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Sample records for hydratase fh fumarase

  1. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC tumor syndrome and congenital fumarase deficiency

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    Tomlinson Ian PM

    2008-03-01

    Full Text Available Abstract Background Fumarate hydratase (HGNC approved gene symbol – FH, also known as fumarase, is an enzyme of the tricarboxylic acid (TCA cycle, involved in fundamental cellular energy production. First described by Zinn et al in 1986, deficiency of FH results in early onset, severe encephalopathy. In 2002, the Multiple Leiomyoma Consortium identified heterozygous germline mutations of FH in patients with multiple cutaneous and uterine leiomyomas, (MCUL: OMIM 150800. In some families renal cell cancer also forms a component of the complex and as such has been described as hereditary leiomyomatosis and renal cell cancer (HLRCC: OMIM 605839. The identification of FH as a tumor suppressor was an unexpected finding and following the identification of subunits of succinate dehydrogenase in 2000 and 2001, was only the second description of the involvement of an enzyme of intermediary metabolism in tumorigenesis. Description The FH mutation database is a part of the TCA cycle gene mutation database (formerly the succinate dehydrogenase gene mutation database and is based on the Leiden Open (source Variation Database (LOVD system. The variants included in the database were derived from the published literature and annotated to conform to current mutation nomenclature. The FH database applies HGVS nomenclature guidelines, and will assist researchers in applying these guidelines when directly submitting new sequence variants online. Since the first molecular characterization of an FH mutation by Bourgeron et al in 1994, a series of reports of both FH deficiency patients and patients with MCUL/HLRRC have described 107 variants, of which 93 are thought to be pathogenic. The most common type of mutation is missense (57%, followed by frameshifts & nonsense (27%, and diverse deletions, insertions and duplications. Here we introduce an online database detailing all reported FH sequence variants. Conclusion The FH mutation database strives to systematically

  2. Genetics Home Reference: fumarase deficiency

    Science.gov (United States)

    ... V, Tomlinson IP. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Genet. 2008 Mar 25;9:20. doi: 10.1186/1471-2350- ...

  3. Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration.

    Science.gov (United States)

    Muller, Marie; Guillaud-Bataille, Marine; Salleron, Julia; Genestie, Catherine; Deveaux, Sophie; Slama, Abdelhamid; de Paillerets, Brigitte Bressac; Richard, Stéphane; Benusiglio, Patrick R; Ferlicot, Sophie

    2018-02-06

    Hereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germline mutations. A prominent eosinophilic macronucleolus with a perinucleolar clear halo is distinctive of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma according to the 2012 ISUP and 2016 WHO kidney tumor classification. From an immunohistochemistry perspective, tumors are often FH-negative and S-(2-succino)-cysteine (2SC) positive. We performed a pathology review of 24 renal tumors in 23 FH mutation carriers, and compared them to 12 type 2 papillary renal cell carcinomas from FH wild-type patients. Prominent eosinophilic nucleoli with perinucleolar halos were present in almost all FH-deficient renal cell carcinomas (23/24). Unexpectedly, they were also present in 58% of type 2 papillary renal cell carcinomas from wild-type patients. Renal cell carcinoma in mutation carriers displayed a complex architecture with multiple patterns, typically papillary, tubulopapillary, and tubulocystic, but also sarcomatoid and rhabdoid. Such pattern diversity was not seen in non-carriers. FH/2SC immunohistochemistry was informative as all hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas were either FH- or 2SC+. For FH and 2SC immunohistochemistries taken separately, sensitivity of negative anti-FH immunohistochemistry was 87.5% and specificity was 100%. For positive anti-2SC immunohistochemistry, sensitivity, and specificity were 91.7% and 91.7%, respectively. All FH wild-type renal cell carcinoma were FH-positive, and all but one were 2SC-negative. In conclusion, multiplicity of architectural patterns, rhabdoid/sarcomatoid components and combined FH/2SC staining, but not prominent eosinophilic nucleoli with perinucleolar halos, differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal

  4. Germline fumarate hydratase mutations in patients with ovarian mucinous cystadenoma

    DEFF Research Database (Denmark)

    Ylisaukko-oja, Sanna K.; Cybulski, Cezary; Lehtonen, Rainer

    2006-01-01

    Germline mutations in the fumarate hydratase (FH) gene were recently shown to predispose to the dominantly inherited syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is characterized by benign leiomyomas of the skin and the uterus, renal cell carcinoma, and uterine...... leiomyosarcoma. The aim of this study was to identify new families with FH mutations, and to further examine the tumor spectrum associated with FH mutations. FH germline mutations were screened from 89 patients with RCC, skin leiomyomas or ovarian tumors. Subsequently, 13 ovarian and 48 bladder carcinomas were...

  5. Identification and characterization of a novel fumarase gene by metagenome expression cloning from marine microorganisms

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    Tang Xian-Lai

    2010-11-01

    Full Text Available Abstract Background Fumarase catalyzes the reversible hydration of fumarate to L-malate and is a key enzyme in the tricarboxylic acid (TCA cycle and in amino acid metabolism. Fumarase is also used for the industrial production of L-malate from the substrate fumarate. Thermostable and high-activity fumarases from organisms that inhabit extreme environments may have great potential in industry, biotechnology, and basic research. The marine environment is highly complex and considered one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms are inaccessible in nature and are not easily cultivated in the laboratory. Metagenomic approaches provide a powerful tool to isolate and identify enzymes with novel biocatalytic activities for various biotechnological applications. Results A plasmid metagenomic library was constructed from uncultivated marine microorganisms within marine water samples. Through sequence-based screening of the DNA library, a gene encoding a novel fumarase (named FumF was isolated. Amino acid sequence analysis revealed that the FumF protein shared the greatest homology with Class II fumarate hydratases from Bacteroides sp. 2_1_33B and Parabacteroides distasonis ATCC 8503 (26% identical and 43% similar. The putative fumarase gene was subcloned into pETBlue-2 vector and expressed in E. coli BL21(DE3pLysS. The recombinant protein was purified to homogeneity. Functional characterization by high performance liquid chromatography confirmed that the recombinant FumF protein catalyzed the hydration of fumarate to form L-malate. The maximum activity for FumF protein occurred at pH 8.5 and 55°C in 5 mM Mg2+. The enzyme showed higher affinity and catalytic efficiency under optimal reaction conditions: Km= 0.48 mM, Vmax = 827 μM/min/mg, and kcat/Km = 1900 mM/s. Conclusions We isolated a novel fumarase gene, fumF, from a sequence-based screen of a plasmid metagenomic library from uncultivated

  6. A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia

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    Julie Adam

    2013-05-01

    Full Text Available The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH, predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target.

  7. Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval

    NARCIS (Netherlands)

    Aissani, B.; Zhang, K.; Mensenkamp, A.R.; Menko, F.H.; Wiener, H.W.

    2015-01-01

    Mutations in fumarate hydratase (FH) on chromosome 1q43 cause a rare cancer syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), but are rare in nonsyndromic and common uterine leiomyoma (UL) or fibroids. Studies suggested that variants in FH or in a linked gene may also predispose to

  8. Immobilized cells of Candida rugosa possessing fumarase activity

    Energy Technology Data Exchange (ETDEWEB)

    Yang, L.; Zhone, L.

    1980-01-01

    Immobilized cells of C. rugosa that possessed fumarase activity were prepared by different methods; the most active immobilized cells were entrapped in polyacrylamide gels. The effects of pH temperature, and divalent cations on the fumarase activity of both immobilized and native cells were the same. Mn/sup 2 +/, Mg/sup 2 +/, Ca/sup 2 +/, and Fe/sup 2 +/ did not protect the immobilized enzyme against thermal inactivation. The activity of immobilized fumarase remained constant during 91 days of storage of 4-6 degrees. The immobilized cell column was used for the continuous production of L-malic acid from 1M fumarate at 30 degrees and pH 8.5. The immobilized column operated steadily for 2 months. Half life of the immobilized fumarase at 30 degrees was 95 days.

  9. F/H Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The F/H Laboratory is the largest of the eight laboratories within the SRS Analytical Area Project with over 100,000 square feet of floor space, 20,000 square foot...

  10. Fumarate Hydratase Deletion in Pancreatic β Cells Leads to Progressive Diabetes

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    Julie Adam

    2017-09-01

    Full Text Available We explored the role of the Krebs cycle enzyme fumarate hydratase (FH in glucose-stimulated insulin secretion (GSIS. Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice appear normal for 6–8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca2+]i elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D. The impaired GSIS in islets from diabetic Fh1βKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D.

  11. Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.

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    Guitart, Amelie V; Panagopoulou, Theano I; Villacreces, Arnaud; Vukovic, Milica; Sepulveda, Catarina; Allen, Lewis; Carter, Roderick N; van de Lagemaat, Louie N; Morgan, Marcos; Giles, Peter; Sas, Zuzanna; Gonzalez, Marta Vila; Lawson, Hannah; Paris, Jasmin; Edwards-Hicks, Joy; Schaak, Katrin; Subramani, Chithra; Gezer, Deniz; Armesilla-Diaz, Alejandro; Wills, Jimi; Easterbrook, Aaron; Coman, David; So, Chi Wai Eric; O'Carroll, Donal; Vernimmen, Douglas; Rodrigues, Neil P; Pollard, Patrick J; Morton, Nicholas M; Finch, Andrew; Kranc, Kamil R

    2017-03-06

    Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure. Reexpression of extramitochondrial Fh1 (which normalized fumarate levels but not maximal mitochondrial respiration) rescued these phenotypes, indicating the causal role of cellular fumarate accumulation. However, HSCs lacking mitochondrial Fh1 (which had normal fumarate levels but defective maximal mitochondrial respiration) failed to self-renew and displayed lymphoid differentiation defects. In contrast, leukemia-initiating cells lacking mitochondrial Fh1 efficiently propagated Meis1 / Hoxa9 -driven leukemia. Thus, we identify novel roles for fumarate metabolism in HSC maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation. © 2017 Guitart et al.

  12. The Succinated Proteome of FH-Mutant Tumours

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    Ming Yang

    2014-08-01

    Full Text Available Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC. Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succinocysteine (2SC. Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH, kelch-like ECH-associated protein 1 (KEAP1 and mitochondrial aconitase (ACO2 can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC.

  13. Molecular Pathways: Fumarate Hydratase-Deficient Kidney Cancer: Targeting the Warburg Effect in Cancer

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    Linehan, W. Marston; Rouault, Tracey A.

    2015-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for development of cutaneous and uterine leiomyomas and an aggressive form of type II papillary kidney cancer. HLRCC is characterized by germline mutation of the tricarboxylic acid cycle (TCA) enzyme, fumarate hydratase (FH). FH-deficient kidney cancer is characterized by impaired oxidative phosphorylation and a metabolic shift to aerobic glycolysis, a form of metabolic reprogramming referred to as the Warburg effect. Increased glycolysis generates ATP needed for increased cell proliferation. In FH-deficient kidney cancer levels of AMPK, a cellular energy sensor, are decreased; resulting in diminished p53 levels, decreased expression of the iron importer, DMT1, leading to low cellular iron levels, and to enhanced fatty acid synthesis by diminishing phosphorylation of acetyl CoA carboxylase, a rate limiting step for fatty acid synthesis. Increased fumarate and decreased iron levels in FH-deficient kidney cancer cells inactivate prolyl hydroxylases, leading to stabilization of HIF1α, and increased expression of genes such as vascular endothelial growth factor (VEGF) and GLUT1 to provide fuel needed for rapid growth demands. Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, LDH-A, the anti-oxidant response pathway, the heme oxygenase pathway and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib. These same types of metabolic shifts, to aerobic glycolysis with decreased oxidative phosphorylation, have been found in a wide variety of other cancer types. Targeting the metabolic basis of a rare cancer such as fumarate hydratase

  14. Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism.

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    Hou, Entai; Li, Xian; Liu, Zerong; Zhang, Fuchang; Tian, Zhongmin

    2018-04-01

    Fumarase catalyzes the interconversion of fumarate and l-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l-malic acid, l-aspartic acid, glycine and l-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. Copyright © 2017 John Wiley & Sons, Ltd.

  15. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

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    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  16. The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels

    KAUST Repository

    Tong, Winghang; Sourbier, Carole; Kovtunovych, Gennadiy; Jeong, Suhyoung; Vira, Manish A.; Ghosh, Manik Chandra; Romero, Vladimir Valera; Sougrat, Rachid; Vaulont, Sophie; Viollet, Benoî t; Kim, Yeongsang; Lee, Sunmin; Trepel, Jane B.; Srinivasan, Ramaprasad; Bratslavsky, Gennady; Yang, Youfeng; Linehan, William Marston; Rouault, Tracey A.

    2011-01-01

    Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels lead to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells. © 2011 Elsevier Inc.

  17. The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels

    KAUST Repository

    Tong, Winghang

    2011-09-01

    Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6. Reduced AMPK levels lead to diminished expression of the DMT1 iron transporter, and the resulting cytosolic iron deficiency activates the iron regulatory proteins, IRP1 and IRP2, and increases expression of the hypoxia inducible factor HIF-1α, but not HIF-2α. Silencing of HIF-1α or activation of AMPK diminishes invasive activities, indicating that alterations of HIF-1α and AMPK contribute to the oncogenic growth of FH-deficient cells. © 2011 Elsevier Inc.

  18. Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Eldirdiri, Abubakr; Bertelsen, Lotte Bonde

    2017-01-01

    (2)] fumarate conversion to [1,4-C-13(2)] malate by fumarase has been proposed as a measure of necrosis in rat tumor models and in chemically induced AKI rats. Here we show that the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and secondly...... that hyperpolarized [1,4-C-13(2)] malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity, in bilateral as well as unilateral AKI models, differentiating moderate and severe AKI as well...... as short-and long-term AKI. Furthermore after verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-C-13] fumarate MR imaging. The combined in vitro and in vivo biomarker of AKI...

  19. Metabolic reprogramming for producing energy and reducing power in fumarate hydratase null cells from hereditary leiomyomatosis renal cell carcinoma.

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    Youfeng Yang

    Full Text Available Fumarate hydratase (FH-deficient kidney cancer undergoes metabolic remodeling, with changes in mitochondrial respiration, glucose, and glutamine metabolism. These changes represent multiple biochemical adaptations in glucose and fatty acid metabolism that supports malignant proliferation. However, the metabolic linkages between altered mitochondrial function, nucleotide biosynthesis and NADPH production required for proliferation and survival have not been elucidated. To characterize the alterations in glycolysis, the Krebs cycle and the pentose phosphate pathways (PPP that either generate NADPH (oxidative or do not (non-oxidative, we utilized [U-(13C]-glucose, [U-(13C,(15N]-glutamine, and [1,2- (13C2]-glucose tracers with mass spectrometry and NMR detection to track these pathways, and measured the oxygen consumption rate (OCR and extracellular acidification rate (ECAR of growing cell lines. This metabolic reprogramming in the FH null cells was compared to cells in which FH has been restored. The FH null cells showed a substantial metabolic reorganization of their intracellular metabolic fluxes to fulfill their high ATP demand, as observed by a high rate of glucose uptake, increased glucose turnover via glycolysis, high production of glucose-derived lactate, and low entry of glucose carbon into the Krebs cycle. Despite the truncation of the Krebs cycle associated with inactivation of fumarate hydratase, there was a small but persistent level of mitochondrial respiration, which was coupled to ATP production from oxidation of glutamine-derived α-ketoglutarate through to fumarate. [1,2- (13C2]-glucose tracer experiments demonstrated that the oxidative branch of PPP initiated by glucose-6-phosphate dehydrogenase activity is preferentially utilized for ribose production (56-66% that produces increased amounts of ribose necessary for growth and NADPH. Increased NADPH is required to drive reductive carboxylation of α-ketoglutarate and fatty acid

  20. Genetics Home Reference: 3-methylglutaconyl-CoA hydratase deficiency

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    ... provide energy for cells. This amino acid is broken down in cell structures called mitochondria , which convert ... 3-methylglutaconyl-CoA hydratase, leucine is not properly broken down, which leads to a buildup of related ...

  1. Mitochondrial import of human and yeast fumarase in live mammalian cells: Retrograde translocation of the yeast enzyme is mainly caused by its poor targeting sequence

    International Nuclear Information System (INIS)

    Singh, Bhag; Gupta, Radhey S.

