Xiaomu; Yan, Meihua; Zhao, Tingting; Zhao, Hailing; Liu, Qian

    2017-01-01

    The aim of this study was to investigate the relationship between the combined effect of MTHFR C677T (rs1801133) and EPHX2 G860A (rs751141) polymorphism and ischemic stroke in Chinese T2DM patients. This case-control study included a total of 626 Chinese T2DM patients (236 T2DM patients with ischemic stroke and 390 T2DM patients without ischemic stroke). The rs1801133 and rs751141 were genotyped using real-time polymerase chain reaction. Statistical analysis was performed with SPSS 17.0. Results showed that the combined effect of MTHFR TT and EPHX2 GG or GA + AA genotype has a higher risk of ischemic stroke compared with the control group (combined effect of MTHFR CC and EPHX2 GA + AA genotypes; OR = 3.46 and OR = 3.42, resp.; P = .001 and P = .002, resp.). The A allele showed marked association with a lower risk of ischemic stroke in patients with the lowest Hcy levels under additive, recessive, and dominant genetic models (OR = 0.45, OR = 0.11, and OR = 0.44, resp.; P = .002, P = .035, and P = .008, resp.), which was not observed in medium or high Hcy level groups. In conclusion, the T allele of rs1801133 and the G allele of rs751141 may be risk factors of ischemic stroke in the Chinese T2DM population.

  16. AutoGen Version 5.0

    NASA Technical Reports Server (NTRS)

    Gladden, Roy E.; Khanampornpan, Teerapat; Fisher, Forest W.

    2010-01-01

    Version 5.0 of the AutoGen software has been released. Previous versions, variously denoted Autogen and autogen, were reported in two articles: Automated Sequence Generation Process and Software (NPO-30746), Software Tech Briefs (Special Supplement to NASA Tech Briefs), September 2007, page 30, and Autogen Version 2.0 (NPO- 41501), NASA Tech Briefs, Vol. 31, No. 10 (October 2007), page 58. To recapitulate: AutoGen (now signifying automatic sequence generation ) automates the generation of sequences of commands in a standard format for uplink to spacecraft. AutoGen requires fewer workers than are needed for older manual sequence-generation processes, and greatly reduces sequence-generation times. The sequences are embodied in spacecraft activity sequence files (SASFs). AutoGen automates generation of SASFs by use of another previously reported program called APGEN. AutoGen encodes knowledge of different mission phases and of how the resultant commands must differ among the phases. AutoGen also provides means for customizing sequences through use of configuration files. The approach followed in developing AutoGen has involved encoding the behaviors of a system into a model and encoding algorithms for context-sensitive customizations of the modeled behaviors. This version of AutoGen addressed the MRO (Mars Reconnaissance Orbiter) primary science phase (PSP) mission phase. On previous Mars missions this phase has more commonly been referred to as mapping phase. This version addressed the unique aspects of sequencing orbital operations and specifically the mission specific adaptation of orbital operations for MRO. This version also includes capabilities for MRO s role in Mars relay support for UHF relay communications with the MER rovers and the Phoenix lander.

  17. Teleport Generation 3 (Teleport Gen 3)

    DTIC Science & Technology

    2016-03-01

    DAMIR) UNCLASSIFIED Teleport Gen 3 2016 MAR UNCLASSIFIED 2 Table of Contents Common Acronyms and Abbreviations for MAIS Programs 3...Information System MAIS OE - MAIS Original Estimate MAR – MAIS Annual Report MDA - Milestone Decision Authority MDD - Materiel Development Decision...U.S.C- United States Code USD(AT&L) - Under Secretary of Defense for Acquisition, Technology, & Logistics Teleport Gen 3 2016 MAR UNCLASSIFIED 3 Mrs

  18. MTHFR C677T, A1298C and MS A2756G Gene Polymorphisms and Male Infertility Risk in a Chinese Population: A Meta-Analysis

    PubMed Central

    Yang, Bo; Fang, Kun; Ren, Shangqing; Liao, Jian; Liu, Shengzhuo; Liu, Liangren; Peng, Zhufeng; Dong, Qiang

    2017-01-01

    Background Methylenetetrahydrofolate reductase gene (MTHFR C677T and A1298C) and methionine synthase gene (MS A2756G) polymorphisms have shown an association with male infertility risk in several ethnic populations. Although several studies have evaluated these associations in Chinese populations, their small sample sizes and inconsistent outcomes have prevented strong conclusions. Therefore, the present meta-analysis was performed with published studies to evaluate the associations of the three single nucleotide polymorphisms (SNPs) and male infertility in a Chinese population. Methods We conducted a search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature (CBM), VIP, and Chinese literature (Wan Fang) databases up to May 31, 2016. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to assess the strength of associations with a random-effect model or a fixed-effect model based on the heterogeneity analysis results. Sensitivity analysis was used to confirm the reliability and stability of the meta-analysis. Results A total of nine studies, including 1,713 cases and 1,104 controls, were included in the meta-analysis. The pooled results indicated that the MTHFR C667T polymorphism was significantly associated with increased risk of male infertility in the Chinese population in the allele model (T vs. C: OR = 1.47, 95%CI = 1.32–1.63), the dominant model (TT + CT vs. CC: OR = 1.51, 95%CI = 1.30–1.77), the additive model (TT vs. CC: OR = 2.08, 95%CI = 1.68–2.58) and the recessive model (TT vs. CT+CC: OR = 1.58, 95%CI = 1.31–1.90), whereas the MTHFR A1298C and MS A2756G polymorphisms were not risk factors. There was no significant heterogeneity in any genotype contrasts among the studies. The sensitivity analysis indicated that the results of this meta-analysis were relatively stable. Conclusion This study suggests that the MTHFR C667T polymorphism may contribute to the genetic

  19. Influence of food groups on plasma total homocysteine for specific MTHFR C677T genotypes in Chinese population

    PubMed Central

    Li, Fan; Xiang, Tianyuan; Wang, Weimin; Ma, Cong; Yang, Chao; Chen, Haixu

    2016-01-01

    1 Scope It has been demonstrated that a mutation of MTHFR C677T increases plasma total homocysteine (Hcy) concentration and decreases folate. Natural foods can improve Hcy levels, but the effect of certain foods remains undetermined. The aim of this study was to investigate the association between food groups and Hcy, and to explore the correlations between Hcy and dietary folate/vitamin (Vit) B12 for genotype‐specific population. 2 Methods and results A total of 4507 adults were enrolled in this study, all of whom underwent physical examinations and genotyping. A dietary recall questionnaire, which assessed the frequency (F) and quantity (Q) of food consumption, was completed by all. For the male CC group, after adjustment for age and BMI, fish (F) was negatively correlated with Hcy; for the male CT group, fish (F) and eggs (F) were negatively associated with Hcy, whereas cereal/wheat (Q) were positively correlated with Hcy; for the male TT group, fish (F), meat (Q), milk (F), and fruits/vegetables (Q) were negatively associated with Hcy, whereas sugar (Q) and salt (Q) were positively associated with Hcy. For the female CC group, fruits/vegetables (Q), eggs (F) and meat (F) were negatively correlated with Hcy, but soy (F) was positively correlated with Hcy; for the female CT group, eggs (F) and meat (Q) were negatively correlated with Hcy, whereas soy (F), fried foods (F) and salt (Q) were positively correlated with Hcy; for the female TT group, fish(F), eggs (F), and fruits/vegetables (F) were negatively associated with Hcy. Furthermore, we found that Hcy was more closely correlated with folate than with Vit B12 for males (CC, CT and TT) and female TT genotype. However, the correlation between Hcy and Vit B12 was stronger for the female CT/CC groups. 3 Conclusion Hcy levels were influenced by food groups to varying degrees, which were based on gender and MTHFR C677T genotypes. Hcy levels were more closely correlated with folate for males (CC, CT and TT) and the

  20. Debroyerella gen. nov. and Ulladulla gen. nov., two new lysianassoid genera (Crustacea, Amphipoda, Lysianassoidea).

    PubMed

    Lowry, J K; Kilgallen, N M

    2015-02-19

    Two new genera and a new species of lysianassoid amphipods are described. Debroyerella gen. nov. is described for three Antarctic species previously assigned to the genus Cheirimedon. Ulladulla gen. nov. is described to accommodate the new species U. selje, from Australian waters. Diagnostic descriptions are given for the genera and all species are described in full.

  1. Unleashing Gen Y: Marketing Mars to Millennials

    NASA Technical Reports Server (NTRS)

    Leahy, Bart D.; Hidalgo, Loretta; Kloberdanz, Cassie

    2007-01-01

    Space advocates need to engage Generation Y (born 1977-1999).This outreach is necessary to recruit the next generation of scientists and engineers to explore Mars. Space advocates in the non-profit, private, and government sectors need to use a combination of technical communication, marketing, and politics, to develop messages that resonate with Gen Y. Until now, space messages have been generated by and for college-educated white males; Gen Y is much more diverse, including as much as one third minorities. Young women, too, need to be reached. My research has shown that messages emphasizing technology, fun, humor, and opportunity are the best means of reaching the Gen Y audience of 60 million (US population is 300 million). The important things space advocates must avoid are talking down to this generation, making false promises, or expecting them to "wait their turn" before they can participate. This is the MTV generation! We need to find ways of engaging Gen Y now to build a future where human beings can live and work on the planet Mars. In addition to the messages themselves, advocates need to keep up with Gen Y' s social networking and use of iPods, cell phones, and the Internet. NASA and space advocacy groups can use these tools for "viral marketing," where young people share targeted space-related information via cell phones or the Internet because they like it. Overall, Gen Y is a socially dynamic and media-savvy group; advocates' space messages need to be sincere, creative, and placed in locations where Gen Y lives. Mars messages must be memorable!

  2. [The normotensive carriers of the MTHFR 677T allele, displaying the increased risk of development of the abdominal aortic aneurysm (AAA), occur at the highest frequency among the smoking patients].

    PubMed

    Strauss, Ewa; Waliszewski, Krzysztof; Pawlak, Andrzej L

    2004-01-01

    Abdominal aortic aneurysm (AAA) presents itself as a progressive dilation of the abdominal aorta, leading--if untreated--to rupture. It is a common disease of the elderly, with a complex etiology. Smoking, hypertension and several genetic factors are recognized as relevant for the pathogenesis of AAA. We studied association between the polymorphism of the MTHFR (methylenetetrahydrofolate reductase) gene within the fourth exon (677C>T) and the occurrence of hypertension and smoking status in the group of 74 male patients with AAA. In the patients group, the smoking hypertensive persons represented the largest subgroup (43%). We determined the the MTHFR 677C>T polymorphism in AAA patients and compared it to that in 71 healthy normotensive males. The frequencies of the 677T allele and MTHFR 677C>T genotypes were similar in both groups, but the subgroup of normotensive AAA patients (n=29) displayed significantly increased frequencies of 677T allele (0.4) and of 677CT and TT genotypes (69%), as compared to those in the control group (0.28 and 46%, respectively). This corresponds to the 3.3-fold greater risk of AAA in normotensive subjects with the 677T allele of MTHFR, as compared to the homo-zygotes 677CC (p<0.03; 95% CI=1.2-9.2). The highest frequencies of MTHFR 677T allele (0.43) and 677CT and TT genotypes (73%) were found in the subgroup of normotensive smoking patients (n=22).

  3. Three new anascosporic genera of the Saccharomycotina: Danielozyma gen. nov., Deakozyma gen. nov. and Middelhovenomyces gen. nov.

    PubMed

    Kurtzman, Cletus P; Robnett, Christie J

    2014-05-01

    Three new non-ascosporic, ascomycetous yeast genera are proposed based on their isolation from currently described species and genera. Phylogenetic placement of the genera was determined from analysis of nuclear gene sequences for D1/D2 large subunit rRNA, small subunit rRNA, translation elongation factor-1α and RNA polymerase II, subunits B1 and B2. The new taxa are: Deakozyma gen. nov., type species Deakozyma indianensis sp. nov. (type strain NRRL YB-1937, CBS 12903); Danielozyma gen. nov., type species Danielozyma ontarioensis comb. nov. (type strain NRRL YB-1246, CBS 8502); D. litseae comb. nov. (type strain NRRL YB-3246, CBS 8799); Middelhovenomyces gen. nov., type species Middelhovenomyces tepae comb. nov. (type strain NRRL Y-17670, CBS 5115) and M. petrohuensis comb. nov. (type strain NRRL Y-17663, CBS 8173).

  4. Development and characterization of reference materials for MTHFR, SERPINA1, RET, BRCA1, and BRCA2 genetic testing.

    PubMed

    Barker, Shannon D; Bale, Sherri; Booker, Jessica; Buller, Arlene; Das, Soma; Friedman, Kenneth; Godwin, Andrew K; Grody, Wayne W; Highsmith, Edward; Kant, Jeffery A; Lyon, Elaine; Mao, Rong; Monaghan, Kristin G; Payne, Deborah A; Pratt, Victoria M; Schrijver, Iris; Shrimpton, Antony E; Spector, Elaine; Telatar, Milhan; Toji, Lorraine; Weck, Karen; Zehnbauer, Barbara; Kalman, Lisa V

    2009-11-01

    Well-characterized reference materials (RMs) are integral in maintaining clinical laboratory quality assurance for genetic testing. These RMs can be used for quality control, monitoring of test performance, test validation, and proficiency testing of DNA-based genetic tests. To address the need for such materials, the Centers for Disease Control and Prevention established the Genetic Testing Reference Material Coordination Program (GeT-RM), which works with the genetics community to improve public availability of characterized RMs for genetic testing. To date, the GeT-RM program has coordinated the characterization of publicly available genomic DNA RMs for a number of disorders, including cystic fibrosis, Huntington disease, fragile X, and several genetic conditions with relatively high prevalence in the Ashkenazi Jewish population. Genotypic information about a number of other cell lines has been collected and is also available. The present study includes the development and commutability/genotype characterization of 10 DNA samples for clinically relevant mutations or sequence variants in the following genes: MTHFR; SERPINA1; RET; BRCA1; and BRCA2. DNA samples were analyzed by 19 clinical genetic laboratories using a variety of assays and technology platforms. Concordance was 100% for all samples, with no differences observed between laboratories using different methods. All DNA samples are available from Coriell Cell Repositories and characterization information can be found on the GeT-RM website.

  5. [Investigation of detoxification polymorphisms genes, methylenetetrahydrofolate-reductase (MTHFR) and P53 in the radiosensitive human cells].

    PubMed

    Shagirova, Zh M; Ushenkova, L N; Mikhaĭlov, V F; Kurbatova, L A; Kuz'mina, N S; Semiachkina, A N; Vasil'eva, I M; Mazurik, V K; Zasukhina, G D

    2010-01-01

    The genes of detoxication, MTHFR and p53 were studied in Down' and Ehlers-Danlos syndrome cells. The frequency GSTM1(0/0) genotype in Down syndrome patients was in 1.5 times higher than in control cells (p < 0.069). Opposite the frequency GSTM1(0/0) genotype in Ehlers-Danlos syndrome was 23.3% 2 times lower than in control cells (p < 0.034). This indication was in 2 times lower in women cells than in men cells and in 3 times lower than in control cells (p < 0.026). The mutations of p53 gene (7th exon) were detected in 4 from 11 Down patients (36.7%; in 2 cases af women and men), in Ehlers-Danlos patients--in 5 cases and only in men (29.4% among all the observed patients). The observations 24 healthy donors weren't revealed any mutations (p < 0.013-0.001). The hypothesis about the connection between gene polymorphisms which take a part in genome stability and radiosensitivity in Down and Ehlers-Danlos patients was developed.

  6. Genetic Variants in MTHFR Gene Predict ≥ 2 Radiation Pneumonitis in Esophageal Squamous Cell Carcinoma Patients Treated with Thoracic Radiotherapy

    PubMed Central

    Zhang, Jian; Li, Hongsheng; Qiao, Yumei; Huang, Chengsuo; Li, Baosheng

    2017-01-01

    Reactive oxygen species (ROS), formed as an indirect production of radiotherapy (RT), could cause DNA damage of normal tissues. Meanwhile, our body possesses the ability to restore the damage by DNA repair pathways. The imbalance between the two systems could finally result in radiation injury. Therefore, in this prospective cohort study, we explored the association of genetic variants in ROS metabolism and DNA repair pathway-related genes with radiation pneumonitis (RP). A total of 265 locally advanced esophageal squamous cell carcinoma (ESCC) patients receiving RT in Chinese Han population were enrolled. Five functional single nucleotide polymorphisms (SNPs) (rs1695 in GSTP1; rs4880 in SOD2; rs3957356 in GSTA1; and rs1801131, rs1801133 in MTHFR) were genotyped using the MassArray system, and rs1801131 was found to be a predictor of ≥ 2 RP. Our results showed that, compared with TT genotype, patients with GG/GT genotypes of rs1801131 had a notably lower risk of developing ≥ 2 RP (HR = 0.339, 95% CI = 0.137–0.839, P = 0.019). Further independent studies are required to confirm this findings. PMID:28046029

  7. Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian population.

    PubMed

    D'Amico, Mario; Pasta, Francesca; Pasta, Linda

    2015-08-15

    The thrombophilic genetic factors (THRGFs), PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q and Prothrombin 20210A, were studied as risk factors in 865 Caucasian patients with liver cirrhosis, consecutively enrolled from June 2008 to January 2014. A total of 582 HCV, 80 HBV, 94 alcohol, (82 with more than one etiologic factor) and 191 cryptogenic patients with liver cirrhosis had been consecutively enrolled; 243 patients showed portal vein thrombosis (PVT). At least one of the above THRGFs was present in 339/865 patients (39.2%). PAI-1 4G-4G and MTHFR 677TT were the most frequent THRGFs, statistically significant in patients with alcohol, cryptogenic liver cirrhosis, and PVT: respectively 24 and 28, 50 and 73, and 65 and 83 (all chi-square tests>3.84, and p values<0.05). Two logistic regression analysis, using PAI-1 4G-4G and MTHFR 677TT, as dependent variable, confirmed the independent significant relationship of these THRGFs with alcohol, cryptogenic liver cirrhosis and PVT. PAI 1 and MTHFR 677 genotypes, deviated from those expected in populations in Hardy-Weinberg equilibrium (all p values<0.05), in the subgroups of patients with alcohol, cryptogenic liver cirrhosis and presence of PVT. Our study shows the pivotal role of PAI-1 4G-4G and MTHFR 677TT in patients with alcohol, cryptogenic liver cirrhosis, and PVT, in a Caucasian population. In conclusion, thrombo and fibro-genetic mechanisms of PAI-1 4G-4G and MTHFR 677TT, could have a role in the development of liver cirrhosis, mainly in patients without HCV and HBV, and PVT.

  8. Colon Cancer on The Rise Among Gen Xers, Millennials

    MedlinePlus

    ... Colon Cancer on the Rise Among Gen Xers, Millennials And an old adversary -- the obesity epidemic -- may ... their early 50s and younger -- Gen Xers and millennials -- are experiencing significant increases in colon and rectal ...

  9. 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.

  10. MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults

    PubMed Central

    2012-01-01

    Background This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d) of folic acid (FA) can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T and/or methionine synthase (MTR) A2756G polymorphisms in hypertensive Chinese adults. Methods A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1) enalapril only (10 mg, control group); 2) enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8 mg, high FA group), once daily for 8 weeks. Results After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (P < 0.05 for either of these genotypes) and TT genotype in the high FA group (P < 0.05). Furthermore, subjects with TT genotype showed a greater homocysteine-lowering response than did subjects with CC genotype in the high FA group (mean percent reduction of homocysteine at week 8: CC 10.8% vs. TT: 22.0%, P = 0.005), but not in the low FA group (CC 9.9% vs. TT 11.2%, P = 0.989). Conclusions This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation. PMID:22230384

  11. Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients.

    PubMed

    Errera, F I V; Silva, M E R; Yeh, E; Maranduba, C M C; Folco, B; Takahashi, W; Pereira, A C; Krieger, J E; Passos-Bueno, M R

    2006-07-01

    Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and epsilon2/epsilon3/epsilon4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (epsilon2, epsilon3 and epsilon4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of epsilon2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/107 (6.5%); P < 0.05]. Therefore, our results suggest that the epsilon2 allele/APOE might be a risk factor for diabetes in the Brazilian population.

  12. MTHFR 677 TT genotype in a mother and her child with Down syndrome, atrioventricular canal and exstrophy of the bladder: implications of a mutual genetic risk factor?

    PubMed

    Reutter, Heiko; Betz, Regina C; Ludwig, Michael; Boemers, Thomas M

    2006-08-01

    Apart from Husmann and Vandersteen [in: Gearhart JP, Matthews R (eds) The Epispadias-Exstrophy Complex. Kluwer, New York, pp 199-206, 1999], we report only the second case of Down syndrome (DS) associated with exstrophy of the bladder (EB). Besides the appearance of DS, the newborn exhibited a complete atrioventricular canal (CAVC) and classical EB, including diastases of the symphysis, an epispadic penis and an open bladder plate. Despite current recommendations, the mother had not supplemented her intake of folic acid during the periconceptional period. In a comparable case, Al-Gazali et al. (Am J Med Genet 103:128-132, 2001) found the homozygous 677T allele of the methylenetetrahydrofolate (MTHFR) gene 677C-->T polymorphism in a mother and her child with DS and cervical meningomyelocele. They found that the mother, who also had not supplemented her folic acid intake, had a secondarily altered folate status with an increased homocysteine level, suggesting that the homozygous TT mutation in the MTHFR gene in both mother and her child had contributed to the presentation of DS and a neural tube defect. The combined clinical findings of the present case and the observations of Al-Gazali et al. led us to investigate the 677C-->T polymorphism in our mother-child pair. Likewise we found that mother and child were homozygous for the mutant 677T allele. Our findings support the suggestion of Al-Gazali et al. that the MTHFR 677TT could be a mutual genetic risk factor for the co-occurrence of trisomy 21 and midline defects, the risk of which may be reduced by periconceptional folic acid supplementation.

  13. Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

    PubMed Central

    Li, Chao; Ni, Juan; Liu, Yao-Xian; Wang, Han; Liang, Zi-Qing; Wang, Xu

    2017-01-01

    Background/Aims Folic acid (FA) is a core micronutrient involved in DNA synthesis/methylation, and the metabolism of FA is responsible for genomic stability. MicroRNAs may affect gene expression during folate metabolism when cellular homeostasis is changed. This study aimed to reveal the relationship between FA deficiency and the expression of miR-22-p/miR-149-5p and the targeted regulation of miR-22-3p/miR-149-5p on the key folate metabolic gene Methylenetetrahydrofolate reductase (MTHFR). Methods Normal (HL-7702 cells) and cancerous (QGY-7703 cells) human hepatocytes were intervened in modified RPMI 1640 with FA deficiency for 21 days. The interaction between MTHFR and the tested miRNAs was verified by Dual-Luciferase Reporter Assays. The changes in the expression of miR-22-3p/miR-149-5p in response to FA deficiency were detected by Poly (A) Tailing RT-qPCR, and the expression of MTHFR at both the transcriptional and translational levels was determined by RT-qPCR and Western blotting, respectively. Result MiR-22-3p/miR-149-5p directly targeted the 3’UTR sequence of the MTHFR gene. FA deficiency led to an upregulation of miR-22-3p/miR-149-5p expression in QGY-7703/HL-7702 cells, while the transcription of MTHFR was decreased in QGY-7703 cells but elevated in HL-7702 cells. Western blotting showed that FA deficiency resulted in a decline of the MTHFR protein in QGY-7703 cells, whereas in HL-7702 cells, the MTHFR protein level remained constant. Conclusion The results suggested that miR-22-3p/miR-149-5p exert different post-transcriptional effects on MTHFR under conditions of FA deficiency in normal and cancerous human hepatocytes. The results also implied that miR-22-3p/miR-149-5p might exert anticancer effects in cases of long-term FA deficiency. PMID:28045918

  14. MTHFR Glu429Ala and ERCC5 His46His Polymorphisms Are Associated with Prognosis in Colorectal Cancer Patients: Analysis of Two Independent Cohorts from Newfoundland

    PubMed Central

    Negandhi, Amit A.; Hyde, Angela; Dicks, Elizabeth; Pollett, William; Younghusband, Banfield H.; Parfrey, Patrick; Green, Roger C.; Savas, Sevtap

    2013-01-01

    Introduction In this study, 27 genetic polymorphisms that were previously reported to be associated with clinical outcomes in colorectal cancer patients were investigated in relation to overall survival (OS) and disease free survival (DFS) in colorectal cancer patients from Newfoundland. Methods The discovery and validation cohorts comprised of 532 and 252 patients, respectively. Genotypes of 27 polymorphisms were first obtained in the discovery cohort and survival analyses were performed assuming the co-dominant genetic model. Polymorphisms associated with disease outcomes in the discovery cohort were then investigated in the validation cohort. Results When adjusted for sex, age, tumor stage and microsatellite instability (MSI) status, four polymorphisms were independent predictors of OS in the discovery cohort MTHFR Glu429Ala (HR: 1.72, 95%CI: 1.04–2.84, p = 0.036), ERCC5 His46His (HR: 1.78, 95%CI: 1.15–2.76, p = 0.01), SERPINE1 −675indelG (HR: 0.52, 95%CI: 0.32–0.84, p = 0.008), and the homozygous deletion of GSTM1 gene (HR: 1.4, 95%CI: 1.03–1.92, p = 0.033). In the validation cohort, the MTHFR Glu429Ala polymorphism was associated with shorter OS (HR: 1.71, 95%CI: 1.18–2.49, p = 0.005), although with a different genotype than the discovery cohort (CC genotype in the discovery cohort and AC genotype in the validation cohort). When stratified based on treatment with 5-Fluorouracil (5-FU)-based regimens, this polymorphism was associated with reduced OS only in patients not treated with 5-FU. In the DFS analysis, when adjusted for other variables, the TT genotype of the ERCC5 His46His polymorphism was associated with shorter DFS in both cohorts (discovery cohort: HR: 1.54, 95%CI: 1.04–2.29, p = 0.032 and replication cohort: HR: 1.81, 95%CI: 1.11–2.94, p = 0.018). Conclusions In this study, associations of the MTHFR Glu429Ala polymorphism with OS and the ERCC5 His46His polymorphism with DFS were identified in two

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

    PubMed Central

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

    2013-01-01

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

  16. Relationship of MTHFR Gene 677C→T Polymorphism, Homocysteine, and Estimated Glomerular Filtration Rate Levels With the Risk of New-Onset Diabetes

    PubMed Central

    Qin, Xianhui; Li, Youbao; Yuan, Hui; Xie, Di; Tang, Genfu; Wang, Binyan; Wang, Xiaobin; Xu, Xin; Xu, Xiping; Hou, Fanfan

    2015-01-01

    Abstract East Asian patients with diabetes have a higher risk for renal complications and strokes than Europeans. We aimed to evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) gene 677C→T polymorphism, which was associated with a higher stroke risk and was common in the Chinese population, as well as homocysteine and estimated glomerular filtration rate (eGFR) levels on the risk of new-onset diabetes (NOD). A total of 2422 subjects without diabetes were followed-up for 7 years. NOD was defined as fasting plasma glucose ≥7.0 mmol/L or self-reported physician diagnosis of diabetes. Compared with subjects with MTHFR 677CC genotype, those with TT genotype had a higher risk of NOD in females (odds ratio 2.78, 95% confidence interval 1.39–5.56) but not in males (0.80, 0.40–1.61, P for interaction = 0.008). Furthermore, MTHFR 677C→T polymorphism was more strongly associated with the risk of NOD among females with higher body mass index (BMI, ≥23 vs <23 kg/m2, P for interaction = 0.009) or lower high-density lipoprotein-cholesterol (HDL-C, <1.3 vs ≥1.3 mmol/L, P for interaction = 0.015) levels. Hyperhomocysteinemia (≥16 vs <10 μmol/L) was not significantly associated with NOD in males (0.88, 0.42–1.85) or females (1.52, 0.65–3.57). However, mildly decreased eGFR (<90 vs 90–120 mL/min/1.73 m2) was associated with NOD mainly in males (1.96, 1.01–3.78; females, 0.74, 0.32–1.72, P for interaction = 0.134). Females with MTHFR 677TT genotype had a significantly higher risk of NOD, particularly those with higher BMI or low HDL-C levels. The higher risk of NOD associated with mildly decreased eGFR also warrants more investigation. Our results provide insights into the ethnic differences of diabetic complications between East Asian patients and Europeans. PMID:25700330

  17. Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review.

    PubMed

    Xiong, Xuan; Lin, Xiao-Kun; Xiao, Xiao; Qin, Dan-Ping; Zhou, Dao-Yuan; Hu, Jian-Guang; Liu, Yan; Zhong, Xiao-Shi

    2016-01-01

    To clarify the effects of MTHFR C677T polymorphism on the risk of diabetic nephropathy (DN) in the Chinese population, an updated meta-analysis was performed. Related studies were identified from PubMed, Springer Link, Ovid and Chinese Databases up to 24 February 2015. A total of 15 studies including 1227 DN cases, 586 healthy controls and 1277 diabetes mellitus (DM) controls were involved in this meta-analysis. Overall, a significantly elevated risk of DN was associated with all variants of MTHFR C677T when compared with the healthy group (T vs C, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.88-2.61; TT vs CC, OR = 4.22, 95% CI = 3.02-5.90; TT + CT vs CC, OR = 2.62, 95% CI = 2.07-3.31; TT vs CC + CT, OR = 2.81, 95% CI = 2.08-3.81) or DM (T vs C, OR = 1.78, 95% CI = 1.59-2.00; TT vs CC, OR = 2.95, 95% CI = 2.33-3.73; TT + CT vs CC, OR = 1.93, 95% CI = 1.63-2.29; TT vs CC + CT, OR = 2.31, 95% CI = 1.87-2.84). In subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. This meta-analysis showed that the MTHFR C677T variants may influence DN risk in Chinese, and further studies with gene-gene and gene-environment interactions are required for definite conclusions.

  18. VitisGen: accelerating grape cultivar improvement

    Technology Transfer Automated Retrieval System (TEKTRAN)

    VitisGen is a multiple institute collaborative project funded by the USDA SCRI program, with a long term goal to accelerate grape cultivar improvement by using cutting-edge molecular marker technologies, rigorous centralized facilities to characterize traits, and molecular breeding expertise. The ge...

  19. 75 FR 56654 - RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... Federal Aviation Administration RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA NextGen Advisory Committee (NAC) SUMMARY: The FAA published a... public of a meeting of RTCA NextGen Advisory Committee. The Agenda in that notice has been revised....

  20. 75 FR 54221 - RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ...] [FR Doc No: 2010-22098] DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA NextGen... NextGen Advisory Committee (NAC). DATES: The meeting will be held September 23, 2010, from 8:30 a.m....

  1. 77 FR 2342 - Fifth Meeting: RTCA, Next Gen Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-17

    ... TRANSPORTATION Federal Aviation Administration Fifth Meeting: RTCA, Next Gen Advisory Committee AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA, NextGen... RTCA, NextGen Advisory Committee. DATES: The meeting will be held February 3, 2012, from 9:30...

  2. VIEW OF GEN. LOGAN STATUE LOOKING SOUTHWEST WITH VISTA AS ...

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

    VIEW OF GEN. LOGAN STATUE LOOKING SOUTHWEST WITH VISTA AS TO THE GEN. THOMAS STATUE DOWN VERMONT AVENUE AND THE GEN. SCOTT STATUE DOWN RHODE ISLAND AVENUE IN THE BACKGROUND - Logan Circle, Vermont Avenue, Rhode Island Avenue, & Thirteenth Street, Washington, District of Columbia, DC

  3. Gen IV Materials Handbook Implementation Plan

    SciTech Connect

    Rittenhouse, P.; Ren, W.

    2005-03-29

    A Gen IV Materials Handbook is being developed to provide an authoritative single source of highly qualified structural materials information and materials properties data for use in design and analyses of all Generation IV Reactor Systems. The Handbook will be responsive to the needs expressed by all of the principal government, national laboratory, and private company stakeholders of Gen IV Reactor Systems. The Gen IV Materials Handbook Implementation Plan provided here addresses the purpose, rationale, attributes, and benefits of the Handbook and will detail its content, format, quality assurance, applicability, and access. Structural materials, both metallic and ceramic, for all Gen IV reactor types currently supported by the Department of Energy (DOE) will be included in the Gen IV Materials Handbook. However, initial emphasis will be on materials for the Very High Temperature Reactor (VHTR). Descriptive information (e.g., chemical composition and applicable technical specifications and codes) will be provided for each material along with an extensive presentation of mechanical and physical property data including consideration of temperature, irradiation, environment, etc. effects on properties. Access to the Gen IV Materials Handbook will be internet-based with appropriate levels of control. Information and data in the Handbook will be configured to allow search by material classes, specific materials, specific information or property class, specific property, data parameters, and individual data points identified with materials parameters, test conditions, and data source. Details on all of these as well as proposed applicability and consideration of data quality classes are provided in the Implementation Plan. Website development for the Handbook is divided into six phases including (1) detailed product analysis and specification, (2) simulation and design, (3) implementation and testing, (4) product release, (5) project/product evaluation, and (6) product

  4. A novel lateral flow assay based on GoldMag nanoparticles and its clinical applications for genotyping of MTHFR C677T polymorphisms

    NASA Astrophysics Data System (ADS)

    Hui, Wenli; Zhang, Sinong; Zhang, Chao; Wan, Yinsheng; Zhu, Juanli; Zhao, Gang; Wu, Songdi; Xi, Dujuan; Zhang, Qinlu; Li, Ningning; Cui, Yali

    2016-02-01

    Current techniques for single nucleotide polymorphism (SNP) detection require tedious experimental procedures and expensive and sophisticated instruments. In this study, a visual genotyping method has been successfully established via combining ARMS-PCR with gold magnetic nanoparticle (GoldMag)-based lateral flow assay (LFA) and applied to the genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T. C677T substitution of the gene MTHFR leads to an increased risk of diseases. The genotyping result is easily achievable by visual observation within 5 minutes after loading of the PCR products onto the LFA device. The system is able to accurately assess a broad detection range of initial starting genomic DNA amounts from 5 ng to 1200 ng per test sample. The limit of detection reaches 5 ng. Furthermore, our PCR-LFA system was applied to clinical trials for screening 1721 individuals for the C677T genotypes. The concordance rate of the genotyping results detected by PCR-LFA was up to 99.6% when compared with the sequencing results. Collectively, our PCR-LFA has been proven to be rapid, accurate, sensitive, and inexpensive. This new method is highly applicable for C677T SNP screening in laboratories and clinical practices. More promisingly, it could also be extended to the detection of SNPs of other genes.

  5. Genotype prevalence and allele frequencies of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation in two caste groups of India.

    PubMed

    Rai, V; Yadav, U; Kumar, P

    2012-06-15

    The aim of the present study was to investigate the distribution of 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism in two caste group populations of eastern Uttar Pradesh. This mutation has been suggested to be positively associated with the risk of several congenital and multifactorial disorders. Frequency of mutant T allele differs in various ethnic and geographical populations of the world. MTHFR C677T mutation analysis was carried out by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) method and the samples studied were randomly selected from the healthy individuals belonging to two caste populations. In Brahmin samples, genotype frequencies of CC, CT and TT were 0.727, 0.25 and 0.023 respectively whereas in Rajput samples, CC genotype was observed in 88 samples, CT genotype in 25 and TT genotype was found in 2 samples. Frequency of mutant T allele was found to be 0.147 in Brahmin and 0.126 in Rajput populations. The percentage of CT genotype and C allele were high in both the populations.

  6. Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

    PubMed

    Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

    2017-03-25

    The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  7. A new and improved method based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the determination of A1298C mutation in the methylenetetrahydrofolate reductase (MTHFR) gene.

    PubMed

    Machnik, Grzegorz; Zapala, Malgorzata; Pelc, Ewa; Gasecka-Czapla, Monika; Kaczmarczyk, Grzegorz; Okopien, Boguslaw

    2013-01-01

    Intracellular folate homeostasis and metabolism is regulated by numerous genes. Among them, 5,10-methylenetetrahydrofolate reductase (MTHFR) is of special interest because of its involvement in regulation of the homocysteine level in the body as a result of folate metabolism. Moreover, some studies demonstrated that the homocysteine plasma level in individuals may be influenced by polymorphisms present in the MTHFR gene. Two common, clinically relevant mutations have been described: MTHFR C677T and MTHFR A1298C. Although several laboratory techniques allow genotyping of both polymorphisms, PCR-RFLP analysis is simple to perform, relatively cheap, and thus one of the most utilized. In the case of A1298C, the PCR-RFLP technique that utilizes MboII endonuclease class II requires an acrylamide gel electrophoresis, since agarose gel electrophoresis is unable to resolve short deoxyribonucleic acid (DNA) fragments after restriction digestion. Agarose gel electrophoresis is commonly preferred over that of acrylamide. To resolve this inconvenience, a novel PCR-RFLP, AjuI-based method to genotype A1298C alleles has been developed that can be performed on standard agarose gel.

  8. Safety Assurance in NextGen

    NASA Technical Reports Server (NTRS)

    HarrisonFleming, Cody; Spencer, Melissa; Leveson, Nancy; Wilkinson, Chris

    2012-01-01

    The generation of minimum operational, safety, performance, and interoperability requirements is an important aspect of safely integrating new NextGen components into the Communication Navigation Surveillance and Air Traffic Management (CNS/ATM) system. These requirements are used as part of the implementation and approval processes. In addition, they provide guidance to determine the levels of design assurance and performance that are needed for each element of the new NextGen procedures, including aircraft, operator, and Air Navigation and Service Provider. Using the enhanced Airborne Traffic Situational Awareness for InTrail Procedure (ATSA-ITP) as an example, this report describes some limitations of the current process used for generating safety requirements and levels of required design assurance. An alternative process is described, as well as the argument for why the alternative can generate more comprehensive requirements and greater safety assurance than the current approach.

  9. GenCade: Introduction, Background, and Formulation

    DTIC Science & Technology

    2012-03-07

    Draft, ft Wood Wood chips Flour Other US Army Corps of Engineers BUILDING STRONG® GenCade Matagorda Ship Channel, TX CMS Shark River Inlet...morphology change Habitat Change • Regional Sediment Management • Beach fills • Inlet bypassing • Channel maintenance • Unifying technology for...to SLR • Habitat evolution (Piping Plover; vegetation) Project Planning & Design 13th Annual CIRP Technology-Transfer Workshop, March 7, 2012 7

  10. GEN3D Ver. 1.37

    SciTech Connect

    2012-01-04

    GEN3D is a three-dimensional mesh generation program. The three-dimensional mesh is generated by mapping a two-dimensional mesh into threedimensions according to one of four types of transformations: translating, rotating, mapping onto a spherical surface, and mapping onto a cylindrical surface. The generated three-dimensional mesh can then be reoriented by offsetting, reflecting about an axis, and revolving about an axis. GEN3D can be used to mesh geometries that are axisymmetric or planar, but, due to three-dimensional loading or boundary conditions, require a three-dimensional finite element mesh and analysis. More importantly, it can be used to mesh complex three-dimensional geometries composed of several sections when the sections can be defined in terms of transformations of two dimensional geometries. The code GJOIN is then used to join the separate sections into a single body. GEN3D reads and writes twodimensional and threedimensional mesh databases in the GENESIS database format; therefore, it is compatible with the preprocessing, postprocessing, and analysis codes used by the Engineering Analysis Department at Sandia National Laboratories, Albuquerque, NM.