    2006-01-01

    Studies on yeast fumarase provide the main evidence for dual localization of a protein in mitochondria and cytosol by means of retrograde translocation. We have examined the subcellular targeting of yeast and human fumarase in live cells to identify factors responsible for this. The cDNAs for mature yeast or human fumarase were fused to the gene for enhanced green fluorescent protein (eGFP) and they contained, at their N-terminus, a mitochondrial targeting sequence (MTS) derived from either yeast fumarase, human fumarase, or cytochrome c oxidase subunit VIII (COX) protein. Two nuclear localization sequences (2x NLS) were also added to these constructs to facilitate detection of any cytosolic protein by its targeting to nucleus. In Cos-1 cells transfected with these constructs, human fumarase with either the native or COX MTSs was detected exclusively in mitochondria in >98% of the cells, while the remainder 1-2% of the cells showed varying amounts of nuclear labeling. In contrast, when human fumarase was fused to the yeast MTS, >50% of the cells showed nuclear labeling. Similar studies with yeast fumarase showed that with its native MTS, nuclear labeling was seen in 80-85% of the cells, but upon fusion to either human or COX MTS, nuclear labeling was observed in only 10-15% of the cells. These results provide evidence that extramitochondrial presence of yeast fumarase is mainly caused by the poor mitochondrial targeting characteristics of its MTS (but also affected by its primary sequence), and that the retrograde translocation mechanism does not play a significant role in the extramitochondrial presence of mammalian fumarase

  2. The aconitate hydratase family from Citrus

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    Cercos Manuel

    2010-10-01

    Full Text Available Abstract Background Research on citrus fruit ripening has received considerable attention because of the importance of citrus fruits for the human diet. Organic acids are among the main determinants of taste and organoleptic quality of fruits and hence the control of fruit acidity loss has a strong economical relevance. In citrus, organic acids accumulate in the juice sac cells of developing fruits and are catabolized thereafter during ripening. Aconitase, that transforms citrate to isocitrate, is the first step of citric acid catabolism and a major component of the citrate utilization machinery. In this work, the citrus aconitase gene family was first characterized and a phylogenetic analysis was then carried out in order to understand the evolutionary history of this family in plants. Gene expression analyses of the citrus aconitase family were subsequently performed in several acidic and acidless genotypes to elucidate their involvement in acid homeostasis. Results Analysis of 460,000 citrus ESTs, followed by sequencing of complete cDNA clones, identified in citrus 3 transcription units coding for putatively active aconitate hydratase proteins, named as CcAco1, CcAco2 and CcAco3. A phylogenetic study carried on the Aco family in 14 plant species, shows the presence of 5 Aco subfamilies, and that the ancestor of monocot and dicot species shared at least one Aco gene. Real-time RT-PCR expression analyses of the three aconitase citrus genes were performed in pulp tissues along fruit development in acidic and acidless citrus varieties such as mandarins, oranges and lemons. While CcAco3 expression was always low, CcAco1 and CcAco2 genes were generally induced during the rapid phase of fruit growth along with the maximum in acidity and the beginning of the acid reduction. Two exceptions to this general pattern were found: 1 Clemenules mandarin failed inducing CcAco2 although acid levels were rapidly reduced; and 2 the acidless "Sucreña" orange

  3. Distinct expression profile in fumarate-hydratase-deficient uterine fibroids

    DEFF Research Database (Denmark)

    Vanharanta, S; Pollard, PJ; Lehtonen, HJ

    2006-01-01

    -related genes. Other significantly up-regulated gene categories in FH mutants were, for example, iron ion homeostasis and oxidoreduction. Genes with lower expression in FH-mutant fibroids belonged to groups such as extracellular matrix, cell adhesion, muscle development and cell contraction. We show that FH...

  4. Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene

    Czech Academy of Sciences Publication Activity Database

    Ezgu, F.; Krejčí, Pavel; Wilcox, W. R.

    2013-01-01

    Roč. 524, č. 2 (2013), s. 403-406 ISSN 0378-1119 Institutional support: RVO:68081707 Keywords : Fumaric aciduria * Novel mutation * Leiomyoma Subject RIV: BO - Biophysics Impact factor: 2.082, year: 2013

  5. Fumarate Production by Torulopsis glabrata: Engineering Heterologous Fumarase Expression and Improving Acid Tolerance.

    Directory of Open Access Journals (Sweden)

    Xiulai Chen

    Full Text Available Fumarate is a well-known biomass building block compound. However, the poor catalytic efficiency of fumarase is one of the major factors preventing its widespread production. To address this issue, we selected residues 159HPND162 of fumarase from Rhizopus oryzae as targets for site-directed mutagenesis based on molecular docking analysis. Twelve mutants were generated and characterized in detail. Kinetic studies showed that the Km values of the P160A, P160T, P160H, N161E, and D162W mutants were decreased, whereas Km values of H159Y, H159V, H159S, N161R, N161F, D162K, and D162M mutants were increased. In addition, all mutants displayed decreased catalytic efficiency except for the P160A mutant, whose kcat/Km was increased by 33.2%. Moreover, by overexpressing the P160A mutant, the engineered strain T.G-PMS-P160A was able to produce 5.2 g/L fumarate. To further enhance fumarate production, the acid tolerance of T.G-PMS-P160A was improved by deleting ade12, a component of the purine nucleotide cycle, and the resulting strain T.G(△ade12-PMS-P160A produced 9.2 g/L fumarate. The strategy generated in this study opens up new avenues for pathway optimization and efficient production of natural products.

  6. 57Fe Moessbauer spectroscopic studies on photosensitive nitrile hydratase (NHase)

    International Nuclear Information System (INIS)

    Kobayashi, Yoshio; Odaka, Masafumi

    2001-01-01

    57 Fe Moessbauer spectroscopy is a very useful technique for elucidating the chemical properties and biological changes of Fe species located at the reaction centers in various biological systems. We have applied 57 Fe Moessbauer spectroscopy to study the mechanism of photoactivation and the structural change caused by light irradiation of nitrile hydratase (NHase). (author)

  7. The Application of Nitrile Hydratases in Organic Synthesis

    NARCIS (Netherlands)

    Van Pelt, S.

    2010-01-01

    Nitrile hydratases (NHases, E.C. 4.2.1.84) catalyse the transformation of nitriles into the corresponding amides and were first discovered 30 years ago in studies on the microbial degradation of toxic cyano-group-containing compounds. The use of NHases in synthetic chemistry is especially

  8. Purification and characterization of enterocin FH 99 produced by a faecal isolate Enterococcus faecium FH 99.

    Science.gov (United States)

    Gupta, H; Malik, R K; Bhardwaj, A; Kaur, G; De, S; Kaushik, J K

    2010-06-01

    Enterococcus faecium FH 99 was isolated from human faeces and selected because of its broad spectrum of inhibitory activity against several Gram-positive foodborne spoilage and pathogenic bacteria. Ent. faecium FH 99 accumulates enterocin in large number in early stationary phase of the growth. The enterocin FH 99 was stable over a wide pH range (2-10) and recovered activity even after treatment at high temperatures (10 min at 100°C). The enterocin was subjected to different purification techniques viz., gel filteration, cation exchange chromatography and reverse-phase high-performance liquid chromatography. The activity was eluted as one individual active fraction. SDSPAGE revealed a molecular weight of less than 6.5 kDa. Studies carried out to identify the genetic determinants for bacteriocin production showed that this trait may be plasmid encoded as loss in both of the plasmids (size>chromosomal DNA) led to loss in bacteriocin production by Ent. faecium FH 99. Ent. faecium strain FH 99 is a newly discovered high bacteriocin producer with Activity Units 1.8 × 10(5) AU ml(-1) and its characteristics indicate that it may have strong potential for application as a protective agent against pathogens and spoilage bacteria in foods.

  9. A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa

    Directory of Open Access Journals (Sweden)

    Uyeda Taro QP

    2005-03-01

    Full Text Available Abstract Background Formins are multidomain proteins defined by a conserved FH2 (formin homology 2 domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1 domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes. Results We present a detailed sequence analysis of the 10 formins (ForA to J identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells. Conclusion Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism.

  10. A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa.

    Science.gov (United States)

    Rivero, Francisco; Muramoto, Tetsuya; Meyer, Ann-Kathrin; Urushihara, Hideko; Uyeda, Taro Q P; Kitayama, Chikako

    2005-03-01

    Formins are multidomain proteins defined by a conserved FH2 (formin homology 2) domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1) domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes. We present a detailed sequence analysis of the 10 formins (ForA to J) identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells. Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism.

  11. Fumarase is involved in DNA double-strand break resection through a functional interaction with Sae2

    DEFF Research Database (Denmark)

    Leshets, Michael; Ramamurthy, Dharanidharan; Lisby, Michael

    2018-01-01

    One of the most severe forms of DNA damage is the double-strand break (DSB). Failure to properly repair the damage can cause mutation, gross chromosomal rearrangements and lead to the development of cancer. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ) are the......One of the most severe forms of DNA damage is the double-strand break (DSB). Failure to properly repair the damage can cause mutation, gross chromosomal rearrangements and lead to the development of cancer. In eukaryotes, homologous recombination (HR) and non-homologous end joining (NHEJ......) are the main DSB repair pathways. Fumarase is a mitochondrial enzyme which functions in the tricarboxylic acid cycle. Intriguingly, the enzyme can be readily detected in the cytosolic compartment of all organisms examined, and we have shown that cytosolic fumarase participates in the DNA damage response...

  12. Sub-minute kinetics of human red cell fumarase: 1 H spin-echo NMR spectroscopy and 13 C rapid-dissolution dynamic nuclear polarization.

    Science.gov (United States)

    Shishmarev, Dmitry; Wright, Alan J; Rodrigues, Tiago B; Pileio, Giuseppe; Stevanato, Gabriele; Brindle, Kevin M; Kuchel, Philip W

    2018-03-01

    Fumarate is an important probe of metabolism in hyperpolarized magnetic resonance imaging and spectroscopy. It is used to detect the release of fumarase in cancer tissues, which is associated with necrosis and drug treatment. Nevertheless, there are limited reports describing the detailed kinetic studies of this enzyme in various cells and tissues. Thus, we aimed to evaluate the sub-minute kinetics of human red blood cell fumarase using nuclear magnetic resonance (NMR) spectroscopy, and to provide a quantitative description of the enzyme that is relevant to the use of fumarate as a probe of cell rupture. The fumarase reaction was studied using time courses of 1 H spin-echo and 13 C-NMR spectra. 1 H-NMR experiments showed that the fumarase reaction in hemolysates is sufficiently rapid to make its kinetics amenable to study in a period of approximately 3 min, a timescale characteristic of hyperpolarized 13 C-NMR spectroscopy. The rapid-dissolution dynamic nuclear polarization (RD-DNP) technique was used to hyperpolarize [1,4- 13 C]fumarate, which was injected into concentrated hemolysates. The kinetic data were analyzed using recently developed FmR α analysis and modeling of the enzymatic reaction using Michaelis-Menten equations. In RD-DNP experiments, the decline in the 13 C-NMR signal from fumarate, and the concurrent rise and fall of that from malate, were captured with high spectral resolution and signal-to-noise ratio, which allowed the robust quantification of fumarase kinetics. The kinetic parameters obtained indicate the potential contribution of hemolysis to the overall rate of the fumarase reaction when 13 C-NMR RD-DNP is used to detect necrosis in animal models of implanted tumors. The analytical procedures developed will be applicable to studies of other rapid enzymatic reactions using conventional and hyperpolarized substrate NMR spectroscopy. Copyright © 2018 John Wiley & Sons, Ltd.

  13. Biochemical Similarities and Differences between the Catalytic [4Fe-4S] Cluster Containing Fumarases FumA and FumB from Escherichia coli

    NARCIS (Netherlands)

    Van Vugt-Lussenburg, B.M.A.; Van der Weel, L.; Hagen, W.R.; Hagedoorn, P.L.

    2013-01-01

    Background: The highly homologous [4Fe-4S] containing fumarases FumA and FumB, sharing 90% amino acid sequence identity, from Escherichia coli are differentially regulated, which suggests a difference in their physiological function. The ratio of FumB over FumA expression levels increases by one to

  14. Purification and characterization of acetylene hydratase of Pelobacter acetylenicus, a tungsten iron-sulfur protein

    OpenAIRE

    Rosner, Bettina M.; Schink, Bernhard

    1995-01-01

    Acetylene hydratase of the mesophilic fermenting bacterium Pelobacter acetylenicus catalyzes the hydration of acetylene to acetaldehyde. Growth of P. acetylenicus with acetylene and specific acetylene hydratase activity depended on tungstate or, to a lower degree, molybdate supply in the medium. The specific enzyme activity in cell extract was highest after growth in the presence of tungstate. Enzyme activity was stable even after prolonged storage of the cell extract or of the purified prote...

  15. A 1024 channel analyser of model FH 465

    International Nuclear Information System (INIS)

    Tang Cunxun

    1988-01-01

    The FH 465 is renewed type of the 1024 Channel Analyser of model FH451. Besides simple operation and fine display, featured by the primary one, the core memory is replaced by semiconductor memory; the integration has been improved; employment of 74LS low power consumpted devices widely used in the world has not only greatly decreased the cost, but also can be easily interchanged with Apple-II, Great Wall-0520-CH or IBM-PC/XT Microcomputers. The operating principle, main specifications and test results are described

  16. F/H Effluent Treatment Facility. Preliminary engineering report

    International Nuclear Information System (INIS)

    1985-01-01

    The Department of Energy is currently proposing to construct the F/H ETF to process wastewater from the Separations Areas and replace the existing seepage basins. Reasons for seepage basin closure are two-fold. First, nonradioactive hazardous materials routinely discharged to the seepage basins may have adversely impacted the quality of the groundwater in the vicinity of the basins. Second, amendments to the Resource Conservation and Recovery Act (RCRA) were approved in 1984, prohibiting the discharge of hazardous wastes to unlined seepage basins after November, 1988. The F/H ETF will consist of wastewater storage facilities and a treatment plant discharging treated effluent to Upper Three Runs Creek. Seepage basin use in F and H Areas wil be discontinued after startup, allowing timely closure of these basins. 3 refs

  17. H Canyon Processing In Correlation With FH Analytical Labs

    International Nuclear Information System (INIS)

    Weinheimer, E.

    2012-01-01

    Management of radioactive chemical waste can be a complicated business. H Canyon and F/H Analytical Labs are two facilities present at the Savannah River Site in Aiken, SC that are at the forefront. In fact H Canyon is the only large-scale radiochemical processing facility in the United States and this processing is only enhanced by the aid given from F/H Analytical Labs. As H Canyon processes incoming materials, F/H Labs provide support through a variety of chemical analyses. Necessary checks of the chemical makeup, processing, and accountability of the samples taken from H Canyon process tanks are performed at the labs along with further checks on waste leaving the canyon after processing. Used nuclear material taken in by the canyon is actually not waste. Only a small portion of the radioactive material itself is actually consumed in nuclear reactors. As a result various radioactive elements such as Uranium, Plutonium and Neptunium are commonly found in waste and may be useful to recover. Specific processing is needed to allow for separation of these products from the waste. This is H Canyon's specialty. Furthermore, H Canyon has the capacity to initiate the process for weapons-grade nuclear material to be converted into nuclear fuel. This is one of the main campaigns being set up for the fall of 2012. Once usable material is separated and purified of impurities such as fission products, it can be converted to an oxide and ultimately turned into commercial fuel. The processing of weapons-grade material for commercial fuel is important in the necessary disposition of plutonium. Another processing campaign to start in the fall in H Canyon involves the reprocessing of used nuclear fuel for disposal in improved containment units. The importance of this campaign involves the proper disposal of nuclear waste in order to ensure the safety and well-being of future generations and the environment. As processing proceeds in the fall, H Canyon will have a substantial

  18. Biotransformation of benzonitrile herbicides via the nitrile hydratase-amidase pathway in rhodococci

    Czech Academy of Sciences Publication Activity Database

    Veselá, Alicja Barbara; Pelantová, Helena; Šulc, Miroslav; Macková, M.; Lovecká, P.; Thimová, P.; Pasquarelli, F.; Pičmanová, Martina; Pátek, Miroslav; Bhalla, T. C.; Martínková, Ludmila

    2012-01-01

    Roč. 39, č. 12 (2012), s. 1811-1819 ISSN 1367-5435 R&D Projects: GA MŠk OC09046; GA ČR(CZ) GAP504/11/0394; GA ČR GD305/09/H008 Keywords : Nitrile hydratase * Amidase * Benzonitrile herbicides Subject RIV: EE - Microbiology, Virology Impact factor: 2.321, year: 2012

  19. Recombinant expression, purification and biochemical characterization of kievitone hydratase from Nectria haematococca.

    Directory of Open Access Journals (Sweden)

    Matthias Engleder

    Full Text Available Kievitone hydratase catalyzes the addition of water to the double bond of the prenyl moiety of plant isoflavonoid kievitone and, thereby, forms the tertiary alcohol hydroxy-kievitone. In nature, this conversion is associated with a defense mechanism of fungal pathogens against phytoalexins generated by host plants after infection. As of today, a gene sequence coding for kievitone hydratase activity has only been identified and characterized in Fusarium solani f. sp. phaseoli. Here, we report on the identification of a putative kievitone hydratase sequence in Nectria haematococca (NhKHS, the teleomorph state of F. solani, based on in silico sequence analyses. After heterologous expression of the enzyme in the methylotrophic yeast Pichia pastoris, we have confirmed its kievitone hydration activity and have assessed its biochemical properties and substrate specificity. Purified recombinant NhKHS is obviously a homodimeric glycoprotein. Due to its good activity for the readily available chalcone derivative xanthohumol (XN, this compound was selected as a model substrate for biochemical studies. The optimal pH and temperature for hydratase activity were 6.0 and 35°C, respectively, and apparent Vmax and Km values for hydration of XN were 7.16 μmol min-1 mg-1 and 0.98 ± 0.13 mM, respectively. Due to its catalytic properties and apparent substrate promiscuity, NhKHS is a promising enzyme for the biocatalytic production of tertiary alcohols.