  11. Methylenetetrahydrofolate reductase (MTHFR) polymorphism A1298C (Glu429Ala) predicts decline in renal function over time in the African-American Study of Kidney Disease and Hypertension (AASK) Trial and Veterans Affairs Hypertension Cohort (VAHC)

    PubMed Central

    Salem, Rany M.; Lipkowitz, Michael S.; Bhatnagar, Vibha; Pandey, Braj; Schork, Nicholas J.; O’Connor, Daniel T.

    2012-01-01

    Background. Hyperhomocysteinemia is associated with increased venous thrombosis and cardiovascular disease (CVD). Mutations in the human methylenetetrahydrofolate reductase (MTHFR) gene have been associated with increased homocysteine levels and risks of CVD in various populations including those with kidney disease. Here, we evaluated the influence of MTHFR variants on progressive loss of kidney function. Methods. We analyzed 821 subjects with hypertensive nephrosclerosis from the longitudinal National Institute of Diabetes and Digestive and Kidney Diseases African-American Study of Kidney Disease and Hypertension (AASK) Trial to determine whether decline in glomerular filtration rate (GFR) over ∼4.2 years was predicted by common genetic variation within MTHFR at non-synonymous positions C677T (Ala222Val) and A1298C (Glu429Ala) or by MTHFR haplotypes. The effect on GFR decline was then supported by a study of 1333 subjects from the San Diego Veterans Affairs Hypertension Cohort (VAHC), followed over ∼4.5 years. Linear effect models were utilized to determine both genotype [single-nucleotide polymorphism (SNP)] and genotype (SNP)-by-time interactions. Results. In AASK, the polymorphism at A1298C predicted the rate of GFR decline: A1298/A1298 major allele homozygosity resulted in a less pronounced decline of GFR, with a significant SNP-by-time interaction. An independent follow-up study in the San Diego VAHC subjects supports that A1298/A1298 homozygotes have the greatest estimated GFR throughout the study. Haplotype analysis with C677T yielded concurring results. Conclusion. We conclude that the MTHFR-coding polymorphism at A1298C is associated with renal decline in African-Americans with hypertensive nephrosclerosis and is supported by a veteran cohort with a primary care diagnosis of hypertension. Further investigation is needed to confirm such findings and to determine what molecular mechanism may contribute to this association. PMID:21613384

  12. Generic classification of the Archiborborinae (Diptera: Sphaeroceridae), with a revision of Antrops Enderlein, Coloantrops gen. nov., Maculantrops gen. nov., Photoantrops gen. nov., and Poecilantrops gen. nov.

    PubMed

    Kits, Joel H; Marshall, Stephen A

    2013-01-01

    The Archiborborinae comprise a diverse clade of flies in the family Sphaeroceridae. We here revise the generic classification, redefining the genus Antrops Enderlein and naming 5 new genera: Boreantrops gen. nov., Coloantrops gen. nov., Maculantrops gen. nov., Photoantrops gen. nov., and Poecilantrops gen. nov. The genus Archiborborus, until recently a paraphyletic assemblage including most of the described species in the subfamily, is treated as a junior synonym of Antrops (syn. nov.) We revise the genera Antrops (53 species, including 40 sp. nov.: Antrops anovariegatus, Antrops aurantifemur, Antrops baeza, Antrops bellavista, Antrops biflavus, Antrops bucki, Antrops carpishensis, Antrops cochabamba, Antrops cochinoca, Antrops coniobaptos, Antrops coroico, Antrops cotopaxi, Antrops didactylos, Antrops diversipennis, Antrops eurus, Antrops fulgiceps, Antrops fuliginosus, Antrops guandera, Antrops guaramacalensis, Antrops inca, Antrops juninensis, Antrops mucarensis, Antrops niger, Antrops papallacta, Antrops pecki, Antrops podocarpus, Antrops quadrilobus, Antrops siberia, Antrops sierrazulensis, Antrops tachira, Antrops tequendama, Antrops tetrastichus, Antrops tumbrensis, Antrops unduavi, Antrops variegatus, Antrops versabilis, Antrops vittatus, Antrops yungas, and Antrops zongo and the following comb. nov.: Antrops annulatus (Richards), Antrops chaetosus (Richards), Antrops femoralis (Blanchard), Antrops hirtus (Bigot), Antrops maculipennis (Duda), Antrops maximus (Richards), Antrops microphthalmus (Richards), Antrops quadrinotus (Bigot), Antrops setosus (Duda), Antrops simplicimanus (Richards), Antrops nitidicollis (Becker), and Antrops orbitalis (Duda)), Coloantrops (1 species: Coloantrops daedalus, sp. nov.), Maculantrops (2 species, Maculantrops hirtipes (Macquart) comb. nov. and Maculantrops altiplanus, sp. nov.), Photoantrops (1 species: Pho-toantrops echinus sp. nov.), and Poecilantrops (10 species: Poecilantrops baorucensis, Poecilantrops boraceiensis

  13. An Gen2 Based Security Authentication Protocol for RFID System

    NASA Astrophysics Data System (ADS)

    Yi, Xiaoluo; Wang, Liangmin; Mao, Dongmei; Zhan, Yongzhao

    EPC Class-1 Generation-2 specification(Gen2 in brief) has been accepted as the standard for RFID tags under grant number ISO18000-6C. However, Gen2 does not pay due attention to security. For this reason, a Gen2 based security authentication protocol is developed in this paper. In details, we study the security requirements presented in the current Gen2 based RFID authentication protocols[7-13]. Then we point out the security flaws of Chien's mutual authentication protocol[7], and improve the protocol based on a 11 security requirements. Our improved protocol merely uses CRC and PRNG operations supported by Gen2 and meets the 11 security requirements. In contrast to the similar work [14,15] on Chien's protocol or other Gen2 based schemes, our protocol is more secure and our security analysis is much more comprehensive and qualitative.

  14. TidGen Power System Commercialization Project

    SciTech Connect

    Sauer, Christopher R.; McEntee, Jarlath

    2013-12-30

    ORPC Maine, LLC, a wholly-owned subsidiary of Ocean Renewable Power Company, LLC (collectively ORPC), submits this Final Technical Report for the TidGen® Power System Commercialization Project (Project), partially funded by the U.S. Department of Energy (DE-EE0003647). The Project was built and operated in compliance with the Federal Energy Regulatory Commission (FERC) pilot project license (P-12711) and other permits and approvals needed for the Project. This report documents the methodologies, activities and results of the various phases of the Project, including design, engineering, procurement, assembly, installation, operation, licensing, environmental monitoring, retrieval, maintenance and repair. The Project represents a significant achievement for the renewable energy portfolio of the U.S. in general, and for the U.S. marine hydrokinetic (MHK) industry in particular. The stated Project goal was to advance, demonstrate and accelerate deployment and commercialization of ORPC’s tidal-current based hydrokinetic power generation system, including the energy extraction and conversion technology, associated power electronics, and interconnection equipment capable of reliably delivering electricity to the domestic power grid. ORPC achieved this goal by designing, building and operating the TidGen® Power System in 2012 and becoming the first federally licensed hydrokinetic tidal energy project to deliver electricity to a power grid under a power purchase agreement in North America. Located in Cobscook Bay between Eastport and Lubec, Maine, the TidGen® Power System was connected to the Bangor Hydro Electric utility grid at an on-shore station in North Lubec on September 13, 2012. ORPC obtained a FERC pilot project license for the Project on February 12, 2012 and the first Maine Department of Environmental Protection General Permit issued for a tidal energy project on January 31, 2012. In addition, ORPC entered into a 20-year agreement with Bangor Hydro Electric

  15. Gen IV Materials Handbook Functionalities and Operation

    SciTech Connect

    Ren, Weiju

    2009-12-01

    This document is prepared for navigation and operation of the Gen IV Materials Handbook, with architecture description and new user access initiation instructions. Development rationale and history of the Handbook is summarized. The major development aspects, architecture, and design principles of the Handbook are briefly introduced to provide an overview of its past evolution and future prospects. Detailed instructions are given with examples for navigating the constructed Handbook components and using the main functionalities. Procedures are provided in a step-by-step fashion for Data Upload Managers to upload reports and data files, as well as for new users to initiate Handbook access.

  16. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials

    PubMed Central

    Holmes, Michael V; Newcombe, Paul; Hubacek, Jaroslav A; Sofat, Reecha; Ricketts, Sally L; Cooper, Jackie; Breteler, Monique MB; Bautista, Leonelo E; Sharma, Pankaj; Whittaker, John C; Smeeth, Liam; Fowkes, F Gerald R; Algra, Ale; Shmeleva, Veronika; Szolnoki, Zoltan; Roest, Mark; Linnebank, Michael; Zacho, Jeppe; Nalls, Michael A; Singleton, Andrew B; Ferrucci, Luigi; Hardy, John; Worrall, Bradford B; Rich, Stephen S; Matarin, Mar; Norman, Paul E; Flicker, Leon; Almeida, Osvaldo P; van Bockxmeer, Frank M; Shimokata, Hiroshi; Khaw, Kay-Tee; Wareham, Nicholas J; Bobak, Martin; Sterne, Jonathan AC; Smith, George Davey; Talmud, Philippa J; van Duijn, Cornelia; Humphries, Steve E; Price, Jackie F; Ebrahim, Shah; Lawlor, Debbie A; Hankey, Graeme J; Meschia, James F; Sandhu, Manjinder S; Hingorani, Aroon D; Casas, Juan P

    2011-01-01

    Summary Background The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials. Methods We established a collaboration of genetic studies consisting of 237 datasets including 59 995 individuals with data for homocysteine and 20 885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45 549 individuals, 2314 stroke events, 269 transient ischaemic attacks). Findings The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 μmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 μmol/L, −0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar

  17. MTHFR 677C>T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

    PubMed Central

    Sekhar, Deepa; Francis, Amirtharaj; Gupta, Nishi; Konwar, Rituraj; Kumar, Sandeep; Kumar, Surender; Thangaraj, Kumarasamy; Rajender, Singh

    2015-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent. Methods and Results We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N=588) and controls (N=508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P=0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR= 1.08, P= 0.067). Conclusion 677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer. PMID:25803740

  18. Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression

    PubMed Central

    Eszlari, N; Kovacs, D; Petschner, P; Pap, D; Gonda, X; Elliott, R; Anderson, I M; Deakin, J F W; Bagdy, G; Juhasz, G

    2016-01-01

    Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development. PMID:26926881

  19. High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism

    PubMed Central

    Aarabi, Mahmoud; San Gabriel, Maria C.; Chan, Donovan; Behan, Nathalie A.; Caron, Maxime; Pastinen, Tomi; Bourque, Guillaume; MacFarlane, Amanda J.; Zini, Armand; Trasler, Jacquetta

    2015-01-01

    Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodeled during spermatogenesis. While high-dose folic acid supplementation (up to 10 times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of 6 months of high-dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility. Blood folate concentrations increased significantly after supplementation with no significant improvements in sperm parameters. Methylation levels of the differentially methylated regions of several imprinted loci (H19, DLK1/GTL2, MEST, SNRPN, PLAGL1, KCNQ1OT1) were normal both before and after supplementation. Reduced representation bisulfite sequencing (RRBS) revealed a significant global loss of methylation across different regions of the sperm genome. The most marked loss of DNA methylation was found in sperm from patients homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common polymorphism in a key enzyme required for folate metabolism. RRBS analysis also showed that most of the differentially methylated tiles were located in DNA repeats, low CpG-density and intergenic regions. Ingenuity Pathway Analysis revealed that methylation of promoter regions was altered in several genes involved in cancer and neurobehavioral disorders including CBFA2T3, PTPN6, COL18A1, ALDH2, UBE4B, ERBB2, GABRB3, CNTNAP4 and NIPA1. Our data reveal alterations of the human sperm epigenome associated with high-dose folic acid supplementation, effects that were exacerbated by a common polymorphism in MTHFR. PMID:26307085

  20. MTHFR, MTR, and MTRR Polymorphisms in Relation to p16INK4A Hypermethylation in Mucosa of Patients with Colorectal Cancer

    PubMed Central

    Wettergren, Yvonne; Odin, Elisabeth; Carlsson, Göran; Gustavsson, Bengt

    2010-01-01

    We recently analyzed the hypermethylation status of the p16INK4a (p16) gene promoter in normal-appearing mucosa obtained from patients with colorectal cancer. Hypermethylation of p16 was associated with reduced survival of these patients. In the present study, germ line polymorphisms in the folate- and methyl-associated genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR), were analyzed in the same patient cohort to find a possible link between these genetic variants and p16 hypermethylation. Genomic DNA was extracted from blood of patients (n = 181) and controls (n = 300). Genotype analyses were run on an ABI PRISM® 7900HT sequence-detection system (Applied Biosystems), using real-time polymerase chain reaction and TaqMan chemistry. The results showed that the genotype distributions of the patient and control groups were similar. No significant differences in cancer-specific or disease-free survival of stage I–III patients according to polymorphic variants were detected, nor were any differences in cancer-specific or disease-free survival detected when patients were subgrouped according to the MTHFR or MTR genotype groups and dichotomized by p16 hypermethylation status in mucosa. However, patients with the MTRR 66 AA/AG genotypes were found to have a significantly worse cancer-specific survival when the mucosa were positive, compared with negative, for p16 hypermethylation (hazard ratio 2.7; 95% confidence interval 1.2–6.4; P = 0.023). In contrast, there was no difference in survival among patients with the MTRR 66 GG genotype stratified by p16 hypermethylation status. These results indicate a relationship between genetic germ-line variants of the MTRR gene and p16 hypermethylation in mucosa, which may affect the clinical outcome of patients with colorectal cancer. PMID:20549016

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. Glucose Tolerance, MTHFR C677T and NOS3 G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

    PubMed Central

    Mutize, Tinashe; Erasmus, Rajiv T.

    2016-01-01

    The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p ≤ 0.033) and in screen-detected diabetes compared to known diabetes on treatment (p = 0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p > 0.999). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β = 0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control. PMID:27990443

  4. A Lower Degree of PBMC L1 Methylation in Women with Lower Folate Status May Explain the MTHFR C677T Polymorphism Associated Higher Risk of CIN in the US Post Folic Acid Fortification Era

    PubMed Central

    Badiga, Suguna; Johanning, Gary L.; Macaluso, Maurizio; Azuero, Andres; Chambers, Michelle M.; Siddiqui, Nuzhat R.; Piyathilake, Chandrika J.

    2014-01-01

    Background Studies in populations unexposed to folic acid (FA) fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+). However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1) The association between MTHFR C677T polymorphism and risk of CIN 2+; 2) The modifying effects of plasma folate concentrations on this association; and 3) The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s), in peripheral blood mononuclear cell (PBMC) DNA, a documented biomarker of CIN risk. Methods The study included 457 US women diagnosed with either CIN 2+ (cases) or ≤ CIN 1 (non-cases). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN. Results The 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR = 2.41, P = 0.030). Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR = 0.28, P = 0.017). Conclusions This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation. PMID:25302494

  5. Back to the FutureGen?

    SciTech Connect

    Buchsbaum, L.

    2009-04-15

    After years of political wrangling, Democrats may green-light the experimental clean coal power plants. The article relates how the project came to be curtailed, how Senator Dick Durbin managed to protect $134 million in funding for FutureGen in Mattoon, and how once Obama was in office a $2 billion line item to fund a 'near zero emissions power plant(s)' was placed in the Senate version of the Stimulus Bill. The final version of the legislation cut the funding to $1 billion for 'fossil energy research and development'. In December 2008 the FutureGen Alliance and the City of Mattoon spent $6.5 billion to purchase the plants eventual 440 acre site. A report by the Government Accountability Office (GAO) said that Bush's inaction may have set back clean coal technology in the US by as much as a decade. If additional funding comes through construction of the plant could start in 2010. 1 fig., 1 photo.

  6. Towards an International Culture: Gen Y Students and SNS?

    ERIC Educational Resources Information Center

    Lichy, Jessica

    2012-01-01

    This article reports the findings of a small-scale investigation into the Internet user behaviour of generation Y (Gen Y) students, with particular reference to social networking sites. The study adds to the literature on cross-cultural Internet user behaviour with specific reference to Gen Y and social networking. It compares how a cohort of…

  7. The Integrated Airport: Building a Successful NextGen Testbed

    ScienceCinema

    Frederick-Recascino, Christina [Embry-Riddle Aeronautical University, Daytona Beach, Florida, United States; Sweigard, Doug [Lockheed Martin Corporation; Lester, Wade [ERAU

    2016-07-12

    This presentation will describe a unique public-private partnership - the Integrated Airport - that was created to engage in research and testing related to NextGen Technology deployment.  NextGen refers to the program that will be initiated to modernize the US National Airspace.  As with any major, multi-decade initiative, such as NextGen, integration of work efforts by multiple partners in the modernization is critical for success.  This talk will focus on the development of the consortium, how the consortium plans for NextGen initiatives, the series of technology demonstrations we have produced and plans for the future of NextGen testing and implementation. 

  8. Proposal for two new genera, Brevibacillus gen. nov. and Aneurinibacillus gen. nov.

    PubMed

    Shida, O; Takagi, H; Kadowaki, K; Komagata, K

    1996-10-01

    16S rRNA gene sequences of the type strains of 11 species belonging to the Bacillus brevis and Bacillus aneurinolyticus groups were determined. On the basis of the results of gene sequence analyses, these species were separated into two clusters. The B. brevis cluster included 10 species, namely, Bacillus brevis, Bacillus agri, Bacillus centrosporus, Bacillus choshinensis, Bacillus parabrevis, Bacillus reuszeri, Bacillus formosus, Bacillus borstelensis, Bacillus laterosporus, and Bacillus thermoruber. Bacillus aneurinolyticus and Bacillus migulanus belonged to the B. aneurinolyticus cluster. Moreover, the two clusters were phylogenetically distinct from other Bacillus, Amphibacillus, Sporolactobacillus, Paenibacillus, and Alicyclobacillus species. On the basis of our data, we propose reclassification of the B. brevis cluster as Brevibacillus gen. nov. and reclassification of the B. aneurinolyticus cluster as Aneurinibacillus gen. nov. By using 16S rRNA gene sequence alignments, two specific PCR amplification primers were designed for differentiating the two new genera from each other and from other aerobic, endospore-forming organisms.

  9. NextGen Future Safety Assessment Game

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Gheorghe, Adian; Jones, Sharon Monica

    2010-01-01

    The successful implementation of the next generation infrastructure systems requires solid understanding of their technical, social, political and economic aspects along with their interactions. The lack of historical data that relate to the long-term planning of complex systems introduces unique challenges for decision makers and involved stakeholders which in turn result in unsustainable systems. Also, the need to understand the infrastructure at the societal level and capture the interaction between multiple stakeholders becomes important. This paper proposes a methodology in order to develop a holistic approach aiming to provide an alternative subject-matter expert (SME) elicitation and data collection method for future sociotechnical systems. The methodology is adapted to Next Generation Air Transportation System (NextGen) decision making environment in order to demonstrate the benefits of this holistic approach.

  10. NextGen Future Safety Assessment Game

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Gheorghe, Adrian; Jones, Sharon Monica

    2011-01-01

    The successful implementation of the next generation infrastructure systems requires solid understanding of their technical, social, political and economic aspects along with their interactions. The lack of historical data that relate to the long-term planning of complex systems introduces unique challenges for decision makers and involved stakeholders which in turn result in unsustainable systems. Also, the need to understand the infrastructure at the societal level and capture the interaction between multiple stakeholders becomes important. This paper proposes a methodology in order to develop a holistic approach aiming to provide an alternative subject-matter expert (SME) elicitation and data collection method for future sociotechnical systems. The methodology is adapted to Next Generation Air Transportation System (NextGen) decision making environment in order to demonstrate the benefits of this holistic approach.

  11. 5,10-Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms: genotype frequency and association with homocysteine and folate levels in middle-southern Italian adults.

    PubMed

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

    2014-01-01

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

  12. Interactions among methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) polymorphisms - a cross-sectional study: multiple heterozygosis as a risk factor for higher homocysteine levels and vaso-occlusive episodes.

    PubMed

    Amaral, F M; Miranda-Vilela, A L; Lordelo, G S; Ribeiro, I F; Daldegan, M B; Grisolia, C K

    2017-02-23

    High plasma homocysteine (Hcy) ​​levels may be responsible for vaso-occlusive episodes and may have acquired and/or genetic causes. This cross-sectional study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C) and cystathionine-β-synthase (CBS; T833C/844ins68, G919A) polymorphisms in serum levels of folic acid, vitamin B12 and Hcy, and to verify a possible association between these polymorphisms and the clinical variability. Blood samples of Brazilian patients with a diagnosis of thrombosis were submitted to genotyping by PCR-based methods and serum dosages of folic acid, vitamin B12 and Hcy. Except for the CBS G919A polymorphism, all other genetic markers were in Hardy-Weinberg equilibrium. An increased risk for venous thrombosis was found for the MTHFR 1298CC carriers (OR = 1.688; 95%CI = 0.839-3.398, P = 0.018) and those homozygously mutant for the CBS haplotype 844ins68/T833C (OR = 2.488; 95%CI = 0.501-12.363, P = 0.031), while heterozygous for this CBS haplotype showed an increased risk for higher Hcy levels (OR = 5.900; 95%CI = 1.003-34.691, P = 0.030). Significant interactions were observed among the MTHFR C677T, MTHFR A1298C and CBS haplotype 844ins68/T833C polymorphisms in the results for Hcy levels (P = 0.000), where heterozygous had higher values. Interactions among these polymorphisms can affect serum Hcy levels, where multiple heterozygosis could be a risk factor for vaso-occlusive episodes.

  13. Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

    PubMed Central

    Jakubowska, A; Rozkrut, D; Antoniou, A; Hamann, U; Scott, R J; McGuffog, L; Healy, S; Sinilnikova, O M; Rennert, G; Lejbkowicz, F; Flugelman, A; Andrulis, I L; Glendon, G; Ozcelik, H; Thomassen, M; Paligo, M; Aretini, P; Kantala, J; Aroer, B; von Wachenfeldt, A; Liljegren, A; Loman, N; Herbst, K; Kristoffersson, U; Rosenquist, R; Karlsson, P; Stenmark-Askmalm, M; Melin, B; Nathanson, K L; Domchek, S M; Byrski, T; Huzarski, T; Gronwald, J; Menkiszak, J; Cybulski, C; Serrano, P; Osorio, A; Cajal, T R; Tsitlaidou, M; Benítez, J; Gilbert, M; Rookus, M; Aalfs, C M; Kluijt, I; Boessenkool-Pape, J L; Meijers-Heijboer, H E J; Oosterwijk, J C; van Asperen, C J; Blok, M J; Nelen, M R; van den Ouweland, A M W; Seynaeve, C; van der Luijt, R B; Devilee, P; Easton, D F; Peock, S; Frost, D; Platte, R; Ellis, S D; Fineberg, E; Evans, D G; Lalloo, F; Eeles, R; Jacobs, C; Adlard, J; Davidson, R; Eccles, D; Cole, T; Cook, J; Godwin, A; Bove, B; Stoppa-Lyonnet, D; Caux-Moncoutier, V; Belotti, M; Tirapo, C; Mazoyer, S; Barjhoux, L; Boutry-Kryza, N; Pujol, P; Coupier, I; Peyrat, J-P; Vennin, P; Muller, D; Fricker, J-P; Venat-Bouvet, L; Johannsson, O Th; Isaacs, C; Schmutzler, R; Wappenschmidt, B; Meindl, A; Arnold, N; Varon-Mateeva, R; Niederacher, D; Sutter, C; Deissler, H; Preisler-Adams, S; Simard, J; Soucy, P; Durocher, F; Chenevix-Trench, G; Beesley, J; Chen, X; Rebbeck, T; Couch, F; Wang, X; Lindor, N; Fredericksen, Z; Pankratz, V S; Peterlongo, P; Bonanni, B; Fortuzzi, S; Peissel, B; Szabo, C; Mai, P L; Loud, J T; Lubinski, J

    2012-01-01

    Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10–2.04 and HR 2.16, 95%CI 1.24–3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. PMID:22669161

  14. Head-Worn Displays for NextGen

    NASA Technical Reports Server (NTRS)

    Bailey, Randall E.; Shelton, Kevin J.; Arthur, J. J.

    2011-01-01

    The operating concepts emerging under the Next Generation air transportation system (NextGen) require new technology and procedures - not only on the ground-side - but also on the flight deck. Flight deck display and decision support technologies are specifically targeted to overcome aircraft safety barriers that might otherwise constrain the full realization of NextGen. One such technology is the very lightweight, unobtrusive head-worn display (HWD). HWDs with an integrated head-tracking system are being researched as they offer significant potential benefit under emerging NextGen operational concepts. Two areas of benefit for NextGen are defined. First, the HWD may be designed to be equivalent to the Head-Up Display (HUD) using Virtual HUD concepts. As such, these operational credits may be provided to significantly more aircraft for which HUD installation is neither practical nor possible. Second, the HWD provides unique display capabilities, such as an unlimited field-of-regard. These capabilities may be integral to emerging NextGen operational concepts, eliminating safety issues which might otherwise constrain the full realization of NextGen. The paper details recent research results, current HWD technology limitations, and future technology development needed to realize HWDs as a enabling technology for NextGen.

  15. RxGen General Optical Model Prescription Generator

    NASA Technical Reports Server (NTRS)

    Sigrist, Norbert

    2012-01-01

    RxGen is a prescription generator for JPL's in-house optical modeling software package called MACOS (Modeling and Analysis for Controlled Optical Systems), which is an expert optical analysis software package focusing on modeling optics on dynamic structures, deformable optics, and controlled optics. The objectives of RxGen are to simplify and automate MACOS prescription generations, reducing errors associated with creating such optical prescriptions, and improving user efficiency without requiring MACOS proficiency. RxGen uses MATLAB (a high-level language and interactive environment developed by MathWorks) as the development and deployment platform, but RxGen can easily be ported to another optical modeling/analysis platform. Running RxGen within the modeling environment has the huge benefit that variations in optical models can be made an integral part of the modeling state. For instance, optical prescription parameters determined as external functional dependencies, optical variations by controlling the in-/exclusion of optical components like sub-systems, and/or controlling the state of all components. Combining the mentioned capabilities and flexibilities with RxGen's optical abstraction layer completely eliminates the hindering aspects for requiring proficiency in writing/editing MACOS prescriptions, allowing users to focus on the modeling aspects of optical systems, i.e., increasing productivity and efficiency. RxGen provides significant enhancements to MACOS and delivers a framework for fast prototyping as well as for developing very complex controlled optical systems.

  16. 98. SWITCH HOUSE MAIN LOBBY, GEN 3 CIRCUIT BREAKER, VIEW ...

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

    98. SWITCH HOUSE MAIN LOBBY, GEN 3 CIRCUIT BREAKER, VIEW OF OPPOSITE SIDE FROM HAER No. PA-505-97 - Delaware County Electric Company, Chester Station, Delaware River at South end of Ward Street, Chester, Delaware County, PA

  17. 1. GENERAL VIEW. Statues: Maj. Gen George Meade by Daniel ...

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

    1. GENERAL VIEW. Statues: Maj. Gen George Meade by Daniel Chester French, south side; Maj. Gen. John Reynolds by Charles Grafly, north side. Equestrian Statues: Maj. Gen George B. McClellan by Edward C. Potter, south side; Maj. Gen Winfield S. Hancock by J.Q.A. Ward, north side. The statue at the base of northern inner pedestal is Richard Smith, a type founder and donor of the Memorial. The niches are filled with eight colossal busts including Union generals, admirals, Pennsylvania governor, Memorial's architects (John T. and James H. Windrim), and executor of Smith's will. The frieze is carved with the names of eighty-four prominent Pennsylvania participants in the Civil War. - Smith Memorial Arch, Philadelphia, Philadelphia County, PA

  18. EPCGen2 Pseudorandom Number Generators: Analysis of J3Gen

    PubMed Central

    Peinado, Alberto; Munilla, Jorge; Fúster-Sabater, Amparo

    2014-01-01

    This paper analyzes the cryptographic security of J3Gen, a promising pseudo random number generator for low-cost passive Radio Frequency Identification (RFID) tags. Although J3Gen has been shown to fulfill the randomness criteria set by the EPCglobal Gen2 standard and is intended for security applications, we describe here two cryptanalytic attacks that question its security claims: (i) a probabilistic attack based on solving linear equation systems; and (ii) a deterministic attack based on the decimation of the output sequence. Numerical results, supported by simulations, show that for the specific recommended values of the configurable parameters, a low number of intercepted output bits are enough to break J3Gen. We then make some recommendations that address these issues. PMID:24721767

  19. New sequestrate fungi from Guyana: Jimtrappea guyanensis gen. sp. nov., Castellanea pakaraimophila gen. sp. nov., and Costatisporus cyanescens gen. sp. nov. (Boletaceae, Boletales).

    PubMed

    Smith, Matthew E; Amses, Kevin R; Elliott, Todd F; Obase, Keisuke; Aime, M Catherine; Henkel, Terry W

    2015-12-01

    Jimtrappea guyanensis gen. sp. nov., Castellanea pakaraimophila gen. sp. nov., and Costatisporus cyanescens gen. sp. nov. are described as new to science. These sequestrate, hypogeous fungi were collected in Guyana under closed canopy tropical forests in association with ectomycorrhizal (ECM) host tree genera Dicymbe (Fabaceae subfam. Caesalpinioideae), Aldina (Fabaceae subfam. Papilionoideae), and Pakaraimaea (Dipterocarpaceae). Molecular data place these fungi in Boletaceae (Boletales, Agaricomycetes, Basidiomycota) and inform their relationships to other known epigeous and sequestrate taxa within that family. Macro- and micromorphological characters, habitat, and multi-locus DNA sequence data are provided for each new taxon. Unique morphological features and a molecular phylogenetic analysis of 185 taxa across the order Boletales justify the recognition of the three new genera.

  20. Skryjelites auritus gen. et sp. nov. and Quasimolites quasimodo gen. et sp. nov.--two new middle Cambrian hyolithids (?Mollusca) from the Czech Republic.

    PubMed

    Valent, Martin; Fatka, Oldřich; Szabad, Michal; Micka, Václav; Marek, Ladislav

    2015-08-28

    Two new endemic genera and species of extinct group of Hyolitha, Skryjelites auritus gen. et sp. nov. and Quasimolites quasimodo gen. et sp. nov. are described and illustrated from the Buchava Formation of the Barrandian area (Czech Republic).

  1. Analysis of Polymorphisms in Genes (AGT, MTHFR, GPIIIa, and GSTP1) Associated with Hypertension, Thrombophilia and Oxidative Stress in Mestizo and Amerindian Populations of México

    PubMed Central

    Juárez-Velázquez, Rocio; Canto, Patricia; Canto-Cetina, Thelma; Rangel-Villalobos, Hector; Rosas-Vargas, Haydee; Rodríguez, Maricela; Canizales-Quinteros, Samuel; Velázquez Wong, Ana Claudia; Ordoñez-Razo, Rosa María; Vilchis-Dorantes, Guadalupe; Coral-Vázquez, Ramón Mauricio

    2010-01-01

    Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1) polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using χ2 tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups. PMID:20592457

  2. Whole genome sequencing identifies ANXA3 and MTHFR mutations in a large family with an unknown equinus deformity associated genetic disorder.

    PubMed

    Zhang, Zhiqun; Kong, Zhuqing; Zhu, Miao; Lu, Wenxiang; Ni, Lei; Bai, Yunfei; Lou, Yue

    2016-10-01

    The aim of this study was to characterize a previously uncharacterized genetic disorder associated with equinus deformity in a large Chinese family at the genetic level. Blood samples were obtained and whole genome sequencing was performed. Differential gene variants were identified and potential impacts on protein structure were predicted. Based on the control sample, several diseases associated variants were identified and selected for further validation. One of the potential variants identified was a ANXA3 gene [chr4, c.C820T(p.R274*)] variant. Further bioinformatic analysis showed that the observed mutation could lead to a three-dimensional conformational change. Moreover, a MTHFR variant that is different from variants associated with clubfoot was also identified. Bioinformatic analysis showed that this mutation could alter the protein binding region. These findings imply that this uncharacterized genetic disorder is not clubfoot, despite sharing some similar symptoms. Furthermore, specific CNV profiles were identified in association with the diseased samples, thus further speaking to the complexity of this multigenerational disorder. This study examined a previously uncharacterized genetic disorder appearing similar to clubfoot and yet having distinct features. Following whole genome sequencing and comparative analysis, several differential gene variants were identified to enable a further distinction from clubfoot. It is hoped that these findings will provide further insight into this disorder and other similar disorders.

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Taxonomy and phylogeny of Laburnicola gen. nov. and Paramassariosphaeria gen. nov. (Didymosphaeriaceae, Massarineae, Pleosporales).

    PubMed

    Wanasinghe, Dhanushka N; Jones, Evan Benjamin Gareth; Camporesi, Erio; Dissanayake, Asha J; Kamolhan, Sutakorn; Mortimer, Peter E; Xu, Jianchu; Abd-Elsalam, Kamel A; Hyde, Kevin D

    2016-11-01

    Laburnicola gen. nov., with four new species, Paramassariosphaeria gen. nov., with a new species and Montagnula saikhuensis sp. nov. are introduced in this paper. The phylogeny of these taxa and genera of Didymosphaeriaceae are resolved based on analysis of combined LSU, SSU, and ITS sequence data. Laburnicola is characterized by obpyriform, immersed ascomata, with a peridium fused to the host tissues, long pedicellate asci and ellipsoidal to fusoid ascospores, whose central cells have longitudinal septa and a rugged surface. Paramassariosphaeria is characterized by globose to subglobose ascomata, papillate ostioles, a peridium comprising pseudoparenchymatous cells of textura angularis, cylindric-clavate to clavate, pedicellate asci and brown, curved-fusoid ascospores, with multiple transverse septa and a mucilaginous sheath. Montagnula saikhuensis has immersed ascomata, with a peridium fused to the host tissues, long pedicellate asci and blackish brown, ellipsoidal ascospores with a single septum. The relationship of these taxa with other Didymosphaeriaceae species is discussed based on comparative morphology and phylogenetic analysis. Munkovalsaria appendiculata and Munkovalsaria donacina are transferred to the genus Montagnula.

  6. SEQ-GEN: A comprehensive multimission sequencing system

    NASA Technical Reports Server (NTRS)

    Salcedo, Jose; Starbird, Thomas J.

    1994-01-01

    SEQ-GEN is a user-interactive computer program used to plan and generate a sequence of commands for spacecraft. Desired activities are specified by the user of SEQ-GEN; SEQ-GEN in turn expands these activities, deriving the spacecraft commands necessary to accomplish the desired activities. SEQ-GEN models the effects on the spacecraft of the commands, predicting the state as a function of time, flagging any conflicts and rule violations. These states, conflicts, and violations are viewable both graphically and textually at the user's request. SEQ-GEN also displays the entire sequence graphically, showing each requested activity as a bar on its graphical timeline. SEQ-GEN immediately revalidates the sequence, updating its models and calculations along with its displays based on these changes. Because it has the ability to recalculate spacecraft states immediately, the user is able to perform 'what-if' sessions easily. SEQ-GEN, a multimission tool, is adaptable to any flight project. A flight project writes its adaptation files containing project unique information including in its simplest form, only spacecraft commands. For more involved projects the adaptation files may also contain flight and mission rules, description of the spacecraft and ground models, and the definition of activities. SEQ-GEN operates at whatever level of detail the adaptation files imply. Simple adaptations are straight forward to do. There is, however, no limit to the complexity of activity definitions or of spacecraft models: both may involve unlimited logical decision points. Commands and activities may involve any number of parameters of a wide variety of data types, including integer, float, time, boolean, and character strings. SEQ-GEN will be used by the Mars Pathfinder, Cassini, and VIM (Voyager Interstellar Mission) project in an effort to speed up adaptation time and to keep sequence generation costs down. SEQ-GEN is hosted on UNIX workstations. It uses MOTIF and X for windowing

  7. A cross-sectional study to find out the relationship of methylenetetrahydrofolate reductase (MTHFR) C677T genotype with plasma levels of folate and total homocysteine by daily folate intake in Japanese.

    PubMed

    Fukuda, Nana; Hamajima, Nobuyuki; Wakai, Kenji; Suzuki, Koji

    2014-01-01

    In those with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, enzyme activity is lowered. Therefore, these individuals might require an increased intake of folate to maintain or control blood levels of plasma folate or total homocysteine (tHcy). We examined associations of dietary folate intake with fasting plasma folate and total homocysteine (tHcy) according to genotype among 554 Japanese (207 men and 347 women aged 39-89 y) recruited in 2009. Intake of folate was estimated with a food frequency questionnaire. The MTHFR polymorphism was genotyped by a polymerase chain reaction with confronting two-pair primers. The log-transformed concentration of folate or tHcy was regressed on energy-adjusted folate intake in a linear regression analysis. Higher folate intake was associated with higher plasma folate among those with the CC (β=0.165, p=0.066) or CT (β=0.248, p<0.001) genotypes, and with lower tHcy levels only among those with the CC (β=-0.141, p=0.013) genotype. Plasma folate was significantly and inversely associated with tHcy, irrespective of MTHFR genotype. When the analysis was restricted to those with tHcy levels higher than the reference range (≥13.5 nmol/mL, n=20), these significant associations were not found. The interaction between folate intake or plasma folate and genotype was not significant in any analysis. In conclusion, dietary folate intake was positively associated with plasma folate among those with the CC or CT genotypes and inversely associated with tHcy among those with the CC genotype, but the associations were not clear among those with higher levels of tHcy.

  8. Breast cancer risk associated with gene expression and genotype polymorphisms of the folate-metabolizing MTHFR gene: a case-control study in a high altitude Ecuadorian mestizo population.

    PubMed

    López-Cortés, Andrés; Echeverría, Carolina; Oña-Cisneros, Fabián; Sánchez, María Eugenia; Herrera, Camilo; Cabrera-Andrade, Alejandro; Rosales, Felipe; Ortiz, Malena; Paz-Y-Miño, César

    2015-08-01

    Breast cancer (BC) is the leading cause of cancer-related death among women in 2014. Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and MTR reductase (MTRR) are enzymes that play an important role in folate metabolism. The single nucleotide polymorphisms, MTHFR C677T, A1298C, MTR A2756G, and MTRR A66G, alter plasmatic folate and homocysteine concentrations, causing problems during the repairment, synthesis, and methylation of the genetic material. Therefore, it is essential to know how BC risk is associated with histopathological and immunohistochemical characteristics, genotype polymorphisms, and gene expression in a high altitude Ecuadorian mestizo population. DNA was extracted from 195 healthy and 114 affected women. Genotypes were determined by restriction enzymes and genomic sequencing. mRNA was extracted from 26 glandular breast tissue samples, both from cancerous tissue and healthy tissue adjacent to the tumor. Relative gene expression was determined with the comparative Livak method (2(-ΔΔCT)). We found significant association between the rs1801133 (A222V) genotypes and an increased risk of BC development: C/T (odds ratio [OR] = 1.8; 95 % confidence interval [CI] = 1.1-3.2; P = 0.039), T/T (OR = 2.9; 95 % CI = 1.2-7.2; P = 0.025), and C/T + T/T (OR = 1.9; 95 % CI = 1.1-3.3; P = 0.019). Regarding relative gene expression, we found significant mRNA subexpression between the combined genotypes C/T + T/T (rs1801133) and triple negative breast cancer (TNBC) (P = 0.034). In brief, the MTHFR gene and its protein could act as potential predictive biomarkers of BC, especially TNBC among the high altitude Ecuadorian mestizo population.