  20. Cyanide hydratases and cyanide dihydratases: emerging tools in the biodegradation and biodetection of cyanide

    Czech Academy of Sciences Publication Activity Database

    Martínková, Ludmila; Veselá, Alicja Barbara; Rinágelová, Anna; Chmátal, Martin

    2015-01-01

    Roč. 99, č. 21 (2015), s. 8875-8882 ISSN 0175-7598 R&D Projects: GA TA ČR TA01021368; GA ČR(CZ) GAP504/11/0394 Institutional support: RVO:61388971 Keywords : Cyanide hydratase * Cyanide dihydratase * Enzyme production Subject RIV: CE - Biochemistry Impact factor: 3.376, year: 2015

  1. Nitrile Hydratase CLEAs: The immobilization and stabilization of an industrially important enzyme

    Czech Academy of Sciences Publication Activity Database

    van Pelt, S.; Quignard, S.; Kubáč, David; Sorokin, D. Y.; van Rantwijk, F.; Sheldon, R. A.

    2008-01-01

    Roč. 10, č. 4 (2008), s. 395-400 ISSN 1463-9262 R&D Projects: GA MŠk OC D25.002 Institutional research plan: CEZ:AV0Z50200510 Keywords : nitrilase hydratase * clea * cross-linking Subject RIV: CE - Biochemistry Impact factor: 4.542, year: 2008

  2. [Effects of nitriles and amides on the growth and the nitrile hydratase activity of the Rhodococcus sp. strain gt1].

    Science.gov (United States)

    Maksimov, A Iu; Kuznetsova, M V; Ovechkina, G V; Kozlov, S V; Maksimova, Iu G; Demakov, V A

    2003-01-01

    Effects of some nitriles and amides, as well as glucose and ammonium, on the growth and the nitrile hydratase (EC 4.2.1.84) activity of the Rhodococcus sp. strain gt1 isolated from soil were studied. The activity of nitrile hydratase mainly depended on carbon and nitrogen supply to cells. The activity of nitrile hydratase was high in the presence of glucose and ammonium at medium concentrations and decreased at concentrations of glucose more than 0.3%. Saturated unsubstituted aliphatic nitriles and amides were found to be a good source of nitrogen and carbon. However, the presence of nitriles and amides in the medium was not absolutely necessary for the expression of the activity of nitrile hydratase isolated from the Rhodococcus sp. strain gt1.

  3. B2FH, the Cosmic Microwave Background and Cosmology*

    Science.gov (United States)

    Burbidge, G.

    In this talk I shall start by describing how we set about and carried out the work that led to the publication of Burbidge et al. (1957, hereafter B2FH). I then shall try and relate this work and the circumstances that surrounded it to the larger problem of the origin and formation of the universe. Here it is necessary to look back at the way that ideas developed and how, in many situations, astronomers went astray. Of course this is a personal view, though I very strongly believe that if he were still here, it is the approach that Fred Hoyle would take. I start by describing the problems originally encountered by Gamow and his associates in trying to decide where the helium was made. This leads me to a modern discussion of the origin of 2D, 3He, 4He and 7Li, originally described by B2FH as due to the x-process. While it is generally argued, following Gamow, Alpher, and Herman, that these isotopes were synthesised in a big bang I shall show that it is equally likely that these isotopes were made in active galactic nuclei, as was the cosmic microwave background (CMB), in a cyclic universe model. The key piece of observational evidence is that the amount of energy released in the conversion of hydrogen to helium in the universe is very close to the energy carried by the CMB, namely ~4.5 × 10-13 erg cm-3.

  4. Expression control of nitrile hydratase and amidase genes in Rhodococcus erythropolis and substrate specificities of the enzymes.

    Science.gov (United States)

    Rucká, Lenka; Volkova, Olga; Pavlík, Adam; Kaplan, Ondřej; Kracík, Martin; Nešvera, Jan; Martínková, Ludmila; Pátek, Miroslav

    2014-06-01

    Bacterial amidases and nitrile hydratases can be used for the synthesis of various intermediates and products in the chemical and pharmaceutical industries and for the bioremediation of toxic pollutants. The aim of this study was to analyze the expression of the amidase and nitrile hydratase genes of Rhodococcus erythropolis and test the stereospecific nitrile hydratase and amidase activities on chiral cyanohydrins. The nucleotide sequences of the gene clusters containing the oxd (aldoxime dehydratase), ami (amidase), nha1, nha2 (subunits of the nitrile hydratase), nhr1, nhr2, nhr3 and nhr4 (putative regulatory proteins) genes of two R. erythropolis strains, A4 and CCM2595, were determined. All genes of both of the clusters are transcribed in the same direction. RT-PCR analysis, primer extension and promoter fusions with the gfp reporter gene showed that the ami, nha1 and nha2 genes of R. erythropolis A4 form an operon transcribed from the Pami promoter and an internal Pnha promoter. The activity of Pami was found to be weakly induced when the cells grew in the presence of acetonitrile, whereas the Pnha promoter was moderately induced by both the acetonitrile or acetamide used instead of the inorganic nitrogen source. However, R. erythropolis A4 cells showed no increase in amidase and nitrile hydratase activities in the presence of acetamide or acetonitrile in the medium. R. erythropolis A4 nitrile hydratase and amidase were found to be effective at hydrolysing cyanohydrins and 2-hydroxyamides, respectively.

  5. NMR Chemical Shift of a Helium Atom as a Probe for Electronic Structure of FH, F-, (FHF)-, and FH2.

    Science.gov (United States)

    Tupikina, E Yu; Efimova, A A; Denisov, G S; Tolstoy, P M

    2017-12-21

    In this work, we present the first results of outer electronic shell visualization by using a 3 He atom as a probe particle. As model objects we have chosen F - , FH, and FH 2 + species, as well as the hydrogen-bonded complex FH···F - at various H···F - distances (3.0, 2.5, 2.0, and 1.5 Å and equilibrium at ca. 1.14 Å). The interaction energy of investigated objects with helium atom (CCSD/aug-cc-pVTZ) and helium atom chemical shift (B3LYP/pcS-2) surfaces were calculated, and their topological analysis was performed. For comparison, the results of standard quantum mechanical approaches to electronic shell visualization were presented (ESP, ELF, ED, ∇ 2 ED). We show that the Laplacian of helium chemical shift, ∇ 2 δ He , is sensitive to fluorine atom lone pair localization regions, and it can be used for the visualization of the outer electronic shell, which could be used to evaluate the proton accepting ability. The sensitivity of ∇ 2 δ He to lone pairs is preserved at distances as large as 2.0-2.5 Å from the fluorine nucleus (in comparison with the distance to ESP minima, located at 1.0-1.5 Å or maxima of ELF, which are as close as 0.6 Å to the fluorine nucleus).

  6. The bacterial catabolism of polycyclic aromatic hydrocarbons: Characterization of three hydratase-aldolase-catalyzed reactions

    Directory of Open Access Journals (Sweden)

    Jake A. LeVieux

    2016-12-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are highly toxic, pervasive environmental pollutants with mutagenic, teratogenic, and carcinogenic properties. There is interest in exploiting the nutritional capabilities of microbes to remove PAHs from various environments including those impacted by improper disposal or spills. Although there is a considerable body of literature on PAH degradation, the substrates and products for many of the enzymes have never been identified and many proposed activities have never been confirmed. This is particularly true for high molecular weight PAHs (e.g., phenanthrene, fluoranthene, and pyrene. As a result, pathways for the degradation of these compounds are proposed to follow one elucidated for naphthalene with limited experimental verification. In this pathway, ring fission produces a species that can undergo a non-enzymatic cyclization reaction. An isomerase opens the ring and catalyzes a cis to trans double bond isomerization. The resulting product is the substrate for a hydratase-aldolase, which catalyzes the addition of water to the double bond of an α,β-unsaturated ketone, followed by a retro-aldol cleavage. Initial kinetic and mechanistic studies of the hydratase-aldolase in the naphthalene pathway (designated NahE and two hydratase-aldolases in the phenanthrene pathway (PhdG and PhdJ have been completed. Crystallographic work on two of the enzymes (NahE and PhdJ provides a rudimentary picture of the mechanism and a platform for future work to identify the structural basis for catalysis and the individual specificities of these hydratase-aldolases.

  7. An Aeroplysinin-1 Specific Nitrile Hydratase Isolated from the Marine Sponge Aplysina cavernicola

    Directory of Open Access Journals (Sweden)

    Peter Proksch

    2013-08-01

    Full Text Available A nitrile hydratase (NHase that specifically accepts the nitrile aeroplysinin-1 (1 as a substrate and converts it into the dienone amide verongiaquinol (7 was isolated, partially purified and characterized from the Mediterranean sponge Aplysina cavernicola; although it is currently not known whether the enzyme is of sponge origin or produced by its symbiotic microorganisms. The formation of aeroplysinin-1 and of the corresponding dienone amide is part of the chemical defence system of A. cavernicola. The latter two compounds that show strong antibiotic activity originate from brominated isoxazoline alkaloids that are thought to protect the sponges from invasion of bacterial pathogens. The sponge was shown to contain at least two NHases as two excised protein bands from a non denaturating Blue Native gel showed nitrile hydratase activity, which was not observed for control samples. The enzymes were shown to be manganese dependent, although cobalt and nickel ions were also able to recover the activity of the nitrile hydratases. The temperature and pH optimum of the studied enzymes were found at 41 °C and pH 7.8. The enzymes showed high substrate specificity towards the physiological substrate aeroplysinin-1 (1 since none of the substrate analogues that were prepared either by partial or by total synthesis were converted in an in vitro assay. Moreover de-novo sequencing by mass spectrometry was employed to obtain information about the primary structure of the studied NHases, which did not reveal any homology to known NHases.

  8. Ferrous and ferric ions-based high-throughput screening strategy for nitrile hydratase and amidase.

    Science.gov (United States)

    Lin, Zhi-Jian; Zheng, Ren-Chao; Lei, Li-Hua; Zheng, Yu-Guo; Shen, Yin-Chu

    2011-06-01

    Rapid and direct screening of nitrile-converting enzymes is of great importance in the development of industrial biocatalytic process for pharmaceuticals and fine chemicals. In this paper, a combination of ferrous and ferric ions was used to establish a novel colorimetric screening method for nitrile hydratase and amidase with α-amino nitriles and α-amino amides as substrates, respectively. Ferrous and ferric ions reacted sequentially with the cyanide dissociated spontaneously from α-amino nitrile solution, forming a characteristic deep blue precipitate. They were also sensitive to weak basicity due to the presence of amino amide, resulting in a yellow precipitate. When amino amide was further hydrolyzed to amino acid, it gave a light yellow solution. Mechanisms of color changes were further proposed. Using this method, two isolates with nitrile hydratase activity towards 2-amino-2,3-dimethyl butyronitrile, one strain capable of hydrating 2-amino-4-(hydroxymethyl phosphiny) butyronitrile and another microbe exhibiting amidase activity against 2-amino-4-methylsulfanyl butyrlamide were obtained from soil samples and culture collections of our laboratory. Versatility of this method enabled it the first direct and inexpensive high-throughput screening system for both nitrile hydratase and amidase. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Characterization of linoleate 10-hydratase of Lactobacillus plantarum and novel antifungal metabolites

    Directory of Open Access Journals (Sweden)

    Yuan Yao Chen

    2016-10-01

    Full Text Available Lactobacilli convert linoleic acid to the antifungal compound 10-hydroxy-12-octadecenoic acid (10-HOE by linoleate 10-hydratase (10-LAH. However, the effect of this conversion on cellularmembrane physiology and properties of the cell surface have not been demonstrated. Moreover, L. plantarum produces 13-hydroxy-9-octadecenoic acid (13-HOE in addition to 10-HOE, but the antifungal activity of 13-HOE was unknown. Phylogenetic analyses conducted in this study did not differentiate between 10-LAH and linoleate 13-hydratase (13-LAH. Thus, linoleate hydratases (LAHs must be characterized through their differences in their activities of linoleate conversion. Four genes encoding putative LAHs from lactobacilli were cloned, heterologous expressed, purified and identified as FAD-dependent 10-LAH. The unsaturated fatty acid substrates stimulated the growth of lactobacilli. We also investigated the role of 10-LAH in ethanol tolerance, membrane fluidity and hydrophobicity of cell surfaces in lactobacilli by disruption of 10-lah. Compared with the L. plantarum 10-lah deficient strain, 10-LAH in wild-type strain did not exert effect on cell survival and membrane fluidity under ethanol stress, but influenced the cell surface hydrophobicity. Moreover, deletion of 10-LAH in L. plantarum facilitated purification of 13-HOE and demonstration of its antifungal activity against Penicillium roquefortii and Aspergillus niger.

  10. "What about FH of my child?" parents' opinion on family history collection in preventive primary pediatric care.

    Science.gov (United States)

    Syurina, Elena V; Gerritsen, Anne-Marie Jm; Hens, Kristien; Feron, Frans Jm

    2015-08-01

    Family history (FH) in Preventive Primary Pediatric Care is to identify children at risk for complex diseases and provide personal preventive strategies. This study was to assess parents' opinion on FH collection. Semi-structured interviews were conducted. Among issues addressed were: former experiences with FH, knowledge about FH, family definition and sharing information about FH. The importance of FH for participants depended on their knowledge, perceived family health status and former experiences. After insight into FH, parents shift to believing it to be important, but certain barriers exist in reporting FH. Parents suggest that the importance of FH should be more emphasized and more trusting relationship with Preventive Primary Pediatric Care should be invested in.

  11. Biotransformation of nitriles to amides using soluble and immobilized nitrile hydratase from Rhodococcus erythropolis A4

    Czech Academy of Sciences Publication Activity Database

    Kubáč, David; Kaplan, Ondřej; Elišáková, Veronika; Pátek, Miroslav; Vejvoda, Vojtěch; Slámová, Kristýna; Tóthová, A.; Lemaire, M.; Gallienne, E.; Lutz-Wahl, S.; Fischer, L.; Kuzma, Marek; Pelantová, Helena; van Pelt, S.; Bolte, J.; Křen, Vladimír; Martínková, Ludmila

    2008-01-01

    Roč. 50, 2-4 (2008), s. 107-113 ISSN 1381-1177 R&D Projects: GA ČR GA203/05/2267; GA MŠk(CZ) LC06010; GA MŠk OC 171 Grant - others:XE(XE) ESF COST D25/0002/02; CZ(CZ) D10-CZ25/06-07; CZ(CZ) D-25 Institutional research plan: CEZ:AV0Z50200510 Keywords : rhodococcus erythropolis * nitrile hydratase * amidase Subject RIV: EE - Microbiology, Virology Impact factor: 2.015, year: 2008

  12. Identification and characterization of an oleate hydratase-encoding gene from Bifidobacterium breve.

    Science.gov (United States)

    O'Connell, Kerry Joan; Motherway, Mary O'Connell; Hennessey, Alan A; Brodhun, Florian; Ross, R Paul; Feussner, Ivo; Stanton, Catherine; Fitzgerald, Gerald F; van Sinderen, Douwe

    2013-01-01

    Bifidobacteria are common commensals of the mammalian gastrointestinal tract. Previous studies have suggested that a bifidobacterial myosin cross reactive antigen (MCRA) protein plays a role in bacterial stress tolerance, while this protein has also been linked to the biosynthesis of conjugated linoleic acid (CLA) in bifidobacteria. In order to increase our understanding on the role of MCRA in bifidobacteria we created and analyzed an insertion mutant of the MCRA-encoding gene of B. breve NCFB 2258. Our results demonstrate that the MCRA protein of B. breve NCFB 2258 does not appear to play a role in CLA production, yet is an oleate hydratase, which contributes to bifidobacterial solvent stress protection.

  13. FH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation

    DEFF Research Database (Denmark)

    Petersen, J; Nielsen, O; Egel, R

    1998-01-01

    of the late G2 cells in a vegetatively growing population. Expression of both FH3-GFP fusions also affected cytokinesis. Overexpression of the spindle pole body component Sad1 altered the distribution of both Sad1 and the FH3-GFP domain. Together these data suggest that proteins at multiple sites can interact...... is required for conjugation, and is localized to the projection tip in cells of mating pairs. We replaced genomic fus1+ with green fluorescent protein (GFP)- tagged versions that lacked either the FH1, FH2, or FH3 domain. Deletion of any FH domain essentially abolished mating. FH3, but neither FH1 nor FH2......, was required for Fus1 localization. An FH3 domain-GFP fusion protein localized to the projection tips of mating pairs. Thus, the FH3 domain alone can direct protein localization. The FH3 domains of both Fus1 and the S. pombe cytokinesis formin Cdc12 were able to localize GFP to the spindle pole body in half...

  14. 4-Oxalocrotonate tautomerase, its homologue YwhB, and active vinylpyruvate hydratase : Synthesis and evaluation of 2-fluoro substrate analogues

    NARCIS (Netherlands)

    Johnson, William H; Wang, Susan C; Stanley, Thanuja M; Czerwinski, Robert M; Almrud, Jeffrey J; Poelarends, Gerrit J; Murzin, Alexey G; Whitman, Christian P

    2004-01-01

    A series of 2-fluoro-4-alkene and 2-fluoro-4-alkyne substrate analogues were synthesized and examined as potential inhibitors of three enzymes: 4-oxalocrotonate tautomerase (4-OT) and vinylpyruvate hydratase (VPH) from the catechol meta-fission pathway and a closely related 4-OT homologue found in

  15. Cyanide hydratase from Aspergillus niger K10: Overproduction in Escherichia coli, purification, characterization and use in continuous cyanide degradation

    Czech Academy of Sciences Publication Activity Database

    Rinágelová, Anna; Kaplan, Ondřej; Veselá, Alicja Barbara; Chmátal, Martin; Křenková, Alena; Plíhal, Ondřej; Pasquarelli, Fabrizia; Cantarella, M.; Martínková, Ludmila

    2014-01-01

    Roč. 49, č. 3 (2014), s. 445-450 ISSN 1359-5113 R&D Projects: GA ČR(CZ) GAP504/11/0394; GA TA ČR TA01021368 Institutional support: RVO:61388971 Keywords : Cyanide hydratase * Nitrilase * Aspergillus niger Subject RIV: CE - Biochemistry Impact factor: 2.516, year: 2014

  16. Expression control of nitrile hydratase and amidase genes in Rhodococcus erythropolis and substrate specificities of the enzymes

    Czech Academy of Sciences Publication Activity Database

    Rucká, Lenka; Volkova, Olga; Pavlík, Adam; Kaplan, Ondřej; Kracík, M.; Nešvera, Jan; Martínková, Ludmila; Pátek, Miroslav

    2014-01-01

    Roč. 105, č. 6 (2014), s. 1179-1190 ISSN 0003-6072 R&D Projects: GA MŠk(CZ) LC06010; GA ČR(CZ) GAP504/11/0394 Institutional support: RVO:61388971 Keywords : Rhodococcus erythropolis * Amidase * Nitrile hydratase Subject RIV: EE - Microbiology, Virology Impact factor: 1.806, year: 2014

  17. The integration of cyanide hydratase and tyrosinase catalysts enables effective degradation of cyanide and phenol in coking wastewaters

    Czech Academy of Sciences Publication Activity Database

    Martínková, Ludmila; Chmátal, Martin

    2016-01-01

    Roč. 102, October (2016), s. 90-95 ISSN 0043-1354 R&D Projects: GA TA ČR TA01021368; GA TA ČR(CZ) TA04021212; GA MŠk(CZ) LD12049 Institutional support: RVO:61388971 Keywords : Cyanide hydratase * Tyrosinase * Cyanide Subject RIV: CE - Biochemistry Impact factor: 6.942, year: 2016

  18. Structure of fumarate hydratase from Rickettsia prowazekii, the agent of typhus and suspected relative of the mitochondria

    International Nuclear Information System (INIS)

    Phan, Isabelle; Subramanian, Sandhya; Olsen, Christian; Edwards, Thomas E.; Guo, Wenjin; Zhang, Yang; Van Voorhis, Wesley C.; Stewart, Lance J.; Myler, Peter J.

    2011-01-01

    Fumarate hydratase is an enzyme of the tricarboxylic acid cycle, one of the metabolic pathways characteristic of the mitochondria. The structure of R. prowazekii class II fumarate hydratase is reported at 2.4 Å resolution and is compared with the available structure of the human homolog. Rickettsiae are obligate intracellular parasites of eukaryotic cells that are the causative agents responsible for spotted fever and typhus. Their small genome (about 800 protein-coding genes) is highly conserved across species and has been postulated as the ancestor of the mitochondria. No genes that are required for glycolysis are found in the Rickettsia prowazekii or mitochondrial genomes, but a complete set of genes encoding components of the tricarboxylic acid cycle and the respiratory-chain complex is found in both. A 2.4 Å resolution crystal structure of R. prowazekii fumarate hydratase, an enzyme catalyzing the third step of the tricarboxylic acid cycle pathway that ultimately converts phosphoenolpyruvate into succinyl-CoA, has been solved. A structure alignment with human mitochondrial fumarate hydratase highlights the close similarity between R. prowazekii and mitochondrial enzymes

  19. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs).

    Science.gov (United States)

    Wang, Huizheng; Zhang, Kai; Zhu, Jie; Song, Weiwei; Zhao, Li; Zhang, Xiuguo

    2013-01-01

    Polyhydroxyalkanoates (PHAs) have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC), which belongs to (R)-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R)-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R)-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. The data in our study reveal the regulatory mechanism of an (R)-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  20. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

    Directory of Open Access Journals (Sweden)

    Huizheng Wang

    Full Text Available Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic.We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC.The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  1. Two novel partial deletions of LDL-receptor gene in Italian patients with familial hypercholesterolemia (FH Siracusa and FH Reggio Emilia).

    Science.gov (United States)

    Garuti, R; Lelli, N; Barozzini, M; Tiozzo, R; Ghisellini, M; Simone, M L; Li Volti, S; Garozzo, R; Mollica, F; Vergoni, W; Bertolini, S; Calandra, S

    1996-03-01

    In the present study we report two novel partial deletions of the LDL-R gene. The first (FH Siracusa), found in an FH-heterozygote, consists of a 20 kb deletion spanning from the 5' flanking region to the intron 2 of the LDL-receptor gene. The elimination of the promoter and the first two exons prevents the transcription of the deleted allele, as shown by Northern blot analysis of LDL-R mRNA isolated from the proband's fibroblasts. The second deletion (FH Reggio Emilia), which eliminates 11 nucleotides of exon 10, was also found in an FH heterozygote. The characterization of this deletion was made possible by a combination of techniques such as single strand conformation polymorphism (SSCP) analysis, direct sequence of exon 10 and cloning of the normal and deleted exon 10 from the proband's DNA. The 11 nt deletion occurs in a region of exon 10 which contains three triplets (CTG) and two four-nucleotides (CTGG) direct repeats. This structural feature might render this region more susceptible to a slipped mispairing during DNA duplication. Since this deletion causes a shift of the BamHI site at the 5' end of exon 10, a method has been devised for its rapid screening which is based on the PCR amplification of exon 10 followed by BamHI digestion. FH Reggio Emilia deletion produces a shift in the reading frame downstream from Lys458, leading to a sequence of 51 novel amino acids before the occurrence of a premature stop codon (truncated receptor). However, since RT-PCR failed to demonstrate the presence of the mutant LDL-R mRNA in proband fibroblasts, it is likely that the amount of truncated receptor produced in these cells is negligible.

  2. Expansion of ribosomally produced natural products: a nitrile hydratase- and Nif11-related precursor family

    Directory of Open Access Journals (Sweden)

    Mitchell Douglas A

    2010-05-01

    Full Text Available Abstract Background A new family of natural products has been described in which cysteine, serine and threonine from ribosomally-produced peptides are converted to thiazoles, oxazoles and methyloxazoles, respectively. These metabolites and their biosynthetic gene clusters are now referred to as thiazole/oxazole-modified microcins (TOMM. As exemplified by microcin B17 and streptolysin S, TOMM precursors contain an N-terminal leader sequence and C-terminal core peptide. The leader sequence contains binding sites for the posttranslational modifying enzymes which subsequently act upon the core peptide. TOMM peptides are small and highly variable, frequently missed by gene-finders and occasionally situated far from the thiazole/oxazole forming genes. Thus, locating a substrate for a particular TOMM pathway can be a challenging endeavor. Results Examination of candidate TOMM precursors has revealed a subclass with an uncharacteristically long leader sequence closely related to the enzyme nitrile hydratase. Members of this nitrile hydratase leader peptide (NHLP family lack the metal-binding residues required for catalysis. Instead, NHLP sequences display the classic Gly-Gly cleavage motif and have C-terminal regions rich in heterocyclizable residues. The NHLP family exhibits a correlated species distribution and local clustering with an ABC transport system. This study also provides evidence that a separate family, annotated as Nif11 nitrogen-fixing proteins, can serve as natural product precursors (N11P, but not always of the TOMM variety. Indeed, a number of cyanobacterial genomes show extensive N11P paralogous expansion, such as Nostoc, Prochlorococcus and Cyanothece, which replace the TOMM cluster with lanthionine biosynthetic machinery. Conclusions This study has united numerous TOMM gene clusters with their cognate substrates. These results suggest that two large protein families, the nitrile hydratases and Nif11, have been retailored for

  3. Mechanism of Nisin, Pediocin 34, and Enterocin FH99 Resistance in Listeria monocytogenes.

    Science.gov (United States)

    Kaur, Gurpreet; Singh, Tejinder Pal; Malik, Ravinder Kumar; Bhardwaj, Arun

    2012-03-01

    Nisin-, pediocin 34-, and enterocin FH99-resistant variants of Listeria monocytogenes ATCC 53135 were developed. In an attempt to clarify the possible mechanisms underlying bacteriocin resistance in L. monocytogenes ATCC 53135, sensitivity of the resistant strains of L. monocytogenes ATCC 53135 to nisin, pediocin 34, and enterocin FH99 in the absence and presence of different divalent cations was assessed, and the results showed that the addition of divalent cations significantly reduced the inhibitory activity of nisin, pediocin 34, and enterocin FH99 against resistant variants of L. monocytogenes ATCC 53135. The addition of EDTA, however, restored this activity suggesting that the divalent cations seem to affect the initial electrostatic interaction between the positively charged bacteriocin and the negatively charged phospholipids of the membrane. Nisin-, pediocin 34-, and enterocin-resistant variants of L. monocytogenes ATCC 53135 were more resistant to lysozyme as compared to the wild-type strain both in the presence as well as absence of nisin, pediocin 34, and enterocin FH99. Ultra structural profiles of bacteriocin-sensitive L. monocytogenes and its bacteriocin-resistant counterparts revealed that the cells of wild-type strain of L. monocytogenes were maximally in pairs or short chains, whereas, its nisin-, pediocin 34-, and enterocin FH99-resistant variants tend to form aggregates. Results indicated that without a cell wall, the acquired nisin, pediocin 34, and enterocin FH99 resistance of the variants was lost. Although the bacteriocin-resistant variants appeared to lose their acquired resistance toward nisin, pediocin 34, and enterocin FH99, the protoplasts of the resistant variants appeared to be more resistant to bacteriocins than the protoplasts of their wild-type counterparts.

  4. Results of the F/H Effluent Treatment Facility biological monitoring program, July 1987--July 1991

    International Nuclear Information System (INIS)

    Specht, W.L.

    1992-07-01

    As required by the South Carolina Department of Health and Environmental Control (SCDHEC) under NPDES Permit SCO000175, biological monitoring was conducted in Upper Three Runs Creek to determine if discharges from the F/H Effluent Treatment Facility have adversely impacted the biotic community of the receiving stream. Data included in this summary report encompass July 1987 through July 1991. As originally designed, the F/H ETF was not expected to remove all of the mercury from the wastewater; therefore, SCDHEC specified that studies be conducted to determine if mercury was bioaccumulating in aquatic biota. Subsequent to approval of the biological monitoring program, an ion exchange column was added to the F/H ETF specifically to remove mercury, which eliminated mercury from the F/H ETF effluent. The results of the biological monitoring program indicate that at the present rate of discharge, the F/H ETF effluent has not adversely affected the receiving stream with respect to any of the parameters that were measured. The effluent is not toxic at the in-stream waste concentration and there is no evidence of mercury bioaccumulation

  5. Arabidopsis FH1 Formin Affects Cotyledon Pavement Cell Shape by Modulating Cytoskeleton Dynamics.

    Science.gov (United States)

    Rosero, Amparo; Oulehlová, Denisa; Stillerová, Lenka; Schiebertová, Petra; Grunt, Michal; Žárský, Viktor; Cvrčková, Fatima

    2016-03-01

    Plant cell morphogenesis involves concerted rearrangements of microtubules and actin microfilaments. We previously reported that FH1, the main Arabidopsis thaliana housekeeping Class I membrane-anchored formin, contributes to actin dynamics and microtubule stability in rhizodermis cells. Here we examine the effects of mutations affecting FH1 (At3g25500) on cell morphogenesis and above-ground organ development in seedlings, as well as on cytoskeletal organization and dynamics, using a combination of confocal and variable angle epifluorescence microscopy with a pharmacological approach. Homozygous fh1 mutants exhibited cotyledon epinasty and had larger cotyledon pavement cells with more pronounced lobes than the wild type. The pavement cell shape alterations were enhanced by expression of the fluorescent microtubule marker GFP-microtubule-associated protein 4 (MAP4). Mutant cotyledon pavement cells exhibited reduced density and increased stability of microfilament bundles, as well as enhanced dynamics of microtubules. Analogous results were also obtained upon treatments with the formin inhibitor SMIFH2 (small molecule inhibitor of formin homology 2 domains). Pavement cell shape in wild-type (wt) and fh1 plants in some situations exhibited a differential response towards anti-cytoskeletal drugs, especially the microtubule disruptor oryzalin. Our observations indicate that FH1 participates in the control of microtubule dynamics, possibly via its effects on actin, subsequently influencing cell morphogenesis and macroscopic organ development. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Purification and characterization of acetylene hydratase of Pelobacter acetylenicus, a tungsten iron-sulfur protein.

    Science.gov (United States)

    Rosner, B M; Schink, B

    1995-10-01

    Acetylene hydratase of the mesophilic fermenting bacterium Pelobacter acetylenicus catalyzes the hydration of acetylene to acetaldehyde. Growth of P. acetylenicus with acetylene and specific acetylene hydratase activity depended on tungstate or, to a lower degree, molybdate supply in the medium. The specific enzyme activity in cell extract was highest after growth in the presence of tungstate. Enzyme activity was stable even after prolonged storage of the cell extract or of the purified protein under air. However, enzyme activity could be measured only in the presence of a strong reducing agent such as titanium(III) citrate or dithionite. The enzyme was purified 240-fold by ammonium sulfate precipitation, anion-exchange chromatography, size exclusion chromatography, and a second anion-exchange chromatography step, with a yield of 36%. The protein was a monomer with an apparent molecular mass of 73 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point was at pH 4.2. Per mol of enzyme, 4.8 mol of iron, 3.9 mol of acid-labile sulfur, and 0.4 mol of tungsten, but no molybdenum, were detected. The Km for acetylene as assayed in a coupled photometric test with yeast alcohol dehydrogenase and NADH was 14 microM, and the Vmax was 69 mumol.min-1.mg of protein-1. The optimum temperature for activity was 50 degrees C, and the apparent pH optimum was 6.0 to 6.5. The N-terminal amino acid sequence gave no indication of resemblance to any enzyme protein described so far.

  7. Real-time PCR detection of Fe-type nitrile hydratase genes from environmental isolates suggests horizontal gene transfer between multiple genera.

    Science.gov (United States)

    Coffey, Lee; Owens, Erica; Tambling, Karen; O'Neill, David; O'Connor, Laura; O'Reilly, Catherine

    2010-11-01

    Nitriles are widespread in the environment as a result of biological and industrial activity. Nitrile hydratases catalyse the hydration of nitriles to the corresponding amide and are often associated with amidases, which catalyze the conversion of amides to the corresponding acids. Nitrile hydratases have potential as biocatalysts in bioremediation and biotransformation applications, and several successful examples demonstrate the advantages. In this work a real-time PCR assay was designed for the detection of Fe-type nitrile hydratase genes from environmental isolates purified from nitrile-enriched soils and seaweeds. Specific PCR primers were also designed for amplification and sequencing of the genes. Identical or highly homologous nitrile hydratase genes were detected from isolates of numerous genera from geographically diverse sites, as were numerous novel genes. The genes were also detected from isolates of genera not previously reported to harbour nitrile hydratases. The results provide further evidence that many bacteria have acquired the genes via horizontal gene transfer. The real-time PCR assay should prove useful in searching for nitrile hydratases that could have novel substrate specificities and therefore potential in industrial applications.

  8. Unveiling of novel regio-selective fatty acid double bond hydratases from Lactobacillus acidophilus involved in the selective oxyfunctionalization of mono- and di-hydroxy fatty acids.

    Science.gov (United States)

    Kim, Kyoung-Rok; Oh, Hye-Jin; Park, Chul-Soon; Hong, Seung-Hye; Park, Ji-Young; Oh, Deok-Kun

    2015-11-01

    The aim of this study is the first time demonstration of cis-12 regio-selective linoleate double-bond hydratase. Hydroxylation of fatty acids, abundant feedstock in nature, is an emerging alternative route for many petroleum replaceable products thorough hydroxy fatty acids, carboxylic acids, and lactones. However, chemical route for selective hydroxylation is still quite challenging owing to low selectivity and many environmental concerns. Hydroxylation of fatty acids by hydroxy fatty acid forming enzymes is an important route for selective biocatalytic oxyfunctionalization of fatty acids. Therefore, novel fatty acid hydroxylation enzymes should be discovered. The two hydratase genes of Lactobacillus acidophilus were identified by genomic analysis, and the expressed two recombinant hydratases were identified as cis-9 and cis-12 double-bond selective linoleate hydratases by in vitro functional validation, including the identification of products and the determination of regio-selectivity, substrate specificity, and kinetic parameters. The two different linoleate hydratases were the involved enzymes in the 10,13-dihydroxyoctadecanoic acid biosynthesis. Linoleate 13-hydratase (LHT-13) selectively converted 10 mM linoleic acid to 13S-hydroxy-9(Z)-octadecenoic acid with high titer (8.1 mM) and yield (81%). Our study will expand knowledge for microbial fatty acid-hydroxylation enzymes and facilitate the designed production of the regio-selective hydroxy fatty acids for useful chemicals from polyunsaturated fatty acid feedstocks. © 2015 Wiley Periodicals, Inc.

  9. Compatibility of Polyvinyl Alcohol with the 241-F/H Tank Farm Liquid Waste

    International Nuclear Information System (INIS)

    Oji, L.N.

    1998-01-01

    This report describes results from laboratory-scale oxidative mineralization of polyvinyl alcohol (PVA), and the evaluation of the F/H Tank Farms as a storage/disposal option for PVA waste solution generated in the Canyons and B-line decontamination operations

  10. F/H Effluent Treatment Facility filtration upgrade alternative evaluations overview

    Energy Technology Data Exchange (ETDEWEB)

    Miles, W.C. Jr.; Poirier, M.R.; Brown, D.F.