  9. GenAnneal: Genetically modified Simulated Annealing

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Lagaris, Isaac E.

    2006-05-01

    A modification of the standard Simulated Annealing (SA) algorithm is presented for finding the global minimum of a continuous multidimensional, multimodal function. We report results of computational experiments with a set of test functions and we compare to methods of similar structure. The accompanying software accepts objective functions coded both in Fortran 77 and C++. Program summaryTitle of program:GenAnneal Catalogue identifier:ADXI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADXI_v1_0 Program available from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: The tool is designed to be portable in all systems running the GNU C++ compiler Installation: University of Ioannina, Greece on Linux based machines Programming language used:GNU-C++, GNU-C, GNU Fortran 77 Memory required to execute with typical data: 200 KB No. of bits in a word: 32 No. of processors used: 1 Has the code been vectorized or parallelized?: No No. of bytes in distributed program, including test data, etc.:84 885 No. of lines in distributed program, including test data, etc.:14 896 Distribution format: tar.gz Nature of physical problem: A multitude of problems in science and engineering are often reduced to minimizing a function of many variables. There are instances that a local optimum does not correspond to the desired physical solution and hence the search for a better solution is required. Local optimization techniques are frequently trapped in local minima. Global optimization is hence the appropriate tool. For example, solving a non-linear system of equations via optimization, employing a "least squares" type of objective, one may encounter many local minima that do not correspond to solutions (i.e. they are far from zero). Typical running time: Depending on the objective function. Method of solution: We modified the process of step selection that the traditional Simulated

  10. [The different genotypes of MTHFR 1298A>C and PON1 -108C>T polymorphisms confer the increased risk of the abdominal aortic aneurysm in the smoking and nonsmoking persons].

    PubMed

    Strauss, Ewa; Waliszewski, Krzysztof; Pawlak, Andrzej L

    2005-01-01

    In abdominal aortic aneurysm (AAA) both the etiology and the pathogenesis are of the multifactorial character. The genetic component in the determination of this disease is proven by its familial occurrence. Smoking represents the best recognized risk factor of the AAA development. Increased concentrations of homocysteine (Hcy) in plasma are the common finding in these patients. It is assumed that the Hcy thiolactone, the most reactive metabolite of Hcy, may participate in the aortic wall destruction in AAA. The polymorphic variants of the methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) influence tissue concentrations of the Hcy. Paraoxonase (PON1), the enzyme associated in plasma with the HDL fraction, as lactonase detoxicates the Hcy thiolactone. The promotor polymorphism of PON1 - 108C>T gene may determine the lower activity of this enzyme. In the case-control study of 106 patients with AAA and 97 healthy persons, the effects of selected genetic and nongenetic risk factors on development of AAA were assessed, considering the possibilities of interaction between them. It was found, that the arterial hypertension, cigarette smoking and the lower HDL fraction are independent risk factors of AAA. The arterial hypertension was a risk factor both in the smoking and the nonsmoking males, whereas the lower HDL fraction has been the risk factor only for the smoking men. By the multivariate analysis in the nonsmoking males the MTHFR 1298 AC and CC genotypes increased the risk of AAA development 4,8-fold in relation to the MTHFR 1298 AA nonsmoking males. In reference to the genotypes of the expected high impact on the metabolism of Hcy and of Hcy thiolactone, the genotypes of MTHFR 677TT and PON1 -108CT and TT were more frequent in smoking ones, but the difference was not significant. This observation fits with the assumption that the influence of smoking on the occurrence of AAA prevails over that of genetic variability. When the patients age was considered

  11. Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study.

    PubMed

    Abrahamsen, Bo; Madsen, Jonna Skov; Tofteng, Charlotte Landbo; Stilgren, Lis; Bladbjerg, Else Marie; Kristensen, Søren Risom; Brixen, Kim; Mosekilde, Leif

    2005-03-01

    We have previously found BMD and fracture risk to be significantly associated with the MTHFR (C677T) polymorphism in healthy postmenopausal women in the first years after menopause. Since then, other cohort studies have suggested that sufficient intake of riboflavin and/or folate may have the potential to prevent development of low BMD in women with the TT genotype. This could to some extent explain why this polymorphism is associated with low BMD or fracture in some study populations and not in others. It would also indicate that fractures associated with the TT genotype could be preventable by vitamin B supplementation. We have, therefore, reviewed baseline food record data from our original study to determine if BMD and fracture associations with the MTHFR genotype depended on the intake of folate, riboflavin, or other members of the vitamin B complex, associated with homocysteine metabolism. We analyzed genotype, BMD, and dietary records from 1700 healthy postmenopausal women who participated in the DOPS study. For the assessment of fracture risk, we used longitudinal observations from 854 women in the control group who remained compliant with their initial allocation of no treatment. Riboflavin intake was significantly correlated with femoral neck (FN) BMD in women with the TT genotype (r = 0.24, P < 0.01). FN and lumbar spine (LS) BMD were only associated with the MTHFR genotype in the lowest quartile of riboflavin intake. At the FN, similar threshold effects were shown for folate, vitamin B12, and vitamin B6. Among these vitamin B complex members, stepwise regression analysis identified riboflavin as the only significant predictor of FN BMD in the TT genotype. In conclusion, we confirm reports that BMD in the MTHFR TT genotype is only significantly reduced in the lowest quartile of riboflavin, B12, B6, and folate intake, at least at the time of menopause. Vitamin B supplementation would only be expected to benefit BMD in about 2% of the population, i

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

    PubMed

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

    2014-09-29

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

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

    PubMed Central

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

    2014-01-01

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

  14. Introducing AstroGen: the Astronomy Genealogy Project

    NASA Astrophysics Data System (ADS)

    Tenn, Joseph S.

    2016-12-01

    The Astronomy Genealogy Project (AstroGen), a project of the Historical Astronomy Division of the American Astronomical Society (AAS), will soon appear on the AAS website. Ultimately, it will list the world's astronomers with their highest degrees, theses for those who wrote them, academic advisors (supervisors), universities, and links to the astronomers or their obituaries, their theses when online, and more. At present the AstroGen team is working on those who earned doctorates with astronomy-related theses. We show what can be learned already, with just ten countries essentially completed.

  15. A Virtual Reality Framework to Optimize Design, Operation and Refueling of GEN-IV Reactors.

    SciTech Connect

    Rizwan-uddin; Nick Karancevic; Stefano Markidis; Joel Dixon; Cheng Luo; Jared Reynolds

    2008-04-23

    many GEN-IV candidate designs are currently under investigation. Technical issues related to material, safety and economics are being addressed at research laboratories, industry and in academia. After safety, economic feasibility is likely to be the most important crterion in the success of GEN-IV design(s). Lessons learned from the designers and operators of GEN-II (and GEN-III) reactors must play a vital role in achieving both safety and economic feasibility goals.

  16. GenStar: A method for de novo drug design

    NASA Astrophysics Data System (ADS)

    Rotstein, Sergio H.; Murcko, Mark A.

    1993-02-01

    A novel method, which we call GenStar, has been developed to suggest chemically reasonable structures which fill the active sites of enzymes. The proposed molecules provide good steric contact with the enzyme and exist in low-energy conformations. These structures are composed entirely of sp3 carbons which are grown sequentially, but which can also branch or form rings. User-selected enzyme seed atoms may be used to determine the area in which structure generation begins. Alternatively, GenStar may begin with a predocked `inhibitor core' from which atoms are grown. For each new atom generated by the program, several hundred candidate positions representing a range of reasonable bond lengths, bond angles, and torsion angles are considered. Each of these candidates is scored, based on a simple enzyme contact model. The selected position is chosen at random from among the highest scoring cases. Duplicate structures may be removed using a variety of criteria. The compounds may be energy minimized and displayed using standard modeling programs. Also, it is possible to analyze the collection of all structures created by GenStar and locate binding motifs for common fragments such as benzene and naphthylene. Tests of the method using HIV protease, FK506 binding protein (FKBP-12) and human carbonic anhydrase (HCA-II) demonstrated that structures similar to known potent inhibitors may be generated with GenStar.

  17. 78 FR 8108 - NextGen Solutions Vendors Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE..., Commerce. ACTION: Notice and request for response. SUMMARY: This notice sets forth a request for responses... Transportation System (NextGen) solutions that meet the requirements of the International Civil...

  18. Meet Mr. and Mrs. Gen X: A New Parent Generation

    ERIC Educational Resources Information Center

    Howe, Neil

    2010-01-01

    Slowly but surely, Generation Xers have been taking over from Baby Boomers as the majority of parents in elementary and secondary education. In the early 1990s, Gen Xers began joining parent-teacher associations in the nation's elementary schools. Around 2005, they became the majority of middle school parents. By the fall of 2008, they took over…

  19. Distributed Generation Market Demand Model (dGen): Documentation

    SciTech Connect

    Sigrin, Benjamin; Gleason, Michael; Preus, Robert; Baring-Gould, Ian; Margolis, Robert

    2016-02-01

    The Distributed Generation Market Demand model (dGen) is a geospatially rich, bottom-up, market-penetration model that simulates the potential adoption of distributed energy resources (DERs) for residential, commercial, and industrial entities in the continental United States through 2050. The National Renewable Energy Laboratory (NREL) developed dGen to analyze the key factors that will affect future market demand for distributed solar, wind, storage, and other DER technologies in the United States. The new model builds off, extends, and replaces NREL's SolarDS model (Denholm et al. 2009a), which simulates the market penetration of distributed PV only. Unlike the SolarDS model, dGen can model various DER technologies under one platform--it currently can simulate the adoption of distributed solar (the dSolar module) and distributed wind (the dWind module) and link with the ReEDS capacity expansion model (Appendix C). The underlying algorithms and datasets in dGen, which improve the representation of customer decision making as well as the spatial resolution of analyses (Figure ES-1), also are improvements over SolarDS.

  20. An electronic flight bag for NextGen avionics

    NASA Astrophysics Data System (ADS)

    Zelazo, D. Eyton

    2012-06-01

    The introduction of the Next Generation Air Transportation System (NextGen) initiative by the Federal Aviation Administration (FAA) will impose new requirements for cockpit avionics. A similar program is also taking place in Europe by the European Organisation for the Safety of Air Navigation (Eurocontrol) called the Single European Sky Air Traffic Management Research (SESAR) initiative. NextGen will require aircraft to utilize Automatic Dependent Surveillance-Broadcast (ADS-B) in/out technology, requiring substantial changes to existing cockpit display systems. There are two ways that aircraft operators can upgrade their aircraft in order to utilize ADS-B technology. The first is to replace existing primary flight displays with new displays that are ADS-B compatible. The second, less costly approach is to install an advanced Class 3 Electronic Flight Bag (EFB) system. The installation of Class 3 EFBs in the cockpit will allow aircraft operators to utilize ADS-B technology in a lesser amount of time with a decreased cost of implementation and will provide additional benefits to the operator. This paper describes a Class 3 EFB, the NexisTM Flight-Intelligence System, which has been designed to allow users a direct interface with NextGen avionics sensors while additionally providing the pilot with all the necessary information to meet NextGen requirements.

  1. Safer Systems: A NextGen Aviation Safety Strategic Goal

    NASA Technical Reports Server (NTRS)

    Darr, Stephen T.; Ricks, Wendell R.; Lemos, Katherine A.

    2008-01-01

    The Joint Planning and Development Office (JPDO), is charged by Congress with developing the concepts and plans for the Next Generation Air Transportation System (NextGen). The National Aviation Safety Strategic Plan (NASSP), developed by the Safety Working Group of the JPDO, focuses on establishing the goals, objectives, and strategies needed to realize the safety objectives of the NextGen Integrated Plan. The three goal areas of the NASSP are Safer Practices, Safer Systems, and Safer Worldwide. Safer Practices emphasizes an integrated, systematic approach to safety risk management through implementation of formalized Safety Management Systems (SMS) that incorporate safety data analysis processes, and the enhancement of methods for ensuring safety is an inherent characteristic of NextGen. Safer Systems emphasizes implementation of safety-enhancing technologies, which will improve safety for human-centered interfaces and enhance the safety of airborne and ground-based systems. Safer Worldwide encourages coordinating the adoption of the safer practices and safer systems technologies, policies and procedures worldwide, such that the maximum level of safety is achieved across air transportation system boundaries. This paper introduces the NASSP and its development, and focuses on the Safer Systems elements of the NASSP, which incorporates three objectives for NextGen systems: 1) provide risk reducing system interfaces, 2) provide safety enhancements for airborne systems, and 3) provide safety enhancements for ground-based systems. The goal of this paper is to expose avionics and air traffic management system developers to NASSP objectives and Safer Systems strategies.

  2. A New Parent Generation: Meet Mr. and Mrs. Gen X

    ERIC Educational Resources Information Center

    Howe, Neil

    2010-01-01

    Slowly but surely, Generation Xers have been taking over from Baby Boomers as the majority of parents in elementary and secondary education. Gen-X parents and Boomer parents belong to two neighboring generations, each possessing its own location in history and its own peer personality. They are similar in some respects, but clearly different in…

  3. ORPC RivGen controller performance raw data - Igiugig 2015

    DOE Data Explorer

    Jarlath McEntee

    2015-12-18

    Contains raw data for operations of Ocean Renewable Power Company (ORPC) RivGen Power System in Igiugig 2015 in Matlab data file format. Two data files capture the data and timestamps for data, including power in, voltage, rotation rate, and velocity.

  4. 78 FR 54509 - Tenth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-04

    ... Federal Aviation Administration Tenth Meeting: RTCA Next Gen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA NextGen... of the RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held September 19, 2013...

  5. 77 FR 25524 - Sixth Meeting: RTCA, NextGen Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-30

    ... Federal Aviation Administration Sixth Meeting: RTCA, NextGen Advisory Committee AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of a meeting of RTCA, NextGen... RTCA, NextGen Advisory Committee. DATES: The meeting will be held May 24, 2012, from 9:00 a.m.-3:00...

  6. 76 FR 22162 - Third Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-20

    ... Federal Aviation Administration Third Meeting RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES:...

  7. 78 FR 5860 - Eighth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ... Federal Aviation Administration Eighth Meeting: RTCA Next Gen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA NextGen... meeting of the RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held February 7,...

  8. 76 FR 54526 - Fourth Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... Federal Aviation Administration Fourth Meeting RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES:...

  9. 78 FR 28940 - Ninth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... Federal Aviation Administration Ninth Meeting: RTCA Next Gen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA NextGen... of the RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held June 4, 2013 from...

  10. 76 FR 3931 - Second Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ... Federal Aviation Administration Second Meeting RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES:...

  11. DOE/NNSA perspective safeguard by design: GEN III/III+ light water reactors and beyond

    SciTech Connect

    Pan, Paul Y

    2010-12-10

    An overview of key issues relevant to safeguards by design (SBD) for GEN III/IV nuclear reactors is provided. Lessons learned from construction of typical GEN III+ water reactors with respect to SBD are highlighted. Details of SBD for safeguards guidance development for GEN III/III+ light water reactors are developed and reported. This paper also identifies technical challenges to extend SBD including proliferation resistance methodologies to other GEN III/III+ reactors (except HWRs) and GEN IV reactors because of their immaturity in designs.

  12. Comparison of telogen hair analyses: genRES MPX-2SP kit versus genRES MPX-SP1 and genRES MPX-SP2 kits.

    PubMed

    Schmid, D; Bayer, B; Anslinger, K

    2008-12-01

    STR investigations of telogen hair are invariably difficult due to the small amounts of nuclear DNA and its degradation products. However, in recent years there has been a considerable improvement. This study examined the suitability of a new STR kit with shortened amplicons for the investigation of hair in routine casework. This kit allows the simultaneous amplification of the eight STR-loci D3S1358, VWA, FGA, TH01, SE33, D8S1179, D18S51, and D21S11, and the sex-determining amelogenin system. It was tested against the genRES MPX-SP1 and genRES MPX-SP2 kits. The sensitivity of the new genRES MPX-2SP kit was demonstrated to be inferior to that of the genRES MPX-SP1, but almost equal to that of the genRES MPX-SP2 kit.

  13. Advanced Vehicle Concepts and Implications for NextGen

    NASA Technical Reports Server (NTRS)

    Blake, Matt; Smith, Jim; Wright, Ken; Mediavilla Ricky; Kirby, Michelle; Pfaender, Holger; Clarke, John-Paul; Volovoi, Vitali; Dorbian, Christopher; Ashok, Akshay; Reynolds, Tom; Waitz, Ian; Hileman, James; Arunachalam, Sarav; Hedrick, Matt; Vempati, Lakshmi; Laroza, Ryan; denBraven, Wim; Henderson, Jeff

    2010-01-01

    This report presents the results of a major NASA study of advanced vehicle concepts and their implications for the Next Generation Air Transportation System (NextGen). Comprising the efforts of dozens of researchers at multiple institutions, the analyses presented here cover a broad range of topics including business-case development, vehicle design, avionics, procedure design, delay, safety, environmental impacts, and metrics. The study focuses on the following five new vehicle types: Cruise-efficient short takeoff and landing (CESTOL) vehicles Large commercial tiltrotor aircraft (LCTRs) Unmanned aircraft systems (UAS) Very light jets (VLJs) Supersonic transports (SST). The timeframe of the study spans the years 2025-2040, although some analyses are also presented for a 3X scenario that has roughly three times the number of flights as today. Full implementation of NextGen is assumed.

  14. SimGen: A General Simulation Method for Large Systems.

    PubMed

    Taylor, William R

    2017-02-03

    SimGen is a stand-alone computer program that reads a script of commands to represent complex macromolecules, including proteins and nucleic acids, in a structural hierarchy that can then be viewed using an integral graphical viewer or animated through a high-level application programming interface in C++. Structural levels in the hierarchy range from α-carbon or phosphate backbones through secondary structure to domains, molecules, and multimers with each level represented in an identical data structure that can be manipulated using the application programming interface. Unlike most coarse-grained simulation approaches, the higher-level objects represented in SimGen can be soft, allowing the lower-level objects that they contain to interact directly. The default motion simulated by SimGen is a Brownian-like diffusion that can be set to occur across all levels of representation in the hierarchy. Links can also be defined between objects, which, when combined with large high-level random movements, result in an effective search strategy for constraint satisfaction, including structure prediction from predicted pairwise distances. The implementation of SimGen makes use of the hierarchic data structure to avoid unnecessary calculation, especially for collision detection, allowing it to be simultaneously run and viewed on a laptop computer while simulating large systems of over 20,000 objects. It has been used previously to model complex molecular interactions including the motion of a myosin-V dimer "walking" on an actin fibre, RNA stem-loop packing, and the simulation of cell motion and aggregation. Several extensions to this original functionality are described.

  15. GEN IV reactors: Where we are, where we should go

    SciTech Connect

    Locatelli, G.; Mancini, M.; Todeschini, N.

    2012-07-01

    GEN IV power plants represent the mid-long term option of the nuclear sector. International literature proposes many papers and reports dealing with these reactors, but there is an evident difference of type and shape of information making impossible each kind of detailed comparison. Moreover, authors are often strongly involved in some particular design; this creates many difficulties in their super-partes position. Therefore it is necessary to put order in the most relevant information to understand strengths and weaknesses of each design and derive an overview useful for technicians and policy makers. This paper presents the state-of the art for GEN IV nuclear reactors providing a comprehensive literature review of the different designs with a relate taxonomy. It presents the more relevant references, data, advantages, disadvantages and barriers to the adoptions. In order to promote an efficient and wide adoption of GEN IV reactors the paper provides the pre-conditions that must be accomplished, enabling factors promoting the implementation and barriers limiting the extent and intensity of its implementation. It concludes outlying the state of the art of the most important R and D areas and the future achievements that must be accomplished for a wide adoption of these technologies. (authors)

  16. The GenABEL Project for statistical genomics

    PubMed Central

    Karssen, Lennart C.; van Duijn, Cornelia M.; Aulchenko, Yurii S.

    2016-01-01

    Development of free/libre open source software is usually done by a community of people with an interest in the tool. For scientific software, however, this is less often the case. Most scientific software is written by only a few authors, often a student working on a thesis. Once the paper describing the tool has been published, the tool is no longer developed further and is left to its own device. Here we describe the broad, multidisciplinary community we formed around a set of tools for statistical genomics. The GenABEL project for statistical omics actively promotes open interdisciplinary development of statistical methodology and its implementation in efficient and user-friendly software under an open source licence. The software tools developed withing the project collectively make up the GenABEL suite, which currently consists of eleven tools. The open framework of the project actively encourages involvement of the community in all stages, from formulation of methodological ideas to application of software to specific data sets. A web forum is used to channel user questions and discussions, further promoting the use of the GenABEL suite. Developer discussions take place on a dedicated mailing list, and development is further supported by robust development practices including use of public version control, code review and continuous integration. Use of this open science model attracts contributions from users and developers outside the “core team”, facilitating agile statistical omics methodology development and fast dissemination. PMID:27347381

  17. Description of Teunomyces gen. nov. for the Candida kruisii clade, Suhomyces gen. nov. for the Candida tanzawaensis clade and Suhomyces kilbournensis sp. nov.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA sequence analysis has shown that species of the Candida kruisii clade and species of the C. tanzawaensis clade represent phylogenetically circumscribed genera, which are described as Teunomyces gen. nov., type species T. kruisii, and Suhomyces gen. nov., type species S. tanzawaensis. Many of the...

  18. From AWE-GEN to AWE-GEN-2d: a high spatial and temporal resolution weather generator

    NASA Astrophysics Data System (ADS)

    Peleg, Nadav; Fatichi, Simone; Paschalis, Athanasios; Molnar, Peter; Burlando, Paolo

    2016-04-01

    A new weather generator, AWE-GEN-2d (Advanced WEather GENerator for 2-Dimension grid) is developed following the philosophy of combining physical and stochastic approaches to simulate meteorological variables at high spatial and temporal resolution (e.g. 2 km x 2 km and 5 min for precipitation and cloud cover and 100 m x 100 m and 1 h for other variables variable (temperature, solar radiation, vapor pressure, atmospheric pressure and near-surface wind). The model is suitable to investigate the impacts of climate variability, temporal and spatial resolutions of forcing on hydrological, ecological, agricultural and geomorphological impacts studies. Using appropriate parameterization the model can be used in the context of climate change. Here we present the model technical structure of AWE-GEN-2d, which is a substantial evolution of four preceding models (i) the hourly-point scale Advanced WEather GENerator (AWE-GEN) presented by Fatichi et al. (2011, Adv. Water Resour.) (ii) the Space-Time Realizations of Areal Precipitation (STREAP) model introduced by Paschalis et al. (2013, Water Resour. Res.), (iii) the High-Resolution Synoptically conditioned Weather Generator developed by Peleg and Morin (2014, Water Resour. Res.), and (iv) the Wind-field Interpolation by Non Divergent Schemes presented by Burlando et al. (2007, Boundary-Layer Meteorol.). The AWE-GEN-2d is relatively parsimonious in terms of computational demand and allows generating many stochastic realizations of current and projected climates in an efficient way. An example of model application and testing is presented with reference to a case study in the Wallis region, a complex orography terrain in the Swiss Alps.

  19. GenCade Version 1 Quick-Start Guide: How to Start a Successful GenCade Project

    DTIC Science & Technology

    2015-03-01

    The CIRP has developed GenCade, a one-dimensional (1D) numerical model that calculates shoreline change and wave-induced longshore sand transport...numerical model developed by the CIRP that calculates shoreline change based on differential wave-driven longshore sand transport rates. The model...has the capability to represent sand transport, accretion, and erosion at inlets and beaches and can include engineering activities such as beach

  20. Pantanalinema gen. nov. and Alkalinema gen. nov.: novel pseudanabaenacean genera (Cyanobacteria) isolated from saline-alkaline lakes.

    PubMed

    Vieira Vaz, Marcelo Gomes Marçal; Genuário, Diego Bonaldo; Andreote, Ana Paula Dini; Malone, Camila Francieli Silva; Sant'Anna, Célia Leite; Barbiero, Laurent; Fiore, Marli Fátima

    2015-01-01

    The genus Leptolyngbya Anagnostidis & Komárek (1988) was described from a set of strains identified as 'LPP-group B'. The morphology within this group is not particularly informative and underestimates the group's genetic diversity. In the present study, two new pseudanabaenacean genera related to Leptolyngbya morphotypes, Pantanalinema gen. nov. and Alkalinema gen. nov., are described under the provisions of the International Code of Nomenclature for Algae, Fungi and Plants, based on a polyphasic approach. Pantanalinema gen. nov. (type species Pantanalinema rosaneae sp. nov.) has sheaths and trichomes with slight gliding motility, which distinguish this genus from Alkalinema gen. nov. (type species Alkalinema pantanalense sp. nov.), which possesses trichomes arranged in an ornate (interwoven) pattern. 16S rRNA gene sequences of strains of Pantanalinema and Alkalinema exhibited low identity to each other (≤91.6 %) and to other sequences from known pseudanabaenacean genera (≤94.3 and 93.7 %, respectively). In a phylogenetic reconstruction, six sequences from strains of Pantanalinema and four from strains of Alkalinema formed two separate and robust clades (99 % bootstrap value), with the genera Oculatella and Phormidesmis, respectively, as the closest related groups. 16S-23S rRNA intergenic spacer sequences and secondary structures of strains of Pantanalinema and Alkalinema did not correspond to any previous descriptions. The strains of Pantanalinema and Alkalinema were able to survive and produce biomass at a range of pH (pH 4-11) and were also able to alter the culture medium to pH values ranging from pH 8.4 to 9.9. These data indicate that cyanobacterial communities in underexplored environments, such as the Pantanal wetlands, are promising sources of novel taxa.

  1. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case-control study in a population with relatively low folate intake.

    PubMed

    Sharp, Linda; Little, Julian; Brockton, Nigel T; Cotton, Seonaidh C; Masson, Lindsey F; Haites, Neva E; Cassidy, Jim

    2008-02-01

    Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case-control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12 or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CT v. CC = 0.77 (95 % CI 0.52, 1.16); OR for TT v. CC = 0.62 (95 % CI 0.31, 1.24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0.81 (95 % CI 0.45, 1.49)). There were significant interactions between total folate and C677T (P = 0.029) and A1298C (P = 0.025), and total vitamin B6 and both polymorphisms (C677T, P = 0.016; A1298C, P = 0.033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.

  2. The Madagascan endemic myrmicine ants related to Eutetramorium (Hymenoptera: Formicidae): taxonomy of the genera Eutetramorium Emery, Malagidris nom. n., Myrmisaraka gen. n., Royidris gen. n., and Vitsika gen. n.

    PubMed

    Bolton, Barry; Fisher, Brian L

    2014-04-24

    The monophyletic group of myrmicine ant genera related to Eutetramorium is described and its taxonomy is documented. The group is endemic in Madagascar and contains five genera: Eutetramorium Emery, 1899 (3 species, 1 of which is new); Malagidris nom. n., a replacement name for Brunella Forel, 1917, junior homonym of Brunella Smith, G.W. 1909 (Crustacea) (6 species, 5 of which are new); Myrmisaraka gen. n. (2 species, both new); Royidris gen. n. (15 species, 11 of which are new); Vitsika gen. n. (14 species, all of which are new). Keys to the worker caste are provided for all genera, and provisional keys to known males are given for Malagidris and Vitsika.

  3. J3Gen: a PRNG for low-cost passive RFID.

    PubMed

    Melià-Seguí, Joan; Garcia-Alfaro, Joaquin; Herrera-Joancomartí, Jordi

    2013-03-19

    Pseudorandom number generation (PRNG) is the main security tool in low-cost passive radio-frequency identification (RFID) technologies, such as EPC Gen2. We present a lightweight PRNG design for low-cost passive RFID tags, named J3Gen. J3Gen is based on a linear feedback shift register (LFSR) configured with multiple feedback polynomials. The polynomials are alternated during the generation of sequences via a physical source of randomness. J3Gen successfully handles the inherent linearity of LFSR based PRNGs and satisfies the statistical requirements imposed by the EPC Gen2 standard. A hardware implementation of J3Gen is presented and evaluated with regard to different design parameters, defining the key-equivalence security and nonlinearity of the design. The results of a SPICE simulation confirm the power-consumption suitability of the proposal.

  4. Arctocypris fuhrmanni, n. gen., n. sp. (Crustacea, Ostracoda, Eucypridinae) from Spitsbergen (Norway).

    PubMed

    Petkovski, Trajan K; Scharf, Burkhard; Keyser, Dietmar

    2016-01-14

    Material from Spitsbergen (Norway) collected by Spitzenberger (1996) was reinvestigated. A new genus Arctocypris and a new species Arctocypris. fuhrmanni n. gen. n. sp. are described in the present paper. A key to the genera of the subfamily Eucypridinae is provided. At the moment Arctocypris n. gen. comprises four species: Arctocypris arctica (Olofsson, 1918) comb. nov.; A. dulcifons (Diebel & Pietrzeniuk, 1969) comb. nov.; A. foveata (Delorme, 1968) comb. nov. and Arctocypris fuhrmanni n. gen., n. sp.

  5. Measurement of the neutron electric form factor GEn in quasielastic scattering

    SciTech Connect

    Donal Day

    2003-07-15

    We have measured the electric form factor of the neutron, GEn, at two momentum transfers (Q2= 0.5 and Q2= 1.0 GeV/c2) through quasielastic scattering in Jefferson Lab's Hall C. Longitudinally polarized electrons scattered from polarized deuterated ammonia and GEn was extracted from the beam-target asymmetry AVed which, in quasielastic kinematics, is particularly sensitive to GEn and insensitive to MEC and FSI.

  6. Recent changes in the GenBank On-line Service.

    PubMed Central

    Benton, D

    1990-01-01

    The GenBank On-line Service provides access to the GenBank and EMBL nucleic acid sequence databases and to the Swiss-Prot and GenPept protein sequence databases. Users can query the databases by sequence similarity and annotation keywords and retrieve entries of interest. This access is available through e-mail servers, anonymous FTP, anonymous interactive login, and login to established, password-protected, individual accounts. PMID:2326192

  7. Phen-Gen: combining phenotype and genotype to analyze rare disorders.

    PubMed

    Javed, Asif; Agrawal, Saloni; Ng, Pauline C

    2014-09-01

    We introduce Phen-Gen, a method that combines patients' disease symptoms and sequencing data with prior domain knowledge to identify the causative genes for rare disorders. Simulations revealed that the causal variant was ranked first in 88% of cases when it was a coding variant-a 52% advantage over a genotype-only approach-and Phen-Gen outperformed other existing prediction methods by 13-58%. If disease etiology was unknown, the causal variant was assigned the top rank in 71% of simulations. Phen-Gen is available at http://phen-gen.org/.

  8. Using GenCade to Create a Sediment Budget in SBAS

    DTIC Science & Technology

    2015-08-01

    change and sand transport model (Frey et al. 2012a), and the Sediment Budget Analysis System (SBAS) (Dopsovic et al. 2003). Two of the main GenCade...GENESIS (Hanson and Kraus 1989) and the regional-scale, planning-level calculations of Cascade (Larson et al. 2003; Connell and Kraus 2006). GenCade...use advanced cards in the GenCade input files for earlier versions of the SMS. A GenCade technical report (Frey et al. 2012a) includes model theory, a

  9. Resolvase OsGEN1 Mediates DNA Repair by Homologous Recombination1[OPEN

    PubMed Central

    Lu, Pingli

    2017-01-01

    Yen1/GEN1 are canonical Holliday junction resolvases that belong to the RAD2/XPG family. In eukaryotes, such as budding yeast, mice, worms, and humans, Yen1/GEN1 work together with Mus81-Mms4/MUS81-EME1 and Slx1-Slx4/SLX1-SLX4 in DNA repair by homologous recombination to maintain genome stability. In plants, the biological function of Yen1/GEN1 remains largely unclear. In this study, we characterized the loss of function mutants of OsGEN1 and OsSEND1, a pair of paralogs of Yen1/GEN1 in rice (Oryza sativa). We first investigated the role of OsGEN1 during meiosis and found a reduction in chiasma frequency by ∼6% in osgen1 mutants, compared to the wild type, suggesting a possible involvement of OsGEN1 in the formation of crossovers. Postmeiosis, OsGEN1 foci were detected in wild-type microspore nuclei, but not in the osgen1 mutant concomitant with an increase in double-strand breaks. Persistent double-strand breaks led to programmed cell death of the male gametes and complete male sterility. In contrast, depletion of OsSEND1 had no effects on plant development and did not enhance osgen1 defects. Our results indicate that OsGEN1 is essential for homologous recombinational DNA repair at two stages of microsporogenesis in rice. PMID:28049740

  10. GenCade Application at Onslow Bay, North Carolina

    DTIC Science & Technology

    2012-08-01

    by Ashley E. Frey, Sophie Munger, Greg L. Williams , Michael J. Wutkowski, and Kevin B. Conner PURPOSE: This Coastal and Hydraulics Engineering...Texas A&M University Corpus Christi, and Greg L. Williams , Michael J. Wutkowski, and Kevin B. Conner of the U.S. Army Engineer District, Wilmington. Dr...follows: Frey, A.E., Munger, S., Williams , G.L., Wutkowski, M.J. and Conner, K.B. 2012. GenCade Application at Onslow Bay, North Carolina. Coastal and

  11. GRAIL and GenQuest Sequence Annotation Tools

    SciTech Connect

    Xu, Ying; Shah, Manesh B.; Einstein, J. Ralph; Parang, Morey; Snoddy, Jay; Petrov, Sergey; Olman, Victor; Zhang, Ge; Mural, Richard J.; Uberbacher, Edward C.

    1997-12-31

    Our goal is to develop and implement an integrated intelligent system which can recognize biologically significant features in DNA sequence and provide insight into the organization and function of regions of genomic DNA. GRAIL is a modular expert system which facilitates the recognition of gene features and provides an environment for the construction of sequence annotation. The last several years have seen a rapid evolution of the technology for analyzing genomic DNA sequences. The current GRAIL systems (including the e-mail, XGRAIL, JAVA-GRAIL and genQuest systems) are perhaps the most widely used, comprehensive, and user friendly systems available for computational characterization of genomic DNA sequence.

  12. Review of the taxonomy of the genus Arthrobacter, emendation of the genus Arthrobacter sensu lato, proposal to reclassify selected species of the genus Arthrobacter in the novel genera Glutamicibacter gen. nov., Paeniglutamicibacter gen. nov., Pseudoglutamicibacter gen. nov., Paenarthrobacter gen. nov. and Pseudarthrobacter gen. nov., and emended description of Arthrobacter roseus.

    PubMed

    Busse, Hans-Jürgen

    2016-01-01

    In this paper, the taxonomy of the genus Arthrobacter is discussed, from its first description in 1947 to the present state. Emphasis is given to intrageneric phylogeny and chemotaxonomic characteristics, concentrating on quinone systems, peptidoglycan compositions and polar lipid profiles. Internal groups within the genus Arthrobacter indicated from homogeneous chemotaxonomic traits and corresponding to phylogenetic grouping and/or high 16S rRNA gene sequence similarities are highlighted. Furthermore, polar lipid profiles and quinone systems of selected species are shown, filling some gaps concerning these chemotaxonomic traits. Based on phylogenetic groupings, 16S rRNA gene sequence similarities and homogeneity in peptidoglycan types, quinone systems and polar lipid profiles, a description of the genus Arthrobacter sensu lato and an emended description of Arthrobacter roseus are provided. Furthermore, reclassifications of selected species of the genus Arthrobacter into novel genera are proposed, namely Glutamicibacter gen. nov. (nine species), Paeniglutamicibacter gen. nov. (six species), Pseudoglutamicibacter gen. nov. (two species), Paenarthrobacter gen. nov. (six species) and Pseudarthrobacter gen. nov. (ten species).

  13. GenGIS: A geospatial information system for genomic data

    PubMed Central

    Parks, Donovan H.; Porter, Michael; Churcher, Sylvia; Wang, Suwen; Blouin, Christian; Whalley, Jacqueline; Brooks, Stephen; Beiko, Robert G.

    2009-01-01

    The increasing availability of genetic sequence data associated with explicit geographic and ecological information is offering new opportunities to study the processes that shape biodiversity. The generation and testing of hypotheses using these data sets requires effective tools for mathematical and visual analysis that can integrate digital maps, ecological data, and large genetic, genomic, or metagenomic data sets. GenGIS is a free and open-source software package that supports the integration of digital map data with genetic sequences and environmental information from multiple sample sites. Essential bioinformatic and statistical tools are integrated into the software, allowing the user a wide range of analysis options for their sequence data. Data visualizations are combined with the cartographic display to yield a clear view of the relationship between geography and genomic diversity, with a particular focus on the hierarchical clustering of sites based on their similarity or phylogenetic proximity. Here we outline the features of GenGIS and demonstrate its application to georeferenced microbial metagenomic, HIV-1, and human mitochondrial DNA data sets. PMID:19635847

  14. Hunting for new restriction enzymes in GenBank

    SciTech Connect

    Roberts, R.J.

    1997-12-01

    Restriction enzyme genes are hard to identify unless their surrounding sequences are available. This is because the best definition of a restriction enzyme gene is an open reading frame, that looks like nothing else in GenBank, but lies close to a DNA methylase gene. There are other clues too, such as nearby reading frames that code control proteins or the DNA specificity subunits of Type I restriction enzymes. We are developing software that searches the daily updates of GenBank to find candidate restriction enzyme genes. This is being followed by bench experiments to see of the predictions are correct. More than 50 potential new restriction enzymes have been predicted and it is quite remarkable that the density of restriction enzyme genes in microbial DNA is greater than one system per 200 Kb. The software development is emphasizing the graphic presentation of the search results. The approach could be used for other situations where a molecular biologist is interested to find new examples of their favorite genes.

  15. GenDecoder: genetic code prediction for metazoan mitochondria

    PubMed Central

    Abascal, Federico; Zardoya, Rafael; Posada, David

    2006-01-01

    Although the majority of the organisms use the same genetic code to translate DNA, several variants have been described in a wide range of organisms, both in nuclear and organellar systems, many of them corresponding to metazoan mitochondria. These variants are usually found by comparative sequence analyses, either conducted manually or with the computer. Basically, when a particular codon in a query-species is linked to positions for which a specific amino acid is consistently found in other species, then that particular codon is expected to translate as that specific amino acid. Importantly, and despite the simplicity of this approach, there are no available tools to help predicting the genetic code of an organism. We present here GenDecoder, a web server for the characterization and prediction of mitochondrial genetic codes in animals. The analysis of automatic predictions for 681 metazoans aimed us to study some properties of the comparative method, in particular, the relationship among sequence conservation, taxonomic sampling and reliability of assignments. Overall, the method is highly precise (99%), although highly divergent organisms such as platyhelminths are more problematic. The GenDecoder web server is freely available from . PMID:16845034

  16. 77 FR 54648 - Seventh Meeting: RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... Meeting: RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Meeting Notice of RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of the seventh meeting of the RTCA...