    1992-01-01

    The F/H Effluent Treatment Facility (ETF) at the Savannah River Site (SRS) was designed to treat process wastewater from the 200-F/H Production Facilities (routine wastewater) as well as intermittent flows from the F/H Retention Basins and F/H Cooling Water Basins (nonroutine wastewater). Since start-up of the ETF at SRS in 1988, the treatment process has experienced difficulties processing routine and nonroutine wastewater. Studies have identified high bacteria and bacterial decomposition products in the wastewater as the cause for excessive fouling of the filtration system. In order to meet Waste Management requirements for the treatment of processed wastewater, an upgrade of the ETF filtration system is being developed. This upgrade must be able to process the nonroutine wastewater at design capacity. As a result, a study of alternative filter technologies was conducted utilizing simulated wastewater. The simulated wastewater tests have been completed. Three filter technologies, centrifugal polymeric ultrafilters, tubular polymeric ultrafilters, and backwashable cartridge filters have been selected for further evaluation utilizing actual ETF wastewater.

  11. F/H Effluent Treatment Facility filtration upgrade alternative evaluations overview

    Energy Technology Data Exchange (ETDEWEB)

    Miles, W.C. Jr.; Poirier, M.R.; Brown, D.F.

    1992-07-01

    The F/H Effluent Treatment Facility (ETF) at the Savannah River Site (SRS) was designed to treat process wastewater from the 200-F/H Production Facilities (routine wastewater) as well as intermittent flows from the F/H Retention Basins and F/H Cooling Water Basins (nonroutine wastewater). Since start-up of the ETF at SRS in 1988, the treatment process has experienced difficulties processing routine and nonroutine wastewater. Studies have identified high bacteria and bacterial decomposition products in the wastewater as the cause for excessive fouling of the filtration system. In order to meet Waste Management requirements for the treatment of processed wastewater, an upgrade of the ETF filtration system is being developed. This upgrade must be able to process the nonroutine wastewater at design capacity. As a result, a study of alternative filter technologies was conducted utilizing simulated wastewater. The simulated wastewater tests have been completed. Three filter technologies, centrifugal polymeric ultrafilters, tubular polymeric ultrafilters, and backwashable cartridge filters have been selected for further evaluation utilizing actual ETF wastewater.

  12. Compatibility of Polyvinyl Alcohol with the 241-F/H Tank Farm Liquid Waste

    Energy Technology Data Exchange (ETDEWEB)

    Oji, L.N.

    1998-11-25

    This report describes results from laboratory-scale oxidative mineralization of polyvinyl alcohol (PVA), and the evaluation of the F/H Tank Farms as a storage/disposal option for PVA waste solution generated in the Canyons and B-line decontamination operations.

  13. F/H effluent treatment facility filtration upgrade alternative evaluations overview

    International Nuclear Information System (INIS)

    Miles, W.C. Jr.; Poirier, M.R.; Brown, D.F.

    1992-01-01

    The F/H Effluent Treatment Facility (ETF) at the Savannah River Site (SRS) was designed to treat process wastewater from the 200-F/H Production Facilities (routine wastewater) as well as intermittent flows from the F/H Retention Basins and F/H Cooling Water Basins (nonroutine wastewater). Since start-up of the ETF at SRS in 1988, the treatment process has experienced difficulties processing routine and nonroutine wastewater. Studies have identified high bacteria and bacterial decomposition products in the wastewater as the cause for excessive fouling of the filtration system. In order to meet Waste Management requirements for the treatment of processed wastewater, an upgrade of the ETF filtration system is being developed. This upgrade must be able to process the nonroutine wastewater at design capacity. As a result, a study of alternative filter technologies was conducted utilizing simulated wastewater. The simulated wastewater tests have been completed. Three filter technologies, centrifugal polymeric ultrafilters, tubular polymeric ultrafilters, and backwashable cartridge filters have been selected for further evaluation utilizing actual ETF wastewater. (author)

  14. Biochemical similarities and differences between the catalytic [4Fe-4S] cluster containing fumarases FumA and FumB from Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Barbara M A van Vugt-Lussenburg

    Full Text Available BACKGROUND: The highly homologous [4Fe-4S] containing fumarases FumA and FumB, sharing 90% amino acid sequence identity, from Escherichia coli are differentially regulated, which suggests a difference in their physiological function. The ratio of FumB over FumA expression levels increases by one to two orders of magnitude upon change from aerobic to anaerobic growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: To understand this difference in terms of structure-function relations, catalytic and thermodynamic properties were determined for the two enzymes obtained from homologous overexpression systems. FumA and FumB are essentially identical in their Michaelis-Menten kinetics of the reversible fumarate to L-malate conversion; however, FumB has a significantly greater catalytic efficiency for the conversion of D-tartrate to oxaloacetate consistent with the requirement of the fumB gene for growth on D-tartrate. Reduction potentials of the [4Fe-4S](2+ Lewis acid active centre were determined in mediated bulk titrations in the presence of added substrate and were found to be approximately -290 mV for both FumA and FumB. CONCLUSIONS/SIGNIFICANCE: This study contradicts previously published claims that FumA and FumB exhibit different catalytic preferences for the natural substrates L-malate and fumarate. FumA and FumB differ significantly only in the catalytic efficiency for the conversion of D-tartrate, a supposedly non-natural substrate. The reduction potential of the substrate-bound [4Fe-4S] active centre is, contrary to previously reported values, close to the cellular redox potential.

  15. Self-subunit swapping occurs in another gene type of cobalt nitrile hydratase.

    Directory of Open Access Journals (Sweden)

    Yi Liu

    Full Text Available Self-subunit swapping is one of the post-translational maturation of the cobalt-containing nitrile hydratase (Co-NHase family of enzymes. All of these NHases possess a gene organization of , which allows the activator protein to easily form a mediatory complex with the α-subunit of the NHase after translation. Here, we discovered that the incorporation of cobalt into another type of Co-NHase, with a gene organization of , was also dependent on self-subunit swapping. We successfully isolated a recombinant NHase activator protein (P14K of Pseudomonas putida NRRL-18668 by adding a Strep-tag N-terminal to the P14K gene. P14K was found to form a complex [α(StrepP14K(2] with the α-subunit of the NHase. The incorporation of cobalt into the NHase of P. putida was confirmed to be dependent on the α-subunit substitution between the cobalt-containing α(StrepP14K(2 and the cobalt-free NHase. Cobalt was inserted into cobalt-free α(StrepP14K(2 but not into cobalt-free NHase, suggesting that P14K functions not only as a self-subunit swapping chaperone but also as a metallochaperone. In addition, NHase from P. putida was also expressed by a mutant gene that was designed with a order. Our findings expand the general features of self-subunit swapping maturation.

  16. Cyanide hydratases and cyanide dihydratases: emerging tools in the biodegradation and biodetection of cyanide.

    Science.gov (United States)

    Martínková, Ludmila; Veselá, Alicja Barbara; Rinágelová, Anna; Chmátal, Martin

    2015-11-01

    The purpose of this study is to summarize the current knowledge of the enzymes which are involved in the hydrolysis of cyanide, i.e., cyanide hydratases (CHTs; EC 4.2.1.66) and cyanide dihydratases (CynD; EC 3.5.5.1). CHTs are probably exclusively produced by filamentous fungi and widely occur in these organisms; in contrast, CynDs were only found in a few bacterial genera. CHTs differ from CynDs in their reaction products (formamide vs. formic acid and ammonia, respectively). Several CHTs were also found to transform nitriles but with lower relative activities compared to HCN. Mutants of CynDs and CHTs were constructed to study the structure-activity relationships in these enzymes or to improve their catalytic properties. The effect of the C-terminal part of the protein on the enzyme activity was determined by constructing the corresponding deletion mutants. CynDs are less active at alkaline pH than CHTs. To improve its bioremediation potential, CynD from Bacillus pumilus was engineered by directed evolution combined with site-directed mutagenesis, and its operation at pH 10 was thus enabled. Some of the enzymes have been tested for their potential to eliminate cyanide from cyanide-containing wastewaters. CynDs were also used to construct cyanide biosensors.

  17. Activity Enhancement Based on the Chemical Equilibrium of Multiple-Subunit Nitrile Hydratase from Bordetella petrii.

    Science.gov (United States)

    Liu, Yi; Liu, Ping; Lin, Lu; Zhao, Yueqin; Zhong, Wenjuan; Wu, Lunjie; Zhou, Zhemin; Sun, Weifeng

    2016-09-01

    The maturation mechanism of nitrile hydratase (NHase) of Pseudomonas putida NRRL-18668 was discovered and named as "self-subunit swapping." Since the NHase of Bordetella petrii DSM 12804 is similar to that of P. putida, the NHase maturation of B. petrii is proposed to be the same as that of P. putida. However, there is no further information on the application of NHase according to these findings. We successfully rapidly purified NHase and its activator through affinity his tag, and found that the cell extracts of NHase possessed multiple types of protein ingredients including α, β, α2β2, and α(P14K)2 who were in a state of chemical equilibrium. Furthermore, the activity was significantly enhanced through adding extra α(P14K)2 to the cell extracts of NHase according to the chemical equilibrium. Our findings are useful for the activity enhancement of multiple-subunit enzyme and for the first time significantly increased the NHase activity according to the chemical equilibrium.

  18. Vibrational deactivation on chemically reactive potential surfaces: An exact quantum study of a low barrier collinear model of H + FH, D + FD, H + FD and D + FH

    International Nuclear Information System (INIS)

    Schatz, G.C.; Kuppermann, A.

    1980-01-01

    We study vibrational deactivation processes on chemically reactive potential energy surfaces by examining accurate quantum mechanical transition probabilities and rate constants for the collinear H + FH(v), D + FD(v), H + FD(v), and D + FH(v) reactions. A low barrier (1.7 kcal/mole) potential surface is used in these calculations, and we find that for all four reactions, the reactive inelastic rate constants are larger than the nonreactive ones for the same initial and final vibrational states. However, the ratios of these reactive and nonreactive rate constants depend strongly on the vibrational quantum number v and the isotopic composition of the reagents. Nonreactive and reactive transition probabilities for multiquantum jump transitions are generally comparable to those for single quantum transitions. This vibrationally nonadiabatic behavior is a direct consequence of the severe distortion of the diatomic that occurs in a collision on a low barrier reactive surface, and can make chemically reactive atoms like H or D more efficient deactivators of HF or DF than nonreactive collision partners. Many conclusions are in at least qualitative agreement with those of Wilkin's three dimensional quasiclassical trajectory study on the same systems using a similar surface. We also present results for H + HF(v) collisions which show that for a higher barrier potential surface (33 rather than 1.7 kcal/mole), the deactivation process becomes similar in character to that for nonreactive partners, with v→v-1 processes dominating

  19. Performance of Adaptive Antennas in FH-GSM Using Conventional Beamforming

    DEFF Research Database (Denmark)

    Mogensen, Preben Elgaard; Leth-Espensen, P; Zetterberg, P.

    2000-01-01

    This paper presents the performance of adaptive antennas in a 1/3 reuse frequency hopping GSM network using conventional beamforming. It mainly focuses on C/I improvement for the purpose of capacity enhancement. The performance evaluation has been conducted by means of network computer simulations...... implementation facilitates a potential capacity gain of x3 in a 1/3 reuse FH-GSM network for an array size of M = 4-6....

  20. Homozygous familial hypercholesterolemia (HoFH in Germany: an epidemiological survey

    Directory of Open Access Journals (Sweden)

    Walzer S

    2013-05-01

    Full Text Available S Walzer,1 K Travers,2 S Rieder,3 E Erazo-Fischer,3 D Matusiewicz41MArS Market Access and Pricing Strategy UG (hb, Weil am Rhein, Germany; 2United Biosource Corporation, Lexington, USA; 3Alcimed GmbH, Cologne, Germany; 4Institute for Health Care Management and Research, Faculty of Economics and Business Administration, University of Duisburg-Essen, Essen, GermanyIntroduction: In Europe a disease is recognized as rare if less than 1 in 2000 people suffer from the specific disease. In patients with familial homozygous hypercholesterolemia (HoFH the accumulation of low-density lipoprotein cholesterol (LDL-C leads to generalized atherosclerosis due to an insufficient functioning of the LDL-C receptors. Patients die early sometimes even in the mid-30s, from myocardial infarction or stroke. For the German population, insufficient epidemiological evidence exists.Methods: A systematic literature search in EMBASE and Medline was performed in conjunction with a targeted manual search for epidemiological HoFH studies. Additionally a nationwide survey was conducted in Germany in all identified apheresis- and lipid centers. The purpose of the survey was the validation of the systematic literature search results based on empirical (practice data.Results: In total 961 publications were found, 874 were excluded based on pre-defined exclusion criteria leaving only 87 for further review. After review of the identified abstracts (n = 87 23 publications were identified as epidemiological studies. Only one publication was found which reported a prevalence of 1:1,000,000. The qualitative survey among 187 physicians in Germany also revealed a low prevalence: 95 HoFH patients were identified in 35 centers.Conclusion: The estimated frequency of homozygous familial hypercholesterolemia patients in Germany is around 95 (1:860,000 and the disease should be recognized as rare according to the definition of the European Medical Agency.Keywords: epidemiology, homozygous

  1. Ferrihydrite-impregnated granular activated carbon (FH@GAC) for efficient phosphorus removal from wastewater secondary effluent.

    Science.gov (United States)

    Mahardika, Dedy; Park, Hak-Soon; Choo, Kwang-Ho

    2018-05-23

    Adsorptive removal of phosphorus from wastewater effluents has attracted attention because of its reduced sludge production and potential P recovery. In this study, we investigated granular activated carbons (GACs) impregnated with amorphous ferrihydrite (FH@GAC) for the sorption of phosphorus from aqueous solutions. Preoxidation of intact GAC surfaces using an oxidant (e.g., hypochlorite) and strong acids (e.g., HNO 3 /H 2 SO 4 ) was performed to create active functional groups (e.g., carboxyl or phenolic) for enhanced iron binding, leading to greater phosphorus uptake. Both the rate and the capacity of phosphorus sorption onto FH@GAC had significant, positive relationships (Pearson correlation coefficient r > 0.9) with the product of surface area and Fe content. The pseudo-second-order reaction kinetics explained the P sorption rate better than the pseudo-first-order reaction kinetics, whereas the Langmuir model fit the P sorption isotherm better than the Freundlich model. The iron content in the FH@GAC increased significantly (>10 mg/g) when GAC (e.g., BMC1050) was preoxidized by a 1:1 (w/w) concentrated HNO 3 /H 2 SO 4 mixture. The Langmuir maximum P sorption capacity of a functionalized FH@BMC1050 adsorbent prepared with acid pretreatment was estimated to be substantial (5.73 mg P/g GAC corresponding to 526 mg P/g Fe). This sorption capacity was superior to that of a FH slurry, possibly because the nano-sized FH formed inside the GAC pores (<2.5 nm) can bind phosphate ions more effectively than FH aggregates. Fixed-bed column reactor operation with bicarbonate regeneration showed potential for efficient, continuous phosphorus removal by FH@GAC media. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Enzyme-substrate binding landscapes in the process of nitrile biodegradation mediated by nitrile hydratase and amidase.

    Science.gov (United States)

    Zhang, Yu; Zeng, Zhuotong; Zeng, Guangming; Liu, Xuanming; Chen, Ming; Liu, Lifeng; Liu, Zhifeng; Xie, Gengxin

    2013-08-01

    The continuing discharge of nitriles in various industrial processes has caused serious environmental consequences of nitrile pollution. Microorganisms possess several nitrile-degrading pathways by direct interactions of nitriles with nitrile-degrading enzymes. However, these interactions are largely unknown and difficult to experimentally determine but important for interpretation of nitrile metabolisms and design of nitrile-degrading enzymes with better nitrile-converting activity. Here, we undertook a molecular modeling study of enzyme-substrate binding modes in the bi-enzyme pathway for degradation of nitrile to acid. Docking results showed that the top substrates having favorable interactions with nitrile hydratase from Rhodococcus erythropolis AJ270 (ReNHase), nitrile hydratase from Pseudonocardia thermophila JCM 3095 (PtNHase), and amidase from Rhodococcus sp. N-771 (RhAmidase) were benzonitrile, 3-cyanopyridine, and L-methioninamide, respectively. We further analyzed the interactional profiles of these top poses with corresponding enzymes, showing that specific residues within the enzyme's binding pockets formed diverse contacts with substrates. This information on binding landscapes and interactional profiles is of great importance for the design of nitrile-degrading enzyme mutants with better oxidation activity toward nitriles or amides in the process of pollutant treatments.

  3. The integration of cyanide hydratase and tyrosinase catalysts enables effective degradation of cyanide and phenol in coking wastewaters.

    Science.gov (United States)

    Martínková, Ludmila; Chmátal, Martin

    2016-10-01

    The aim of this study was to design an effective method for the bioremediation of coking wastewaters, specifically for the concurrent elimination of their highly toxic components - cyanide and phenols. Almost full degradation of free cyanide (0.32-20 mM; 8.3-520 mg L(-1)) in the model and the real coking wastewaters was achieved by using a recombinant cyanide hydratase in the first step. The removal of cyanide, a strong inhibitor of tyrosinase, enabled an effective degradation of phenols by this enzyme in the second step. Phenol (16.5 mM, 1,552 mg L(-1)) was completely removed from a real coking wastewater within 20 h and cresols (5.0 mM, 540 mg L(-1)) were removed by 66% under the same conditions. The integration of cyanide hydratase and tyrosinase open up new possibilities for the bioremediation of wastewaters with complex pollution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency

    NARCIS (Netherlands)

    Bedoyan, Jirair K.; Yang, Samuel P.; Ferdinandusse, Sacha; Jack, Rhona M.; Miron, Alexander; Grahame, George; DeBrosse, Suzanne D.; Hoppel, Charles L.; Kerr, Douglas S.; Wanders, Ronald J. A.