  17. How is the Xpert MRSA Gen 3 assay (Cepheid) performing on pooled eSwab medium?

    PubMed

    Jonckheere, Stijn; Van Vaerenbergh, Kristien; Boel, An; Vankeerberghen, Anne; De Beenhouwer, Hans

    2015-11-01

    The performance of the Xpert MRSA Gen 3 was compared to the Xpert MRSA on pooled eSwab media from nose, throat, and perineum using broth enriched cultured as gold standard. A lower specificity was found for the Xpert MRSA Gen 3 compared to the Xpert MRSA (91.8% versus 97.9%; P<0.05).

  18. CottonGen: a genomics, genetics and breeding database for cotton research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CottonGen (http://www.cottongen.org) is a curated and integrated web-based relational database providing access to publicly available genomic, genetic and breeding data for cotton. CottonGen supercedes CottonDB and the Cotton Marker Database, with enhanced tools for easier data sharing, mining, vis...

  19. VitisGen on the road: mapping the way to the next generation of grapes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The USDA-NIFA VitisGen project (Award No. 2011-51181-30635) aims to optimize grape cultivar improvement through the integration of grape breeding, cutting edge genomics technology, precision phenotyping, socioeconomic research, and extension. VitisGen is a five-year project involving 25 co-PIs at 11...

  20. What Can a Historian Do with AstroGen?

    NASA Astrophysics Data System (ADS)

    Tenn, Joseph S.

    2015-01-01

    "Astrogen", the Astronomy Genealogy Project, is in the development stage. Patterned after the Mathematics Genealogy Project at http://genealogy.math.ndsu.nodak.edu, it will eventually include most of the world's astronomers, past and present, and provide information about their years of life, highest degrees, universities, and thesis titles. There will also be links to online theses, home pages, and obituaries when these are available. Although a few details remain to be worked out before it becomes public, it is possible to make some use of what has already been compiled. I will give an example, comparing graduates of Harvard University, the University of California at Berkeley, and the University of Chicago from different decades, with information about their professional careers and publication records. The author welcomes queries about AstroGen and is seeking more participants.

  1. Two-dimensional MHD generator model. [GEN code

    SciTech Connect

    Geyer, H. K.; Ahluwalia, R. K.; Doss, E. D.

    1980-09-01

    A steady state, two-dimensional MHD generator code, GEN, is presented. The code solves the equations of conservation of mass, momentum, and energy, using a Von Mises transformation and a local linearization of the equations. By splitting the source terms into a part proportional to the axial pressure gradient and a part independent of the gradient, the pressure distribution along the channel is easily obtained to satisfy various criteria. Thus, the code can run effectively in both design modes, where the channel geometry is determined, and analysis modes, where the geometry is previously known. The code also employs a mixing length concept for turbulent flows, Cebeci and Chang's wall roughness model, and an extension of that model to the effective thermal diffusities. Results on code validation, as well as comparisons of skin friction and Stanton number calculations with experimental results, are presented.

  2. Commissioning and Performance Analysis of WhisperGen Stirling Engine

    NASA Astrophysics Data System (ADS)

    Pradip, Prashant Kaliram

    Stirling engine based cogeneration systems have potential to reduce energy consumption and greenhouse gas emission, due to their high cogeneration efficiency and emission control due to steady external combustion. To date, most studies on this unit have focused on performance based on both experimentation and computer models, and lack experimental data for diversified operating ranges. This thesis starts with the commissioning of a WhisperGen Stirling engine with components and instrumentation to evaluate power and thermal performance of the system. Next, a parametric study on primary engine variables, including air, diesel, and coolant flowrate and temperature were carried out to further understand their effect on engine power and efficiency. Then, this trend was validated with the thermodynamic model developed for the energy analysis of a Stirling cycle. Finally, the energy balance of the Stirling engine was compared without and with heat recovery from the engine block and the combustion chamber exhaust.

  3. New Boletaceae taxa from Guyana: Binderoboletus segoi gen. and sp. nov., Guyanaporus albipodus gen. and sp. nov., Singerocomus rubriflavus gen. and sp. nov., and a new combination for Xerocomus inundabilis.

    PubMed

    Henkel, Terry W; Obase, Keisuke; Husbands, Dillon; Uehling, Jessie K; Bonito, Gregory; Aime, M Catherine; Smith, Matthew E

    2016-01-01

    Binderoboletus segoi gen. and sp. nov., Guyanaporus albipodus gen. and sp. nov. and Singerocomus rubriflavus gen. and sp. nov. (Boletaceae, Boletales, Basidiomycota) are described from the Pakaraima Mountains and adjacent lowlands of Guyana. Xerocomus inundabilis, originally described from the central Brazilian Amazon and based solely on the type collection, is redescribed from numerous collections from Guyana and transferred into Singerocomus. These boletes occur in Neotropical forests dominated by ectomycorrhizal trees in the genera Dicymbe (Fabaceae subfam. Caesalpinioideae), Aldina (Fabaceae subfam. Papilionoideae) and Pakaraimaea (Dipterocarpaceae). Three of the species were repeatedly found in a multiyear sporocarp survey in Dicymbe corymbosa-monodominant forest. Macromorphological, micromorphological, habitat and multilocus DNA sequence data are provided for each species. A molecular phylogenetic analysis based on a large taxon set across the Boletaceae justifies erection of the new genera.

  4. Hand-held optical imager (Gen-2): improved instrumentation and target detectability.

    PubMed

    Gonzalez, Jean; Decerce, Joseph; Erickson, Sarah J; Martinez, Sergio L; Nunez, Annie; Roman, Manuela; Traub, Barbara; Flores, Cecilia A; Roberts, Seigbeh M; Hernandez, Estrella; Aguirre, Wenceslao; Kiszonas, Richard; Godavarty, Anuradha

    2012-08-01

    Hand-held optical imagers are developed by various researchers towards reflectance-based spectroscopic imaging of breast cancer. Recently, a Gen-1 handheld optical imager was developed with capabilities to perform two-dimensional (2-D) spectroscopic as well as three-dimensional (3-D) tomographic imaging studies. However, the imager was bulky with poor surface contact (~30%) along curved tissues, and limited sensitivity to detect targets consistently. Herein, a Gen-2 hand-held optical imager that overcame the above limitations of the Gen-1 imager has been developed and the instrumentation described. The Gen-2 hand-held imager is less bulky, portable, and has improved surface contact (~86%) on curved tissues. Additionally, the forked probe head design is capable of simultaneous bilateral reflectance imaging of both breast tissues, and also transillumination imaging of a single breast tissue. Experimental studies were performed on tissue phantoms to demonstrate the improved sensitivity in detecting targets using the Gen-2 imager. The improved instrumentation of the Gen-2 imager allowed detection of targets independent of their location with respect to the illumination points, unlike in Gen-1 imager. The developed imager has potential for future clinical breast imaging with enhanced sensitivity, via both reflectance and transillumination imaging.

  5. Role of polymorphisms in factor V (FV Leiden), prothrombin, plasminogen activator inhibitor type-1 (PAI-1), methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) genes as risk factors for thrombophilias.

    PubMed

    Miranda-Vilela, A L

    2012-09-01

    Thrombophilias are defined as a predisposition to thrombosis due to hematological changes which induce blood hypercoagulability; they can be inherited or acquired. They are individually characterized by a large phenotypic variability, even when they occur within the same family. Hereditary thrombophilias are, in most cases, due to changes related to physiological coagulation inhibitors or mutations in the genes of coagulation factors. High levels of plasma homocysteine may also be responsible for vaso-occlusive episodes and may have acquired (nutritional deficiencies of folate and vitamins B6 and B12) and/or genetic causes (mutations in the genes responsible for expression of enzymes involved in the intracellular metabolism of homocysteine). Considering that: (1) thromboses are events of multigenic and multifactorial etiopathology; (2) the presence of mutations in several genes significantly increases the risk of their occurrence; (3) the vascular territory (venous and/or arterial) affected involves different pathophysiological mechanisms and treatments, knowledge of genetic variants that may contribute to the risk and variability of the phenotypic manifestations of these diseases is extremely important. This understanding may provide support for a more individualized and therefore more effective treatment for thrombophilia carriers. Thus, this mini-review aims to address a comprehensive summary of thrombophilias and thrombosis, and discuss the role of polymorphisms in Factor V (FV Leiden), Prothrombin, Plasminogen activator inhibitor type-1 (PAI-1), Methylenetetrahydrofolate reductase (MTHFR) and Cystathionine β-synthase (CBS) genes as risk factors for thrombophilias.

  6. GenASiS: A full GR-RMHD simulation framework: overview, goals, and preliminary tests

    NASA Astrophysics Data System (ADS)

    Tsatsin, Petr; Budiardja, Reuben; Cardall, Christian; Endeve, Eirik; Marronetti, Pedro; Mezzacappa, Anthony

    2011-04-01

    I present an overview of the General Astrophysics Simulation System (GenASiS). GenASiS is currently under development by a collaboration between researchers at the Oak Ridge National Laboratory (ORNL) and Florida Atlantic University (FAU) and features a high-resolution magnetohydrodynamics solver, a full general relativistic description of gravity based on the BSSN formalism, and will feature a two-moment multi-frequency neutrino radiation field evolution. We intend to use GenASiS to study core collapse supernovae, neutron star mergers, and their associated gamma-ray bursts.

  7. The Early Retirement of Gen Ronald R. Fogleman, Chief of Staff, United States Air Force

    DTIC Science & Technology

    2001-01-01

    The Early Retirement of Gen Ronald R. Fogleman, Chief of Staff, United States Air Force *EDITED by DR. RICHARD H. KOHN Editorial Abstract: Air...Force chief of staff Gen Ronald Fogleman’s early retirement in 1997 has caused great speculation. Was this a “resignation in protest”? Here for the...COVERED 00-00-2001 to 00-00-2001 4. TITLE AND SUBTITLE The Early Retirement of Gen Ronald R. Fogleman, Chief of Staff, United States Air Force 5a

  8. gSeaGen: A GENIE-based code for neutrino telescopes

    NASA Astrophysics Data System (ADS)

    Distefano, Carla

    2016-04-01

    The gSeaGen code is a GENIE based application to generate neutrino-induced events in an underwater neutrino detector. The gSeaGen code is able to generate events induced by all neutrino flavours, taking into account topological differences between track-type and shower-like events. The neutrino interaction is simulated taking into account the density and the composition of the media surrounding the detector. The main features of gSeaGen will be presented together with some examples of its application within ANTARES and KM3NeT.

  9. Characterization of Romboutsia ilealis gen. nov., sp. nov., isolated from the gastro-intestinal tract of a rat, and proposal for the reclassification of five closely related members of the genus Clostridium into the genera Romboutsia gen. nov., Intestinibacter gen. nov., Terrisporobacter gen. nov. and Asaccharospora gen. nov.

    PubMed

    Gerritsen, Jacoline; Fuentes, Susana; Grievink, Wieke; van Niftrik, Laura; Tindall, Brian J; Timmerman, Harro M; Rijkers, Ger T; Smidt, Hauke

    2014-05-01

    A Gram-positive staining, rod-shaped, non-motile, spore-forming obligately anaerobic bacterium, designated CRIBT, was isolated from the gastro-intestinal tract of a rat and characterized. The major cellular fatty acids of strain CRIBT were saturated and unsaturated straight-chain C12-C19 fatty acids, with C16:0 being the predominant fatty acid. The polar lipid profile comprised six glycolipids, four phospholipids and one lipid that did not stain with any of the specific spray reagents used. The only quinone was MK-6. The predominating cell-wall sugars were glucose and galactose. The peptidoglycan type of strain CRIBT was A1σ lanthionine-direct. The genomic DNA G+C content of strain CRIBT was 28.1 mol%. On the basis of 16S rRNA gene sequence similarity, strain CRIBT was most closely related to a number of species of the genus Clostridium, including Clostridium lituseburense (97.2%), Clostridium glycolicum (96.2%), Clostridium mayombei (96.2%), Clostridium bartlettii (96.0%) and Clostridium irregulare (95.5%). All these species show very low 16S rRNA gene sequence similarity (<85%) to the type strain of Clostridium butyricum, the type species of the genus Clostridium. DNA-DNA hybridization with closely related reference strains indicated reassociation values below 32%. On the basis of phenotypic and genetic studies, a novel genus, Romboutsia gen. nov., is proposed. The novel isolate CRIBT (=DSM 25109T=NIZO 4048T) is proposed as the type strain of the type species, Romboutsia ilealis gen. nov., sp. nov., of the proposed novel genus. It is proposed that C. lituseburense is transferred to this genus as Romboutsia lituseburensis comb. nov. Furthermore, the reclassification into novel genera is proposed for C. bartlettii, as Intestinibacter bartlettii gen. nov., comb. nov. (type species of the genus), C. glycolicum, as Terrisporobacter glycolicus gen. nov., comb. nov. (type species of the genus), C. mayombei, as Terrisporobacter mayombei gen. nov., comb. nov., and C

  10. On the new monotypic wolf spider genus Ovia gen. nov. (Araneae: Lycosidae, Lycosinae).

    PubMed

    Sankaran, Pradeep M; Malamel, Jobi J; Sebastian, Pothalil A

    2017-01-17

    A new monotypic wolf spider genus, Ovia gen. nov. is proposed to accommodate a misplaced species: Pardosa procurva Yu & Song, 1988. Ovia procurva comb. nov. is redescribed, illustrated and designated as the type species for the genus. The subfamily placement of the new genus is discussed and it is considered as a member of Lycosinae Sundevall, 1833 and possibly closely related to Alopecosa Simon, 1885. The presence of an apical process (spur) on the median apophysis is proposed as the putative synapomorphy of Ovia gen. nov. The possible sister-taxon relationship of Ovia gen. nov. with Alopecosa is discussed and evidence on the occurrence of sexual dimorphism and mating plug within the genus are presented. Ovia gen. nov. is assumed to be of Holarctic origin, from which it has migrated to the Indomalayan region. Additionally, a current distribution map for the genus is provided.

  11. Description of Teunomyces gen. nov. for the Candida kruisii clade, Suhomyces gen. nov. for the Candida tanzawaensis clade and Suhomyces kilbournensis sp. nov.

    PubMed

    Kurtzman, Cletus P; Robnett, Christie J; Blackwell, Meredith

    2016-08-01

    DNA sequence analysis has shown that species of the Candida kruisii clade and species of the C. tanzawaensis clade represent phylogenetically circumscribed genera, which are described as Teunomyces gen. nov., type species T kruisii, and Suhomyces gen. nov., type species S tanzawaensis Many of the species are distributed worldwide and they are often isolated from fungus-feeding insects and their habitats. Included is the description of S. kilbournensis (type strain NRRL Y-17864, CBS 14276), a species found almost exclusively on maize kernels (Zea mays) in IL, USA.

  12. Erections of Changa gen. nov. and Songga gen. nov. of Aolina (Hemiptera: Cicadidae: Cicadinae: Dundubiini) with taxonomic notes and a synonymization.

    PubMed

    Lee, Young June

    2016-02-29

    Two new genera, Changa gen. nov. and Songga gen. nov., are erected in the subtribe Aolina Boulard, 2012, with the designations of Cosmopsaltria sita Distant, 1881 and Pomponia scitula Distant, 1888 as the type species, respectively. Khimbya sita (Distant, 1881) becomes Changa sita (Distant, 1881) comb. nov. Haphsa scitula (Distant, 1888) becomes Songga scitula (Distant, 1888) comb. nov. Haphsa jsguillotsi (Boulard, 2005) is transferred to Changa to become Changa jsguillotsi (Boulard, 2005) comb. nov. Haphsa stellata Lee, 2009 syn. nov. is synonymized with Changa sita. Haphsa sulaeyai (Boulard, 2005) is transferred to Macrosemia Kato, 1925 to become Macrosemia sulaeyai (Boulard, 2005) comb. nov. A revised key to the genera of Aolina is provided.

  13. Integrated Design and Production Reference Integration with ArchGenXML V1.00

    SciTech Connect

    Barter, R H

    2004-07-20

    ArchGenXML is a tool that allows easy creation of Zope products through the use of Archetypes. The Integrated Design and Production Reference (IDPR) should be highly configurable in order to meet the needs of a diverse engineering community. Ease of configuration is key to the success of IDPR. The purpose of this paper is to describe a method of using a UML diagram editor to configure IDPR through ArchGenXML and Archetypes.

  14. Saccharibacillus sacchari gen. nov., sp. nov., isolated from sugar cane.

    PubMed

    Rivas, Raúl; García-Fraile, Paula; Zurdo-Piñeiro, José Luis; Mateos, Pedro F; Martínez-Molina, Eustoquio; Bedmar, Eulogio J; Sánchez-Raya, Juan; Velázquez, Encarna

    2008-08-01

    A bacterial strain designated GR21T was isolated from apoplastic fluid of Saccharum officinarum (sugar cane). Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate forms a separate branch within the family 'Paenibacillaceae', with Paenibacillus as the closest related genus. Within this genus, the closest related species is Paenibacillus xylanilyticus, with 93.4 % similarity to the sequence of the type strain. The isolate has Gram-variable, facultatively anaerobic, rod-shaped cells, motile by polar and subpolar flagella. Round, non-ornamented, central or subterminal spores are formed in unswollen sporangia. The strain is catalase-positive and oxidase-negative on nutrient agar medium. Cellulose and aesculin were hydrolysed, whereas xylan, starch and gelatin were not. Growth was supported by many carbohydrates as carbon sources. Strain GR21T displayed a lipid profile consisting of diphosphatidylglycerol, phosphatidylglycerol, an unknown aminophospholipid, two unknown glycolipids and an unknown phosphoglycolipid. MK-7 was the predominant menaquinone and anteiso-C15: 0 was the major fatty acid. The DNA G+C content was 57.8 mol%. Phylogenetic and phenotypic analyses, including assimilation of carbon sources and exoenzyme production commonly used for classification within the family 'Paenibacillaceae', showed that strain GR21T belongs to a new genus within this family, for which the name Saccharibacillus sacchari gen. nov., sp. nov. is proposed. The type strain of Saccharibacillus sacchari is GR21T (=LMG 24085T =DSM 19268T).

  15. Cleaning the GenBank Arabidopsis thaliana data set.

    PubMed Central

    Korning, P G; Hebsgaard, S M; Rouze, P; Brunak, S

    1996-01-01

    Data driven computational biology relies on the large quantities of genomic data stored in international sequence data banks. However, the possibilities are drastically impaired if the stored data is unreliable. During a project aiming to predict splice sites in the dicot Arabidopsis thaliana, we extracted a data set from the A.thaliana entries in GenBank. A number of simple 'sanity' checks, based on the nature of the data, revealed an alarmingly high error rate. More than 15% of the most important entries extracted did contain erroneous information. In addition, a number of entries had directly conflicting assignments of exons and introns, not stemming from alternative splicing. In a few cases the errors are due to mere typographical misprints, which may be corrected by comparison to the original papers, but errors caused by wrong assignments of splice sites from experimental data are the most common. It is proposed that the level of error correction should be increased and that gene structure sanity checks should be incorporated--also at the submitter level--to avoid or reduce the problem in the future. A non-redundant and error corrected subset of the data for A.thaliana is made available through anonymous FTP. PMID:8628656

  16. Dinghuibacter silviterrae gen. nov., sp. nov., isolated from forest soil.

    PubMed

    Lv, Ying-Ying; Wang, Jia; Chen, Mei-Hong; You, Jia; Qiu, Li-Hong

    2016-04-01

    A novel Gram-stain negative, non-motile, rod-shaped, aerobic bacterial strain, designated DHOA34T, was isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, China. Comparative 16S rRNA gene sequence analysis showed that it exhibited highest similarity with Flavisolibacter ginsengiterrae Gsoil 492T and Flavitalea populi HY-50RT, at 90.89 and 90.83%, respectively. In the neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, DHOA34T formed an independent lineage within the family Chitinophagaceae but was distinct from all recognized species and genera of the family. The major cellular fatty acids of DHOA34T included iso-C15:0, anteiso-C15:0, iso-C17:0 3-OH and summed feature 3 (C16:1ω6c and/or C16:1ω7c). The DNA G+C content was 51.6 mol% and the predominant quinone was menaquinone 7 (MK-7). Flexirubin pigments were produced. The phenotypic, chemotaxonomic and phylogenetic data demonstrate consistently that strain DHOA34T represents a novel species of a new genus in the family Chitinophagaceae, for which the name Dinghuibacter silviterrae gen. nov., sp. nov. is proposed. The type strain of Dinghuibacter silviterrae is DHOA34T (=CGMCC 1.15023T=KCTC 42632T).

  17. Preliminary Investigation of Civil Tiltrotor in NextGen Airspace

    NASA Technical Reports Server (NTRS)

    Young, Larry A.; Salvano, Dan; Wright, Ken; Chung, William; Young, Ray; Miller, David; Paris, Alfanso; Gao, Huina; Cheng, Victor

    2010-01-01

    Presentation intro: Tiltrotor aircraft have long been envisioned as being a potentially viable means of commercial aviation transport. Preliminary results from an ongoing study into the operational and technological considerations of Civil Tiltrotor (CTR) operation in the Next Generation airspace, circa the 2025 time-frame, are presented and discussed. In particular, a fleet of CTR aircraft has been conceptually designed. The performance characteristics of this CTR fleet was subsequently translated into BADA (Base of Aircraft DAta) models that could be used as input to emulate CTR aircraft operations in the ACES and AvTerminal airspace and terminal area simulation tools. A network of nine North-Eastern corridor airports is the focus of the airspace simulation effort; the results from this airport network viII then be extrapolated to provide insights into systemic impact of CTRs on the National Airspace System (NAS). Future work will also be detailed as to attempts to model the systemic effects of noise and emissions from this fleet of new aircraft as well as assess their leveraged impact on public service missions, in time of need, such as major regional/national disaster relief efforts. The ideal outcome of this study is a set of results whereby Next Gen airspace CONOPs can be refined to reflect potential CTR capabilities and, conversely, CTR technology development efforts can be better informed as to key performance requirement thresholds needed to be met in order to successfully introduce these aircraft into civilian aviation operation.

  18. Methylohalomonas lacus gen. nov., sp. nov. and Methylonatrum kenyense gen. nov., sp. nov., methylotrophic gammaproteobacteria from hypersaline lakes.

    PubMed

    Sorokin, Dimitry Yu; Trotsenko, Yuri A; Doronina, Nina V; Tourova, Tatjana P; Galinski, Erwin A; Kolganova, Tatjana V; Muyzer, Gerard

    2007-12-01

    Aerobic enrichment at 4 M NaCl, pH 7.5, with methanol as carbon and energy source from sediments of hypersaline chloride-sulfate lakes in Kulunda Steppe (Altai, Russia) resulted in the isolation of a moderately halophilic and obligately methylotrophic bacterium, strain HMT 1(T). The bacterium grew with methanol and methylamine within a pH range of 6.8-8.2 with an optimum at pH 7.5 and at NaCl concentrations of 0.5-4 M with an optimum at 2 M. In addition to methanol and methylamine, it can oxidize ethanol, formate, formaldehyde and dimethylamine. Carbon is assimilated via the serine pathway. The main compatible solute is glycine betaine. 16S rRNA gene sequence analysis placed the isolate as a new lineage in the family Ectothiorhodospiraceae (Gammaproteobacteria). It is proposed, therefore, to accommodate this bacterium within a novel genus and species, Methylohalomonas lacus gen. nov., sp. nov., with HMT 1(T) (=DSM 15733(T) =NCCB 100208(T) =UNIQEM U237(T)) as the type strain. Two strains were obtained in pure culture from sediments of soda lake Magadi in Kenya and the Kulunda Steppe (Russia) on a mineral medium at pH 10 containing 0.6 M total Na(+) using methanol as a substrate. Strain AMT 1(T) was enriched with methanol, while strain AMT 3 originated from an enrichment culture with CO. The isolates are restricted facultative methylotrophs, capable of growth with methanol, formate and acetate as carbon and energy sources. With methanol, the strains grew within a broad salinity range from 0.3 to 3.5-4 M total Na(+), with an optimum at 0.5-1 M. The pH range for growth was between 8.3 and 10.5, with an optimum at pH 9.5, which characterized the soda lake isolates as obligate haloalkaliphiles. Carbon is assimilated autotrophically via the Calvin-Benson cycle. Sequence analysis of the gene coding for the key enzyme RuBisCO demonstrated that strain AMT 1(T) possessed a single cbbL gene of the 'green' form I, clustering with members of the family Ectothiorhodospiraceae

  19. Critical Issues on Materials for Gen-IV Reactors

    SciTech Connect

    Caro, M; Marian, J; Martinez, E; Erhart, P

    2009-02-27

    Within the LDRD on 'Critical Issues on Materials for Gen-IV Reactors' basic thermodynamics of the Fe-Cr alloy and accurate atomistic modeling were used to help develop the capability to predict hardening, swelling and embrittlement using the paradigm of Multiscale Materials Modeling. Approaches at atomistic and mesoscale levels were linked to build-up the first steps in an integrated modeling platform that seeks to relate in a near-term effort dislocation dynamics to polycrystal plasticity. The requirements originated in the reactor systems under consideration today for future sources of nuclear energy. These requirements are beyond the present day performance of nuclear materials and calls for the development of new, high temperature, radiation resistant materials. Fe-Cr alloys with 9-12% Cr content are the base matrix of advanced ferritic/martensitic (FM) steels envisaged as fuel cladding and structural components of Gen-IV reactors. Predictive tools are needed to calculate structural and mechanical properties of these steels. This project represents a contribution in that direction. The synergy between the continuous progress of parallel computing and the spectacular advances in the theoretical framework that describes materials have lead to a significant advance in our comprehension of materials properties and their mechanical behavior. We took this progress to our advantage and within this LDRD were able to provide a detailed physical understanding of iron-chromium alloys microstructural behavior. By combining ab-initio simulations, many-body interatomic potential development, and mesoscale dislocation dynamics we were able to describe their microstructure evolution. For the first time in the case of Fe-Cr alloys, atomistic and mesoscale were merged and the first steps taken towards incorporating ordering and precipitation effects into dislocation dynamics (DD) simulations. Molecular dynamics (MD) studies of the transport of self-interstitial, vacancy and

  20. Marinagarivorans algicola gen. nov., sp. nov., isolated from marine algae.

    PubMed

    Guo, Ling-Yun; Li, Dong-Qi; Sang, Jin; Chen, Guan-Jun; Du, Zong-Jun

    2016-01-27

    Novel agar-degrading, Gram-staining-negative, motile, heterotrophic, facultatively anaerobic and pale yellow-pigmented bacterial strains, designated Z1T and JL1, were isolated from marine algae Gelidium amansii (Lamouroux) and Gracilaria verrucosa, respectively. Growth of the isolates was optimal at 28-30 °C, pH 7.0-7.5 and 1-3% (w/v) NaCl. Both strains contained Q-8 as the sole respiratory quinone. The major cellular fatty acids in strain Z1T were C18:1 ω7c, C16:0 and summed feature 3 (C16:1 ω7c and/or iso-C15:0 2-OH). The predominant polar lipids in strain Z1T were phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and aminolipid (AL). The genomic DNA G+C content of both strains was 45.1 mol%. Strains Z1T and JL1 were closely related, with 99.9% 16S rRNA gene sequence similarity. The average nucleotide identity (ANI) value between strains Z1T and JL1 was 99.3%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains Z1T and JL1 form a distinct phyletic line within the class Gammaproteobacteria, with less than 92.3% similarity to their closest relatives. Based on data from the current polyphasic study, the isolates are proposed to belong to a new genus and species designated Marinagarivorans algicola gen. nov., sp. nov. The type strain of Marinagarivorans algicola is Z1T (=ATCC BAA-2617T=CICC 10859T).

  1. Haloactinomyces albus gen. nov., sp. nov., isolated from Dead Sea.

    PubMed

    Lai, Hangxian; Jiang, Yingying; Chen, Xiu; Li, Qinyuan; Jiang, Chenglin; Jiang, Yi; Wei, Xiaomin

    2017-01-10

    A novel halophilic, filamentous actinomycete strain, designated AFM 10258T, was isolated from a sediment sample collected from Dead Sea of Israel. The isolate grew with 10-35% NaCl and did not grow without NaCl. The isolate formed white aerial mycelium and long spore chains, and two spores were separated by sterile mycelium. The spores were non-motile, spherical and rugose-surfaced. The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and galactose and arabinose as the major whole-cell sugars. The polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and three unknown phospholipids. Major fatty acids were anteiso-C17:0, iso-C16:0 and iso-C15:0. MK-9(H4) was the predominant menaquinone and the DNA G+C content was 62.8 mol%. 16S rRNA gene sequence analysis indicated that strain AFM 10258T shared low sequence similarity with the closely related representatives of the families Pseudonocardiaceae (below 94.47%) and Actinopolysporaceae (below 93.76%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain AFM 10258T formed a robust clade with members of the family Actinopolysporaceae. On the basis of analysis of phenotypic, chemical and molecular characteristics, strain AFM 10258T is considered to represent a novel species of a new genus , for which the name Haloactinomyces albus gen. nov., sp. nov., is proposed. The type strain is AFM 10258T (=DSM 45977T = CGMCC 4.7115T).

  2. Ethanoligenens harbinense gen. nov., sp. nov., isolated from molasses wastewater.

    PubMed

    Xing, Defeng; Ren, Nanqi; Li, Qiubo; Lin, Ming; Wang, Aijie; Zhao, Lihua

    2006-04-01

    Two strictly anaerobic bacterial strains (YUAN-3T and X-29) were isolated from anaerobic activated sludge of molasses wastewater in a continuous stirred-tank reactor. The strains were Gram-positive, non-spore-forming, mesophilic and motile. Cells were regular rods (0.4-0.8 x 1.5-8.0 microm) and occurred singly, in pairs and sometimes in chains of up to eight. Autoaggregative and autofluorescent growth of strain YUAN-3T and non-aggregative growth of strain X-29 were observed at 20-44 degrees C and pH 3.5-9.0. Both strains hydrolysed gelatin and aesculin and fermented several kinds of mono-, di- and oligosaccharides. Fermentation end products formed from glucose were acetate, ethanol, hydrogen and carbon dioxide. The predominant cellular fatty acids were the branched-chain fatty acids iso-C(16 : 0) (44.18 %) and iso-C(12 : 0) (26.67 %). The DNA G+C contents of strains YUAN-3T and X-29 were 47.8 and 49.0 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolates represent a novel phyletic sublineage within the Clostridium cellulosi rRNA cluster, with <92 % 16S rRNA gene sequence similarity to currently known species. On the basis of polyphasic evidence from this study, it is proposed that the unknown bacterium should be classified in a new genus as a novel species, Ethanoligenens harbinense gen. nov., sp. nov. The type strain of Ethanoligenens harbinense is YUAN-3T (=JCM 12961T = CGMCC 1.5033T).

  3. Rhabdobacter roseus gen. nov., sp. nov., isolated from soil.

    PubMed

    Dahal, Ram Hari; Kim, Jaisoo

    2016-01-01

    An aerobic, Gram-stain-negative, oxidase- and catalase-positive, non-motile, non-spore-forming, rod-shaped, pink-pigmented bacterium, designated strain R49T, was isolated from soil. Flexirubin-type pigments were absent. Phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain R49T formed a lineage within the family Cytophagaceae of the phylum Bacteroidetes that was distinct from the most closely related genera Dyadobacter (91.98-93.85 % sequence similarity), Persicitalea (88.69 %) and Runella (84.79-85.81 %). The major isoprenoid quinone was menaquinone-7 (MK-7) and the major polar lipid was phosphatidylethanolamine. The major cellular fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0, C16 : 1ω5c, C16 : 0 and iso-C17 : 0 3-OH. The DNA G+C content of strain R49T was 53.9 mol%. On the basis of phenotypic, genotypic and phylogenetic analysis, strain R49T represents a novel species of a new genus in the family Cytophagaceae, for which the name Rhabdobacter roseus gen. nov., sp. nov. is proposed. The type strain of Rhabdobacter roseus is R49T ( = KEMB 9005-318T = KACC 18395T = JCM 30685T).

  4. Scopulibacillus darangshiensis gen. nov., sp. nov., isolated from rock.

    PubMed

    Lee, Soon Dong; Lee, Dong Wan

    2009-12-01

    A novel, Gram-positive bacterium, designated DLS-06(T), was isolated from scoria (volcanic ash) under rock on the peak of small mountain (300 m above the sea level; known as Darangshi Oreum) in Jeju, Republic of Korea. The cells of the isolate were aerobic, oxidase-negative, catalase-positive, endospore-forming, non-motile rods. The organism grew at 25 approximately 30 degrees C and initial pH 6.1 approximately 9.1. A neighbour-joining tree based on 16S rRNA gene sequences showed that the organism was related to members of the family "Sporolactobacillaceae" and related taxa. The phylogenetic neighbours were Pullulanibacillus naganoensis (95.2% 16S rRNA gene sequence similarity), Tuberibacillus calidus (95.0%) and Sporolactobacillus (91.8 approximately 94.2%). Levels of 16S rRNA gene sequence similarity of the isolate to representatives of other genera were in the range of 87.2 approximately 93.7%. The organism contained meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The predominant menaquinone was MK-7. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, an unknown ninhydrin-positive phospholipid, three unknown phospholipids and an unknown lipid. The major fatty acids were anteiso-C(15:0) and anteiso-C(17:0). The G+C content of the DNA was 50.8 mol%. On the basis of the phenotypic and phylogenetic data presented in this study, this organism represents a novel genus and species in the order Bacillales, for which the name Scopulibacillus darangshiensis gen. nov., sp. nov. is proposed. The type strain is DLS-06(T) (=DSM 19377(T) =KCTC 13161(T)).

  5. Prevalence of metilentetrahidrofolate reductase C677T polymorphism, consumption of vitamins B6, B9, B12 and determination of lipidic hydroperoxides in obese and normal weight Mexican population.

    PubMed

    Hernández-Guerrero, César; Romo-Palafox, Inés; Díaz-Gutiérrez, Mary Carmen; Iturbe-García, Mariana; Texcahua-Salazar, Alejandra; Pérez-Lizaur, Ana Bertha

    2013-11-01

    Introducción. El estrés oxidativo es un factor clave en el inicio y el desarrollo de las comorbilidades de la obesidad. La enzima metiltetrahidrofolato reductasa (MTHFR) participa en el metabolismo del folato con la acción de las vitaminas B9 y B12. El gen MTHFR puede presentar un polimorfismo de un solo nucleótido (SNP) en la posición 677 (C677T), que puede promover homocisteinemia asociada a la producción de radicales libres. Objetivo. Determinar la frecuencia del SNP C677T de la MTHFR, evaluar el consumo de vitaminas B6, B9, B12 y determinar la concentración de hidroperóxidos lipídicos (LOOH) en plasma en un grupo de obesos y testigo. Métodos. Se clasificaron 128 mexicanos mestizos de acuerdo a su índice de masa corporal en normopeso (Nw; n=75) y obesidad (ObeI-III; n=53). Se identificó el SNP C677T de la MTHFR mediante la técnica de PCR-RFLP. El consumo de vitaminas B6, B9 y B12 se evaluó mediante una encuesta validada. Se determinaron LOOH como un indicador de estrés oxidativo periférico. Resultados. No hubo diferencia estadística significativa en la frecuencia del polimorfismo C677T entre homocigotos TT en Nw (0.19) y ObeI-III (0.25). La frecuencia del alelo T en Nw fue de 0.45, y 0.51 en el grupo ObeI-III. Los LOOH mostraron diferencia estadística significativa (p.

  6. Electronic and magnetic properties of CrGen (15 ⩽ n ⩽ 29) clusters: A DFT study

    NASA Astrophysics Data System (ADS)

    Mahtout, Sofiane; Tariket, Yacine

    2016-06-01

    We report ab initio calculations of electronic and magnetic properties of medium-sized CrGen (15 ⩽ n ⩽ 29) clusters using density functional theory. The encapsulation of Cr atoms within Gen clusters leads to stable Cr encapsulated Gen clusters. The binding energies generally increase while the differences between the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO-LUMO gaps) generally decrease with the increasing of cluster size. The clusters of CrGen at size 16, 17, 19, 22, 24 and 29 exhibit high stabilities when compared to their neighbors. This has been discussed in terms of their structures, energies and the effect of the position of doping atom. Doping of Gen clusters with one Cr atom leads to CrGen clusters with magnetic moment depending on the structure of the clusters and the position of Cr atom in the clusters. Moreover, vertical ionization potential, vertical electronic affinity, and chemical hardness are also analyzed.

  7. Wave Data Processing and Analysis, Part 2: Codes for Coupling GenCade and CMS-Wave

    DTIC Science & Technology

    2013-09-01

    coastal modeling system , Report 2: CMS -Wave. ERDC/CHL-TR-11-10. Vicksburg, MS: US Army Engineer Research and Development Center. Connell, K. J. and...Coupling GenCade and CMS -Wave by Rusty Permenter, Kenneth J. Connell, and Zeki Demirbilek PURPOSE: This Coastal and Hydraulics Engineering...to GenCade. This is the second CHETN in a two‐part series detailing the process of coupling CMS ‐Wave with GenCade. This CHETN focuses on

  8. ATLAS Versus NextGen Model Atmospheres: A Combined Analysis of Synthetic Spectral Energy Distributions

    NASA Astrophysics Data System (ADS)

    Bertone, E.; Buzzoni, A.; Chávez, M.; Rodríguez-Merino, L. H.

    2004-08-01

    We carried out a critical appraisal of the two theoretical models, Kurucz' ATLAS9 and PHOENIX/NextGen, for stellar atmosphere synthesis. Our tests relied on the theoretical fit of spectral energy distributions (SEDs) for a sample of 334 target stars along the whole spectral-type sequence, from the classical optical catalogs of Gunn & Stryker and Jacoby et al. The best-fitting physical parameters (Teff, logg) of stars allowed an independent calibration of the temperature and bolometric scale versus empirical classification parameters (i.e., spectral type and MK luminosity class); in addition, the comparison of the synthetic templates from the ATLAS and NextGen grids allowed us to probe the capability of the models to match spectrophotometric properties of real stars and assess the impact of the different input physics. We can sketch the following main conclusions of our analysis: (1) Fitting accuracy of both theoretical libraries drastically degrades at low Teff at which both ATLAS and NextGen models still fail to properly account for the contribution of molecular features in the observed SED of K-M stars. (2) Compared with empirical calibrations, both ATLAS and NextGen fits tend, on average, to predict slightly warmer (by 4%-8%) Teff for both giant and dwarf stars of fixed spectral type, but ATLAS provides, in general, a sensibly better fit (a factor of 2 lower σ of flux residuals) than NextGen. (3) There is a striking tendency of NextGen to label target stars with an effective temperature and surface gravity higher than that of ATLAS. The effect is especially evident for MK I-III objects for which about one in four stars is clearly misclassified by NextGen in logg. This is a consequence of some ``degeneracy'' in the solution space, partly induced by the different input physics and geometry constraints in the computation of the integrated emerging flux (ATLAS model atmospheres assume standard plane-parallel layers, while NextGen adopts, for low-gravity stars, a

  9. Initial Investigation of Operational Concept Elements for NASA's NextGen-Airportal Project Research

    NASA Technical Reports Server (NTRS)

    Lohr, Gary; Lee, Jonathan; Poage, James L.; Tobias, Leonard

    2009-01-01

    The NextGen-Airportal Project is organized into three research focus areas: Safe and Efficient Surface Operations, Coordinated Arrival/Departure Operations Management, and Airportal Transition and Integration Management. The content in this document was derived from an examination of constraints and problems at airports for accommodating future increases in air traffic, and from an examination of capabilities envisioned for NextGen. The concepts are organized around categories of constraints and problems and therefore do not precisely match, but generally reflect, the research focus areas. The concepts provide a framework for defining and coordinating research activities that are, and will be, conducted by the NextGen-Airportal Project. The concepts will help the research activities function as an integrated set focused on future needs for airport operations and will aid aligning the research activities with NextGen key capabilities. The concepts are presented as concept elements with more detailed sub-elements under each concept element. For each concept element, the following topics are discussed: constraints and problems being addressed, benefit descriptions, required technology and infrastructure, and an initial list of potential research topics. Concept content will be updated and more detail added as the research progresses. The concepts are focused on enhancing airportal capacity and efficiency in a timeframe 20 to 25 years in the future, which is similar to NextGen's timeframe.