    2017-01-01

    Mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. We describe a case compound heterozygous for ECHS1 mutations c.836T>C (novel) and c.8C>A identified by whole exome sequencing of proband and

  5. Construction of diabatic energy surfaces for LiFH with artificial neural networks

    Science.gov (United States)

    Guan, Yafu; Fu, Bina; Zhang, Dong H.

    2017-12-01

    A new set of diabatic potential energy surfaces (PESs) for LiFH is constructed with artificial neural networks (NNs). The adiabatic PESs of the ground state and the first excited state are directly fitted with NNs. Meanwhile, the adiabatic-to-diabatic transformation (ADT) angles (mixing angles) are obtained by simultaneously fitting energy difference and interstate coupling gradients. No prior assumptions of the functional form of ADT angles are used before fitting, and the ab initio data including energy difference and interstate coupling gradients are well reproduced. Converged dynamical results show remarkable differences between adiabatic and diabatic PESs, which suggests the significance of non-adiabatic processes.

  6. Insights into catalytic activity of industrial enzyme Co-nitrile hydratase. Docking studies of nitriles and amides.

    Science.gov (United States)

    Peplowski, Lukasz; Kubiak, Karina; Nowak, Wieslaw

    2007-07-01

    Nitrile hydratase (NHase) is an enzyme containing non-corrin Co3+ in the non-standard active site. NHases from Pseudonocardia thermophila JCM 3095 catalyse hydration of nitriles to corresponding amides. The efficiency of the enzyme is 100 times higher for aliphatic nitriles then aromatic ones. In order to understand better this selectivity dockings of a series of aliphatic and aromatic nitriles and related amides into a model protein based on an X-ray structure were performed. Substantial differences in binding modes were observed, showing better conformational freedom of aliphatic compounds. Distinct interactions with postranslationally modified cysteines present in the active site of the enzyme were observed. Modeling shows that water molecule activated by a metal ion may easily directly attack the docked acrylonitrile to transform this molecule into acryloamide. Thus docking studies provide support for one of the reaction mechanisms discussed in the literature.

  7. The First Example of a Nitrile Hydratase Model Complex that Reversibly Binds Nitriles

    Science.gov (United States)

    Shearer, Jason; Jackson, Henry L.; Schweitzer, Dirk; Rittenberg, Durrell K.; Leavy, Tanya M.; Kaminsky, Werner; Scarrow, Robert C.; Kovacs, Julie A.

    2015-01-01

    Nitrile hydratase (NHase) is an iron-containing metalloenzyme that converts nitriles to amides. The mechanism by which this biochemical reaction occurs is unknown. One mechanism that has been proposed involves nucleophilic attack of an Fe-bound nitrile by water (or hydroxide). Reported herein is a five-coordinate model compound ([FeIII(S2Me2N3(Et,Pr))]+) containing Fe(III) in an environment resembling that of NHase, which reversibly binds a variety of nitriles, alcohols, amines, and thiocyanate. XAS shows that five-coordinate [FeIII(S2Me2N3(Et,Pr))]+ reacts with both methanol and acetonitrile to afford a six-coordinate solvent-bound complex. Competitive binding studies demonstrate that MeCN preferentially binds over ROH, suggesting that nitriles would be capable of displacing the H2O coordinated to the iron site of NHase. Thermodynamic parameters were determined for acetonitrile (ΔH = −6.2(±0.2) kcal/mol, ΔS = −29.4(±0.8) eu), benzonitrile (−4.2(±0.6) kcal/mol, ΔS = −18(±3) eu), and pyridine (ΔH = −8(±1) kcal/mol, ΔS = −41(±6) eu) binding to [FeIII(S2Me2N3(Et,Pr))]+ using variable-temperature electronic absorption spectroscopy. Ligand exchange kinetics were examined for acetonitrile, iso-propylnitrile, benzonitrile, and 4-tert-butylpyridine using 13C NMR line-broadening analysis, at a variety of temperatures. Activation parameters for ligand exchange were determined to be ΔH‡ = 7.1(±0.8) kcal/mol, ΔS‡ = −10(±1) eu (acetonitrile), ΔH‡ = 5.4(±0.6) kcal/mol, ΔS‡ = −17(±2) eu (iso-propionitrile), ΔH‡ = 4.9(±0.8) kcal/mol, ΔS‡ = −20(±3) eu (benzonitrile), and ΔH‡ = 4.7(±1.4) kcal/mol ΔS‡ = −18(±2) eu (4-tert-butylpyridine). The thermodynamic parameters for pyridine binding to a related complex, [FeIII(S2Me2N3(Pr,Pr))]+ (ΔH = −5.9(±0.8) kcal/mol, ΔS = −24(±3) eu), are also reported, as well as kinetic parameters for 4-tert-butylpyridine exchange (ΔH‡ = 3.1(±0.8) kcal/mol, ΔS‡)−25(±3) eu

  8. Fabrication and dispersion evaluation of single-wall carbon nanotubes produced by FH-arc discharge method.

    Science.gov (United States)

    Chen, B; Zhao, X; Inoue, S; Ando, Y

    2010-06-01

    In this work, we produced SWNTs by a hydrogen DC arc discharge with evaporation of carbon anode containing 1 at% Fe catalyst in H2-Ar mixture gas. This was named as FH-arc discharge method. The as-grown SWNTs synthesized by FH-arc discharge method have high crystallinity. An oxidation purification process of as-grown SWNTs with H2O2 has been developed to remove the coexisting Fe catalyst nanoparticles. As a result, SWNTs with purity higher than 90 at% have been achieved. To exhibit remarkable characteristics, CNTs should be separated from the bundles and kept in homogeneous and stable suspensions. For this purpose, the SWNTs prepared by FH-arc discharge method also have been treated by Nanomizer process with some surfactants. SPM images showed that the SWNTs bundles had become thinner and shorter.

  9. F/H seepage basin groundwater influent, effluent, precipitated sludge characterization task technical plan

    International Nuclear Information System (INIS)

    Siler, J.L.

    1993-01-01

    A treatability study to support the development of a remediation system which would reduce the contaminant levels in groundwater removed from the aquifers in the vicinity of the F/H seepage basins and southwest of the Mixed Waste Management Facility (MWMF) at the Savannah River facility was conducted. Proposed changes in the remediation system require an additional study to determine whether precipitated sludge generated from the proposed remediation system will be hazardous as defined by RCRA. Several contaminants, such as lead and mercury, are above the groundwater protection standards. The presence of radionuclides and other contaminants in the sludge does not present a problem provided that the sludge can pass the Toxicity Characteristic Leaching Procedure (TCLP) test. The study has been developed in such a manner as to cover the possible range of treatment options that may be used

  10. Cloning, purification, crystallization and preliminary X-ray diffraction analysis of nitrile hydratase from the themophilic Bacillus smithii SC-J05-1

    International Nuclear Information System (INIS)

    Hourai, Shinji; Ishii, Takeshi; Miki, Misao; Takashima, Yoshiki; Mitsuda, Satoshi; Yanagi, Kazunori

    2005-01-01

    The nitrile hydratase from the themophilic B. smithii SC-J05-1 (Bs NHase) has been purified, cloned and crystallized. Nitrile hydratase (NHase) converts nitriles to the corresponding amides and is recognized as having important industrial applications. Purification, cloning, crystallization and initial crystallographic studies of the NHase from Bacillus smithii SC-J05-1 (Bs NHase) were conducted to analyze the activity, specificity and thermal stability of this hydrolytic enzyme. Bs NHase was purified to homogeneity from microbial cells of B. smithii SC-J05-1 and the nucleotide sequences of both the α- and β-subunits were determined. Purified Bs NHase was used for crystallization and several crystal forms were obtained by the vapour-diffusion method. Microseeding and the addition of magnesium ions were essential components to obtain crystals suitable for X-ray diffraction analysis

  11. [Effect of melaxen and valdoxan on free radical processes intensity, aconitate hydratase activity and citrate content in rats tissues under hyperthyroidism].

    Science.gov (United States)

    Gorbenko, M V; Popova, T N; Shul'gin, K K; Popov, S S; Agarkov, A A

    2014-01-01

    The influence of melaxen and valdoxan on the biochemiluminescence parameters, aconitate hydratase activity and citrate level in rats heart and liver during development of experimental hyperthyroidism has been investigated. Administration of these substances promoted a decrease of biochemiluminescence parameters, which had been increased in tissues of rats in response to the development of oxidative stress under hyperthyroidism. Aconitate hydratase activity and citrate concentration in rats liver and heart, growing at pathological conditions, changed towards control value after administration of the drugs correcting melatonin level. The results indicate the positive effect of valdoxan and melaxen on oxidative status of the organism under the development of experimental hyperthyroidism that is associated with antioxidant action of melatonin.

  12. Characterization of LDL-receptors of freshly isolated mononuclear cells of healthy subjects and of FH-patients

    International Nuclear Information System (INIS)

    Banyai, M.

    1991-05-01

    The central role of the LDL (=low density lipoproteins) receptor in artherosclerosis was first appreciated when it was shown that its absence was responsible for FH (familial hypercholesterolemia). To determine the high affinity cell surface binding activity in circulating human mononuclear cells (MNCs), these cells were incubated with low concentrations (1-50 μg protein/ml) of 123 I-LDL or 111 In-LDL either in the presence or absence of an excess of unlabeled LDL at 4 deg C for 45 minutes. MNCs of healthy subjects and of heterozygous FH-patients were found to possess high affinity LDL receptors immediately after they were isolated from the blood stream. The results indicate that the FH-patients enclosed in this study possess a reduced number of the same high affinity binding sites as healthy subjects confirming the diagnosis of heterozygous FH. In this study 123 I-LDL binding and 111 In-LDL binding to MNCs has been shown to saturable, reversible and displaceable and time-dependent. 123 I-LDL and 111 In-LDL as well can be recommended for the in-vitro determination of LDL-receptor binding activity as both binding processes show approximately the same characteristics. (author)

  13. Development of Two FhSAP2 Recombinant–Based Assays for Immunodiagnosis of Human Chronic Fascioliasis

    Science.gov (United States)

    Shin, Sun Hee; Hsu, Angel; Chastain, Holly M.; Cruz, Lorna A.; Elder, Eric S.; Sapp, Sarah G. H.; McAuliffe, Isabel; Espino, Ana M.; Handali, Sukwan

    2016-01-01

    In the United States, infection with Fasciola hepatica has been identified as an emerging disease, primarily in immigrants, refugees, and travelers. The laboratory test of choice for diagnosis of fascioliasis is detection of disease specific antibodies, most commonly uses excretory-secretory antigens for detection of IgG antibodies. Recently, recombinant proteins such as F. hepatica antigen (FhSAP2) have been used to detect IgG antibodies. The glutathione S-transferase (GST)–FhSAP2 recombinant antigen was used to develop Western blot (WB) and fluorescent bead-based (Luminex) assays to detect F. hepatica total IgG and IgG4 antibodies. The sensitivity and specificity of GST-FhSAP2 total IgG and IgG4 WB were similar at 94% and 98%, respectively. For the IgG Luminex assay, the sensitivity and specificity were 94% and 97%, and for the IgG4, the values were 100% and 99%, respectively. In conclusion, the GST-FhSAP2 antigen performs well in several assay formats and can be used for clinical diagnosis. PMID:27549636

  14. Development of Two FhSAP2 Recombinant-Based Assays for Immunodiagnosis of Human Chronic Fascioliasis.

    Science.gov (United States)

    Shin, Sun Hee; Hsu, Angel; Chastain, Holly M; Cruz, Lorna A; Elder, Eric S; Sapp, Sarah G H; McAuliffe, Isabel; Espino, Ana M; Handali, Sukwan

    2016-10-05

    In the United States, infection with Fasciola hepatica has been identified as an emerging disease, primarily in immigrants, refugees, and travelers. The laboratory test of choice for diagnosis of fascioliasis is detection of disease specific antibodies, most commonly uses excretory-secretory antigens for detection of IgG antibodies. Recently, recombinant proteins such as F. hepatica antigen (FhSAP2) have been used to detect IgG antibodies. The glutathione S-transferase (GST)-FhSAP2 recombinant antigen was used to develop Western blot (WB) and fluorescent bead-based (Luminex) assays to detect F. hepatica total IgG and IgG 4 antibodies. The sensitivity and specificity of GST-FhSAP2 total IgG and IgG 4 WB were similar at 94% and 98%, respectively. For the IgG Luminex assay, the sensitivity and specificity were 94% and 97%, and for the IgG 4 , the values were 100% and 99%, respectively. In conclusion, the GST-FhSAP2 antigen performs well in several assay formats and can be used for clinical diagnosis. © The American Society of Tropical Medicine and Hygiene.

  15. Waste characterization for the F/H Effluent Treatment Facility in support of waste certification

    International Nuclear Information System (INIS)

    Brown, D.F.

    1994-01-01

    The Waste Acceptance Criteria (WAC) procedures define the rules concerning packages of solid Low Level Waste (LLW) that are sent to the E-area vaults (EAV). The WACs tabulate the quantities of 22 radionuclides that require manifesting in waste packages destined for each type of vault. These quantities are called the Package Administrative Criteria (PAC). If a waste package exceeds the PAC for any radionuclide in a given vault, then specific permission is needed to send to that vault. To avoid reporting insignificant quantities of the 22 listed radionuclides, the WAC defines the Minimum Reportable Quantity (MRQ) of each radionuclide as 1/1000th of the PAC. If a waste package contains less than the MRQ of a particular radionuclide, then the package's manifest will list that radionuclide as zero. At least one radionuclide has to be reported, even if all are below the MRQ. The WAC requires that the waste no be ''hazardous'' as defined by SCDHEC/EPA regulations and also lists several miscellaneous physical/chemical requirements for the packages. This report evaluates the solid wastes generated within the F/H Effluent Treatment Facility (ETF) for potential impacts on waste certification

  16. Simulation and Comparison Between Slow and Fast FH/BPSK Spread Spectrum Using Matlab

    Directory of Open Access Journals (Sweden)

    Sanaa Said Kadhim

    2018-02-01

    Full Text Available This paper investigates the properties and applications of Frequency Hopping Spread Spectrum (FHSS.  FHSS is radio communication technique by which the sender of information sends the data on a radio channel, which changes the frequency of transmission based on a predetermined sequence of code. The FHSS has many advantages over traditional modulation methods, it can overcome fading, multipath channels and interferences. Hence the interception becomes difficult. This security feature makes FHSS more preferable for  military applications. At the receiver side, the signal is demodulated by the same carrier signal for which frequency changes by the same code sequences used by the sender. This paper presents two types of FHSS, slow and fast. The  simulation procedures of both types were  implemented and applied on   Frequency Hopping /Binary Phase Shift Keying (FH/BPSK spread spectrum system using MATLAB. The simulation sequences for fast and slow frequency hopping is the same in number  and frequencies of spreading carriers and both used BPSK traditional modulation type. The  comparison  results  based on their power spectral density   show that the fast frequency hopping is more resistive to noise the slow one.

  17. ESS-FH: Enhanced Security Scheme for Fast Handover in Hierarchical Mobile IPv6

    Science.gov (United States)

    You, Ilsun; Lee, Jong-Hyouk; Sakurai, Kouichi; Hori, Yoshiaki

    Fast Handover for Hierarchical Mobile IPv6 (F-HMIPv6) that combines advantages of Fast Handover for Mobile IPv6 (FMIPv6) and Hierarchical Mobile IPv6 (HMIPv6) achieves the superior performance in terms of handover latency and signaling overhead compared with previously developed mobility protocols. However, without being secured, F-HMIPv6 is vulnerable to various security threats. In 2007, Kang and Park proposed a security scheme, which is seamlessly integrated into F-HMIPv6. In this paper, we reveal that Kang-Park's scheme cannot defend against the Denial of Service (DoS) and redirect attacks while largely relying on the group key. Then, we propose an Enhanced Security Scheme for F-HMIPv6 (ESS-FH) that achieves the strong key exchange and the key independence as well as addresses the weaknesses of Kang-Park's scheme. More importantly, it enables fast handover between different MAP domains. The proposed scheme is formally verified based on BAN-logic, and its handover latency is analyzed and compared with that of Kang-Park's scheme.

  18. ESP's Tank 42 washwater transfer to the 241-F/H tank farms

    International Nuclear Information System (INIS)

    Aponte, C.I.; Lee, E.D.

    1997-12-01

    As a result of the separation of the High-Level Liquid Waste Department into three separate organizations (formerly there were two) (Concentration, Storage, and Transfer (CST), Waste Pre-Treatment (WPT) and Waste Disposition (WD)) process interface controls were required. One of these controls is implementing the Waste the waste between CST and WPT. At present, CST's Waste Acceptance Criteria is undergoing revision and WPT has not prepared the required Waste Compliance Plan (WCP). The Waste Pre-Treatment organization is making preparations for transferring spent washwater in Tank 42 to Tank 43 and/or Tank 22. The washwater transfer is expected to complete the washing steps for preparing ESP batch 1B sludge. This report is intended to perform the function of a Waste Compliance Plan for the proposed transfer. Previously, transfers between the Tank Farm and ITP/ESP were controlled by requirements outlined in the Tank Farm's Technical Standards and ITP/ESP's Process Requirements. Additionally, these controls are implemented primarily in operating procedure 241-FH-7TSQ and ITP Operations Manual SW16.1-SOP-WTS-1 which will be completed prior to performing the waste transfers

  19. Enhancement of thermo-stability and product tolerance of Pseudomonas putida nitrile hydratase by fusing with self-assembling peptide.