  10. Safety Sufficiency for NextGen: Assessment of Selected Existing Safety Methods, Tools, Processes, and Regulations

    NASA Technical Reports Server (NTRS)

    Xu, Xidong; Ulrey, Mike L.; Brown, John A.; Mast, James; Lapis, Mary B.

    2013-01-01

    NextGen is a complex socio-technical system and, in many ways, it is expected to be more complex than the current system. It is vital to assess the safety impact of the NextGen elements (technologies, systems, and procedures) in a rigorous and systematic way and to ensure that they do not compromise safety. In this study, the NextGen elements in the form of Operational Improvements (OIs), Enablers, Research Activities, Development Activities, and Policy Issues were identified. The overall hazard situation in NextGen was outlined; a high-level hazard analysis was conducted with respect to multiple elements in a representative NextGen OI known as OI-0349 (Automation Support for Separation Management); and the hazards resulting from the highly dynamic complexity involved in an OI-0349 scenario were illustrated. A selected but representative set of the existing safety methods, tools, processes, and regulations was then reviewed and analyzed regarding whether they are sufficient to assess safety in the elements of that OI and ensure that safety will not be compromised and whether they might incur intolerably high costs.

  11. Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage

    PubMed Central

    Lee, Shun-Hsiao; Princz, Lissa Nicola; Klügel, Maren Felizitas; Habermann, Bianca; Pfander, Boris; Biertümpfel, Christian

    2015-01-01

    Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution. The GEN1 core is similar to other Rad2/XPG nucleases. However, unlike other members of the superfamily, GEN1 contains a chromodomain as an additional DNA interaction site. Chromodomains are known for their chromatin-targeting function in chromatin remodelers and histone(de)acetylases but they have not previously been found in nucleases. The GEN1 chromodomain directly contacts DNA and its truncation severely hampers GEN1’s catalytic activity. Structure-guided mutations in vitro and in vivo in yeast validated our mechanistic findings. Our study provides the missing structure in the Rad2/XPG family and insights how a well-conserved nuclease core acquires versatility in recognizing diverse substrates for DNA repair and maintenance. DOI: http://dx.doi.org/10.7554/eLife.12256.001 PMID:26682650

  12. Mechanism of Holliday junction resolution by the human GEN1 protein

    PubMed Central

    Rass, Ulrich; Compton, Sarah A.; Matos, Joao; Singleton, Martin R.; Ip, Stephen C.Y.; Blanco, Miguel G.; Griffith, Jack D.; West, Stephen C.

    2010-01-01

    Holliday junction (HJ) resolution is essential for chromosome segregation at meiosis and the repair of stalled/collapsed replication forks in mitotic cells. All organisms possess nucleases that promote HJ resolution by the introduction of symmetrically related nicks in two strands at, or close to, the junction point. GEN1, a member of the Rad2/XPG nuclease family, was isolated recently from human cells and shown to promote HJ resolution in vitro and in vivo. Here, we provide the first biochemical/structural characterization of GEN1, showing that, like the Escherichia coli HJ resolvase RuvC, it binds specifically to HJs and resolves them by a dual incision mechanism in which nicks are introduced in the pair of continuous (noncrossing) strands within the lifetime of the GEN1–HJ complex. In contrast to RuvC, but like other Rad2/XPG family members such as FEN1, GEN1 is a monomeric 5′-flap endonuclease. However, the unique feature of GEN1 that distinguishes it from other Rad2/XPG nucleases is its ability to dimerize on HJs. This functional adaptation provides the two symmetrically aligned active sites required for HJ resolution. PMID:20634321

  13. NextGen Operations in a Simulated NY Area Airspace

    NASA Technical Reports Server (NTRS)

    Smith, Nancy M.; Parke, Bonny; Lee, Paul; Homola, Jeff; Brasil, Connie; Buckley, Nathan; Cabrall, Chris; Chevalley, Eric; Lin, Cindy; Morey, Susan; Omar, Faisal; Rein-Weston, Daphne; Yoo, Hyo-Sang

    2013-01-01

    A human-in-the-loop simulation conducted in the Airspace Operations Laboratory (AOL) at NASA Ames Research Center explored the feasibility of a Next Generation Air Transportation System (NextGen) solution to address airspace and airport capacity limitations in and around the New York metropolitan area. A week-long study explored the feasibility of a new Optimal Profile Descent (OPD) arrival into the airspace as well as a novel application of a Terminal Area Precision Scheduling and Spacing (TAPSS) enhancement to the Traffic Management Advisor (TMA) arrival scheduling tool to coordinate high volume arrival traffic to intersecting runways. In the simulation, four en route sector controllers and four terminal radar approach control (TRACON) controllers managed traffic inbound to Newark International Airport's primary runway, 22L, and its intersecting overflow runway, 11. TAPSS was used to generate independent arrival schedules for each runway and a traffic management coordinator participant adjusted the arrival schedule for each runway 11 aircraft to follow one of the 22L aircraft. TAPSS also provided controller-managed spacing tools (slot markers with speed advisories and timelines) to assist the TRACON controllers in managing the arrivals that were descending on OPDs. Results showed that the tools significantly decreased the occurrence of runway violations (potential go-arounds) when compared with a Baseline condition with no tools. Further, the combined use of the tools with the new OPD produced a peak arrival rate of over 65 aircraft per hour using instrument flight rules (IFR), exceeding the current maximum arrival rate at Newark Liberty International Airport (EWR) of 52 per hour under visual flight rules (VFR). Although the participants rated the workload as relatively low and acceptable both with and without the tools, they rated the tools as reducing their workload further. Safety and coordination were rated by most participants as acceptable in both

  14. GenMin: An enhanced genetic algorithm for global optimization

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Lagaris, I. E.

    2008-06-01

    A new method that employs grammatical evolution and a stopping rule for finding the global minimum of a continuous multidimensional, multimodal function is considered. The genetic algorithm used is a hybrid genetic algorithm in conjunction with a local search procedure. We list results from numerical experiments with a series of test functions and we compare with other established global optimization methods. The accompanying software accepts objective functions coded either in Fortran 77 or in C++. Program summaryProgram title: GenMin Catalogue identifier: AEAR_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAR_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 35 810 No. of bytes in distributed program, including test data, etc.: 436 613 Distribution format: tar.gz Programming language: GNU-C++, GNU-C, GNU Fortran 77 Computer: The tool is designed to be portable in all systems running the GNU C++ compiler Operating system: The tool is designed to be portable in all systems running the GNU C++ compiler RAM: 200 KB Word size: 32 bits Classification: 4.9 Nature of problem: A multitude of problems in science and engineering are often reduced to minimizing a function of many variables. There are instances that a local optimum does not correspond to the desired physical solution and hence the search for a better solution is required. Local optimization techniques are frequently trapped in local minima. Global optimization is hence the appropriate tool. For example, solving a nonlinear system of equations via optimization, employing a least squares type of objective, one may encounter many local minima that do not correspond to solutions (i.e. they are far from zero). Solution method: Grammatical evolution and a stopping rule. Running time: Depending on the

  15. The natural history of cutaneous propionibacteria, and reclassification of selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov.

    PubMed

    Scholz, Christian F P; Kilian, Mogens

    2016-11-01

    The genus Propionibacterium in the family Propionibacteriaceaeconsists of species of various habitats, including mature cheese, cattle rumen and human skin. Traditionally, these species have been grouped as either classical or cutaneous propionibacteria based on characteristic phenotypes and source of isolation. To re-evaluate the taxonomy of the family and to elucidate the interspecies relatedness we compared 162 public whole-genome sequences of strains representing species of the family Propionibacteriaceae. We found substantial discrepancies between the phylogenetic signals of 16S rRNA gene sequence analysis and our high-resolution core-genome analysis. To accommodate these discrepancies, and to address the long-standing issue of the taxonomically problematic Propionibacterium propionicum, we propose three novel genera, Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov., and an amended description of the genus Propionibacterium. Furthermore, our genome-based analyses support the amounting evidence that the subdivision of Propionibacterium freudenreichii into subspecies is not warranted. Our proposals are supported by phylogenetic analyses, DNA G+C content, peptidoglycan composition and patterns of the gene losses and acquisitions in the cutaneous propionibacteria during their adaptation to the human host.

  16. Leptojacobus dorci n. gen., n. sp. (Nematoda: Diplogastridae), an Associate of Dorcus Stag Beetles (Coleoptera: Lucanidae).

    PubMed

    Kanzaki, Natsumi; Ragsdale, Erik J; Susoy, Vladislav; Sommer, Ralf J

    2014-03-01

    A new species of diplogastrid nematode, Leptojacobus dorci n. gen., n. sp., was isolated from adults of the stag beetle Dorcus ritsemae (Coleoptera: Lucanidae) that were purchased from a pet shop in Japan. Leptojacobus n. gen. is circumscribed by a very thin, delicate body and by a small stoma with minute armature. A combination of other stomatal characters, namely the division of the cheilostom into adradial plates, the symmetry of the subventral stegostomatal sectors, and the presence of a thin, conical dorsal tooth, further distinguishes Leptojacobus n. gen. from other genera of Diplogastridae. Phylogenetic analysis of nearly full-length SSU rRNA sequences support the new species, together with an isolate identified previously as Koerneria luziae, to be excluded from a clade including all other molecularly characterized diplogastrids with teeth and stomatal dimorphism. Therefore, the new species will be of importance for reconstruction of ancestral character histories in Diplogastridae, a family circumscribed by a suite of feeding-related novelties.

  17. Tools for Designing, Evaluating, and Certifying NextGen Technologies and Procedures: Automation Roles and Responsibilities

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    2011-01-01

    Barbara Kanki from NASA Ames Research Center will discuss research that focuses on the collaborations between pilots, air traffic controllers and dispatchers that will change in NextGen systems as automation increases and roles and responsibilities change. The approach taken by this NASA Ames team is to build a collaborative systems assessment template (CSAT) based on detailed task descriptions within each system to establish a baseline of the current operations. The collaborative content and context are delineated through the review of regulatory and advisory materials, policies, procedures and documented practices as augmented by field observations and interviews. The CSAT is developed to aid the assessment of key human factors and performance tradeoffs that result from considering different collaborative arrangements under NextGen system changes. In theory, the CSAT product may be applied to any NextGen application (such as Trajectory Based Operations) with specified ground and aircraft capabilities.

  18. Thalassomermis megamphis n. gen., n. sp. (Mermithidae: Nemata) from the Bathyal South Atlantic Ocean

    PubMed Central

    Tchesunov, A.V.; Hope, W. D.

    1997-01-01

    Thalassomermis megamphis n. gen., n. sp. (Mermithidae: Nemata) was extracted from sediment collected off the coast of Brazil at a depth of approximately 1,000 m. Although the food of this new nematode is unknown, the reduction of the stoma and esophagus and presence of a trophosome indicate that it is parasitic in its juvenile stages. Thalassomermis megaraphis n. gen., n. sp. is assigned to Mermithidae because of its similarity to that family in the appearance of the cephalic sensory receptors, the long and tubular vagina, and copulatory muscles of the male extending posteriorly throughout most of the length of the tail. Thalassomermis megamphis n. gen., n. sp. differs from all other members of Mermithidae by the large, lenticular, intracuticular amphidial fovea with coiled, emergent terminal filaments as well as the small amphidial aperture situated over the center of the fovea. PMID:19274181

  19. SIPSMetGen: It's Not Just For Aircraft Data and ECS Anymore.

    NASA Astrophysics Data System (ADS)

    Schwab, M.

    2015-12-01

    The SIPSMetGen utility, developed for the NASA EOSDIS project, under the EED contract, simplified the creation of file level metadata for the ECS System. The utility has been enhanced for ease of use, efficiency, speed and increased flexibility. The SIPSMetGen utility was originally created as a means of generating file level spatial metadata for Operation IceBridge. The first version created only ODL metadata, specific for ingest into ECS. The core strength of the utility was, and continues to be, its ability to take complex shapes and patterns of data collection point clouds from aircraft flights and simplify them to a relatively simple concave hull geo-polygon. It has been found to be a useful and easy to use tool for creating file level metadata for many other missions, both aircraft and satellite. While the original version was useful it had its limitations. In 2014 Raytheon was tasked to make enhancements to SIPSMetGen, this resulted a new version of SIPSMetGen which can create ISO Compliant XML metadata; provides optimization and streamlining of the algorithm for creating the spatial metadata; a quicker runtime with more consistent results; a utility that can be configured to run multi-threaded on systems with multiple processors. The utility comes with a java based graphical user interface to aid in configuration and running of the utility. The enhanced SIPSMetGen allows more diverse data sets to be archived with file level metadata. The advantage of archiving data with file level metadata is that it makes it easier for data users, and scientists to find relevant data. File level metadata unlocks the power of existing archives and metadata repositories such as ECS and CMR and search and discovery utilities like Reverb and Earth Data Search. Current missions now using SIPSMetGen include: Aquarius, Measures, ARISE, and Nimbus.

  20. Genome-scale data suggest reclassifications in the Leisingera-Phaeobacter cluster including proposals for Sedimentitalea gen. nov. and Pseudophaeobacter gen. nov.

    PubMed

    Breider, Sven; Scheuner, Carmen; Schumann, Peter; Fiebig, Anne; Petersen, Jörn; Pradella, Silke; Klenk, Hans-Peter; Brinkhoff, Thorsten; Göker, Markus

    2014-01-01

    Earlier phylogenetic analyses of the marine Rhodobacteraceae (class Alphaproteobacteria) genera Leisingera and Phaeobacter indicated that neither genus might be monophyletic. We here used phylogenetic reconstruction from genome-scale data, MALDI-TOF mass-spectrometry analysis and a re-assessment of the phenotypic data from the literature to settle this matter, aiming at a reclassification of the two genera. Neither Phaeobacter nor Leisingera formed a clade in any of the phylogenetic analyses conducted. Rather, smaller monophyletic assemblages emerged, which were phenotypically more homogeneous, too. We thus propose the reclassification of Leisingera nanhaiensis as the type species of a new genus as Sedimentitalea nanhaiensis gen. nov., comb. nov., the reclassification of Phaeobacter arcticus and Phaeobacter leonis as Pseudophaeobacter arcticus gen. nov., comb. nov. and Pseudophaeobacter leonis comb. nov., and the reclassification of Phaeobacter aquaemixtae, Phaeobacter caeruleus, and Phaeobacter daeponensis as Leisingera aquaemixtae comb. nov., Leisingera caerulea comb. nov., and Leisingera daeponensis comb. nov. The genera Phaeobacter and Leisingera are accordingly emended.

  1. Batwanema gen. n. and Chokwenema gen. n. (Oxyurida, Hystrignathidae), new nematode genera as parasites of Passalidae (Coleoptera) from the Democratic Republic of Congo

    PubMed Central

    Morffe, Jans; García, Nayla

    2013-01-01

    Abstract Two new genera and species parasitizing passalid beetles from the Democratic Republic of Congo are described. Batwanema congo gen. n. et sp. n. is characterized by having females with the cervical cuticle armed with scale-like projections, arranged initially in rows of eight elements that gradually divide and form pointed spines toward the end of the spiny region, two cephalic annuli, clavate procorpus and genital tract monodelphic-prodelphic. Two Malagasian species of Artigasia Christie, 1934 were placed in this genus as B. latum (Van Waerebeke, 1973) comb. n. and B. annulatum (Van Waerebeke, 1973) comb. n. Chokwenema lepidophorum gen. n. et sp. n. is characterized by having females with the cervical cuticle armed with scale-like projections, arranged initially in rows of eight elements (similar to Batwanema) that divide gradually, forming spines; a single cephalic annule cone-like, truncated, moderately inflated; procorpus sub-cylindrical and genital tract didelphic-amphidelphic. PMID:24363593

  2. Castellaniella gen. nov., to accommodate the phylogenetic lineage of Alcaligenes defragrans, and proposal of Castellaniella defragrans gen. nov., comb. nov. and Castellaniella denitrificans sp. nov.

    PubMed

    Kämpfer, P; Denger, K; Cook, A M; Lee, S-T; Jäckel, U; Denner, E B M; Busse, H-J

    2006-04-01

    Comparative 16S rRNA gene sequence analysis indicates that two distinct sublineages exist within the genus Alcaligenes: the Alcaligenes faecalis lineage, comprising Alcaligenes aquatilis and A. faecalis (with the three subspecies A. faecalis subsp. faecalis, A. faecalis subsp. parafaecalis and A. faecalis subsp. phenolicus), and the Alcaligenes defragrans lineage, comprising A. defragrans. This phylogenetic discrimination is supported by phenotypic and chemotaxonomic differences. It is proposed that the A. defragrans lineage constitutes a distinct genus, for which the name Castellaniella gen. nov. is proposed. The type strain for Castellaniella defragrans gen. nov., comb. nov. is 54PinT (=CCUG 39790T = CIP 105602T = DSM 12141T). Finally, on the basis of data from the literature and new DNA-DNA hybridization and phenotypic data, the novel species Castellaniella denitrificans sp. nov. (type strain NKNTAUT = DSM 11046T = CCUG 39541T) is proposed for two strains previously identified as strains of A. defragrans.

  3. Description of a new genus, Galgoria gen. nov. (Hemiptera: Cicadidae: Cicadinae: Leptopsaltriini: Leptopsaltriina).

    PubMed

    Lee, Young June

    2016-05-10

    A new cicada genus, Galgoria gen. nov., is described with Tanna herzbergi Schmidt, 1932 (from southern China) as its type species, which is placed in the subtribe Leptopsaltriina Moulton, 1923 of the tribe Leptopsaltriini Moulton, 1923 in the subfamily Cicadinae Latreille, 1802 (Hemiptera: Cicadidae). Tanna herzbergi Schmidt, 1932 is transferred from Tanna Distant, 1905 to Galgoria gen. nov. to become Galgoria herzbergi (Schmidt, 1932) comb. nov. Tanna apicalis Chen, 1940 syn. nov. and Tanna pseudocalis Lei & Chou, 1997 syn. nov. are synonymized here with Galgoria herzbergi (Schmidt, 1932) comb. nov.

  4. Massilibacterium senegalense gen. nov., sp. nov., a new bacterial genus isolated from the human gut

    PubMed Central

    Tidjani Alou, M.; Rathored, J.; Lagier, J.-C.; Khelaifia, S.; Labas, N.; Sokhna, C.; Diallo, A.; Raoult, D.; Dubourg, G.

    2016-01-01

    Massilibacterium senegalense gen. nov., sp. nov., strain mt8T, is the type strain of Massilibacterium gen. nov., a new genus within the Bacillaceae family. This Gram-negative facultative anaerobic rod was isolated from the gut microbiota of a severely malnourished boy. Its phenotypic description is hereby presented with a complete annotation of its genome sequence. This genome is 5 697 950 bp long and contains 5615 protein-coding genes and 178 RNA genes, among which are 40 rRNA genes. PMID:26933503

  5. GenCade Version 1 Model Theory and User’s Guide

    DTIC Science & Technology

    2012-12-01

    scale processes to the smaller ultra scale processes as shown in Figure 1. GenCade is developed and maintained by the U.S. Army Engineer Research and...wavelength in deep water (m). The deepwater wavelength is calculated from linear wave theory as  2 / 2oL gT  , in which g is the acceleration...littoral zone under extreme waves. In the framework of GenCade, DLTo is calculated at each time step from the deepwater wave data and is assumed to

  6. Acerca del moho

    EPA Pesticide Factsheets

    El moho forma parte del medio ambiente natural. Afuera del hogar, el moho juega un papel en la naturaleza al desintegrar materias organicas tales como las hojas que se han caido o los arboles muertos. El moho puede crecer adentro del hogar cuando las espor

  7. 75 FR 35018 - GenConn Energy LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission GenConn Energy LLC; Supplemental Notice That Initial Market-Based Rate... notice in the above-referenced proceeding of GenConn Energy LLC's application for market-based...

  8. Discourses in Conflict: The Relationship between Gen Y Pre-Service Teachers, Digital Technologies and Lifelong Learning

    ERIC Educational Resources Information Center

    Donnison, Sharn

    2009-01-01

    This paper analyses Gen Y pre-service primary school teachers' conceptualisations of lifelong learning. It is situated within a context of improving the provision and delivery of pre-service teacher education. This paper argues that Gen Y's understanding of lifelong learning has been influenced by their engagements with digital technologies and…

  9. 75 FR 80487 - Cambria CoGen Company; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Cambria CoGen Company; Supplemental Notice That Initial Market- Based Rate... notice in the above-referenced proceeding of Cambria CoGen Company's application for market-based...

  10. 78 FR 49507 - OriGen Energy LLC ; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission OriGen Energy LLC ; Supplemental Notice That Initial Market-Based Rate...-referenced proceeding of OriGen Energy LLC's application for market-based rate authority, with...

  11. 77 FR 56839 - GenOn Marsh Landing, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission GenOn Marsh Landing, LLC; Supplemental Notice That Initial Market-Based Rate...-referenced proceeding, of GenOn Marsh Landing, LLC's application for market-based rate authority, with...

  12. Microcenoscelis n. gen. (Coleoptera: Tenebrionidae: Ulomini) from tropical Africa, with description of a blind species from Zimbabwe.

    PubMed

    Schawaller, Wolfgang

    2015-10-05

    Microcenoscelis n. gen. (Coleoptera: Tenebrionidae: Ulomini) caeca n. sp. is described from Zimbabwe, a small and completely blind species. A second known species, however with completely developed eyes, and originally described as Uloma minuscula Ardoin, 1969, was also placed in the new genus. Microcenoscelis n. gen. seems to be mostly related to the genera Cenoscelis Wollaston, 1867, and Cneocnemis Gebien, 1914.

  13. Descriptions of Kashmira dimorphicauda gen. n., sp. n. and Aphelenchoides hypotris sp. n. from Kashmir Valley, India

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kashmira dimorphicauda gen. n., sp. n. and Aphelenchoides hypotris sp. n. are described and illustrated from freshwater stream soil in Kashmir Valley, India. Kashmira gen. n. is characterized by having dimorphic tails: coinoid-spicate tail in female and subcylindroid with rounded, non-spicate tip wi...

  14. 78 FR 77670 - AlphaGen Power LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission AlphaGen Power LLC; Supplemental Notice That Initial Market-Based Rate...-referenced proceeding, of AlphaGen Power LLC's application for market-based rate authority, with...

  15. 76 FR 28973 - Terra-Gen Dixie Valley, LLC; Order on Rehearing and Accepting Tariff Filing, Subject to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... rejecting Terra-Gen's proposed OATT provisions that would provide ``an OATT exemption for its existing and...- Gen explains that its OATT has non-conforming provisions that include limiting the applicability of... the pro forma OATT provisions related to the provision of ] network transmission service,...

  16. PZT piezoelectric films on glass for Gen-X imaging

    NASA Astrophysics Data System (ADS)

    Wilke, Rudeger H. T.; Trolier-McKinstry, Susan; Reid, Paul B.; Schwartz, Daniel A.

    2010-09-01

    The proposed adaptive optics system for the Gen-X telescope uses piezoelectric lead zirconate titanate (PZT) films deposited on flexible glass substrates. The low softening transition of the glass substrates imposes several processing challenges that require the development of new approaches to deposit high quality PZT thin films. Synthesis and optimization of chemical solution deposited 1 μm thick films of PbZr0.52Ti0.48O3 on small area (1 in2) and large area (16 in2) Pt/Ti/glass substrates has been performed. In order to avoid warping of the glass at temperatures typically used to crystallize PZT films ({700°C), a lower temperature, two-step crystallization process was employed. An {80 nm thick seed layer of PbZr0.30Ti0.70O3 was deposited to promote the growth of the perovskite phase. After the deposition of the seed layer, the films were annealed in a rapid thermal annealing (RTA) furnace at 550°C for 3 minutes to nucleate the perovskite phase. This was followed by isothermal annealing at 550°C for 1 hour to complete crystallization. For the subsequent PbZr0.52Ti0.48O3 layers, the same RTA protocol was performed, with the isothermal crystallization implemented following the deposition of three PbZr0.52Ti0.48O3 spin-coated layers. Over the frequency range of 1 kHz to 100 kHz, films exhibit relative permittivity values near 800 with loss tangents below 0.07. Hysteresis loops show low levels of imprint with coercive fields of 40-50 kV/cm in the forward direction and 50-70 kV/cm in the reverse direction. The remanent polarization varied from 25-35 μC/cm2 and e31,f values were approximately -5.0 C/m2. In scaling up the growth procedure to large area films, where warping becomes more pronounced due to the increased size of the substrate, the pyrolysis and crystallization conditions were performed in a box furnace to improve the temperature uniformity. By depositing films on both sides of the glass substrate, the tensile stresses are balanced, providing a

  17. Chitinozoan faunas from the Rügen Ordovician (Rügen 5/66 and Binz 1/73 wells), NE Germany.

    PubMed

    Samuelsson, J; Verniers, J; Vecoli, M

    2000-12-01

    The island of Rügen (NE Germany), situated close to the Trans-European Suture Zone (TESZ), in the southern Baltic Sea is underlain by sedimentary rocks of an Early Palaeozoic age, known only from boreholes. The wells, Rügen 5/66 and Binz 1/73, were investigated for their chitinozoan assemblages to improve the earlier biostratigraphic dating (graptolites and acritarchs) and to facilitate comparisons with other chitinozoan assemblages on both sides of the TESZ. In the lower part of the Rügen 5/66 core (3794.7-3615.8m), Lagenochitina destombesi Elaouad-Debbaj is indicative of an early late Tremadoc age. In the upper part of the same well (3287.3-1709.7m), the observed chitinozoan taxa suggest an age spanning the early Llanvirn to the Caradoc. The entire sampled interval of the Binz 1/73 core (5217.6-5041.8m) is interpreted as belonging to the Siphonochitina formosa Biozone (early-early late Abereiddian, corresponding to the early Llanvirn). The chitinozoan data corroborate the earlier suggested biostratigraphic ages, based on acritarchs and graptolites. The chitinozoans from the Binz 1/73 well point to a high latitude provenance of the investigated host sediments at time of deposition.

  18. The family Coriobacteriaceae: reclassification of Eubacterium exiguum (Poco et al. 1996) and Peptostreptococcus heliotrinreducens (Lanigan 1976) as Slackia exigua gen. nov., comb. nov. and Slackia heliotrinireducens gen. nov., comb. nov., and Eubacterium lentum (Prevot 1938) as Eggerthella lenta gen. nov., comb. nov.

    PubMed

    Wade, W G; Downes, J; Dymock, D; Hiom, S J; Weightman, A J; Dewhirst, F E; Paster, B J; Tzellas, N; Coleman, B

    1999-04-01

    16S rRNA gene sequences were determined for Eubacterium exiguum and Peptostreptococcus heliotrinreducens. These species were found to be closely related and, together with Eubacterium lentum, to constitute a branch of the Coriobacteriaceae. Two new genera are proposed on the basis of phenotypic characteristics and 16S rRNA gene sequence comparisons: Slackia to include the bile-sensitive species Eubacterium exiguum and P. heliotrinreducens, and Eggerthella to include the bile-resistant Eubacterium lentum. It is proposed that Eubacterium exiguum and Peptostreptococcus heliotrinreducens are transferred to the genus Slackia gen. nov. as Slackia exigua gen. nov., comb. nov. (type strain ATCC 700122T) and Slackia heliotrinireducens gen. nov., comb. nov. (type strain NTCC 11029T), respectively, and Eubacterium lentum is transferred to the genus Eggerthella gen. nov. as Eggerthella lenta gen. nov., comb. nov. with Eggerthella lenta as the type species.

  19. Mobilicoccus pelagius gen. nov., sp. nov. and Piscicoccus intestinalis gen. nov., sp. nov., two new members of the family Dermatophilaceae, and reclassification of Dermatophilus chelonae (Masters et al. 1995) as Austwickia chelonae gen. nov., comb. nov.

    PubMed

    Hamada, Moriyuki; Iino, Takao; Iwami, Takahiro; Harayama, Shigeaki; Tamura, Tomohiko; Suzuki, Ken-ichiro

    2010-01-01

    Two Gram-positive bacteria, designated strains Aji5-31(T) and Ngc37-23(T), were isolated from the intestinal tracts of fishes. 16S rRNA gene sequence analysis indicated that both strains were related to the members of the family Dermatophilaceae, with 95.6-96.9% 16S rRNA gene sequence similarities. The family Dermatophilaceae contains 2 genera and 3 species: Dermatophilus congolensis, Dermatophilus chelonae and Kineosphaera limosa. However, it has been suggested that the taxonomic position of D. chelonae should be reinvestigated using a polyphasic approach, because the chemotaxonomic characteristics are not known (Stackebrandt, 2006; Stackebrandt and Schumann, 2000). Our present study revealed that strains Aji5-31(T), Ngc37-23(T) and D. chelonae NBRC 105200(T) should be separated from the other members of the family Dermatophilaceae on the basis of the following characteristics: the predominant menaquinone of strain Aji5-31(T) is MK-8(H(2)), strain Ngc37-23(T) possesses iso- branched fatty acids as major components, and the menaquinone composition of D. chelonae is MK-8(H(4)), MK-8 and MK-8(H(2)) (5 : 3 : 2, respectively). On the basis of these distinctive phenotypic characteristics and phylogenetic analysis results, it is proposed that strains Aji5-31(T) and Ngc37-23(T) be classified as two novel genera and species of the family Dermatophilaceae. The names are Mobilicoccus pelagius gen. nov., sp. nov. and Piscicoccus intestinalis gen. nov., sp. nov., and the type strains are Aji5-31(T) (=NBRC 104925(T) =DSM 22762(T)) and Ngc37-23(T) (=NBRC 104926(T) =DSM 22761(T)), respectively. In addition, D. chelonae should be reassigned to a new genus of the family Dermatophilaceae with the name Austwickia chelonae gen. nov., comb. nov.

  20. Wukongibacter baidiensis gen. nov., sp. nov., an anaerobic bacterium isolated from hydrothermal sulfides, and proposal for the reclassification of the closely related Clostridium halophilum and Clostridium caminithermale within Maledivibacter gen. nov. and Paramaledivibacter gen. nov., respectively.

    PubMed

    Li, Guangyu; Zeng, Xiang; Liu, Xiupian; Zhang, Xiaobo; Shao, Zongze

    2016-11-01

    An anaerobic, Gram-stain-positive, spore-forming bacterium, designated DY30321T, was isolated from a sample of mixed hydrothermal sulfides collected during cruise DY30 of R/V Da Yang Yi Hao. Cells of strain DY30321T were rod-shaped with rounded ends, and were not motile. Strain DY30321T grew optimally at pH 8.0, at 30 °C and at a salinity (sea salts) of 30-40 g l-1. The principal fatty acids of strain DY30321T were C14 : 0 and summed feature 1 (comprising iso H-C15 : 1/C13 : 0 3-OH). The predominant polar lipids of strain DY30321T were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. No respiratory quinone was detected. The G+C content of the genomic DNA of strain DY30321T was 33.4 mol%. Phylogenetically, strain DY30321T branched within the family Peptostreptococcaceae, with (misclassified) Clostridium halophilum M1T being its closest phylogenetic relative (94.6 % 16S rRNA gene sequence similarity), followed by (misclassified) Clostridium caminithermale DVird3T (92.1 %). These strains showed very low 16S rRNA gene sequence similarity (<84 %) to Clostrdium butyricum ATCC 19398T, the type species of the genus Clostridium sensu stricto. On the basis of its phenotypic, phylogenetic and chemotaxonomic characteristics, strain DY30321T (=KCTC 15549T=MCCC 1A01532T) is considered as the type strain of a novel species of a new genus in the family Peptostreptococcaceae, for which the name Wukongibacterbaidiensis gen. nov., sp. nov. is proposed. Maledivibacter gen. nov. is proposed to accommodate Clostridium halophilum as Maledivibacter halophilus comb. nov. (type species of the genus), and Paramaledivibacter gen. nov. to accommodate Clostridium caminithermale as Paramaledivibacter caminithermalis comb. nov. (type species of the genus).

  1. Revision of "Phyllobrotica" from Taiwan with description of Jolibrotica gen. n. (Coleoptera, Chrysomelidae, Galerucinae).

    PubMed

    Lee, Chi-Feng; Bezděk, Jan

    2015-01-01

    All Taiwanese species formerly classified the genus Phyllobrotica Chevrolat, 1836 are revised. Jolibrotica Lee & Bezděk, gen. n., is described for Phyllobrotica sauteri (Chûjô, 1935) (Taiwan, China: Guangxi) and Phyllobrotica chujoi Kimoto, 1969 (Taiwan). Phyllobrotica shirozui Kimoto, 1969 is transferred to the genus Haplosomoides. All species are redescribed and their diagnostic characters illustrated.

  2. Working with Gen Y Teachers: Dealing with a Changing Teacher Workforce

    ERIC Educational Resources Information Center

    Williamson, Ronald; Meyer-Looze, Catherine

    2010-01-01

    A significant change is coming to American classrooms. As Baby Boomer teachers retire and are replaced by members of Generation Y (born between 1977 and 1995) there is growing evidence that they come from a far different set of experiences, experiences that will shape their lives and their careers (Coggins, 2008). Members of Gen Y share several…

  3. The Esophageal Glands of Pratylenchus Filipjev and Apratylenchoides belli n. gen. n. sp. (Nematoda: Tylenchoidea)

    PubMed Central

    Sher, S. A.

    1973-01-01

    The esophageal glands in the genus Pratylenchus occur in a large, single ventral lobe except for four populations in which a few specimens had the glands located dorsally. Apratylenchoides belli n. gen. n. sp. in the subfamily Radopholinae is proposed for a species having two esophageal glands in a large dorsal lobe and one gland in a smaller, shorter ventral lobe. PMID:19319335

  4. Gen Otto P. Weyland: Close Air Support in the Korean War

    DTIC Science & Technology

    2007-03-01

    over four years. In 1931, the young bachelor got mar- ried and was assigned to Luke Field, Hawaii, where he flew both observa- tion and bombardment...University Press, 1936. Smith, Brig Gen Dale O. U.S. Military Doctrine, A Study and Appraisal. New York: Duell, Sloan and Pearce, Inc., 1955. Smith

  5. [Morphological and histological studies on the Chinese drug shan-dou-gen].

    PubMed

    Fang, L Q; Guo, J X

    1992-01-01

    The Chinese drug "Shan-Dou-Gen" has been used for removing toxic heat, promoting the subsidence of swelling and soothing the sore throat since the ancient time. The authors made a survey of the drug "Shan-Dou-Gen" available in drug markets as well as the plant origin from the drug producing districts. The results showed that the drug "Shan-Dou-Gen" used in different regions in China at present are the roots or rhizomes derived from 9 species: Sophora tonkinensis Gagnep. (Leguminosae), Menispermum dauricum DC. (Menispermaceae), Indigofera amblyantha Craib (Leguminosae), I. carlesii Carib, I., fortunei Craib, I. decoa Lindl. var. ichangensis Y. Y. Fang et C. Z. Zheng, I. kirilowii Maxim. et Palibin, I. potaninii Craib, and Beesia calthaefolia (Maxim.) Ulbr. (Ranuculaceae). In this paper, the morphological characters of the crude drugs are described, compared and illustrated with photographs. The histological structures of the used parts are described, compared and illustrated with line drawings. The morphological and histological similarities and differences found among the above 9 species are summarized, and the key for the identification of the crude drugs is provided. As the drug "Shan-Dou-Gen" derived from different species has different actions and dosages, it is necessary to give different names to different species and use them correctly.

  6. A gilled mushroom, Gerontomyces lepidotus gen. et sp. nov. (Basidiomycota: Agaricales), in Baltic amber.

    PubMed

    Poinar, George

    2016-09-01

    A densely scaled small mushroom in Baltic amber is described as Gerontomyces lepidotus gen. et sp. nov. and is characterized by a convex pileus 1.0 mm in diameter, distant to subdistant lamellae with smooth margins and a centrally inserted cylindrical, solid stipe. Its taxonomic placement is uncertain. This is the first mushroom described from Baltic amber.

  7. pGenN, a Gene Normalization Tool for Plant Genes and Proteins in Scientific Literature

    PubMed Central

    Ding, Ruoyao; Arighi, Cecilia N.; Lee, Jung-Youn; Wu, Cathy H.; Vijay-Shanker, K.

    2015-01-01

    Background Automatically detecting gene/protein names in the literature and connecting them to databases records, also known as gene normalization, provides a means to structure the information buried in free-text literature. Gene normalization is critical for improving the coverage of annotation in the databases, and is an essential component of many text mining systems and database curation pipelines. Methods In this manuscript, we describe a gene normalization system specifically tailored for plant species, called pGenN (pivot-based Gene Normalization). The system consists of three steps: dictionary-based gene mention detection, species assignment, and intra species normalization. We have developed new heuristics to improve each of these phases. Results We evaluated the performance of pGenN on an in-house expertly annotated corpus consisting of 104 plant relevant abstracts. Our system achieved an F-value of 88.9% (Precision 90.9% and Recall 87.2%) on this corpus, outperforming state-of-art systems presented in BioCreative III. We have processed over 440,000 plant-related Medline abstracts using pGenN. The gene normalization results are stored in a local database for direct query from the pGenN web interface (proteininformationresource.org/pgenn/). The annotated literature corpus is also publicly available through the PIR text mining portal (proteininformationresource.org/iprolink/). PMID:26258475

  8. FutureGen: Pathway to Near-Zero Emissions and Sustainable Energy

    SciTech Connect

    Zitney, S E; Sarkus, T A

    2007-11-04

    This presentation will highlight the U.S. Department of Energy’s (DOE) FutureGen project - a $1 billion government-industry partnership to design, build, and operate a near-zero emissions coal-fueled power plant. The lead organization for the FutureGen initiative is the National Energy Technology Laboratory (NETL), a multi-purpose laboratory operated by the U.S. DOE’s Office of Fossil Energy. NETL has a mission to conduct R&D from fundamental science to technology demonstration for resolving the environmental, supply, and reliability constraints of producing and using fossil energy resources. The commercial-scale FutureGen R&D facility is a pathway toward future fossil-energy power plants that will produce hydrogen and electricity while nearly eliminating emissions, including carbon dioxide. The 275-megawatt FutureGen plant will initiate operations around 2012 and employ advanced coal gasification technology integrated with combined cycle electricity generation, hydrogen production, and carbon capture and sequestration. Low carbon emissions would be achieved by integrating CO2 capture and sequestration operations with the power plant.

  9. CottonGen: a genomics, genetics and breeding database for cotton research

    PubMed Central

    Yu, Jing; Jung, Sook; Cheng, Chun-Huai; Ficklin, Stephen P.; Lee, Taein; Zheng, Ping; Jones, Don; Percy, Richard G.; Main, Dorrie

    2014-01-01

    CottonGen (http://www.cottongen.org) is a curated and integrated web-based relational database providing access to publicly available genomic, genetic and breeding data for cotton. CottonGen supercedes CottonDB and the Cotton Marker Database, with enhanced tools for easier data sharing, mining, visualization and data retrieval of cotton research data. CottonGen contains annotated whole genome sequences, unigenes from expressed sequence tags (ESTs), markers, trait loci, genetic maps, genes, taxonomy, germplasm, publications and communication resources for the cotton community. Annotated whole genome sequences of Gossypium raimondii are available with aligned genetic markers and transcripts. These whole genome data can be accessed through genome pages, search tools and GBrowse, a popular genome browser. Most of the published cotton genetic maps can be viewed and compared using CMap, a comparative map viewer, and are searchable via map search tools. Search tools also exist for markers, quantitative trait loci (QTLs), germplasm, publications and trait evaluation data. CottonGen also provides online analysis tools such as NCBI BLAST and Batch BLAST. PMID:24203703

  10. Plant MetGenMAP: an integrative analysis system for plant systems biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have developed a web-based system, Plant MetGenMAP, which can identify significantly altered biochemical pathways and highly affected biological processes, predict functional roles of pathway genes, and potential pathway-related regulatory motifs from transcript and metabolite profile datasets. P...

  11. Characterization and design of the FutureGen 2.0 carbon storage site

    SciTech Connect

    Gilmore, Tyler; Bonneville, Alain; Sullivan, Charlotte; Kelley, Mark; Appriou, Delphine; Vermeul, Vince; White, Signe; Zhang, Fred; Bjornstad, Bruce; Cornet, Francois; Gerst, Jacqueline; Gupta, Neeraj; Hund, Gretchen; Horner, Jake; Last, George; Lanigan, Dave; Oostrom, Mart; McNeil, Caitlin; Moody, Mark; Rockhold, Mark; Elliott, Mike; Spane, Frank; Strickland, Chris; Swartz, Lucy; Thorne, Paul; Brown, Christopher; Hoffmann, Jeffrey; Humphreys, Kenneth

    2016-10-01

    The objective of the FutureGen 2.0 Project was to demonstrate, at the commercial scale, the technical feasibility of implementing carbon capture and storage (CCS) in a deep saline formation in Illinois, USA. Over approximately 5 years, the FutureGen Alliance conducted a detailed site-selection process and identified a site for carbon sequestration storage in Morgan County, Illinois. The storage site was fully characterized, including the collection of seismic data and the drilling and characterization of a stratigraphic borehole. The characterization data provided critical input for developing a site-specific conceptual model and subsequent numerical modeling simulations. The modeling simulations, coupled with the upstream designs of the pipeline and power plant supported the development of a detailed 90 percent design that included the injection wells and associated control and monitoring infrastructure. Collectively, all these data were used by the FutureGen Alliance to develop the required documentation to support the applications for four underground injection control (UIC) permits (one for each proposed well). In August 2014, the U.S. Environmental Protection Agency issued four, first-of-their-kind, Class VI UIC permits for carbon sequestration in the United States to the FutureGen Alliance. The information and data generated under this project have been made publically available through reports and publications, including this journal and others.

  12. FY13 Annual Report: PHEV Advanced Series Gen-set Development/Demonstration Activity

    SciTech Connect

    Chambon, Paul H.

    2013-12-01

    The objective of this project is to integrate ORNL advancements in vehicle technologies to properly design, and size a gen-set for various vehicle applications and then simulate multiple advanced series hybrid (HEV/PHEV) vehicles with the genset models.

  13. Revision of “Phyllobrotica” from Taiwan with description of Jolibrotica gen. n. (Coleoptera, Chrysomelidae, Galerucinae)

    PubMed Central

    Lee, Chi-Feng; Bezděk, Jan

    2015-01-01

    Abstract All Taiwanese species formerly classified the genus Phyllobrotica Chevrolat, 1836 are revised. Jolibrotica Lee & Bezděk, gen. n., is described for Phyllobrotica sauteri (Chûjô, 1935) (Taiwan, China: Guangxi) and Phyllobrotica chujoi Kimoto, 1969 (Taiwan). Phyllobrotica shirozui Kimoto, 1969 is transferred to the genus Haplosomoides. All species are redescribed and their diagnostic characters illustrated. PMID:26798315

  14. List of Predicted Simple Sequence Repeats from Sugar Beet GenBank Accessions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beta vulgaris ESTs from GenBank as of January 2005 collapsed into 13,618 unique clusters (4,023 Tentative Consensus sequences, 9,595 singletons), and 35% were contributed via work partially supported through the BSDF. These sequences were parsed through SSR-Primer software for discovering potential...

  15. Macrostylopyga gen. nov., a new genus of cockroaches (Dictyoptera: Blattidae), with descriptions of two new species.

    PubMed

    Anisyutkin, Leonid N; Anichkin, Alexandr E; Thinh, Nguyen Van

    2013-01-01

    The genus Macrostylopyga gen. nov. and two species (M. grandis sp. nov. and M. bidupi sp. nov.) are described. A detailed morphological description with special attention to the male genitalic structures is provided. Some aspects of the evolution of wingless cockroaches are briefly discussed.

  16. Visualizing and Sharing Results in Bioinformatics Projects: GBrowse and GenBank Exports

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effective tools for presenting and sharing data are necessary for collaborative projects, typical for bioinformatics. In order to facilitate sharing our data with other genomics, molecular biology, and bioinformatics researchers, we have developed software to export our data to GenBank and combined ...

  17. Oswaldotrema nacinovici gen. nov. sp. nov. (Digenea: Philophthalmidae) from Numenius phaeopus (Aves: Scolopacidae) in Brazil.

    PubMed

    Muniz-Pereira, L C; Pinto, R M

    2000-01-01

    A new genus, Oswaldotrema gen. nov. is proposed. Oswaldotrema nacinovici sp. nov. is descibed from Numenius phaeopus Latham, 1790. Differentiation from the other related genera, namely Philophthalmus, Pygorchis, Proctobium, Parorchis, Echinostephila, Cloacitrema, Pittacium, Ophthalmotrema, Skrjabinovermis and Paratrema, was based on morphological characters, mainly on those referring to the body surface, body shape, head, esophagus, pharynx, acetabulum, vitellaria, vitelline reservoir and seminal vesicle.

  18. Gen Y Recruitment: Understanding Graduate Intentions to Join an Organisation Using the Theory of Planned Behaviour

    ERIC Educational Resources Information Center

    Warmerdam, Amanda; Lewis, Ioni; Banks, Tamara

    2015-01-01

    Purpose: Using the Theory of Planned Behaviour (TPB) framework, the purpose of this paper is to explore whether the standard TPB constructs explained variance in Generation Y (Gen Y) individuals' intentions to join their ideal organisation. Design/methodology/approach: A mixed methods approach was used featuring qualitative and quantitative…

  19. The GenTechnique Project: Developing an Open Environment for Learning Molecular Genetics.

    ERIC Educational Resources Information Center

    Calza, R. E.; Meade, J. T.

    1998-01-01

    The GenTechnique project at Washington State University uses a networked learning environment for molecular genetics learning. The project is developing courseware featuring animation, hyper-link controls, and interactive self-assessment exercises focusing on fundamental concepts. The first pilot course featured a Web-based module on DNA…

  20. Targeted Amplicon Sequencing (TAS): A Scalable Next-Gen Approach to Multilocus, Multitaxa Phylogenetics

    PubMed Central

    Bybee, Seth M.; Bracken-Grissom, Heather; Haynes, Benjamin D.; Hermansen, Russell A.; Byers, Robert L.; Clement, Mark J.; Udall, Joshua A.; Wilcox, Edward R.; Crandall, Keith A.

    2011-01-01

    Next-gen sequencing technologies have revolutionized data collection in genetic studies and advanced genome biology to novel frontiers. However, to date, next-gen technologies have been used principally for whole genome sequencing and transcriptome sequencing. Yet many questions in population genetics and systematics rely on sequencing specific genes of known function or diversity levels. Here, we describe a targeted amplicon sequencing (TAS) approach capitalizing on next-gen capacity to sequence large numbers of targeted gene regions from a large number of samples. Our TAS approach is easily scalable, simple in execution, neither time-nor labor-intensive, relatively inexpensive, and can be applied to a broad diversity of organisms and/or genes. Our TAS approach includes a bioinformatic application, BarcodeCrucher, to take raw next-gen sequence reads and perform quality control checks and convert the data into FASTA format organized by gene and sample, ready for phylogenetic analyses. We demonstrate our approach by sequencing targeted genes of known phylogenetic utility to estimate a phylogeny for the Pancrustacea. We generated data from 44 taxa using 68 different 10-bp multiplexing identifiers. The overall quality of data produced was robust and was informative for phylogeny estimation. The potential for this method to produce copious amounts of data from a single 454 plate (e.g., 325 taxa for 24 loci) significantly reduces sequencing expenses incurred from traditional Sanger sequencing. We further discuss the advantages and disadvantages of this method, while offering suggestions to enhance the approach. PMID:22002916

  1. Builders Challenge High Performance Builder Spotlight - NextGen Home, Las Vegas, Nevada

    SciTech Connect

    2009-01-01

    Building America Builders Challenge fact sheet on the NextGen demo home built in Las Vegas. The home has a Home Energy Rating System (HERS) index score of 44 with R-40 spray foam attic insulation, R-40 insulated concrete walls, and a 4kW DC solar laminate

  2. Microcetus lappus gen. nov., sp. nov.: new species of ciliated protozoon from the bovine rumen.

    PubMed Central

    Orpin, C G; Mathiesen, S D

    1986-01-01

    A new species of small, ciliated protozoon, Microcetus lappus gen. nov., sp. nov., from the rumen of Norwegian Red cattle is described. M. lappus possesses a novel cytopharyngeal apparatus of two rod-shaped structures, one situated on the dorsal side of the buccal cavity and one on the ventral side, suggesting that it belongs to a previously undescribed taxon. Images PMID:3094449

  3. GenGIS 2: Geospatial Analysis of Traditional and Genetic Biodiversity, with New Gradient Algorithms and an Extensible Plugin Framework

    PubMed Central

    Parks, Donovan H.; Mankowski, Timothy; Zangooei, Somayyeh; Porter, Michael S.; Armanini, David G.; Baird, Donald J.; Langille, Morgan G. I.; Beiko, Robert G.

    2013-01-01

    GenGIS is free and open source software designed to integrate biodiversity data with a digital map and information about geography and habitat. While originally developed with microbial community analyses and phylogeography in mind, GenGIS has been applied to a wide range of datasets. A key feature of GenGIS is the ability to test geographic axes that can correspond to routes of migration or gradients that influence community similarity. Here we introduce GenGIS version 2, which extends the linear gradient tests introduced in the first version to allow comprehensive testing of all possible linear geographic axes. GenGIS v2 also includes a new plugin framework that supports the development and use of graphically driven analysis packages: initial plugins include implementations of linear regression and the Mantel test, calculations of alpha-diversity (e.g., Shannon Index) for all samples, and geographic visualizations of dissimilarity matrices. We have also implemented a recently published method for biomonitoring reference condition analysis (RCA), which compares observed species richness and diversity to predicted values to determine whether a given site has been impacted. The newest version of GenGIS supports vector data in addition to raster files. We demonstrate the new features of GenGIS by performing a full gradient analysis of an Australian kangaroo apple data set, by using plugins and embedded statistical commands to analyze human microbiome sample data, and by applying RCA to a set of samples from Atlantic Canada. GenGIS release versions, tutorials and documentation are freely available at http://kiwi.cs.dal.ca/GenGIS, and source code is available at https://github.com/beiko-lab/gengis. PMID:23922841

  4. Transfer of Pseudomonas flectens Johnson 1956 to Phaseolibacter gen. nov., in the family Enterobacteriaceae, as Phaseolibacter flectens gen. nov., comb. nov.

    PubMed

    Halpern, Malka; Fridman, Svetlana; Aizenberg-Gershtein, Yana; Izhaki, Ido

    2013-01-01

    Pseudomonas flectens Johnson 1956, a plant-pathogenic bacterium on the pods of the French bean, is no longer considered to be a member of the genus Pseudomonas sensu stricto. A polyphasic approach that included examination of phenotypic properties and phylogenetic analyses based on 16S rRNA, rpoB and atpD gene sequences supported the transfer of Pseudomonas flectens Johnson 1956 to a new genus in the family Enterobacteriaceae as Phaseolibacter flectens gen. nov., comb. nov. Two strains of Phaseolibacter flectens were studied (ATCC 12775(T) and LMG 2186); the strains shared 99.8 % sequence similarity in their 16S rRNA genes and the housekeeping gene sequences were identical. Strains of Phaseolibacter flectens shared 96.6 % or less 16S rRNA gene sequence similarity with members of different genera in the family Enterobacteriaceae and only 84.7 % sequence similarity with Pseudomonas aeruginosa LMG 1242(T), demonstrating that they are not related to the genus Pseudomonas. As Phaseolibacter flectens formed an independent phyletic lineage in all of the phylogenetic analyses, it could not be affiliated to any of the recognized genera within the family Enterobacteriaceae and therefore was assigned to a new genus. Cells were Gram-negative, straight rods, motile by means of one or two polar flagella, fermentative, facultative anaerobes, oxidase-negative and catalase-positive. Growth occurred in the presence of 0-60 % sucrose. The DNA G+C content of the type strain was 44.3 mol%. On the basis of phenotypic properties and phylogenetic distinctiveness, Pseudomonas flectens Johnson 1956 is transferred to the novel genus Phaseolibacter gen. nov. as Phaseolibacter flectens gen. nov., comb. nov. The type strain of Phaseolibacter flectens is ATCC 12775(T) = CFBP 3281(T) = ICMP 745(T) = LMG 2187(T) = NCPPB 539(T).

  5. Libkindia masarykiana gen. nov. et sp. nov., Yurkovia mendeliana gen. nov. et sp. nov., and Leucosporidium krtinense f.a. sp. nov., isolated from temperate forest soils.

    PubMed

    Mašínová, Tereza; Pontes, Ana; Carvalho, Cláudia; Sampaio, José Paulo; Baldrian, Petr

    2016-11-30

    One hundred and ninety-eight isolates of soil yeasts were isolated from mixed temperate forests in the Czech Republic, and their abundance and distribution in the litter and soil were evaluated using amplicon sequencing of soil fungal communities. Abundant taxa with no close identified hits were selected for further characterization as potential novel species of yeasts. Phylogenetic analyses using sequences of the D1/D2 domains, the ITS region and RPB1 and TEF1 genes support the recognition of the following three new species belonging to the subphylum Pucciniomycotina, class Microbotryomycetes: Leucosporidium krtinense f.a. sp. nov. (type strain CBS 14304T = PYCC 6879T = DSM 101892T), Yurkovia mendeliana sp. nov. (type strain CBS 14273T = PYCC 6884T = DSM 101889T), and Libkindia masarykiana sp. nov. (type strain CBS 14275T = PYCC 6886T = DSM 101891T). Since the later two novel taxa cannot be assigned to existing genera, two new genera, Libkindia gen. nov. and Yurkovia gen. nov. are also described.

  6. Molecular phylogeny of Urosomoida agilis, and new combinations: Hemiurosomoida longa gen. nov., comb. nov., and Heterourosomoida lanceolata gen. nov., comb. nov. (Ciliophora, Hypotricha).

    PubMed

    Singh, Jasbir; Kamra, Komal

    2015-02-01

    For years, systematics of three species, Urosomoida agilis (Engelmann, 1862) Hemberger in Foissner, 1982, Urosomoida longa (Gelei and Szabados, 1950) Foissner et al., 1991 and Oxytricha lanceolata Shibuya, 1930, has remained unresolved due to lack of adequate molecular data. Though, it is known since several years that the three species are not very closely related. In the present paper, 18S rRNA gene sequences for two key species, U. agilis and U. longa, and their morphology and morphometry have been analyzed. Molecular phylogeny inferred from maximum likelihood, neighbour joining and maximum parsimony methods has adequately removed ambiguity over their systematics. In phylogenetic trees, U. agilis clustered consistently with non-stylonychine oxytrichids. Both Urosomoida longa and Oxytricha lanceolata clustered consistently away from U. agilis and O. granulifera, the type species of the genera Urosomoida and Oxytricha, respectively. As a result of the current molecular phylogenetic investigation and based on previously inferred morphological and morphogenetic data it is proposed to remove Urosomoida longa and Oxytricha lanceolata from Urosomoida and incertae sedis in Oxytricha, respectively, and establish two new generic combinations, Hemiurosomoida longa gen. nov., comb. nov. and Heterourosomoida lanceolata gen. nov., comb. nov. for them.

  7. Phyllonema aviceniicola gen. et sp. nov. and Foliisarcina bertiogensis gen. et. sp. nov., novel epiphyllic cyanobacteria associated with Avicennia schaueriana leaves.

    PubMed

    Alvarenga, Danillo Oliveira; Rigonato, Janaina; Branco, Luis Henrique Zanini; Melo, Itamar Soares; Fiore, Marli Fatima

    2015-11-17

    Cyanobacteria dwelling on the salt-excreting leaves of the mangrove tree Avicennia schaueriana were isolated and characterized by ecological, morphological, and genetic approaches. Leaves were collected in a mangrove with a history of oil contamination in the coastline of São Paulo state, Brazil, and isolation was achieved by smearing leaves on the surface of solid media or by submerging leaves in liquid media. Twenty-nine strains isolated were shown to belong to four cyanobacterial orders (thirteen Synechococcales, seven Nostocales, seven Pleurocapsales, one Chroococcales, and one Oscillatoriales) according to morphological and 16S rDNA sequence evaluations. More detailed investigations pointed six Rivulariacean and four Xenococcacean strains as novel taxa. These strains were classified as Phyllonema gen. nov. (type-species P. aviceniicola sp. nov.) and Foliisarcina gen. nov. (type-species F. bertiogensis sp. nov.) according to the International Code of Nomenclature for Algae, Fungi, and Plants. This investigation shows some of the unique cyanobacteria inhabiting the phyllosphere of A. schaueriana can be retrieved by culturing techniques, improving current taxonomy and providing new insights into the evolution, ecology, and biogeography of this phylum.

  8. Roseimaritima ulvae gen. nov., sp. nov. and Rubripirellula obstinata gen. nov., sp. nov. two novel planctomycetes isolated from the epiphytic community of macroalgae.

    PubMed

    Bondoso, Joana; Albuquerque, Luciana; Nobre, M Fernanda; Lobo-da-Cunha, Alexandre; da Costa, Milton S; Lage, Olga Maria

    2015-02-01

    Four isolates, belonging to the deep-branching phylum Planctomycetes, were recovered from the biofilm of two marine macroalgae, Ulva sp. and Laminaria sp., from the Northern coast of Portugal. These strains were light pink- or red-pigmented; the cells were variable in shape and usually organized in rosettes. They had a dimorphic cell cycle with budding reproduction. The organisms were chemoheterotrophic, strictly aerobic and mesophilic. The 16S rRNA gene sequence analysis showed that the strains belong to the family Planctomycetaceae with Rhodopirellula as the closest genus. The isolates form two separate branches (strain LF1(T) forms one branch and the strains UC8(T), UF3 and UF42 form a second branch) clearly separated from Rhodopirellula baltica with 94.2% and 93.8% 16S rRNA gene sequence similarity, respectively. Based on differential characteristics that distinguish the novel genera from R. baltica, such as cell size and shape, ultrastructure, enzymatic activities, substrate utilization pattern, fatty acid composition, phospholipid profiles and phylogeny we propose that the isolates represent two novel genera of the order Planctomycetales, Roseimaritima ulvae gen. nov., sp. nov. (type strain is UC8(T)=DSM 25454(T)=LMG 27778(T)) and Rubripirellula obstinata gen. nov., sp. nov. (type strain is LF1(T)=LMG 27779(T)=CECT 8602(T)).

  9. Two New Freshwater Woloszynskioids Asulcocephalium miricentonis gen. et sp. nov. and Leiocephalium pseudosanguineum gen. et sp. nov. (Suessiaceae, Dinophyceae) Lacking an Apical Furrow Apparatus.

    PubMed

    Takahashi, Kazuya; Moestrup, Øjvind; Jordan, Richard W; Iwataki, Mitsunori

    2015-12-01

    Two new woloszynskioid dinoflagellates, Asulcocephalium miricentonis gen. et sp. nov. and Leiocephalium pseudosanguineum gen. et sp. nov., are described from Japanese freshwater ponds on the basis of bright field and fluorescence light microscopy, scanning and transmission electron microscopy, and molecular phylogeny inferred from rDNA sequences. Asulcocephalium miricentonis has a spherical anterior nucleus and chloroplast with a pyrenoid penetrated by the cytoplasm. This species has 9-12 latitudinal series of amphiesmal vesicles (AVs), including an apparently large AV on the right ventral side of the epicone. Leiocephalium pseudosanguineum has a U-shaped nucleus in the epicone and chloroplasts without a pyrenoid. This species has at least 24 latitudinal series of AVs. The characteristic features of both species were brick-like material (type E) in the eyespot and the lack of an apical furrow. These features coincide with those of Polarella glacialis, but the two species differ in cell shape, number and arrangement of AVs, shape of resting cysts, and habitats; i.e., P. glacialis has been reported only from marine cold waters. Molecular phylogeny revealed that A. miricentonis and L. pseudosanguineum were positioned in the Suessiaceae and closely related to Piscinoodinium sp., but their relationship to Polarella and other reported taxa was not supported.

  10. Taxonomic revision of Chlamydomonas subg. Amphichloris (Volvocales, Chlorophyceae), with resurrection of the genus Dangeardinia and descriptions of Ixipapillifera gen. nov. and Rhysamphichloris gen. nov.

    PubMed

    Nakada, Takashi; Tomita, Masaru; Wu, Jiunn-Tzong; Nozaki, Hisayoshi

    2016-04-01

    Chlamydomonas (Cd.) is one of the largest but most polyphyletic genera of freshwater unicellular green algae. It consists of 400-600 morphological species and requires taxonomic revision. Toward reclassification, each morphologically defined classical subgenus (or subgroup) should be examined using culture strains. Chlamydomonas subg. Amphichloris is characterized by a central nucleus between two axial pyrenoids, however, the phylogenetic structure of this subgenus has yet to be examined using molecular data. Here, we examined 12 strains including six newly isolated strains, morphologically identified as Chlamydomonas subg. Amphichloris, using 18S rRNA gene phylogeny, light microscopy, and mitochondria fluorescent microscopy. Molecular phylogenetic analyses revealed three independent lineages of the subgenus, separated from the type species of Chlamydomonas, Cd. reinhardtii. These three lineages were further distinguished from each other by light and fluorescent microscopy-in particular by the morphology of the papillae, chloroplast surface, stigmata, and mitochondria-and are here assigned to three genera: Dangeardinia emend., Ixipapillifera gen. nov., and Rhysamphichloris gen. nov. Based on the molecular and morphological data, two to three species were recognized in each genus, including one new species, I. pauromitos. In addition, Cd. deasonii, which was previously assigned to subgroup "Pleiochloris," was included in the genus Ixipapillifera as I. deasonii comb. nov.

  11. Wilsonosiphonia gen. nov. (Rhodomelaceae, Rhodophyta) based on molecular and morpho-anatomical characters.

    PubMed

    Bustamante, Danilo E; Won, Boo Yeon; Miller, Kathy Ann; Cho, Tae Oh

    2017-01-12

    Morphological, anatomical, and molecular sequence data were used to assess the establishment and phylogenetic position of the genus Wilsonosiphonia gen. nov. Phylogenies based on rbcL and concatenated rbcL and cox1 loci support recognition of Wilsonosiphonia gen. nov., sister to Herposiphonia. Diagnostic features for Wilsonosiphonia are rhizoids located at distal ends of pericentral cells and taproot-shaped multicellular tips of rhizoids. Wilsonosiphonia includes three species with diagnostic rbcL and cox1 sequences, Wilsonosiphonia fujiae sp. nov. (the generitype), W. howei comb. nov., and W. indica sp. nov. These three species resemble each other in external morphology, but W. fujiae is distinguished by having two tetrasporangia per segment rather than one, W. indica by having abundant and persistent trichoblasts, and W. howei by having few and deciduous trichoblasts.

  12. Internal combustion engine report: Spark ignited ICE GenSet optimization and novel concept development

    SciTech Connect

    Keller, J.; Blarigan, P. Van

    1998-08-01

    In this manuscript the authors report on two projects each of which the goal is to produce cost effective hydrogen utilization technologies. These projects are: (1) the development of an electrical generation system using a conventional four-stroke spark-ignited internal combustion engine generator combination (SI-GenSet) optimized for maximum efficiency and minimum emissions, and (2) the development of a novel internal combustion engine concept. The SI-GenSet will be optimized to run on either hydrogen or hydrogen-blends. The novel concept seeks to develop an engine that optimizes the Otto cycle in a free piston configuration while minimizing all emissions. To this end the authors are developing a rapid combustion homogeneous charge compression ignition (HCCI) engine using a linear alternator for both power take-off and engine control. Targeted applications include stationary electrical power generation, stationary shaft power generation, hybrid vehicles, and nearly any other application now being accomplished with internal combustion engines.

  13. Towards Structuring Unstructured GenBank Metadata for Enhancing Comparative Biological Studies.

    PubMed

    Chen, Elizabeth S; Sarkar, Indra Neil

    2011-01-01

    Within large sequence repositories such as GenBank there is a wealth of metadata providing contextual information that may enhance search and retrieval of relevant sequences for a range of subsequent analyses. One challenge is the use of free-text in these metadata fields where approaches are needed to extract, structure, and encode essential information. The goal of the present study was to explore the feasibility of using a combination of existing resources for annotating unstructured GenBank metadata, initially focusing on the "host" and "isolation_source" fields. This paper summarizes early results for 10 host organisms that include a characterization of associated isolation sources with respect to biomedical ontologies and semantic types. The findings from this preliminary study provide insights to the rich amount of information captured within these unstructured metadata, guidance for addressing the challenges and issues encountered, and highlight the potential value for enriching comparative biological studies towards improving human health.

  14. Gen 2.0 Mixer/Ejector Nozzle Test at LSAF June 1995 to July 1996

    NASA Technical Reports Server (NTRS)

    Arney, L. D.; Sandquist, D. L.; Forsyth, D. W.; Lidstone, G. L.; Long-Davis, Mary Jo (Technical Monitor)

    2005-01-01

    Testing of the HSCT Generation 2.0 nozzle model hardware was conducted at the Boeing Low Speed Aeroacoustic Facility, LSAF. Concurrent measurements of noise and thrust were made at critical takeoff design conditions for a variety of mixer/ejector model hardware. Design variables such as suppressor area ratio, mixer area ratio, liner type and thickness, ejector length, lobe penetration, and mixer chute shape were tested. Parallel testing was conducted at G.E.'s Cell 41 acoustic free jet facility to augment the LSAF test. The results from the Gen 2.0 testing are being used to help shape the current nozzle baseline configuration and guide the efforts in the upcoming Generation 2.5 and 3.0 nozzle tests. The Gen 2.0 results have been included in the total airplane system studies conducted at MDC and Boeing to provide updated noise and thrust performance estimates.

  15. Parametric Modeling of the Safety Effects of NextGen Terminal Maneuvering Area Conflict Scenarios

    NASA Technical Reports Server (NTRS)

    Rogers, William H.; Waldron, Timothy P.; Stroiney, Steven R.

    2011-01-01

    The goal of this work was to analytically identify and quantify the issues, challenges, technical hurdles, and pilot-vehicle interface issues associated with conflict detection and resolution (CD&R)in emerging operational concepts for a NextGen terminal aneuvering area, including surface operations. To this end, the work entailed analytical and trade studies focused on modeling the achievable safety benefits of different CD&R strategies and concepts in the current and future airport environment. In addition, crew-vehicle interface and pilot performance enhancements and potential issues were analyzed based on review of envisioned NextGen operations, expected equipage advances, and human factors expertise. The results of perturbation analysis, which quantify the high-level performance impact of changes to key parameters such as median response time and surveillance position error, show that the analytical model developed could be useful in making technology investment decisions.

  16. A REVIEW PAPER ON AGING EFFECTS IN ALLOY 617 FOR GEN IVNUCLEAR REACTOR APPLICATIONS

    SciTech Connect

    Ren, Weiju; Swindeman, Robert W

    2009-01-01

    To understand the response of Alloy 617 to long-time exposure conditions and determine the supplementary data needs for structural components in Gen IV nuclear reactors, the literature of aging and aging effects in the alloy was reviewed. Most of the reviewed data were produced in connection with the international research effort supporting High Temperature Gas-Cooled Reactor (HTGR) projects in the 1970s and 1980s. Topics considered included microstructural changes, hardness, tensile properties, toughness, creep-rupture, fatigue, and crack growth. It became clear that, for the long-time, very high temperature conditions of the Gen IV reactors, a significant effort would be needed to fully understand and characterize property changes. Several topics for further research were recommended.

  17. Mercury: Next-gen Data Analysis and Annotation Pipeline (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    SciTech Connect

    Sexton, David

    2012-06-01

    David Sexton (Baylor) gives a talk titled "Mercury: Next-gen Data Analysis and Annotation Pipeline" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  18. No quenching of magnetic moment for the GenCo (n=1-13) clusters: First-principles calculations

    NASA Astrophysics Data System (ADS)

    Jing, Qun; Tian, Fu-yang; Wang, Yuan-xu

    2008-03-01

    The authors predict that for the GenCo (n=1-13) clusters the magnetic moment does not quench, which is dark contrast to the previous results with transition-metal-doped Sin clusters. It may be due to the unpaired electrons of the Co atom in the clusters. For the ground state structures of the GenCo (n⩾9) clusters, the Co atom completely falls into the center of the Ge outer frame, forming metal-encapsulated Gen cages. The doping of the Co atom enhances the stability of the host Gen clusters. The Ge10Co cluster with the bicapped tetragonal antiprism structure is more stable than others, which agrees very well with the results of the experiment of the Co /Ge binary clusters by the laser vaporization.

  19. Mercury: Next-gen Data Analysis and Annotation Pipeline (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    ScienceCinema

    Sexton, David [Baylor

    2016-07-12

    David Sexton (Baylor) gives a talk titled "Mercury: Next-gen Data Analysis and Annotation Pipeline" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  20. Squamasnema amazonica n. gen. n. sp. (Heligmonellinae): A new parasite of Proechimys roberti (Rodentia: Echimyidae) in the Brazilian Amazon.

    PubMed

    Cordeiro, Helrik da Costa; Melo, Francisco Tiago de Vasconcelos; Furtado, Adriano Penha; Giese, Elane Guerreiro; Maldonado, Arnaldo; dos Santos, Jeannie Nascimento

    2015-08-01

    A new species of nematode, Squamasnema amazonica n. gen. n. sp., is described based on specimens found parasitizing the small intestine of Proechimys roberti (Rodentia: Echimyidae) collected during a survey of the fauna of Tapirapé-Aquirí National Forest (Brazil, Eastern Brazilian Amazon). The nematodes were fixed and processed for light microscopy and scanning electron microscopy (SEM). These nematodes were classified under the family Heligmonellidae and the subfamily Heligmonellinae. Although several species in the family Heligmonellidae exhibit discontinuous ridges, Squamasnema n. gen. and Trichotravassosia are the only genera with columns of scales along their entire body, as an apomorphy of the synlophe. Squamasnema n. gen. has columns of cuticular cells along its body, except for on the left flank, and exhibits a synlophe with no size gradient or inclination and does not present chitinized structures supporting the synlophe. Therefore, due to these morphological differences of Squamasnema n. gen., the creation of a new genus was necessary.

  1. 78 FR 56263 - HydroGen Corp., QueryObject Systems Corp., Security Intelligence Technologies, Inc., Skins, Inc...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-12

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION HydroGen Corp., QueryObject Systems Corp., Security Intelligence Technologies, Inc., Skins, Inc... and accurate information concerning the securities of Security Intelligence Technologies, Inc....

  2. Development of an Enhanced GenVARR™ (Generator Volt Ampere Reactive Reserve) System

    SciTech Connect

    Schatz, Joe E.

    2009-03-12

    Transmission system operators require near real time knowledge of reactive power capability to reliably operate large electric power transmission systems. Reactive power produced by, or capable of being produced by, a power generator is often estimated based on a series of mega volt amperes (MVA) capability curves for the generator. These curves indicate the ability of the generator to produce real and reactive power under a variety of conditions. In transmission planning and operating studies, it is often assumed, based on estimates for these capability curves, that the generator can provide its rated MVA capability output when needed for system stability However, generators may not always operate at levels depicted by the maximum MVA capability curve due to present constraints. Transmission system operators utilizing the generators’ capability curves for operation decisions regarding transmission system stability or for planning horizons may overestimate the capability of the generators to supply reactive power when required. Southern Company has enhanced GenVARR(TM), the system of plant data query, retrieval, and analysis and calculates the actual – not estimated -- remaining reactive power output capability. The remaining reactive output is considered spinning reserve and is displayed graphically to transmission control center and generating plant operators to identify real time VAR limits. GenVARR is capable of aggregating generators from a defined region, or other user selectable combinations, to represent the available reserves that the operators are specifically interested in. GenVARR(TM) has been put into live production operation and is expected to significantly improve the overall visibility of the reactive reserve capability of the system. This new version of GenVARR(TM) significantly enhances the products structure and performance, and enables links to other key transmission system operation tools.

  3. Implementing genetic education in primary care: the Gen-Equip programme.

    PubMed

    Paneque, Milena; Cornel, Martina C; Curtisova, Vaclava; Houwink, Elisa; Jackson, Leigh; Kent, Alastair; Lunt, Peter; Macek, Milan; Stefansdottir, Vigdis; Turchetti, Daniela; Skirton, Heather

    2017-03-13

    Genetics and genomics are increasingly relevant to primary healthcare but training is unavailable to many practitioners. Education that can be accessed by practitioners without cost or travel is essential. The Gen-Equip project was formed to provide effective education in genetics for primary healthcare in Europe and so improve patient care. Partners include patient representatives and specialists in genetics and primary care from six countries. Here, we report the progress and challenges involved in creating a European online educational program in genetics.

  4. Geochemical Monitoring Considerations for the FutureGen 2.0 Project

    SciTech Connect

    Amonette, James E.; Johnson, Timothy A.; Spencer, Clayton F.; Zhong, Lirong; Szecsody, James E.; Vermeul, Vince R.

    2014-12-31

    Geochemical monitoring is an essential component of a suite of monitoring technologies designed to evaluate CO2 mass balance and detect possible loss of containment at the FutureGen 2.0 geologic sequestration site near Jacksonville, IL. This presentation gives an overview of the potential geochemical approaches and tracer technologies that were considered, and describes the evaluation process by which the most cost-effective and robust of these were selected for implementation

  5. Complexity analysis of the Next Gen Air Traffic Management System: trajectory based operations.

    PubMed

    Lyons, Rhonda

    2012-01-01

    According to Federal Aviation Administration traffic predictions currently our Air Traffic Management (ATM) system is operating at 150 percent capacity; forecasting that within the next two decades, the traffic with increase to a staggering 250 percent [17]. This will require a major redesign of our system. Today's ATM system is complex. It is designed to safely, economically, and efficiently provide air traffic services through the cost-effective provision of facilities and seamless services in collaboration with multiple agents however, contrary the vision, the system is loosely integrated and is suffering tremendously from antiquated equipment and saturated airways. The new Next Generation (Next Gen) ATM system is designed to transform the current system into an agile, robust and responsive set of operations that are designed to safely manage the growing needs of the projected increasingly complex, diverse set of air transportation system users and massive projected worldwide traffic rates. This new revolutionary technology-centric system is dynamically complex and is much more sophisticated than it's soon to be predecessor. ATM system failures could yield large scale catastrophic consequences as it is a safety critical system. This work will attempt to describe complexity and the complex nature of the NextGen ATM system and Trajectory Based Operational. Complex human factors interactions within Next Gen will be analyzed using a proposed dual experimental approach designed to identify hazards, gaps and elicit emergent hazards that would not be visible if conducted in isolation. Suggestions will be made along with a proposal for future human factors research in the TBO safety critical Next Gen environment.

  6. Gen IV Materials Handbook Beta Release for Structural and Functional Evaluation

    SciTech Connect

    Ren, Weiju; Luttrell, Claire

    2006-09-12

    Development of the Gen IV Materials Handbook is briefly summarized up to date. Current status of the Handbook website construction is described. The developed Handbook components and access control of the beta version are discussed for the present evaluation release. Detailed instructions and examples are given to provide guidance for evaluators to browse the constructed parts and use all the currently developed functionalities of the Handbook in evaluation.

  7. MicroGen: a MIAME compliant web system for microarray experiment information and workflow management

    PubMed Central

    Burgarella, Sarah; Cattaneo, Dario; Pinciroli, Francesco; Masseroli, Marco

    2005-01-01

    Background Improvements of bio-nano-technologies and biomolecular techniques have led to increasing production of high-throughput experimental data. Spotted cDNA microarray is one of the most diffuse technologies, used in single research laboratories and in biotechnology service facilities. Although they are routinely performed, spotted microarray experiments are complex procedures entailing several experimental steps and actors with different technical skills and roles. During an experiment, involved actors, who can also be located in a distance, need to access and share specific experiment information according to their roles. Furthermore, complete information describing all experimental steps must be orderly collected to allow subsequent correct interpretation of experimental results. Results We developed MicroGen, a web system for managing information and workflow in the production pipeline of spotted microarray experiments. It is constituted of a core multi-database system able to store all data completely characterizing different spotted microarray experiments according to the Minimum Information About Microarray Experiments (MIAME) standard, and of an intuitive and user-friendly web interface able to support the collaborative work required among multidisciplinary actors and roles involved in spotted microarray experiment production. MicroGen supports six types of user roles: the researcher who designs and requests the experiment, the spotting operator, the hybridisation operator, the image processing operator, the system administrator, and the generic public user who can access the unrestricted part of the system to get information about MicroGen services. Conclusion MicroGen represents a MIAME compliant information system that enables managing workflow and supporting collaborative work in spotted microarray experiment production. PMID:16351755

  8. Dual-track CCS stakeholder engagement: Lessons learned from FutureGen in Illinois

    USGS Publications Warehouse

    Hund, G.; Greenberg, S.E.

    2011-01-01

    FutureGen, as originally planned, was to be the world's first coal-fueled, near-zero emissions power plant with fully integrated, 90% carbon capture and storage (CCS). From conception through siting and design, it enjoyed strong support from multiple stakeholder groups, which benefited the overall project. Understanding the stakeholder engagement process for this project provides valuable insights into the design of stakeholder programs for future CCS projects. FutureGen is one of few projects worldwide that used open competition for siting both the power plant and storage reservoir. Most site proposals were coordinated by State governments. It was unique in this and other respects relative to the site selection method used on other DOE-supported projects. At the time of site selection, FutureGen was the largest proposed facility designed to combine an integrated gasification combined cycle (IGCC) coal-fueled power plant with a CCS system. Stakeholder engagement by states and the industry consortium responsible for siting, designing, building, and operating the facility took place simultaneously and on parallel tracks. On one track were states spearheading state-wide site assessments to identify candidate sites that they wanted to propose for consideration. On the other track was a public-private partnership between an industry consortium of thirteen coal companies and electric utilities that comprised the FutureGen Alliance (Alliance) and the U.S. Department of Energy (DOE). The partnership was based on a cooperative agreement signed by both parties, which assigned the lead for siting to the Alliance. This paper describes the stakeholder engagement strategies used on both of these tracks and provides examples from the engagement process using the Illinois semi-finalist sites. ?? 2011 Published by Elsevier Ltd.