    Science.gov (United States)

    Liu, Yi; Cui, Wenjing; Liu, Zhongmei; Cui, Youtian; Xia, Yuanyuan; Kobayashi, Michihiko; Zhou, Zhemin

    2014-09-01

    Self-assembling amphipathic peptides (SAPs) are the peptides that can spontaneously assemble into ordered nanostructures. It has been reported that the attachment of SAPs to the N- or C-terminus of an enzyme can benefit the thermo-stability of the enzyme. Here, we discovered that the thermo-stability and product tolerance of nitrile hydratase (NHase) were enhanced by fusing with two of the SAPs (EAK16 and ELK16). When the ELK16 was fused to the N-terminus of β-subunit, the resultant NHase (SAP-NHase-2) became an active inclusion body; EAK16 fused NHase in the N-terminus of β-subunit (SAP-NHase-1) and ELK16 fused NHase in the C-terminus of β-subunit (SAP-NHase-10) did not affect NHase solubility. Compared with the deactivation of the wild-type NHase after 30 min incubation at 50°C, SAP-NHase-1, SAP-NHase-2 and SAP-NHase-10 retained 45%, 30% and 50% activity; after treatment in the buffer containing 10% acrylamide, the wild-type retained 30% activity, while SAP-NHase-1, SAP-NHase-2 and SAP-NHase-10 retained 52%, 42% and 55% activity. These SAP-NHases with enhanced thermo-stability and product tolerance would be helpful for further industrial applications of the NHase. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Nitrile hydratase of Rhodococcus erythropolis: characterization of the enzyme and the use of whole cells for biotransformation of nitriles.

    Science.gov (United States)

    Kamble, Ashwini L; Banoth, Linga; Meena, Vachan Singh; Singh, Amit; Chisti, Yusuf; Banerjee, U C

    2013-08-01

    The intracellular cobalt-type nitrile hydratase was purified from the bacterium Rhodococcuserythropolis. The pure enzyme consisted of two subunits of 29 and 30 kDa. The molecular weight of the native enzyme was estimated to be 65 kDa. At 25 °C the enzyme had a half-life of 25 h. The Michaelis-Menten constants K m and v max for the enzyme were 0.624 mM and 5.12 μmol/min/mg, respectively, using 3-cyanopyridine as the substrate. The enzyme-containing freely-suspended bacterial cells and the cells immobilized within alginate beads were evaluated for converting the various nitriles to amides. In a packed bed reactor, alginate beads (2 % alginate; 3 mm bead diameter) containing 200 mg/mL of cells, achieved a conversion of >90 % for benzonitrile and 4-cyanopyridine in 38 h (25 °C, pH 7.0) at a feed substrate concentration of 100 mM. The beads could be reused for up to six reaction cycles.

  1. Is the tungsten(IV complex (NEt42[WO(mnt2] a functional analogue of acetylene hydratase?

    Directory of Open Access Journals (Sweden)

    Matthias Schreyer

    2017-11-01

    Full Text Available The tungsten(IV complex (Et4N2[W(O(mnt2] (1; mnt = maleonitriledithiolate was proposed (Sarkar et al., J. Am. Chem. Soc. 1997, 119, 4315 to be a functional analogue of the active center of the enzyme acetylene hydratase from Pelobacter acetylenicus, which hydrates acetylene (ethyne; 2 to acetaldehyde (ethanal; 3. In the absence of a satisfactory mechanistic proposal for the hydration reaction, we considered the possibility of a metal–vinylidene type activation mode, as it is well established for ruthenium-based alkyne hydration catalysts with anti-Markovnikov regioselectivity. To validate the hypothesis, the regioselectivity of tungsten-catalyzed alkyne hydration of a terminal, higher alkyne had to be determined. However, complex 1 was not a competent catalyst for the hydration of 1-octyne under the conditions tested. Furthermore, we could not observe the earlier reported hydration activity of complex 1 towards acetylene. A critical assessment of, and a possible explanation for the earlier reported results are offered. The title question is answered with "no".

  2. A Cognitive Radio based Solution to Coexistence of FH and OFDM Signals Implemented on USRP N210 Platform

    Directory of Open Access Journals (Sweden)

    M. Janjić

    2017-06-01

    Full Text Available A new concept development and practical implementation of an OFDM based secondary cognitive link are presented in this paper. Coexistence of a secondary user employing Orthogonal Frequency Division Multiplexing (OFDM and a primary user employing Frequency Hopping (FH is achieved. Secondary and primary links are realized using Universal Software Radio Peripheral (USRP N210 platforms. Cognitive features of spectrum sensing and changing transmission parameters are implemented. Some experimental results are presented.

  3. Kinetic effects of sulfur oxidation on catalytic nitrile hydration: nitrile hydratase insights from bioinspired ruthenium(II) complexes.

    Science.gov (United States)

    Kumar, Davinder; Nguyen, Tho N; Grapperhaus, Craig A

    2014-12-01

    Kinetic investigations inspired by the metalloenzyme nitrile hydratase were performed on a series of ruthenium(II) complexes to determine the effect of sulfur oxidation on catalytic nitrile hydration. The rate of benzonitrile hydration was quantified as a function of catalyst, nitrile, and water concentrations. Precatalysts L(n)RuPPh3 (n = 1-3; L(1) = 4,7-bis(2'-methyl-2'-mercapto-propyl)-1-thia-4,7-diazacyclononane; L(2) = 4-(2'-methyl-2'-sulfinatopropyl)-7-(2'-methyl-2'-mercapto-propyl)-1-thia-4,7-diazacyclononane; L(3) = 4-(2'-methyl-2'-sulfinatopropyl)-7-(2'-methyl-2'-sulfenato-propyl)-1-thia-4,7-diazacyclononane) were activated by substitution of triphenylphosphine with substrate in hot dimethylformamide solution. Rate measurements are consistent with a dynamic equilibrium between inactive aqua (L(n)Ru-OH2) and active nitrile (L(n)Ru-NCR) derivatives with K = 21 ± 1, 9 ± 0.9, and 23 ± 3 for L(1) to L(3), respectively. Subsequent hydration of the L(n)Ru-NCR intermediate yields the amide product with measured hydration rate constants (k's) of 0.37 ± 0.01, 0.82 ± 0.07, and 1.59 ± 0.12 M(-1) h(-1) for L(1) to L(3), respectively. Temperature dependent studies reveal that sulfur oxidation lowers the enthalpic barrier by 27 kJ/mol, but increases the entropic barrier by 65 J/(mol K). Density functional theory (DFT) calculations (B3LYP/LanL2DZ (Ru); 6-31G(d) (all other atoms)) support a nitrile bound catalytic cycle with lowering of the reaction barrier as a consequence of sulfur oxidation through enhanced nitrile binding and attack of the water nucleophile through a highly organized transition state.

  4. Antibacterial efficacy of Nisin, Pediocin 34 and Enterocin FH99 against Listeria monocytogenes and cross resistance of its bacteriocin resistant variants to common food preservatives.

    Science.gov (United States)

    Kaur, G; Singh, T P; Malik, R K

    2013-01-01

    Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.

  5. Antibacterial efficacy of Nisin, Pediocin 34 and Enterocin FH99 against Listeria monocytogenes and cross resistance of its bacteriocin resistant variants to common food preservatives

    Directory of Open Access Journals (Sweden)

    G. Kaur

    2013-01-01

    Full Text Available Antilisterial efficiency of three bacteriocins, viz, Nisin, Pediocin 34 and Enterocin FH99 was tested individually and in combination against Listeria mononcytogenes ATCC 53135. A greater antibacterial effect was observed when the bacteriocins were combined in pairs, indicating that the use of more than one LAB bacteriocin in combination have a higher antibacterial action than when used individually. Variants of Listeria monocytogenes ATCC 53135 resistant to Nisin, Pediocin 34 and Enterocin FH99 were developed. Bacteriocin cross-resistance of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class. Resistance to Pediocin 34 conferred cross resistance to Enterocin FH 99 but not to Nisin. Similarly resistance to Enterocin FH99 conferred cross resistance to Pediocin 34 but not to Nisin. Also, the sensitivity of Nisin, Pediocin 34 and Enterocin FH99 resistant variants of Listeria monocytogenes to low pH, salt, sodium nitrite, and potassium sorbate was assayed in broth and compared to the parental wild-type strain. The Nisin, Pediocin 34 and Enterocin FH99 resistant variants did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the bacteriocin resistant Listeria monocytogenes variants examined were more resistant to inhibitors than the parental strains.

  6. Myosin-cross-reactive antigen (MCRA protein from Bifidobacterium breve is a FAD-dependent fatty acid hydratase which has a function in stress protection

    Directory of Open Access Journals (Sweden)

    Ross R

    2011-02-01

    Full Text Available Abstract Background The aim of this study was to determine the catalytic activity and physiological role of myosin-cross-reactive antigen (MCRA from Bifidobacterium breve NCIMB 702258. MCRA from B. breve NCIMB 702258 was cloned, sequenced and expressed in heterologous hosts (Lactococcus and Corynebacterium and the recombinant proteins assessed for enzymatic activity against fatty acid substrates. Results MCRA catalysed the conversion of palmitoleic, oleic and linoleic acids to the corresponding 10-hydroxy fatty acids, but shorter chain fatty acids were not used as substrates, while the presence of trans-double bonds and double bonds beyond the position C12 abolished hydratase activity. The hydroxy fatty acids produced were not metabolised further. We also found that heterologous Lactococcus and Corynebacterium expressing MCRA accumulated increasing amounts of 10-HOA and 10-HOE in the culture medium. Furthermore, the heterologous cultures exhibited less sensitivity to heat and solvent stresses compared to corresponding controls. Conclusions MCRA protein in B. breve can be classified as a FAD-containing double bond hydratase, within the carbon-oxygen lyase family, which may be catalysing the first step in conjugated linoleic acid (CLA production, and this protein has an additional function in bacterial stress protection.

  7. Myosin-cross-reactive antigen (MCRA) protein from Bifidobacterium breve is a FAD-dependent fatty acid hydratase which has a function in stress protection.

    Science.gov (United States)

    Rosberg-Cody, Eva; Liavonchanka, Alena; Göbel, Cornelia; Ross, R Paul; O'Sullivan, Orla; Fitzgerald, Gerald F; Feussner, Ivo; Stanton, Catherine

    2011-02-17

    The aim of this study was to determine the catalytic activity and physiological role of myosin-cross-reactive antigen (MCRA) from Bifidobacterium breve NCIMB 702258. MCRA from B. breve NCIMB 702258 was cloned, sequenced and expressed in heterologous hosts (Lactococcus and Corynebacterium) and the recombinant proteins assessed for enzymatic activity against fatty acid substrates. MCRA catalysed the conversion of palmitoleic, oleic and linoleic acids to the corresponding 10-hydroxy fatty acids, but shorter chain fatty acids were not used as substrates, while the presence of trans-double bonds and double bonds beyond the position C12 abolished hydratase activity. The hydroxy fatty acids produced were not metabolised further. We also found that heterologous Lactococcus and Corynebacterium expressing MCRA accumulated increasing amounts of 10-HOA and 10-HOE in the culture medium. Furthermore, the heterologous cultures exhibited less sensitivity to heat and solvent stresses compared to corresponding controls. MCRA protein in B. breve can be classified as a FAD-containing double bond hydratase, within the carbon-oxygen lyase family, which may be catalysing the first step in conjugated linoleic acid (CLA) production, and this protein has an additional function in bacterial stress protection.

  8. Myosin-cross-reactive antigen (MCRA) protein from Bifidobacterium breve is a FAD-dependent fatty acid hydratase which has a function in stress protection

    LENUS (Irish Health Repository)

    Rosberg-Cody, Eva

    2011-02-17

    Abstract Background The aim of this study was to determine the catalytic activity and physiological role of myosin-cross-reactive antigen (MCRA) from Bifidobacterium breve NCIMB 702258. MCRA from B. breve NCIMB 702258 was cloned, sequenced and expressed in heterologous hosts (Lactococcus and Corynebacterium) and the recombinant proteins assessed for enzymatic activity against fatty acid substrates. Results MCRA catalysed the conversion of palmitoleic, oleic and linoleic acids to the corresponding 10-hydroxy fatty acids, but shorter chain fatty acids were not used as substrates, while the presence of trans-double bonds and double bonds beyond the position C12 abolished hydratase activity. The hydroxy fatty acids produced were not metabolised further. We also found that heterologous Lactococcus and Corynebacterium expressing MCRA accumulated increasing amounts of 10-HOA and 10-HOE in the culture medium. Furthermore, the heterologous cultures exhibited less sensitivity to heat and solvent stresses compared to corresponding controls. Conclusions MCRA protein in B. breve can be classified as a FAD-containing double bond hydratase, within the carbon-oxygen lyase family, which may be catalysing the first step in conjugated linoleic acid (CLA) production, and this protein has an additional function in bacterial stress protection.

  9. Remedial technology and characterization development at the SRS F/H Retention Basins using the DOE SAFER methodology

    International Nuclear Information System (INIS)

    Miles, W.C. Jr.; Kuelske, K.J.

    1994-01-01

    The Streamlined Approach For Environmental Restoration (SAFER) is a strategy used to accelerate and improve the environmental assessment and remediation of the F/H Retention Basins at the Savannah River Site (SRS). TMs strategy combines the data quality objectives (DQO) process and the observational approach to focus on data collection and converge on a remedial action early. This approach emphasizes stakeholder involvement throughout the Remedial Investigation/Feasibility Study (RI/FS) process. The SAFER methodology is being applied to the characterization, technology development, and remediation tasks for the F/H Retention Basins. This ''approach was initiated in the scoping phase of these projects through the involvment of major stakeholders; Department of Energy (DOE)-Savannah River Field Office, DOE-Headquarters, Westinghouse Savannah River Company, United States Environmental Protection Agency (EPA) Region IV, and the state of South Carolina Department of Health and Environmental Control (SCDHEC), in the development of the Remedial Investigation (RI) workplans. A major activity that has been initiated is the development and implementation of a phase I workplan to identify preliminary contaminants of concern (pCOCs). A sampling plan was developed and approved by the major stakeholders for preliminary characterization of wastes remaining in the F/H Retention Basins. The involvement of stakeholders, development of a site conceptual model, development of remedial objectives for probable conditions, identification of the problem and reasonable deviations, and development of initial decision rules in the planning stages will ensure that preliminary data needs are identified and obtained prior to the initiation of the assessment and implementation phases of the projects resulting in the final remediation of the sites in an accelerated and more cost effective manner

  10. Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review.

    Science.gov (United States)

    Wang, Ting; Guo, Rixin; Zhou, Guohong; Zhou, Xidan; Kou, Zhenzhen; Sui, Feng; Li, Chun; Tang, Liying; Wang, Zhuju

    2016-07-21

    Panax notoginseng (Burk.) F.H. Chen is a widely used traditional Chinese medicine known as Sanqi or Tianqi in China. This plant, which is distributed primarily in the southwest of China, has wide-ranging pharmacological effects and can be used to treat cardiovascular diseases, pain, inflammation and trauma as well as internal and external bleeding due to injury. This paper provides up-to-date information on investigations of this plant, including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. The possible uses and perspectives for future investigation of this plant are also discussed. The relevant information on Panax notoginseng (Burk.) F.H. Chen was collected from numerous resources, including classic books about Chinese herbal medicine, and scientific databases, including Pubmed, SciFinder, ACS, Ebsco, Elsevier, Taylor, Wiley and CNKI. More than 200 chemical compounds have been isolated from Panax notoginseng (Burk.) F.H. Chen, including saponins, flavonoids and cyclopeptides. The plant has pharmacological effects on the cardiovascular system, immune system as well as anti-inflammatory, anti-atherosclerotic, haemostatic and anti-tumour activities, etc. Panax notoginseng is a valuable traditional Chinese medical herb with multiple pharmacological effects. This review summarizes the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of P. notoginseng, and presents the constituents and their corresponding chemical structures found in P. notoginseng comprehensively for the first time. Future research into its phytochemistry of bio-active components should be performed by using bioactivity-guided isolation strategies. Further work on elucidation of the structure-function relationship among saponins, understanding of multi-target network pharmacology of P. notoginseng, as well as developing its new clinical usage and comprehensive utilize will enhance the therapeutic potentials of P. notoginseng. Copyright © 2016

  11. Trace elements controlling the atmospheric circulation. Atmospheric environmental research as part of future FhG research

    Energy Technology Data Exchange (ETDEWEB)

    1986-11-01

    Atmospheric trace substances such as methane (CH/sub 4/), ozone and nitrogen oxides (NO/sub x/) essentially influence the biosphere. FhG research work will be consisting in the long-term measurement of trace substance concentrations in different places (e.g. South Africa, Italy, Thailand or China). An air container packed with measuring instruments and data storage equipment was sent to South America with scientists on board measuring the distribution of trace substances over the northern and southern hemisphere.