  9. Airpower Leadership on the Front Line: Lt Gen George H. Brett and Combat Command

    DTIC Science & Technology

    2006-09-01

    perspective to the project and his amicable encouragement to me personally. Col Larry Thompson receives my thanks for connecting me with his friend, Lt...a major general, Arnold dispatched him to conduct lend-lease discussions with the British and to make a tour of Africa. This trip turned out much...book examines how well Gen George Brett executed the duties he was assigned during his tour in the Far East. The examination will focus on the

  10. Description of Distorhabditis poonchiana n. gen., n. sp. (Nematoda: Rhabditidae) from Jammu and Kashmir, India

    PubMed Central

    Shah, Ali Asghar; Vaid, Shavish; Hussain, Abid; Ahmad, Rakeeb

    2015-01-01

    Distorhabditis poonchiana n. gen., n. sp. from humus in Jammu and Kashmir, India, is described and illustrated. The new genus is characterized by a small body; slightly setoff labial region; long tubular gymnostom; prominently cuticularized cheilostom; absence of glottoid apparatus; monoprodelphic reproductive system; vulva (V) = 81 to 84; spicules with trifurcated distal ends, simple gubernaculum, peloderan bursa with eight pairs of bursal papillae arranged in 1 + 1 + 1 + 2 + 1 + 2 arrangement. PMID:26941466

  11. Sclerostylus n. gen. from Panama and Other Neotropical Species of LeptonIchoidea (Dorylaimida).

    PubMed

    G Goseco, C; Ferris, V R; Ferris, J M

    1981-01-01

    Leptonchoid species found in soil samples taken in lowland and mid-elevation seasonal forests at four locations in Panama were as follows: Sclerostylus karri n. gen., n. sp., Basirotyleptus saccatus n. sp., B. nemoralis, B. acus, B. penetrans, Doryllium neotropicum n. sp., D. minor, Tyleptus gymnochilus, Gerthus jamesi, Dorylaimoides micoletzkyi, and Tylencholaimellus macrophallus. The discoveries corroborate our earlier suggestion of a Gondwanian origin for Tyleptus and Basirotyleptus and provide data for additional biogeographical study.

  12. Yamaguchia toyensis n. sp., n. gen. (Annelida, Clitellata, Lumbriculidae) from profundal lake habitat in Japan

    USGS Publications Warehouse

    Fend, S.V.; Ohtaka, A.

    2004-01-01

    Yamaguchia toyensis n. sp., n. gen. is described from an oligotrophic caldera lake, Lake Toya, Hokkaido, Japan. Although the taxonomic affinities are unknown, the genus differs from all other Lumbriculidae in having the combination of testes and atria in X, a single, prosoporous male funnel per atrium, and spermathecae in XI. Unlike other Japanese lakes that have thus far been surveyed, Lake Toya supports abundant populations of lumbriculids in the profundal benthos.

  13. Effects of Ge Gen Decoction on PGE2 content and COX activity in the degenarated cervical intervertebral discs of rats.

    PubMed

    Jun, Zhou; Fang, Suping; Huo, Hairu; Qi, Yun; Guo, Shuying; Jiang, Tingliang; Shi, Qi

    2005-09-01

    After the rat model of cervical spondylosis was developed for 6 months, the PGE2 content and COX activity in the cervical intervertebral discs were determined respectively by radioimmunoassay and catalytic activity assay. The results indicated that the PGE2 content and COX activity in the model rat increased significantly, and that Ge Gen Decoction could down-regulate the PGE2 content and inhibit COX activity. This is possibly one of the mechanisms of Ge Gen Decoction for treating cervical spondylosis.

  14. CardioGenBase: A Literature Based Multi-Omics Database for Major Cardiovascular Diseases

    PubMed Central

    V, Alexandar; Nayar, Pradeep G.; Murugesan, R.; Mary, Beaulah; P, Darshana; Ahmed, Shiek S. S. J.

    2015-01-01

    Cardiovascular diseases (CVDs) account for high morbidity and mortality worldwide. Both, genetic and epigenetic factors are involved in the enumeration of various cardiovascular diseases. In recent years, a vast amount of multi-omics data are accumulated in the field of cardiovascular research, yet the understanding of key mechanistic aspects of CVDs remain uncovered. Hence, a comprehensive online resource tool is required to comprehend previous research findings and to draw novel methodology for understanding disease pathophysiology. Here, we have developed a literature-based database, CardioGenBase, collecting gene-disease association from Pubmed and MEDLINE. The database covers major cardiovascular diseases such as cerebrovascular disease, coronary artery disease (CAD), hypertensive heart disease, inflammatory heart disease, ischemic heart disease and rheumatic heart disease. It contains ~1,500 cardiovascular disease genes from ~2,4000 research articles. For each gene, literature evidence, ontology, pathways, single nucleotide polymorphism, protein-protein interaction network, normal gene expression, protein expressions in various body fluids and tissues are provided. In addition, tools like gene-disease association finder and gene expression finder are made available for the users with figures, tables, maps and venn diagram to fit their needs. To our knowledge, CardioGenBase is the only database to provide gene-disease association for above mentioned major cardiovascular diseases in a single portal. CardioGenBase is a vital online resource to support genome-wide analysis, genetic, epigenetic and pharmacological studies. PMID:26624015

  15. CardioGenBase: A Literature Based Multi-Omics Database for Major Cardiovascular Diseases.

    PubMed

    V, Alexandar; Nayar, Pradeep G; Murugesan, R; Mary, Beaulah; P, Darshana; Ahmed, Shiek S S J

    2015-01-01

    Cardiovascular diseases (CVDs) account for high morbidity and mortality worldwide. Both, genetic and epigenetic factors are involved in the enumeration of various cardiovascular diseases. In recent years, a vast amount of multi-omics data are accumulated in the field of cardiovascular research, yet the understanding of key mechanistic aspects of CVDs remain uncovered. Hence, a comprehensive online resource tool is required to comprehend previous research findings and to draw novel methodology for understanding disease pathophysiology. Here, we have developed a literature-based database, CardioGenBase, collecting gene-disease association from Pubmed and MEDLINE. The database covers major cardiovascular diseases such as cerebrovascular disease, coronary artery disease (CAD), hypertensive heart disease, inflammatory heart disease, ischemic heart disease and rheumatic heart disease. It contains ~1,500 cardiovascular disease genes from ~2,4000 research articles. For each gene, literature evidence, ontology, pathways, single nucleotide polymorphism, protein-protein interaction network, normal gene expression, protein expressions in various body fluids and tissues are provided. In addition, tools like gene-disease association finder and gene expression finder are made available for the users with figures, tables, maps and venn diagram to fit their needs. To our knowledge, CardioGenBase is the only database to provide gene-disease association for above mentioned major cardiovascular diseases in a single portal. CardioGenBase is a vital online resource to support genome-wide analysis, genetic, epigenetic and pharmacological studies.

  16. Taxonomy of the Proisotoma complex. V. Sexually dimorphic Ephemerotoma gen. nov. (Collembola: Isotomidae).

    PubMed

    Potapov, Mikhail; Kahrarian, Morteza; Deharveng, Louis; Shayanmehr, Masoumeh

    2015-12-03

    A new genus is proposed based on a new species from Iran, Ephemerotoma skarzynskii gen. et sp. nov., and three known species: E. huadongensis (Chen, 1985) comb. nov., E. multituberculata (Martynova, 1971) comb. nov. and E. porcella (Ellis, 1976) comb. nov. The genus shares the characters of Subisotoma Stach and Proctostephanus Börner and is distributed in southern areas of Eurasia (Eastern Mediterranean, Iran, Tajikistan, China). Ephemerotoma gen. nov. belongs to the Proisotoma-complex and is characterized by a simple maxillary palp, only 4 guards on labial papilla E and 2 prelabral chaetae. Four s-chaetae on Abd.V are arranged in two rows, two anterior and two posterior chaetae. All members of Ephemerotoma gen. nov. are redescribed or discussed based on type or fresh material, and a key to species of the genus is given. Scutisotoma potapovi Xie & Chen, 2008 is considered a synonym of E. huadongensis, while Proisotoma anopolitana is moved to the genus Proctostephanus. Sexual dimorphism is described for three species.

  17. Leptojacobus dorci n. gen., n. sp. (Nematoda: Diplogastridae), an Associate of Dorcus Stag Beetles (Coleoptera: Lucanidae)

    PubMed Central

    Kanzaki, Natsumi; Ragsdale, Erik J.; Susoy, Vladislav; Sommer, Ralf J.

    2014-01-01

    A new species of diplogastrid nematode, Leptojacobus dorci n. gen., n. sp., was isolated from adults of the stag beetle Dorcus ritsemae (Coleoptera: Lucanidae) that were purchased from a pet shop in Japan. Leptojacobus n. gen. is circumscribed by a very thin, delicate body and by a small stoma with minute armature. A combination of other stomatal characters, namely the division of the cheilostom into adradial plates, the symmetry of the subventral stegostomatal sectors, and the presence of a thin, conical dorsal tooth, further distinguishes Leptojacobus n. gen. from other genera of Diplogastridae. Phylogenetic analysis of nearly full-length SSU rRNA sequences support the new species, together with an isolate identified previously as Koerneria luziae, to be excluded from a clade including all other molecularly characterized diplogastrids with teeth and stomatal dimorphism. Therefore, the new species will be of importance for reconstruction of ancestral character histories in Diplogastridae, a family circumscribed by a suite of feeding-related novelties. PMID:24644371

  18. Enhanced and Synthetic Vision for Terminal Maneuvering Area NextGen Operations

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Bailey, Randall E.; Ellis, Kyle K. E.; Norman, R. Michael; Williams, Steven P.; Arthur, Jarvis J., III; Shelton, Kevin J.; Prinzel, Lawrence J., III

    2011-01-01

    Synthetic Vision Systems and Enhanced Flight Vision System (SVS/EFVS) technologies have the potential to provide additional margins of safety for aircrew performance and enable operational improvements for low visibility operations in the terminal area environment with equivalent efficiency as visual operations. To meet this potential, research is needed for effective technology development and implementation of regulatory and design guidance to support introduction and use of SVS/EFVS advanced cockpit vision technologies in Next Generation Air Transportation System (NextGen) operations. A fixed-base pilot-in-the-loop simulation test was conducted at NASA Langley Research Center that evaluated the use of SVS/EFVS in NextGen low visibility ground (taxi) operations and approach/landing operations. Twelve crews flew approach and landing operations in a simulated NextGen Chicago O Hare environment. Various scenarios tested the potential for EFVS for operations in visibility as low as 1000 ft runway visibility range (RVR) and SVS to enable lower decision heights (DH) than can currently be flown today. Expanding the EFVS visual segment from DH to the runway in visibilities as low as 1000 RVR appears to be viable as touchdown performance was excellent without any workload penalties noted for the EFVS concept tested. A lower DH to 150 ft and/or possibly reduced visibility minima by virtue of SVS equipage appears to be viable when implemented on a Head-Up Display, but the landing data suggests further study for head-down implementations.

  19. GenColors-based comparative genome databases for small eukaryotic genomes.

    PubMed

    Felder, Marius; Romualdi, Alessandro; Petzold, Andreas; Platzer, Matthias; Sühnel, Jürgen; Glöckner, Gernot

    2013-01-01

    Many sequence data repositories can give a quick and easily accessible overview on genomes and their annotations. Less widespread is the possibility to compare related genomes with each other in a common database environment. We have previously described the GenColors database system (http://gencolors.fli-leibniz.de) and its applications to a number of bacterial genomes such as Borrelia, Legionella, Leptospira and Treponema. This system has an emphasis on genome comparison. It combines data from related genomes and provides the user with an extensive set of visualization and analysis tools. Eukaryote genomes are normally larger than prokaryote genomes and thus pose additional challenges for such a system. We have, therefore, adapted GenColors to also handle larger datasets of small eukaryotic genomes and to display eukaryotic gene structures. Further recent developments include whole genome views, genome list options and, for bacterial genome browsers, the display of horizontal gene transfer predictions. Two new GenColors-based databases for two fungal species (http://fgb.fli-leibniz.de) and for four social amoebas (http://sacgb.fli-leibniz.de) were set up. Both new resources open up a single entry point for related genomes for the amoebozoa and fungal research communities and other interested users. Comparative genomics approaches are greatly facilitated by these resources.

  20. Transitioning Resolution Responsibility between the Controller and Automation Team in Simulated NextGen Separation Assurance

    NASA Technical Reports Server (NTRS)

    Cabrall, C.; Gomez, A.; Homola, J.; Hunt, S..; Martin, L.; Merccer, J.; Prevott, T.

    2013-01-01

    As part of an ongoing research effort on separation assurance and functional allocation in NextGen, a controller- in-the-loop study with ground-based automation was conducted at NASA Ames' Airspace Operations Laboratory in August 2012 to investigate the potential impact of introducing self-separating aircraft in progressively advanced NextGen timeframes. From this larger study, the current exploratory analysis of controller-automation interaction styles focuses on the last and most far-term time frame. Measurements were recorded that firstly verified the continued operational validity of this iteration of the ground-based functional allocation automation concept in forecast traffic densities up to 2x that of current day high altitude en-route sectors. Additionally, with greater levels of fully automated conflict detection and resolution as well as the introduction of intervention functionality, objective and subjective analyses showed a range of passive to active controller- automation interaction styles between the participants. Not only did the controllers work with the automation to meet their safety and capacity goals in the simulated future NextGen timeframe, they did so in different ways and with different attitudes of trust/use of the automation. Taken as a whole, the results showed that the prototyped controller-automation functional allocation framework was very flexible and successful overall.

  1. Geophysical Monitoring Methods Evaluation for the FutureGen 2.0 Project

    SciTech Connect

    Strickland, Chris E.; USA, Richland Washington; Vermeul, Vince R.; USA, Richland Washington; Bonneville, Alain; USA, Richland Washington; Sullivan, E. Charlotte; USA, Richland Washington; Johnson, Tim C.; USA, Richland Washington; Spane, Frank A.; USA, Richland Washington; Gilmore, Tyler J.; USA, Richland Washington

    2014-12-31

    A comprehensive monitoring program will be needed in order to assess the effectiveness of carbon sequestration at the FutureGen 2.0 carbon capture and storage (CCS) field-site. Geophysical monitoring methods are sensitive to subsurface changes that result from injection of CO2 and will be used for: (1) tracking the spatial extent of the free phase CO2 plume, (2) monitoring advancement of the pressure front, (3) identifying or mapping areas where induced seismicity occurs, and (4) identifying and mapping regions of increased risk for brine or CO2 leakage from the reservoir. Site-specific suitability and cost effectiveness were evaluated for a number of geophysical monitoring methods including: passive seismic monitoring, reflection seismic imaging, integrated surface deformation, time-lapse gravity, pulsed neutron capture logging, cross-borehole seismic, electrical resistivity tomography, magnetotellurics and controlled source electromagnetics. The results of this evaluation indicate that CO2 injection monitoring using reflection seismic methods would likely be difficult at the FutureGen 2.0 site. Electrical methods also exhibited low sensitivity to the expected CO2 saturation changes and would be affected by metallic infrastructure at the field site. Passive seismic, integrated surface deformation, time-lapse gravity, and pulsed neutron capture monitoring were selected for implementation as part of the FutureGen 2.0 storage site monitoring program.

  2. Geophysical Monitoring Methods Evaluation for the FutureGen 2.0 Project

    DOE PAGES

    Strickland, Chris E.; USA, Richland Washington; Vermeul, Vince R.; ...

    2014-12-31

    A comprehensive monitoring program will be needed in order to assess the effectiveness of carbon sequestration at the FutureGen 2.0 carbon capture and storage (CCS) field-site. Geophysical monitoring methods are sensitive to subsurface changes that result from injection of CO2 and will be used for: (1) tracking the spatial extent of the free phase CO2 plume, (2) monitoring advancement of the pressure front, (3) identifying or mapping areas where induced seismicity occurs, and (4) identifying and mapping regions of increased risk for brine or CO2 leakage from the reservoir. Site-specific suitability and cost effectiveness were evaluated for a number ofmore » geophysical monitoring methods including: passive seismic monitoring, reflection seismic imaging, integrated surface deformation, time-lapse gravity, pulsed neutron capture logging, cross-borehole seismic, electrical resistivity tomography, magnetotellurics and controlled source electromagnetics. The results of this evaluation indicate that CO2 injection monitoring using reflection seismic methods would likely be difficult at the FutureGen 2.0 site. Electrical methods also exhibited low sensitivity to the expected CO2 saturation changes and would be affected by metallic infrastructure at the field site. Passive seismic, integrated surface deformation, time-lapse gravity, and pulsed neutron capture monitoring were selected for implementation as part of the FutureGen 2.0 storage site monitoring program.« less

  3. Structures and stability of metal-doped GenM (n = 9, 10) clusters

    NASA Astrophysics Data System (ADS)

    Qin, Wei; Lu, Wen-Cai; Xia, Lin-Hua; Zhao, Li-Zhen; Zang, Qing-Jun; Wang, C. Z.; Ho, K. M.

    2015-06-01

    The lowest-energy structures of neutral and cationic GenM (n = 9, 10; M = Si, Li, Mg, Al, Fe, Mn, Pb, Au, Ag, Yb, Pm and Dy) clusters were studied by genetic algorithm (GA) and first-principles calculations. The calculation results show that doping of the metal atoms and Si into Ge9 and Ge10 clusters is energetically favorable. Most of the metal-doped Ge cluster structures can be viewed as adding or substituting metal atom on the surface of the corresponding ground-state Gen clusters. However, the neutral and cationic FeGe9,10,MnGe9,10 and Ge10Al are cage-like with the metal atom encapsulated inside. Such cage-like transition metal doped Gen clusters are shown to have higher adsorption energy and thermal stability. Our calculation results suggest that Ge9,10Fe and Ge9Si would be used as building blocks in cluster-assembled nanomaterials because of their high stabilities.

  4. Sensitivity of IceCube-Gen2 Phase I to tau neutrino appearance

    NASA Astrophysics Data System (ADS)

    de André, João Pedro A. M.; IceCube-Gen2 Collaboration Collaboration

    2017-01-01

    Looking towards the future of IceCube we are planning both high-energy and low-energy (PINGU) extensions. The first step towards these upgrade, ``IceCube-Gen2 Phase I'', consists of 7 additional strings inserted in the denser region DeepCore of the IceCube Neutrino Observatory. These additional photo-multipliers will more than double the number of sensors in the DeepCore region and with that significantly improve our ability to reconstruct low-energy events. This will lead to a significant improvement in the sensitivity to measure nutau appearance thanks to improved precision in reconstruction of nutau events. Also along with the additional photo-multipliers, new calibration devices will also be deployed with IceCube-Gen2 Phase I. These new devices will also further improve our understanding of the surrounding ice, and with that reduce the impact of some of our dominant systematics. The reduction of these systematics will also improve the sensitivity of IceCube to high-energy neutrinos through the re-analysis of the archival data with the improved detector systemtatics. We will present status of the tau neutrino appearance analysis using IceCube-Gen2 Phase I, both from thanks to the additional photomultiplier tubes deployed and from the extended calibration capabilities.

  5. Swedish Plectida (Nematoda). Part 6. Neocamacolaimus parasiticus gen. n., sp. n.

    PubMed

    Holovachov, Oleksandr; Boström, Sven

    2014-06-25

    A new genus Neocamacolaimus gen. n., with one new species N. parasiticus gen. n., sp. n. is described from the benthic polychaete Sphaerosyllis cf. hystrix collected in the Skagerrak off the west coast of Sweden. Neocamacolaimus gen. n. is placed in the family Camacolaimidae and is particularly characterised by having annulated cuticle with lateral alae; setiform cephalic sensilla located at level with amphids; amphidial fovea ventrally spiral; buccal cavity without armament; pharynx muscular; nerve ring located at base of pharynx; male reproductive system diorchic with outstretched testes; spicules weakly arcuate with straight manubrium; gubernaculum absent; alveolar supplements located in the pharyngeal region; tubular supplements absent; tail conoid; caudal glands and spinneret present. Juveniles of this genus are particularly characterised by their parasitic lifestyle and the following unique morphological features: lips form a dorso-ventrally elongated perioral disc with internal sclerotizations: one midventral and two dorsosublateral (right and left); cephalic sensilla setiform, subventral sensilla are noticeably longer than the subdorsal ones; intestine extends posterior to rectum and anal opening, forming a post-anal pouch.

  6. GenColors-based comparative genome databases for small eukaryotic genomes

    PubMed Central

    Felder, Marius; Romualdi, Alessandro; Petzold, Andreas; Platzer, Matthias; Sühnel, Jürgen; Glöckner, Gernot

    2013-01-01

    Many sequence data repositories can give a quick and easily accessible overview on genomes and their annotations. Less widespread is the possibility to compare related genomes with each other in a common database environment. We have previously described the GenColors database system (http://gencolors.fli-leibniz.de) and its applications to a number of bacterial genomes such as Borrelia, Legionella, Leptospira and Treponema. This system has an emphasis on genome comparison. It combines data from related genomes and provides the user with an extensive set of visualization and analysis tools. Eukaryote genomes are normally larger than prokaryote genomes and thus pose additional challenges for such a system. We have, therefore, adapted GenColors to also handle larger datasets of small eukaryotic genomes and to display eukaryotic gene structures. Further recent developments include whole genome views, genome list options and, for bacterial genome browsers, the display of horizontal gene transfer predictions. Two new GenColors-based databases for two fungal species (http://fgb.fli-leibniz.de) and for four social amoebas (http://sacgb.fli-leibniz.de) were set up. Both new resources open up a single entry point for related genomes for the amoebozoa and fungal research communities and other interested users. Comparative genomics approaches are greatly facilitated by these resources. PMID:23193285

  7. Enhanced and synthetic vision for terminal maneuvering area NextGen operations

    NASA Astrophysics Data System (ADS)

    Kramer, Lynda J.; Bailey, Randall E.; Ellis, Kyle K. E.; Norman, R. Michael; Williams, Steven P.; Arthur, Jarvis J., III; Shelton, Kevin J.; Prinzel, Lawrence J., III

    2011-06-01

    Synthetic Vision Systems and Enhanced Flight Vision System (SVS/EFVS) technologies have the potential to provide additional margins of safety for aircrew performance and enable operational improvements for low visibility operations in the terminal area environment with equivalent efficiency as visual operations. To meet this potential, research is needed for effective technology development and implementation of regulatory and design guidance to support introduction and use of SVS/EFVS advanced cockpit vision technologies in Next Generation Air Transportation System (NextGen) operations. A fixed-base pilot-in-the-loop simulation test was conducted at NASA Langley Research Center that evaluated the use of SVS/EFVS in NextGen low visibility ground (taxi) operations and approach/landing operations. Twelve crews flew approach and landing operations in a simulated NextGen Chicago O'Hare environment. Various scenarios tested the potential for EFVS for operations in visibility as low as 1000 ft runway visibility range (RVR) and SVS to enable lower decision heights (DH) than can currently be flown today. Expanding the EFVS visual segment from DH to the runway in visibilities as low as 1000 RVR appears to be viable as touchdown performance was excellent without any workload penalties noted for the EFVS concept tested. A lower DH to 150 ft and/or possibly reduced visibility minima by virtue of SVS equipage appears to be viable when implemented on a Head-Up Display, but the landing data suggests further study for head-down implementations.

  8. Description of Mogibacterium pumilum gen. nov., sp. nov. and Mogibacterium vescum gen. nov., sp. nov., and reclassification of Eubacterium timidum (Holdeman et al. 1980) as Mogibacterium timidum gen. nov., comb. nov.

    PubMed

    Nakazawa, F; Sato, M; Poco, S E; Hashimura, T; Ikeda, T; Kalfas, S; Sundqvist, G; Hoshino, E

    2000-03-01

    A new genus, Mogibacterium, is proposed for anaerobic, non-spore-forming, Gram-positive, rod-shaped bacteria which have been isolated from the periodontal pockets of adult human patients with periodontal disease and infected root canals. The novel isolates, strains D2-18T, BA11a-f and D5-2T, were inert in most of the conventional biochemical tests and phenotypically resemble asaccharolytic Eubacterium species. The protein profiles of whole cells on SDS-PAGE gels and Western immunoblotting reaction analysis distinguished these organisms from type strains belonging to the previously described Eubacterium species. The G + C content of the DNA is 45-46 mol% for Mogibacterium pumilum and 46 mol% for Mogibacterium vescum. The levels of DNA-DNA relatedness of these new species to other Eubacterium species, including Eubacterium limosum, Eubacterium brachy, Eubacterium lentum, Eubacterium nodatum, Eubacterium saphenum, and the more recently proposed Eubacterium minutum and Eubacterium exiguum (reclassified as Slackia exigua), are less than 2%. The DNA-DNA hybridization value between M. pumilum and M. vescum was 30%. Eubacterium timidum exhibited DNA homologies with Mogibacterium species which were low (17 and 18%) but clearly higher than with all the other Eubacterium species. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the closest phylogenetic neighbour of Mogibacterium species was E. timidum, and that these three species represent a novel lineage distinct from the previously described genera of Gram-positive, rod-shaped bacteria. On the basis of phenotypic characteristics and 16S rRNA gene sequence comparisons, it is also proposed that E. timidum is transferred to the genus Mogibacterium gen. nov. as Mogibacterium timidum gen. nov., comb. nov. (type strain ATCC 33093T).

  9. Identification and Characterization of Key Human Performance Issues and Research in the Next Generation Air Transportation System (NextGen)

    NASA Technical Reports Server (NTRS)

    Lee, Paul U.; Sheridan, Tom; Poage, james L.; Martin, Lynne Hazel; Jobe, Kimberly K.

    2010-01-01

    This report identifies key human-performance-related issues associated with Next Generation Air Transportation System (NextGen) research in the NASA NextGen-Airspace Project. Four Research Focus Areas (RFAs) in the NextGen-Airspace Project - namely Separation Assurance (SA), Airspace Super Density Operations (ASDO), Traffic Flow Management (TFM), and Dynamic Airspace Configuration (DAC) - were examined closely. In the course of the research, it was determined that the identified human performance issues needed to be analyzed in the context of NextGen operations rather than through basic human factors research. The main gaps in human factors research in NextGen were found in the need for accurate identification of key human-systems related issues within the context of specific NextGen concepts and better design of the operational requirements for those concepts. By focusing on human-system related issues for individual concepts, key human performance issues for the four RFAs were identified and described in this report. In addition, mixed equipage airspace with components of two RFAs were characterized to illustrate potential human performance issues that arise from the integration of multiple concepts.

  10. FutureGen: Stepping-Stone to Sustainable Fossil-Fuel Power Generation

    SciTech Connect

    Zitney, S.E.

    2006-11-01

    This presentation will highlight the U.S. Department of Energy's FutureGen Initiative. The nearly $1 billion government-industry project is a stepping-stone toward future coal-fired power plants that will produce hydrogen and electricity with zero-emissions, including carbon dioxide. The 275-megawatt FutureGen plant will initiate operations around 2012 and employ advanced coal gasification technology integrated with combined cycle electricity generation, hydrogen production, and carbon capture and sequestration. The initiative is a response to a presidential directive to develop a hydrogen economy by drawing upon the best scientific research to address the issue of global climate change. The FutureGen plant will be based on cutting-edge power generation technology as well as advanced carbon capture and sequestration systems. The centerpiece of the project will be coal gasification technology that can eliminate common air pollutants such as sulfur dioxide and nitrogen oxides and convert them to useable by-products. Gasification will convert coal into a highly enriched hydrogen gas, which can be burned much more cleanly than directly burning the coal itself. Alternatively, the hydrogen can be used in a fuel cell to produce ultra-clean electricity, or fed to a refinery to help upgrade petroleum products. Carbon sequestration will also be a key feature that will set the Futuregen plant apart from other electric power plant projects. The initial goal will be to capture 90 percent of the plant's carbon dioxide, but capture of nearly 100 percent may be possible with advanced technologies. Once captured, the carbon dioxide will be injected as a compressed fluid deep underground, perhaps into saline reservoirs. It could even be injected into oil or gas reservoirs, or into unmineable coal seams, to enhance petroleum or coalbed methane recovery. The ultimate goal for the FutureGen plant is to show how new technology can eliminate environmental concerns over the future use of

  11. Alkalimonas amylolytica gen. nov., sp. nov., and Alkalimonas delamerensis gen. nov., sp. nov., novel alkaliphilic bacteria from soda lakes in China and East Africa.

    PubMed

    Ma, Yanhe; Xue, Yanfen; Grant, William D; Collins, Nadine C; Duckworth, Andrew W; Van Steenbergen, Robert P; Jones, Brian E

    2004-06-01

    Two related novel alkaliphilic and slightly halophilic bacteria are described. They are strain N10 from Lake Chahannor in China and strain 1E1 from Lake Elmenteita in East Africa. Both strains are strictly aerobic, heterotrophic, alkaliphilic, mesophilic, and require NaCl for growth. The optimal conditions for growth were at pH 10-10.5 and 2-3% (w/v) NaCl. Cells of both strains were Gram-negative, rod-shaped, non-spore-forming, and motile with a single polar flagellum. Cellular fatty acids in both strains were predominantly saturated and mono-unsaturated straight-chain fatty acids (16:0, 16:1omega7c and 18:1omega7c). The major isoprenoid quinone of both strains was Q8. The major polar lipids are phosphatidylglycerol, diphosphatidylglycerol, phosphatidylglycerol phosphate and phosphatidylethanolamine. The guanine plus cytosine (G + C) content of the DNA was 52.5 mol% and 55.4 mol%, respectively. Phylogenetic analysis revealed that the two strains formed a distinct lineage within the gamma-3 subclass of the Proteobacteria. The strains shared a 16S rDNA sequence similarity of 96.1% and showed less than 93.7% of sequence similarity to any other known species. Based on polyphasic data, the two strains were differentiated from currently recognized genera and represent a new genus, Alkalimonas gen. nov., with two species, Alkalimonas amylolytica sp. nov. (type strain is N10T = AS 1.3430) and Alkalimonas delamerensis sp. nov. ( type strain is 1E1(P, T) = CBS 391.94). The GenBank accession numbers for the 16S rRNA gene sequence of strains N10 and 1E1 are AF250323 and X92130, respectively.

  12. Espectroscopia del Cometa Halley

    NASA Astrophysics Data System (ADS)

    Naranjo, O.; Fuenmayor, F.; Ferrin, L.; Bulka, P.; Mendoza, C.

    1987-05-01

    Se reportan observaciones espectroscópicas del cometa Halley. Los espectros fueron tomados usando el espectrógrafo del telescopio reflector de 1 metro del Observatorio Nacional de Venezuela. Se utilizó óptica azul, con una red de difracción de 600 lineas/min, obteniéndose una dispersión de 74.2 A/mm y una resolución de 2.5 A, en el rango espectral de 3500 a 6500 A. Seis placas fueron tomadas con emulsión IIa-O y dos con IIa-D. Los tiempos de exposición fueron entre 10 y 150 minutos. El cometa se encontraba entre 0.70 y 1.04 UA del Sol, y entre 1.28 y 0.73 UA de la Tierra. Las emisiones más prominentes en el espectro, son las del CN, C2, y C3. Otras emisiones detectadas corresponden a CH, NH2 y Na. Los espectros muestran un fuerte continuo, indicando un contenido significativo de polvo. Se detectó mayor intensidad del contínuo, en la dirección anti solar, lo cual es evidencia de la cola de polvo.

  13. Next Gen NEAR: Near Earth Asteroid Human Robotic Precursor Mission Concept

    NASA Technical Reports Server (NTRS)

    Rivkin, Andrew S.; Kirby, Karen; Cheng, Andrew F.; Gold, Robert; Kelly, Daniel; Reed, Cheryl; Abell, Paul; Garvin, James; Landis, Rob

    2012-01-01

    Asteroids have long held the attention of the planetary science community. In particular, asteroids that evolve into orbits near that of Earth, called near-Earth objects (NEO), are of high interest as potential targets for exploration due to the relative ease (in terms of delta V) to reach them. NASA's Flexible Path calls for missions and experiments to be conducted as intermediate steps towards the eventual goal of human exploration of Mars; piloted missions to NEOs are such example. A human NEO mission is a valuable exploratory step beyond the Earth-Moon system enhancing capabilities that surpass our current experience, while also developing infrastructure for future mars exploration capabilities. To prepare for a human rendezvous with an NEO, NASA is interested in pursuing a responsible program of robotic NEO precursor missions. Next Gen NEAR is such a mission, building on the NEAR Shoemaker mission experience at the JHU/APL Space Department, to provide an affordable, low risk solution with quick data return. Next Gen NEAR proposes to make measurements needed for human exploration to asteroids: to demonstrate proximity operations, to quantify hazards for human exploration and to characterize an environment at a near-Earth asteroid representative of those that may be future human destinations. The Johns Hopkins University Applied Physics Laboratory has demonstrated exploration-driven mission feasibility by developing a versatile spacecraft design concept using conventional technologies that satisfies a set of science, exploration and mission objectives defined by a concept development team in the summer of 2010. We will describe the mission concept and spacecraft architecture in detail. Configuration options were compared with the mission goals and objectives in order to select the spacecraft design concept that provides the lowest cost, lowest implementation risk, simplest operation and the most benefit for the mission implementation. The Next Gen NEAR

  14. GenSalt: rationale, design, methods and baseline characteristics of study participants.

    PubMed

    2007-08-01

    Hypertension is a complex disorder influenced by genetic and environmental determinants and their interactions. The objectives of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) are to localize and identify genes related to blood pressure (BP) responses to dietary sodium and potassium intervention. GenSalt utilizes a family feeding-study design. Each family was ascertained through a proband with untreated prehypertension or stage-1 hypertension in rural China. A medical history, lifestyle risk factors and responses to cold pressor tests, were obtained at baseline visits while BP, weight, blood and urine specimens were collected at baseline and follow-up visits. The dietary intervention included a 7-day low-sodium feeding (51.3 mmol/day), a 7-day high-sodium feeding (307.8 mmol/day) and a 7-day high-sodium feeding with an oral potassium supplementation (60 mmol/day). Microsatellite markers for genome-wide linkage scan and single nucleotide polymorphism (SNP) markers in candidate genes will be genotyped. Overall, 3153 participants from 658 families were recruited for GenSalt. The mean systolic and diastolic BPs were 128.0 and 80.3, 111.6 and 71.0, 112.6 and 72.6, 106.6 and 65.3 and 136.7 and 75.0 mm Hg for probands, siblings, spouses, offspring and parents, respectively. The mean urinary excretion of sodium and potassium were 232.5 and 38.6, 222.9 and 38.2, 213.1 and 37.8 and 207.3 and 36.0 mmol/24-h for probands, siblings, spouses and offspring, respectively. Our study will identify novel genes that influence significantly the effect of dietary sodium and potassium intake on BP. This information is useful for development of targeted intervention for the prevention and treatment of hypertension.

  15. An evaluation of the metabolic syndrome in the HyperGEN study

    PubMed Central

    Kraja, Aldi T; Hunt, Steven C; Pankow, James S; Myers, Richard H; Heiss, Gerardo; Lewis, Cora E; Rao, DC; Province, Michael A

    2005-01-01

    Background In 2001 the National Cholesterol Education Program (NCEP) provided a categorical definition for metabolic syndrome (c-MetS). We studied the extent to which two ethnic groups, Blacks and Whites were affected by c-MetS. The groups were members of the Hypertension Genetic Epidemiology Network (HyperGEN), a part of the Family Blood Pressure Program, supported by the NHLBI. Although the c-MetS definition is of special interest in particular to the clinicians, the quantitative latent traits of the metabolic syndrome (MetS) are also important in order to gain further understanding of its etiology. In this study, quantitative evaluation of the MetS latent traits (q-MetS) was based on the statistical multivariate method factor analysis (FA). Results The prevalence of the c-MetS was 34% in Blacks and 39% in Whites. c-MetS showed predominance of obesity, hypertension, and dyslipidemia. Three and four factor domains were identified through FA, classified as "Obesity," "Blood pressure," "Lipids," and "Central obesity." They explained approximately 60% of the variance in the 11 original variables. Two factors classified as "Obesity" and "Central Obesity" overlapped when FA was performed without rotation. All four factors in FA with Varimax rotation were consistent between Blacks and Whites, between genders and also after excluding type 2 diabetes (T2D) participants. Fasting insulin (INS) associated mainly with obesity and lipids factors. Conclusions MetS in the HyperGEN study has a compound phenotype with separate domains for obesity, blood pressure, and lipids. Obesity and its relationship to lipids and insulin is clearly the dominant factor in MetS. Linkage analysis on factor scores for components of MetS, in familial studies such as HyperGEN, can assist in understanding the genetic pathways for MetS and their interactions with the environment, as a first step in identifying the underlying pathophysiological causes of this syndrome. PMID:15656912

  16. GenClust: A genetic algorithm for clustering gene expression data

    PubMed Central

    Di Gesú, Vito; Giancarlo, Raffaele; Lo Bosco, Giosué; Raimondi, Alessandra; Scaturro, Davide

    2005-01-01

    Background Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering. Results GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means. Conclusion Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology. PMID:16336639

  17. Enhanced Flight Vision Systems and Synthetic Vision Systems for NextGen Approach and Landing Operations

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Bailey, Randall E.; Ellis, Kyle K. E.; Williams, Steven P.; Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Shelton, Kevin J.

    2013-01-01

    Synthetic Vision Systems and Enhanced Flight Vision System (SVS/EFVS) technologies have the potential to provide additional margins of safety for aircrew performance and enable operational improvements for low visibility operations in the terminal area environment with equivalent efficiency as visual operations. To meet this potential, research is needed for effective technology development and implementation of regulatory standards and design guidance to support introduction and use of SVS/EFVS advanced cockpit vision technologies in Next Generation Air Transportation System (NextGen) operations. A fixed-base pilot-in-the-loop simulation test was conducted at NASA Langley Research Center that evaluated the use of SVS/EFVS in NextGen low visibility approach and landing operations. Twelve crews flew approach and landing operations in a simulated NextGen Chicago O'Hare environment. Various scenarios tested the potential for using EFVS to conduct approach, landing, and roll-out operations in visibility as low as 1000 feet runway visual range (RVR). Also, SVS was tested to evaluate the potential for lowering decision heights (DH) on certain instrument approach procedures below what can be flown today. Expanding the portion of the visual segment in which EFVS can be used in lieu of natural vision from 100 feet above the touchdown zone elevation to touchdown and rollout in visibilities as low as 1000 feet RVR appears to be viable as touchdown performance was acceptable without any apparent workload penalties. A lower DH of 150 feet and/or possibly reduced visibility minima using SVS appears to be viable when implemented on a Head-Up Display, but the landing data suggests further study for head-down implementations.

  18. Data-link and surface map traffic intent displays for NextGen 4DT and equivalent visual surface operations

    NASA Astrophysics Data System (ADS)

    Shelton, Kevin J.; Prinzel, Lawrence (Lance) J., III; Arthur, Jarvis (Trey) J., III; Jones, Denise R.; Allamandola, Angela S.; Bailey, Randall E.

    2009-05-01

    By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a consortium of industry, academia and government agencies have proposed a revolutionary new concept for U.S. aviation operations, termed the Next Generation Air Transportation System or "NextGen". Many key capabilities are being identified to enable NextGen, including the concept of "net-centric" operations whereby each aircraft and air services provider shares information to allow real-time adaptability to ever-changing factors such as weather, traffic, flight trajectories, and security. Data-link is likely to be the primary source of communication in NextGen. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen.

  19. Data-Link and Surface Map Traffic Intent Displays for NextGen 4DT and Equivalent Visual Surface Operations

    NASA Technical Reports Server (NTRS)

    Shelton, Kevin J.; Prinzel, Lawrence J., III; Arthur, Jarvis J., III; Jones, Deise R.; Allamandola, Angela S.; Bailey, Randall E.

    2009-01-01

    By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a consortium of industry, academia and government agencies have proposed a revolutionary new concept for U.S. aviation operations, termed the Next Generation Air Transportation System or "NextGen". Many key capabilities are being identified to enable NextGen, including the concept of "net-centric" operations whereby each aircraft and air services provider shares information to allow real-time adaptability to ever-changing factors such as weather, traffic, flight trajectories, and security. Data-link is likely to be the primary source of communication in NextGen. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen.

  20. Clinical utility of Beckman-Coulter Gen's reticulocyte analysis in the study of anemia of chronic disease (ACD).

    PubMed

    Rodrigues, Ana; Ortega, Carlos; Santos, Luís; Teixeira, Alexandre; Dinis, Maria Joáo; Vasconcelos, Iponina; Lacerda, Jorge; Fonseca, Elisa

    2007-01-01

    The aim of this study is to analyze the reticulocyte parameters (classical and research parameters) acquired by the Beckman Coulter GEN'S blood counter (GEN'S; Brea, CA, USA) to establish the "reticulocyte profile" characteristics of patients with anemia of chronic disease (ACD). The reticulocyte parameters and profile provided by the GEN'S were studied in 38 anemic patients who fulfilled the diagnostic criteria for the ACD, and the results were compared with those of 38 healthy controls in a multivariate statistical analysis using the Student t-test and the receiver operating characteristics (ROC) curve analysis.Statistically significant (P <.05) differences between the 2 population groups were observed in several of the reticulocyte parameters provided by the GEN'S: mean volume of the reticulocyte population (MRV) (high), percentage of high light scatter reticulocytes HLR% (high), mean volume of the whole sphered red cell and reticulocyte population (MSCV) (high) MCV-MSCV (low) with the highest diagnostic value, as measured by the area under the ROC curve (>0.9), for the IRF (high) and the reticulocyte population data: mean channel scatter retics (high) and the mean channel conductivity retics (high). This study establishes the reticulocyte parameters and reticulocyte profile as provided by the GEN'S and characteristic of patients with ACD as compared with normal subjects. This should provide the basis for further studies comparing the reticulocyte profile of patients with ACD with those found in other types of anemia.

  1. Reclassification of Gemmobacter changlensis to a new genus as Cereibacter changlensis gen. nov., comb. nov.

    PubMed

    Suresh, G; Sasikala, Ch; Ramana, Ch V

    2015-03-01

    We propose a new genus to accommodate the phototrophic bacterium Gemmobacter changlensis [Chen W. M., Cho, N. T., Huang, W. C., Young, C. C. & Sheu, S. Y. (2013) Int J Syst Evol Microbiol 63, 470-478] based on multiple strain analysis. Differences in the major diagnostic properties such as ability to grow phototrophically, the presence of internal photosynthetic membranes, the light harvesting complexes, fatty acids, carotenoids, bacterial chlorophylls, polar lipid composition and some other phenotypic properties warrant the creation of a new genus, designated Cereibacter gen. nov., to accommodate the phototrophic members of the genus Gemmobacter, as represented by the type species Cereibacter changlensis comb. nov.

  2. Electromagnetic Interactions GenERalized (EIGER): Applications at Johnson Space Center

    NASA Technical Reports Server (NTRS)

    Dobbins, Justin A.; Fink, Patrick W.; Scully, Robert C.

    2003-01-01

    This slide presentation reviews the software framework for the analysis and design of complex electromagnetic systems. The system called Electromagnetic Interactions GenERalized (EIGER) is a hybrid finite element solution for wave equations and deru=ives boundary element solutions for integral equation formulations. Written in Fortran 90 Eiger uses object-oriented design methods to abstract key analysis components. EIGER has been applied to higher order modeling for analysis of antennas to assist in the design of the antennas of a mini-AERCam. EIGER might also be used to model the Ion Cyclotron Resonant heating stage for the VAriable Specific Impulse Magnetoplasma Rocket (VASIMR).

  3. Modeling Off-Nominal Recovery in NextGen Terminal-Area Operations

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.

    2011-01-01

    Robust schedule-based arrival management requires efficient recovery from off-nominal situations. This paper presents research on modeling off-nominal situations and plans for recovering from them using TRAC, a route/airspace design, fast-time simulation, and analysis tool for studying NextGen trajectory-based operations. The paper provides an overview of a schedule-based arrival-management concept and supporting controller tools, then describes TRAC implementations of methods for constructing off-nominal scenarios, generating trajectory options to meet scheduling constraints, and automatically producing recovery plans.

  4. Irradiation effects in oxide dispersion strengthened (ODS) Ni-base alloys for Gen. IV nuclear reactors

    NASA Astrophysics Data System (ADS)

    Oono, Naoko; Ukai, Shigeharu; Kondo, Sosuke; Hashitomi, Okinobu; Kimura, Akihiko

    2015-10-01

    Oxide particle dispersion strengthened (ODS) Ni-base alloys are irradiated by using simulation technique (Fe/He dual-ion irradiation) to investigate the reliability to Gen. IV high-temperature reactors. The fine oxide particles with less than 10 nm in average size and approximately 8.0 × 1022 m-3 in number density remained after 101 dpa irradiation. The tiny helium bubbles were inside grains, not at grain-boundaries; it is advantageous effect of oxide particles which trap the helium atoms at the particle-matrix interface. Ni-base ODS alloys demonstrated their great ability to overcome He embrittlement.

  5. GenToS: Use of Orthologous Gene Information to Prioritize Signals from Human GWAS

    PubMed Central

    Schlosser, Pascal; Backofen, Rolf; Lausch, Ekkehart; Köttgen, Anna

    2016-01-01

    Genome-wide association studies (GWAS) evaluate associations between genetic variants and a trait or disease of interest free of prior biological hypotheses. GWAS require stringent correction for multiple testing, with genome-wide significance typically defined as association p-value <5*10−8. This study presents a new tool that uses external information about genes to prioritize SNP associations (GenToS). For a given list of candidate genes, GenToS calculates an appropriate statistical significance threshold and then searches for trait-associated variants in summary statistics from human GWAS. It thereby allows for identifying trait-associated genetic variants that do not meet genome-wide significance. The program additionally tests for enrichment of significant candidate gene associations in the human GWAS data compared to the number expected by chance. As proof of principle, this report used external information from a comprehensive resource of genetically manipulated and systematically phenotyped mice. Based on selected murine phenotypes for which human GWAS data for corresponding traits were publicly available, several candidate gene input lists were derived. Using GenToS for the investigation of candidate genes underlying murine skeletal phenotypes in data from a large human discovery GWAS meta-analysis of bone mineral density resulted in the identification of significantly associated variants in 29 genes. Index variants in 28 of these loci were subsequently replicated in an independent GWAS replication step, highlighting that they are true positive associations. One signal, COL11A1, has not been discovered through GWAS so far and represents a novel human candidate gene for altered bone mineral density. The number of observed genes that contained significant SNP associations in human GWAS based on murine candidate gene input lists was much greater than the number expected by chance across several complex human traits (enrichment p-value as low as 10−10

  6. Gen IV Materials Handbook Functionalities and Operation (4A) Handbook Version 4.0

    SciTech Connect

    Ren, Weiju

    2013-09-01

    This document is prepared for navigation and operation of the Gen IV Materials Handbook, with architecture description and new user access initiation instructions. Development rationale and history of the Handbook is summarized. The major development aspects, architecture, and design principles of the Handbook are briefly introduced to provide an overview of its past evolution and future prospects. Detailed instructions are given with examples for navigating the constructed Handbook components and using the main functionalities. Procedures are provided in a step-by-step fashion for Data Upload Managers to upload reports and data files, as well as for new users to initiate Handbook access.

  7. Gen IV Materials Handbook Functionalities and Operation (2B) Handbook Version 2.0

    SciTech Connect

    Ren, Weiju

    2011-08-01

    This document is prepared for navigation and operation of the Gen IV Materials Handbook, with architecture description and new user access initiation instructions. Development rationale and history of the Handbook is summarized. The major development aspects, architecture, and design principles of the Handbook are briefly introduced to provide an overview of its past evolution and future prospects. Detailed instructions are given with examples for navigating the constructed Handbook components and using the main functionalities. Procedures are provided in a step-by-step fashion for Data Upload Managers to upload reports and data files, as well as for new users to initiate Handbook access.

  8. Traffic Generator (TrafficGen) Version 1.4.2: Users Guide

    DTIC Science & Technology

    2016-06-01

    TrafficGen Graphical User Interface (GUI) 3 3.1 Anatomy of the User Interface 3 3.2 Scenario Configuration and MGEN Files 4 4. Working with...4.6.1 Node Name Conflict Resolution 11 4.7 Import Existing MGEN Files 12 4.8 Edit an Existing Node 12 4.9 Edit an Existing Flow 13 4.10 Edit an...Save a Scenario 18 4.19.1 Save a Scenario to a Different Name 18 4.20 Export Scenario Data 19 4.20.1 Export SDT File 19 4.20.2 Export MGEN Timeline

  9. Havispora longyearbyenensis gen. et sp. nov.: an arctic marine fungus from Svalbard, Norway.

    PubMed

    Pang, Ka-Lai; Chiang, Michael W L; Vrijmoed, Lilian L P

    2008-01-01

    Information on the diversity and ecology of arctic marine fungi is lacking. During a short visit to Longyearbyen (78 degrees 13'N 15 degrees 33'E), Svalbard, Norway, a new marine fungus growing on driftwood collected at the shore was encountered. This taxon belongs to the Halosphaeriales (Ascomycota), a fungal order of mostly marine species. Havispora longyearbyenensis gen. et sp. nov. is morphologically similar to Nautosphaeria and Nereiospora, all with tufts of appendages at polar and equatorial positions of the ascospore but differing in color and septation of the ascospore and morphology and ontogeny of the ascospore appendage.

  10. Hemichloris antarctica, gen. et sp. nov. (Chlorococcales, Chlorophyta), a cryptoendolithic alga from Antarctica.

    PubMed

    Tschermak-Woess, E; Friedmann, E I

    1984-01-01

    Hemichloris antarctica gen. et sp. nov. (Oocystaceae, Chlorococcales) is characterized by a single, articulated, pyrenoid-less, thick saucer-shaped chloroplast, which generally fills less than half of the cell periphery. Multiplication is only by autospores. The species is psychrophilic and is damaged at temperatures above 20 degree C. Hemichloris antarctica is a member of the cryptoendolithic microbial community living in porous sandstone rocks of the Antarctica cold desert. It inhabits the zone below that of cryptoendolithic lichens and survives at extremely low light intensities. In the natural habitat, morphology is somewhat different from that in culture, as chloroplasts are smaller and without articulation, and the cells develop a gelatinous sheath.

  11. Trematodes of marine fishes from South Australia. I. Paraneocreadium australiense gen. et sp. n. (Lepocreadiidae).

    PubMed

    Kruse, G O

    1978-06-01

    Paraneocreadium australiense gen. et sp. n. (Lepocreadiidae) is described from Psilocranium nigricans (Richardson) from the Aldinga Reef of South Australia. Paraneocreadium is most similar to Neocreadium Howell 1966 from Geniagnus in New Zealand and Neolepocreadium Thomas 1960 from Trachinotus in Ghana. It differs from both genera in being ovoid rather than elongate, in having a coiled rather than saccate internal seminal vesicle, and having no viteline follicles between the gonads. It differs further from Neocreadium in lacking lymphatic vessels and in the position of the genital pore.

  12. Thermal stability study for candidate stainless steels of GEN IV reactors

    NASA Astrophysics Data System (ADS)

    Simeg Veternikova, J.; Degmova, J.; Pekarcikova, M.; Simko, F.; Petriska, M.; Skarba, M.; Mikula, P.; Pupala, M.

    2016-11-01

    Candidate stainless steels for GEN IV reactors were investigated in term of thermal and corrosion stability at high temperatures. New austenitic steel (NF 709), austenitic ODS steel (ODS 316) and two ferritic ODS steels (MA 956 and MA 957) were exposed to around 1000 °C in inert argon atmosphere at pressure of ∼8 MPa. The steels were further studied in a light of vacancy defects presence by positron annihilation spectroscopy and their thermal resistance was confronted to classic AISI steels. The thermal strain supported a creation of oxide layers observed by scanning electron microscopy (SEM).

  13. First Insertions of Carbene Ligands into Ge-N and Si-N Bonds.

    PubMed

    Álvarez-Rodríguez, Lucía; Cabeza, Javier A; García-Álvarez, Pablo; Gómez-Gallego, Mar; Merinero, Alba D; Sierra, Miguel A

    2017-03-28

    The insertion of carbene ligands into Ge-N (three examples) and Si-N (one example) bonds has been achieved for the first time by treating Fischer carbene complexes (M=W, Cr) with bulky amidinatotetrylenes (E=Ge, Si). These reactions, which start with a nucleophilic attack of the amidinatotetrylene heavier group 14 atom to the carbene C atom, proceed through a stereoselective insertion of the carbene fragment into an E-N bond of the amidinatotetrylene ENCN four-membered ring, leading to [M(CO)5 L] derivatives in which L belongs to a novel family of tetrylene ligands comprising an ECNCN five-membered ring.

  14. Reclassification of rhizosphere bacteria including strains causing corky root of lettuce and proposal of Rhizorhapis suberifaciens gen. nov., comb. nov., Sphingobium mellinum sp. nov., Sphingobium xanthum sp. nov. and Rhizorhabdus argentea gen. nov., sp. nov.

    PubMed

    Francis, Isolde M; Jochimsen, Kenneth N; De Vos, Paul; van Bruggen, Ariena H C

    2014-04-01

    The genus Rhizorhapis gen. nov. (to replace the illegitimate genus name Rhizomonas) is proposed for strains of Gram-negative bacteria causing corky root of lettuce, a widespread and important lettuce disease worldwide. Only one species of the genus Rhizomonas was described, Rhizomonas suberifaciens, which was subsequently reclassified as Sphingomonas suberifaciens based on 16S rRNA gene sequences and the presence of sphingoglycolipid in the cell envelope. However, the genus Sphingomonas is so diverse that further reclassification was deemed necessary. Twenty new Rhizorhapis gen. nov.- and Sphingomonas-like isolates were obtained from lettuce or sow thistle roots, or from soil using lettuce seedlings as bait. These and previously reported isolates were characterized in a polyphasic study including 16S rRNA gene sequencing, DNA-DNA hybridization, DNA G+C content, whole-cell fatty acid composition, morphology, substrate oxidation, temperature and pH sensitivity, and pathogenicity to lettuce. The isolates causing lettuce corky root belonged to the genera Rhizorhapis gen. nov., Sphingobium, Sphingopyxis and Rhizorhabdus gen. nov. More specifically, we propose to reclassify Rhizomonas suberifaciens as Rhizorhapis suberifaciens gen. nov., comb. nov. (type strain, CA1(T) = LMG 17323(T) = ATCC 49355(T)), and also propose the novel species Sphingobium xanthum sp. nov., Sphingobium mellinum sp. nov. and Rhizorhabdus argentea gen. nov., sp. nov. with the type strains NL9(T) ( = LMG 12560(T) = ATCC 51296(T)), WI4(T) ( = LMG 11032(T) = ATCC 51292(T)) and SP1(T) ( = LMG 12581(T) = ATCC 51289(T)), respectively. Several strains isolated from lettuce roots belonged to the genus Sphingomonas, but none of them were pathogenic.

  15. Roseitalea porphyridii gen. nov., sp. nov., isolated from a red alga and reclassification of Hoeflea suaedae (Chung et al., 2013) as Pseudohoeflea suaedae gen. nov., comb. nov.

    PubMed

    Hyeon, Jong Woo; Jeong, Sang Eun; Baek, Kyunghwa; Jeon, Che Ok

    2016-11-02

    A Gram-staining-negative, strictly aerobic bacterial strain, designated MA7-20T, was isolated from a marine alga, Porphyridium marinum, in Korea. Cells showing oxidase-positive and catalase-positive activities were motile rods with bipolar flagella. Growth of strain MA7-20T was observed at 15-45 C (optimum, 30-37 C), at pH 6.0-10.5 (optimum, pH 7.0-8.0) and in the presence of 0-7 % (w/v) NaCl (optimum, 2-3 %). Strain MA7-20T contained summed feature 8 (comprising C18:1 ω7c/C18:1 ω6c) and 11-methyl-C18:1 ω7c and C18:0 as the major fatty acids and ubiquinone-10 as the sole isoprenoid quinone. The major polar lipids were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidyl-N-methylethanolamine. The G+C content of the genomic DNA was 61.5 mol%. Strain MA7-20T was most closely related to Hoeflea suaedae YC6898T, Oricola cellulosilytica CC-AMH-OT and Nitratireductor basaltis J3T with 96.0 %, 95.8 % and 95.8 % 16S rRNA gene sequence similarities, respectively, but the strain formed a distinct phylogenetic lineage from them within the family Phyllobacteriaceae with a low bootstrap value. H. suaedae also formed a clearly distinct phylogenetic lineage from other members of the genus Hoeflea and closely related genera. On the basis of phenotypic, chemotaxonomic and molecular properties, strain MA7-20T represents a novel genus of the family Phyllobacteriaceae, for which the name Roseitalea porphyridii gen. nov., sp. nov. is proposed. The type strain is MA7-20T (=KACC 18807T =JCM 31538T). In addition, H. suaedae is also reclassified as Pseudohoeflea suaedae gen. nov., comb. nov. (type strain YC6898T =KACC 14911T =NBRC 107700T).

  16. Comparison between NuGEN's WT-Ovation Pico and one-direct amplification systems.

    PubMed

    Morse, Alison M; Carballo, Valentina; Baldwin, Donald A; Taylor, Christopher G; McIntyre, Lauren M

    2010-09-01

    Differential gene expression between groups of homogenous cell types is a biological question whose time has come. RNA can be extracted from small numbers of cells, such as those isolated by laser-capture microdissection, but the small amounts obtained often require amplification to enable whole genome transcriptome profiling by technologies such as microarray analysis and RNA-seq. Recently, advances in amplification procedures make amplification directly from whole cell lysates possible. The aim of this study was to compare two amplification systems for variations in observed RNA abundance attributable to the amplification procedure for use with small quantities of cells isolated by laser-capture microdissection. Arabidopsis root cells undergoing giant cell formation as a result of nematode infestation and uninfested control root cells were laser-captured and used to evaluate two amplification systems. One, NuGEN's WT-Ovation Pico (Pico) amplification system, uses total RNA as starting material, and the other, NuGEN's WT-One-Direct (One-Direct) amplification system, uses lysate containing the captured cells. The reproducibility of whole genome transcript profiling and correlations of both systems were investigated after microarray analysis. The One-Direct system was less reproducible and more variable than the Pico system. The Pico amplification kit resulted in the detection of thousands of differentially expressed genes between giant cells and control cells. This is in marked contrast to the relatively few genes detected after amplification with the One-Direct amplification kit.

  17. Aurantibacter crassamenti gen. nov., sp. nov., a bacterium isolated from marine sediment.

    PubMed

    Yoon, Jaewoo; Kasai, Hiroaki

    2017-01-01

    A Gram-stain-negative, strictly aerobic, orange-colored, rod-shaped, chemoheterotrophic bacterium, designated HG732(T), was isolated from marine sediment in Japan. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the novel marine strain was affiliated with the family Flavobacteriaceae of the phylum Bacteroidetes and that it shared the highest (94.1 %) sequence similarity with Kriegella aquimaris KMM 3665(T). The strain could be differentiated phenotypically from related members of the family Flavobacteriaceae. Major fatty acids of strain HG732(T) were iso-C15:1 G, iso-C15:0 and iso-C17:0 3-OH. The polar lipid profile consisted of phosphatidylglycerol, three unidentidied aminolipids and two unidentified lipids. The DNA G+C content of the strain was determined to be 35.2 mol%, and the major respiratory quinone was identified as menaquinone 6 (MK-6). From the distinct phylogenetic position and combination of genotypic and phenotypic characteristics, the strain is considered to represent a novel genus in the family Flavobacteriaceae, for which the name Aurantibacter crassamenti gen. nov., sp. nov. is proposed. The type strain of A. crassamenti gen. nov., sp. nov. is HG732(T) (= KCTC 52207(T) = NBRC 112211(T)).

  18. IceCube Gen2: The Next Generation of Neutrino Astronomy

    NASA Astrophysics Data System (ADS)

    Blaufuss, Erik; IceCube Collaboration

    2017-01-01

    The observations of an astrophysical flux of neutrinos by the IceCube neutrino observatory signaled the start of the era of neutrino astronomy. While the source of these astrophysical neutrinos remains unclear, many strong constraints have already been made. Unfortunately, the limits of the current detector are becoming clear and the design of the next generation of Antarctic neutrino observatory is well underway. The IceCube-Gen2 high-energy array will instrument a 10km3 volume of clear glacial ice at the South Pole to deliver substantially larger astrophysical samples of all neutrino flavors. This contribution will highlight the science case and detector sensitivity studies performed in the design process. Additionally, astrophysical neutrino sensitivity can be increased by the addition of an extensive surface detector to identify and reject atmospheric backgrounds originating from the southern hemisphere. This large detector, in combination with the existing IceCube neutrino observatory and the rest of the IceCube-Gen2 facility, will be the flagship experiment of the new field of neutrino astronomy.

  19. Molecular phylogeny of Cercomonadidae and kinetid patterns of Cercomonas and Eocercomonas gen. nov. (Cercomonadida, Cercozoa).

    PubMed

    Karpov, Serguei A; Bass, David; Mylnikov, Alexander P; Cavalier-Smith, Thomas

    2006-06-01

    Cercomonads are among the most abundant and widespread zooflagellates in soil and freshwater. We cultured 22 strains and report their complete 18S rRNA sequences and light microscopic morphology. Phylogenetic analysis of 51 Cercomonas rRNA genes shows in each previously identified major clade (A, B) two very robust, highly divergent, multi-species subclades (A1, A2; B1, B2). We studied kinetid ultrastructure of five clade A representatives by serial sections. All have two closely associated left ventral posterior microtubular roots, an anterior dorsal root, a microtubule-nucleating left anterior root, and a cone of microtubules passing to the nucleus. Anterior centrioles (=basal bodies, kinetosomes) of A1 have cartwheels; the posterior centriole does not, suggesting it is older, and implying flagellar transformation similar to other bikonts. Strain C-80 (subclade A2) differs greatly, having a dorsal posterior microtubule band, but lacking the A1-specific fibrillar striated root, nuclear extension to the centrioles, centriolar diaphragm, extrusomes; both mature centrioles lack cartwheels. For clade A2 we establish Eocercomonas gen. n., with type Eocercomonas ramosa sp. n., and for clade B1 Paracercomonas gen. n. (type Paracercomonas marina sp. n.). We establish Paracercomonas ekelundi sp. n. for culture SCCAP C1 and propose a Cercomonas longicauda neotype and Cercomonas (=Neocercomonas) jutlandica comb. n. and Paracercomonas (=Cercomonas) metabolica comb. n.

  20. Advanced Technology Development Program for Lithium-Ion Batteries: Gen 2 Performance Evaluation Final Report

    SciTech Connect

    Jon P. Christophersen; Ira Bloom; Edward V. Thomas; Kevin L. Gering; Gary L. Henriksen; Vincent S. Battaglia; David Howell

    2006-07-01

    The Advanced Technology Development Program has completed performance testing of the second generation of lithium-ion cells (i.e., Gen 2 cells). The 18650-size Gen 2 cells, with a baseline and variant chemistry, were distributed over a matrix consisting of three states-of-charge (SOCs) (60, 80, and 100% SOC), four temperatures (25, 35, 45, and 55°C), and three life tests (calendar-, cycle-, and accelerated-life). The calendar- and accelerated-life cells were clamped at an open-circuit voltage corresponding to the designated SOC and were subjected to a once-per-day pulse profile. The cycle-life cells were continuously pulsed using a profile that was centered around 60% SOC. Life testing was interrupted every four weeks for reference performance tests (RPTs), which were used to quantify changes in cell degradation as a function of aging. The RPTs generally consisted of C1/1 and C1/25 static capacity tests, a low-current hybrid pulse power characterization test, and electrochemical impedance spectroscopy. The rate of cell degradation generally increased with increasing test temperature, and SOC. It was also usually slowest for the calendar-life cells and fastest for the accelerated-life cells. Detailed capacity-, power-, and impedance-based performance results are reported.

  1. Gen-2 hand-held optical imager towards cancer imaging: reflectance and transillumination phantom studies.

    PubMed

    Gonzalez, Jean; Roman, Manuela; Hall, Michael; Godavarty, Anuradha

    2012-01-01

    Hand-held near-infrared (NIR) optical imagers are developed by various researchers towards non-invasive clinical breast imaging. Unlike these existing imagers that can perform only reflectance imaging, a generation-2 (Gen-2) hand-held optical imager has been recently developed to perform both reflectance and transillumination imaging. The unique forked design of the hand-held probe head(s) allows for reflectance imaging (as in ultrasound) and transillumination or compressed imaging (as in X-ray mammography). Phantom studies were performed to demonstrate two-dimensional (2D) target detection via reflectance and transillumination imaging at various target depths (1-5 cm deep) and using simultaneous multiple point illumination approach. It was observed that 0.45 cc targets were detected up to 5 cm deep during transillumination, but limited to 2.5 cm deep during reflectance imaging. Additionally, implementing appropriate data post-processing techniques along with a polynomial fitting approach, to plot 2D surface contours of the detected signal, yields distinct target detectability and localization. The ability of the gen-2 imager to perform both reflectance and transillumination imaging allows its direct comparison to ultrasound and X-ray mammography results, respectively, in future clinical breast imaging studies.

  2. Paragnomoxyala gen. nov. (Xyalidae, Monhysterida, Nematoda) from the East China Sea.

    PubMed

    Jiang, Weijun; Huang, Yong

    2015-11-05

    A new genus, Paragnomoxyala gen. nov., and a new species, Paragnomoxyala breviseta sp. nov. are described from the East China Sea. Paragnomoxyala gen. nov. is characterized by having large funnel-shaped buccal cavity with cuticularized walls and extended anteriorly; lips very high; striated cuticle; four cephalic setae, absence of outer labial setae; circular amphidial fovea; straight spicules and absence of gubernaculum; tail conico-cylindrical with three terminal setae; female monodelphic with an anterior outstretched ovary. It differs from similar genera by having a large buccal cavity unique in Xyalidae, straight spicules, lacking gubernaculum, and conico-cylindrical tail with terminal setae. Paragnomoxyala breviseta sp. nov. is characterized by having a large funnel-shaped buccal cavity, with cuticularized walls and extended anteriorly, 1.6-1.8 hd long and 63-79% cbd wide; four cephalic setae 3-4 µm long; circular amphids 6-9 µm in diameter; spicules straight but slightly bent at both ends; absence of gubernaculum and precloacal supplement.

  3. Aliterella atlantica gen. nov., sp. nov., and Aliterella antarctica sp. nov., novel members of coccoid Cyanobacteria.

    PubMed

    Rigonato, Janaina; Gama, Watson Arantes; Alvarenga, Danillo Oliveira; Branco, Luis Henrique Zanini; Brandini, Frederico Pereira; Genuário, Diego Bonaldo; Fiore, Marli Fatima

    2016-09-01

    Two Cyanobacteria isolated from South Atlantic Ocean continental shelf deep water and from a marine green algae inhabiting the Admiralty Bay, King George Island, Antarctica were investigated based on morphological and ultrastructural traits, phylogeny of 16S rRNA gene sequences, secondary structure of the 16S-23S internal transcribed spacer regions and phylogenomic analyses. The majority of these evaluations demonstrated that both strains differ from the genera of cyanobacteria with validly published names and, therefore, supported the description of the novel genus as Aliterella gen. nov. The identity and phylogeny of 16S rRNA gene sequences, together with the secondary structure of D1D1' and BoxB intergenic regions, further supported the two strains representing distinct species: Aliterella atlantica gen. nov., sp. nov. (type SP469036, strain CENA595T) and Aliterella antarctica sp. nov. (type SP469035, strain CENA408T). The phylogenomic analysis of A. atlantica sp. nov. CENA595T, based on 21 protein sequences, revealed that this genus belongs to the cyanobacterial order Chroococcidiopsidales. The isolation and cultivation of two geographically distant unicellular members of a novel cyanobacterial genus and the sequenced genome of the type strain bring new insights into the current classification of the coccoid group, and into the reconstruction of their evolutionary history.

  4. Comparison between NuGEN's WT-Ovation Pico and One-Direct Amplification Systems

    PubMed Central

    Morse, Alison M.; Carballo, Valentina; Baldwin, Donald A.; Taylor, Christopher G.; McIntyre, Lauren M.

    2010-01-01

    Differential gene expression between groups of homogenous cell types is a biological question whose time has come. RNA can be extracted from small numbers of cells, such as those isolated by laser-capture microdissection, but the small amounts obtained often require amplification to enable whole genome transcriptome profiling by technologies such as microarray analysis and RNA-seq. Recently, advances in amplification procedures make amplification directly from whole cell lysates possible. The aim of this study was to compare two amplification systems for variations in observed RNA abundance attributable to the amplification procedure for use with small quantities of cells isolated by laser-capture microdissection. Arabidopsis root cells undergoing giant cell formation as a result of nematode infestation and uninfested control root cells were laser-captured and used to evaluate two amplification systems. One, NuGEN's WT-Ovation Pico (Pico) amplification system, uses total RNA as starting material, and the other, NuGEN's WT-One-Direct (One-Direct) amplification system, uses lysate containing the captured cells. The reproducibility of whole genome transcript profiling and correlations of both systems were investigated after microarray analysis. The One-Direct system was less reproducible and more variable than the Pico system. The Pico amplification kit resulted in the detection of thousands of differentially expressed genes between giant cells and control cells. This is in marked contrast to the relatively few genes detected after amplification with the One-Direct amplification kit. PMID:20808643

  5. Distribution of hammerhead and hammerhead-like RNA motifs through the GenBank.

    PubMed

    Ferbeyre, G; Bourdeau, V; Pageau, M; Miramontes, P; Cedergren, R

    2000-07-01

    Hammerhead ribozymes previously were found in satellite RNAs from plant viroids and in repetitive DNA from certain species of newts and schistosomes. To determine if this catalytic RNA motif has a wider distribution, we decided to scrutinize the GenBank database for RNAs that contain hammerhead or hammerhead-like motifs. The search shows a widespread distribution of this kind of RNA motif in different sequences suggesting that they might have a more general role in RNA biology. The frequency of the hammerhead motif is half of that expected from a random distribution, but this fact comes from the low CpG representation in vertebrate sequences and the bias of the GenBank for those sequences. Intriguing motifs include those found in several families of repetitive sequences, in the satellite RNA from the carrot red leaf luteovirus, in plant viruses like the spinach latent virus and the elm mottle virus, in animal viruses like the hepatitis E virus and the caprine encephalitis virus, and in mRNAs such as those coding for cytochrome P450 oxidoreductase in the rat and the hamster.

  6. Flight Deck Technologies to Enable NextGen Low Visibility Surface Operations

    NASA Technical Reports Server (NTRS)

    Prinzel, Lawrence (Lance) J., III; Arthur, Jarvis (Trey) J.; Kramer, Lynda J.; Norman, Robert M.; Bailey, Randall E.; Jones, Denise R.; Karwac, Jerry R., Jr.; Shelton, Kevin J.; Ellis, Kyle K. E.

    2013-01-01

    Many key capabilities are being identified to enable Next Generation Air Transportation System (NextGen), including the concept of Equivalent Visual Operations (EVO) . replicating the capacity and safety of today.s visual flight rules (VFR) in all-weather conditions. NASA is striving to develop the technologies and knowledge to enable EVO and to extend EVO towards a Better-Than-Visual operational concept. This operational concept envisions an .equivalent visual. paradigm where an electronic means provides sufficient visual references of the external world and other required flight references on flight deck displays that enable Visual Flight Rules (VFR)-like operational tempos while maintaining and improving safety of VFR while using VFR-like procedures in all-weather conditions. The Langley Research Center (LaRC) has recently completed preliminary research on flight deck technologies for low visibility surface operations. The work assessed the potential of enhanced vision and airport moving map displays to achieve equivalent levels of safety and performance to existing low visibility operational requirements. The work has the potential to better enable NextGen by perhaps providing an operational credit for conducting safe low visibility surface operations by use of the flight deck technologies.

  7. A Precision Optical Calibration Module (POCAM) for IceCube-Gen2

    NASA Astrophysics Data System (ADS)

    Jurkovič, M.; Abraham, K.; Holzapfel, K.; Krings, K.; Resconi, E.; Veenkamp, J.

    2016-04-01

    We present here a new concept of an in-situ self-calibrated isotropic light source for the future IceCube-Gen2 neutrino detector called the Precision Optical Calibration Module (POCAM). IceCube-Gen2 will be a matrix of light sensors buried deep in the ice at the geographic South Pole. The timing, the location, and the amount of Cherenkov light deposited by the secondary charged particles are used to reconstruct the properties of the incident neutrinos. The reconstruction relies on a detailed detector model that includes the response of optical modules to the Cherenkov light, as well as the optical properties of the detector medium - the natural Antarctic ice. To understand these properties, both natural, and artificial light sources are already used for calibration. New calibration devices are being developed in order to improve the precision of these measurements, and reduce systematic errors. The POCAM concept is based on the principle of an inverted integrating sphere. The main components are LEDs emitting light at several wavelengths and solid-state light sensors e.g. calibrated photodiode or silicon photomultipliers to monitor the emitted light intensity. We report on the current status of the POCAM R&D.

  8. Advanced Technology Development Program for Lithium-Ion Batteries: Gen 2 GDR Performance Evaluation Report

    SciTech Connect

    Jon P. Christophersen; Chinh D. Ho; Gary L. Henriksen; David Howell

    2006-07-01

    The Advanced Technology Development Program has completed the performance evaluation of the second generation of lithium-ion cells (i.e., Gen 2 cells). This report documents the testing and analysis of the Gen 2 GDR cells, which were used to learn and debug the newly developed Technology Life Verification Test Manual. The purpose of the manual is to project a 15-year, 150,000 mile battery life capability with a 90% confidence interval using predictive models and short-term testing. The GDR cells were divided into two different matrices. The core-life test matrix consisted of calendar- and cycle-life cells with various changes to the four major acceleration factors (temperature, state-of-charge, throughput, and power rating). The supplemental-life test matrix consisted of cells subjected either to a path dependence study, or a comparison between the standard hybrid pulse power characterization test and the newly-developed minimum pulse power characterization test. Resistance and capacity results are reported.

  9. Structures and stability of metal-doped GenM (n = 9, 10) clusters

    DOE PAGES

    Qin, Wei; Lu, Wen-Cai; Xia, Lin-Hua; ...

    2015-06-26

    The lowest-energy structures of neutral and cationic Ge nM (n = 9, 10; M = Si, Li, Mg, Al, Fe, Mn, Pb, Au, Ag, Yb, Pm and Dy) clusters were studied by genetic algorithm (GA) and first-principles calculations. The calculation results show that doping of the metal atoms and Si into Ge9 and Ge10 clusters is energetically favorable. Most of the metal-doped Ge cluster structures can be viewed as adding or substituting metal atom on the surface of the corresponding ground-state Gen clusters. However, the neutral and cationic FeGe9,10,MnGe9,10 and Ge10Al are cage-like with the metal atom encapsulated inside. Suchmore » cage-like transition metal doped Gen clusters are shown to have higher adsorption energy and thermal stability. Our calculation results suggest that Ge9,10Fe and Ge9Si would be used as building blocks in cluster-assembled nanomaterials because of their high stabilities.« less

  10. Memoan ciceroi gen. et sp. nov., a remarkable new firefly genus and species from the Atlantic Rainforest (Coleoptera: Lampyridae).

    PubMed

    Da Silveira, Luiz Felipe Lima; Mermudes, José Ricardo M

    2013-01-01

    A species of firefly discovered in a fragile and rapidly disappearing Atlantic Rainforest biome in Brazil does not fit into any of the existing subfamilies nor described generic categories in the Lampyridae and is described here as Memoan ciceroi gen. et sp. nov. and classed as Lampyridae Incertae sedis, as it exhibits features of both the Amydetinae and Lampyrinae. An overview of subfamily arrangements and relevant generic characters is given to support this action. Memoan gen. nov. can be distinguished by its alveolate pronotum and elytra; subserrate antennae, antenommeres II-IX compressed, antennal sockets obliquely inserted on tubercles; labial palp one-segmented and obconic, and by its conspicuous pleuroventral suture.

  11. A REVIEW ON CURRENT STATUS OF ALLOYS 617 AND 230 FOR GEN IV NUCLEAR REACTOR INTERNALS AND HEAT EXCHANGERS

    SciTech Connect

    Ren, Weiju; Swindeman, Robert W

    2009-01-01

    Alloys 617 and 230 are currently identified as two leading candidate metallic materials in the down selection for applications at temperatures above 760 C in the Gen IV Nuclear Reactor Systems. Qualifying the materials requires significant information related to Codification, mechanical behavior modeling, metallurgical stability, environmental resistance, and many other aspects. In the present paper, material requirements for the Gen IV Nuclear Reactor Systems are discussed; certain available information regarding the two alloys under consideration for the intended applications are reviewed and analyzed. Suggestions are presented for further R&D activities for the materials selection.

  12. Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells.

    PubMed

    Tao, Lei; Wei, Libing; Liu, Yishi; Ding, Yang; Liu, Xiuting; Zhang, Xin; Wang, Xiaoping; Yao, Yuyuan; Lu, Jinrong; Wang, Qing; Hu, Rong

    2017-02-01

    We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and proliferation of human breast cancer cells in concentration and time-dependent manners. It was found that Gen-27 induced mitochondrial-mediated apoptosis, characterized by the dissipation of mitochondrial membrane potential (ΔΨm), cytochrome c (Cyt c) release from mitochondria to cytosol, activation of caspases and induction of poly (ADP-ribose) polymerase (PARP). In addition, Gen-27 inhibited the glycolysis in human breast cancer cells. After treatment with Gen-27, the expression of HKII was down-regulated, accompanied by weakened interaction of HKII and VDAC. Further research revealed that the induction of mitochondrial apoptosis was associated with the decrease of HKII expression by Gen-27. Finally, in vivo studies demonstrated that Gen-27 significantly suppressed the growth and promoted apoptosis of MDA-MB-231 breast cancer orthotopic tumors with low systemic toxicity. In conclusion,