  12. PENAMPILAN REPRODUKSI SAPI PERAH FRIESIAN HOLSTEIN (FH PADA BERBAGAI PARITAS DAN BULAN LAKTASI DI KETINGGIAN TEMPAT YANG BERBEDA

    Directory of Open Access Journals (Sweden)

    Aju Tjatur N. K

    2012-04-01

    Full Text Available ABSTRAK Suatu penelitian dengan tujuan untuk mengetahui penampilan reproduksi sapi perah FH pada berbagai paritas dan bulan laktasi di ketinggian tempat yang berbeda telah dilakukan. Penelitian dilaksanakan di Koperasi Usaha Sapi Perah Nongkojajar (daerah dataran tinggi dan Koperasi Usaha Sapi Perah Grati (daerah dataran rendah Kabupaten Pasuruan. Hasil penelitian menyimpulkan bahwa  sapi FH yang dipelihara di dataran tinggi lebih baik penampilan reproduksinya dibandingkan yang dipelihara di dataran rendah.. Rata-rata nilai DO, CI dan S/C di dataran tinggi masing-masing 110,84±46,45 hari, 382,58±45,76 hari dan 1,58±0,78 sedangkan di dataran rendah  129,91±32,05 hari, 40,47±32,84 hari dan 2,82±0,77. Efisiensi reproduksi ternak di dataran tinggi menunjukkan penampilan  yang lebih baik daripada di dataran rendah. Paritas dan bulan laktasi tidak memberikan pengaruh yang nyata terhadap penampilan  reproduksi sapi perah FH.   Kata kunci: penampilan reproduksi, paritas, bulan laktasi dan  ketinggian tempat   The Performances of Reproductive Friesian Holstein (FH  Dairy Cows at Various Parity and Month of Lactation in Different Altitude   ABSTRACT The aim of the research was to know  the reproductive performance of dairy cows Friesian Holstein (FH at various parity and month of lactation in different altitude. The research was conducted at KPSP Setia Kawan Nongkojajar (highlands and KUTT Suka Makmur  Grati (lowlands Pasuruan regency. The results concluded that reproductive performance dairy cows at high altitude better than low altitude. The average value of DO, CI and S / C at highlands 110.84 ± 46.45 days, 382.58 ± 45.76 days and 1.58 ± 0.78 while at lowlands 129.91 ± 32.05 days, 401.47 ± 32.84 days and 2.82 ± 0.77. The parity and month of lactation not significant affected on the reproductive performance dairy cows..   Keywords: reproductive performance,  parity, month of lactation and altitude

  13. Generation of iPSC line iPSC-FH2.1 in hypoxic conditions from human foreskin fibroblasts

    Directory of Open Access Journals (Sweden)

    María Questa

    2016-03-01

    Full Text Available Human foreskin fibroblasts were used to generate the iPSC line iPSC-FH2.1 using the EF1a-hSTEMCCA-loxP vector expressing OCT4, SOX2, c-MYC and KLF4, in 5% O2 culture conditions. Stemness was confirmed, as was pluripotency both in vivo and in vitro, in normoxia and hypoxia. Human Embryonic Stem Cell (hESC line WA-09 and reprogrammed fibroblast primary culture HFF-FM were used as controls.

  14. Effect of growth media on cell envelope composition and nitrile hydratase stability in Rhodococcus rhodochrous strain DAP 96253.

    Science.gov (United States)

    Tucker, Trudy-Ann; Crow, Sidney A; Pierce, George E

    2012-11-01

    Rhodococcus is an important industrial microorganism that possesses diverse metabolic capabilities; it also has a cell envelope, composed of an outer layer of mycolic acids and glycolipids. Selected Rhodococcus species when induced are capable of transforming nitriles to the corresponding amide by the enzyme nitrile hydratase (NHase), and subsequently to the corresponding acid via an amidase. This nitrile biochemistry has generated interest in using the rhodococci as biocatalysts. It was hypothesized that altering sugars in the growth medium might impact cell envelope components and have effects on NHase. When the primary carbon source in growth media was changed from glucose to fructose, maltose, or maltodextrin, the NHase activity increased. Cells grown in the presence of maltose and maltodextrin showed the highest activities against propionitrile, 197 and 202 units/mg cdw, respectively. Stability of NHase was also affected as cells grown in the presence of maltose and maltodextrin retained more NHase activity at 55 °C (45 and 23 %, respectively) than cells grown in the presence of glucose or fructose (19 and 10 %, respectively). Supplementation of trehalose in the growth media resulted in increased NHase stability at 55 °C, as cells grown in the presence of glucose retained 40 % NHase activity as opposed to 19 % without the presence of trehalose. Changes in cell envelope components, such mycolic acids and glycolipids, were evaluated by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC), respectively. Changing sugars and the addition of inducing components for NHase, such as cobalt and urea in growth media, resulted in changes in mycolic acid profiles. Mycolic acid content increased 5 times when cobalt and urea were added to media with glucose. Glycolipids levels were also affected by the changes in sugars and addition of inducing components. This research demonstrates that carbohydrate selection impacts NHase activity and

  15. Discriminative ability of LDL-cholesterol to identify patients with familial hypercholesterolemia: a cross-sectional study in 26,406 individuals tested for genetic FH.

    Science.gov (United States)

    Huijgen, Roeland; Hutten, Barbara A; Kindt, Iris; Vissers, Maud N; Kastelein, John J P

    2012-06-01

    Screening for familial hypercholesterolemia (FH) within affected families is often based on cutoff values for low-density lipoprotein cholesterol (LDL-C). However, the diagnostic accuracy of LDL-C levels is influenced by the magnitude of the LDL-C overlap between FH patients and unaffected relatives. The purpose of the current study was to assess to what extent this overlap is influenced by the severity of specific FH mutations. Individuals were eligible if they underwent family screening for FH between 2003 and 2010. The entire cohort was then compared with those who were investigated for the presence of the most severe mutations (class 1). The area under the receiver operating characteristics curve and the sensitivity of the 90th percentile of LDL-C were calculated for both cohorts. We included 26 406 individuals, of whom 9169 (35%) carried an FH-causing mutation. In the entire cohort at baseline, mean LDL-C was 4.63 ± 1.44 mmol/L for FH carriers (n=5372) and 2.96 ± 0.96 mmol/L for unaffected relatives (n=15 148); P<0.001. The corresponding operating characteristics curve (95% CI) was 86.6% (85.9%-87.2%), and the cutoff level of LDL-C above the 90th percentile showed a sensitivity of 68.5%. The operating characteristics curve and sensitivity significantly improved when the 5933 individuals tested for class 1 mutations were assessed separately; 96.2% (95.3%-97.1%) and 91.3%, respectively. In summary, the overlap in terms of LDL-C levels between those with molecularly proven FH and unaffected relatives is to a large extent because of the high prevalence of modestly severe LDL-receptor mutations in the Netherlands.

  16. PENAMPILAN PRODUKSI SAPI PERAH FRIESIAN HOLSTEIN (FH PADA BERBAGAI PARITAS DAN BULAN LAKTASI DI KETINGGIAN TEMPAT YANG BERBEDA

    Directory of Open Access Journals (Sweden)

    Aju Tjatur Nugroho K.

    2010-04-01

    Full Text Available The aim of the research was to know the performance of milk yield Holstein Friesian (FH of dairy cows at various parities and month of lactation in different altitude. The research was conducted from January to March 2010 at Setia Kawan dairy cooperative in Nongkojajar (highlands and Suka Makmur dairy cooperative in Grati (lowlands. Both cooperatives were located in Pasuruan regency. The research materials used totally 90 heads of FH dairy cows (45 heads in Nongkojajar and 45 heads in Grati which consisted of parity 2 (15 heads, parity 3 (15 heads and parity 4 (15 heads. Each parity consisted of 2nd lactation (5 heads, 3rd lactation (5 heads and 4th lactation (5 heads. The variables were daily milk yield, and environmental factors related to milk yield and reproductive performance of dairy cows that is temperature and air humidity, temperature humidity index (THI and feed consumption. The method of the research was case study. The data had been analyzed by ANOVA and if there were significant influences it would be further tested using Duncan multiple range test. The results showed that the altitude significantly affected milk yield (P<0.05. Average milk yield at lowlands and highlands were 10.17±2.57 liters and 13.10±3.20 liters, but the 2nd, 3rd and 4th parities did not significantly affect milk yield. Another finding showed that the month of lactation significantly affected milk yield (P<0.05. Average milk yield in the 2nd, 3rd and 4th lactations were 12.98±3.61, 11.28±2.76 and 10.63±2.92 litters respectively. Based on the results it was concluded that the altitude and the month of lactation affected milk yield performances of FH dairy cows. It was suggested to improve environmental conditions at lowlands through controlling the temperature and humidity (THI for not more than 72 so that appropriate for dairy cows and to improve management of productivity, reproductive and feeding practices. Keywords: milk yield, dairy cow, parity, month

  17. Metabolic reconstructions identify plant 3-methylglutaconyl-CoA hydratase that is crucial for branched-chain amino acid catabolism in mitochondria.

    Science.gov (United States)

    Latimer, Scott; Li, Yubing; Nguyen, Thuong T H; Soubeyrand, Eric; Fatihi, Abdelhak; Elowsky, Christian G; Block, Anna; Pichersky, Eran; Basset, Gilles J

    2018-05-09

    The proteinogenic branched-chain amino acids (BCAAs) leucine, isoleucine and valine are essential nutrients for mammals. In plants, BCAAs double as alternative energy sources when carbohydrates become limiting, the catabolism of BCAAs providing electrons to the respiratory chain and intermediates to the tricarboxylic acid cycle. Yet, the actual architecture of the degradation pathways of BCAAs is not well understood. In this study, gene network modeling in Arabidopsis and rice, and plant-prokaryote comparative genomics detected candidates for 3-methylglutaconyl-CoA hydratase (4.2.1.18), one of the missing plant enzymes of leucine catabolism. Alignments of these protein candidates sampled from various spermatophytes revealed non-homologous N-terminal extensions that are lacking in their bacterial counterparts, and green fluorescent protein-fusion experiments demonstrated that the Arabidopsis protein, product of gene At4g16800, is targeted to mitochondria. Recombinant At4g16800 catalyzed the dehydration of 3-hydroxymethylglutaryl-CoA into 3-methylglutaconyl-CoA, and displayed kinetic features similar to those of its prokaryotic homolog. When at4g16800 knockout plants were subjected to dark-induced carbon starvation, their rosette leaves displayed accelerated senescence as compared to control plants, and this phenotype was paralleled by a marked increase in the accumulation of free and total leucine, isoleucine and valine. The seeds of the at4g16800 mutant showed a similar accumulation of free BCAAs. These data suggest that 3-methylglutaconyl-CoA hydratase is not solely involved in the degradation of leucine, but is also a significant contributor to that of isoleucine and valine. Furthermore, evidence is shown that unlike the situation observed in Trypanosomatidae, leucine catabolism does not contribute to the formation of the terpenoid precursor mevalonate. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights

  18. Expression of GFP-mTalin reveals an actin-related role for the Arabidopsis Class II formin AtFH12

    Czech Academy of Sciences Publication Activity Database

    Cvrčková, F.; Grunt, M.; Žárský, Viktor

    2012-01-01

    Roč. 56, č. 3 (2012), s. 431-440 ISSN 0006-3134 R&D Projects: GA ČR GAP305/10/0433 Institutional research plan: CEZ:AV0Z50380511 Keywords : FH2 proteins * genetic redundancy * salt stress Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.692, year: 2012

  19. Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.

    Science.gov (United States)

    Yoon, Ji-Yong; Cho, Hyun-Soo; Lee, Jeong-Ju; Lee, Hyo-Jung; Jun, Soo Young; Lee, Jae-Hye; Song, Hyuk-Hwan; Choi, SangHo; Saloura, Vassiliki; Park, Choon Gil; Kim, Cheol-Hee; Kim, Nam-Soon

    2016-04-01

    TRAIL (TNF-related apoptosis inducing ligand) is a promising anti-cancer drug target that selectively induces apoptosis in cancer cells. However, many cancer cells are resistant to TRAIL-induced apoptosis. Therefore, reversing TRAIL resistance is an important step for the development of effective TRAIL-based anti-cancer therapies. We previously reported that knockdown of the TOR signaling pathway regulator-like (TIPRL) protein caused TRAIL-induced apoptosis by activation of the MKK7-c-Jun N-terminal Kinase (JNK) pathway through disruption of the MKK7-TIPRL interaction. Here, we identified Taraxacum officinale F.H. Wigg (TO) as a novel TRAIL sensitizer from a set of 500 natural products using an ELISA system and validated its activity by GST pull-down analysis. Furthermore, combination treatment of Huh7 cells with TRAIL and TO resulted in TRAIL-induced apoptosis mediated through inhibition of the MKK7-TIPRL interaction and subsequent activation of MKK7-JNK phosphorylation. Interestingly, HPLC analysis identified chicoric acid as a major component of the TO extract, and combination treatment with chicoric acid and TRAIL induced TRAIL-induced cell apoptosis via JNK activation due to inhibition of the MKK7-TIPRL interaction. Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  20. Catalytic Mechanism of Nitrile Hydratase Proposed by Time-resolved X-ray Crystallography Using a Novel Substrate, tert-Butylisonitrile*S⃞

    Science.gov (United States)

    Hashimoto, Koichi; Suzuki, Hiroyuki; Taniguchi, Kayoko; Noguchi, Takumi; Yohda, Masafumi; Odaka, Masafumi

    2008-01-01

    Nitrile hydratases (NHases) have an unusual iron or cobalt catalytic center with two oxidized cysteine ligands, cysteine-sulfinic acid and cysteine-sulfenic acid, catalyzing the hydration of nitriles to amides. Recently, we found that the NHase of Rhodococcus erythropolis N771 exhibited an additional catalytic activity, converting tert-butylisonitrile (tBuNC) to tert-butylamine. Taking advantage of the slow reactivity of tBuNC and the photoreactivity of nitrosylated NHase, we present the first structural evidence for the catalytic mechanism of NHase with time-resolved x-ray crystallography. By monitoring the reaction with attenuated total reflectance-Fourier transform infrared spectroscopy, the product from the isonitrile carbon was identified as a CO molecule. Crystals of nitrosylated inactive NHase were soaked with tBuNC. The catalytic reaction was initiated by photo-induced denitrosylation and stopped by flash cooling. tBuNC was first trapped at the hydrophobic pocket above the iron center and then coordinated to the iron ion at 120 min. At 440 min, the electron density of tBuNC was significantly altered, and a new electron density was observed near the isonitrile carbon as well as the sulfenate oxygen of αCys114. These results demonstrate that the substrate was coordinated to the iron and then attacked by a solvent molecule activated by αCys114-SOH. PMID:18948265

  1. Proteomic analysis of Fasciola hepatica excretory and secretory products (FhESPs) involved in interacting with host PBMCs and cytokines by shotgun LC-MS/MS.

    Science.gov (United States)

    Liu, Qing; Huang, Si-Yang; Yue, Dong-Mei; Wang, Jin-Lei; Wang, Yujian; Li, Xiangrui; Zhu, Xing-Quan

    2017-02-01

    Fasciola hepatica is a helminth parasite with a worldwide distribution, which can cause chronic liver disease, fasciolosis, leading to economic losses in the livestock and public health in many countries. Control is mostly reliant on the use of drugs, and as a result, drug resistance has now emerged. The identification of F. hepatica genes involved in interaction between the parasite and host immune system is utmost important to elucidate the evasion mechanisms of the parasite and develop more effective strategies against fasciolosis. In this study, we aimed to identify molecules in F. hepatica excretory and secretory products (FhESPs) interacting with the host peripheral blood mononuclear cells (PBMCs), Th1-like cytokines (IL2 and IFN-γ), and Th17-like cytokines (IL17) by Co-IP combined with tandem mass spectrometry. The results showed that 14, 16, and 9 proteins in FhESPs could bind with IL2, IL17, and IFN-γ, respectively, which indicated that adult F. hepatica may evade the host immune responses through directly interplaying with cytokines. In addition, nine proteins in FhESPs could adhere to PBMCs. Our findings provided potential targets as immuno-regulators, and will be helpful to elucidate the molecular basis of host-parasite interactions and search for new potential proteins as vaccine and drug target candidates.

  2. Ab initio calculation of reaction energies. III. Basis set dependence of relative energies on the FH2 and H2CO potential energy surfaces

    International Nuclear Information System (INIS)

    Frisch, M.J.; Binkley, J.S.; Schaefer, H.F. III

    1984-01-01

    The relative energies of the stationary points on the FH 2 and H 2 CO nuclear potential energy surfaces relevant to the hydrogen atom abstraction, H 2 elimination and 1,2-hydrogen shift reactions have been examined using fourth-order Moller--Plesset perturbation theory and a variety of basis sets. The theoretical absolute zero activation energy for the F+H 2 →FH+H reaction is in better agreement with experiment than previous theoretical studies, and part of the disagreement between earlier theoretical calculations and experiment is found to result from the use of assumed rather than calculated zero-point vibrational energies. The fourth-order reaction energy for the elimination of hydrogen from formaldehyde is within 2 kcal mol -1 of the experimental value using the largest basis set considered. The qualitative features of the H 2 CO surface are unchanged by expansion of the basis set beyond the polarized triple-zeta level, but diffuse functions and several sets of polarization functions are found to be necessary for quantitative accuracy in predicted reaction and activation energies. Basis sets and levels of perturbation theory which represent good compromises between computational efficiency and accuracy are recommended

  3. El género Agaricus en España. VII.Agaricus aestivalis (F.H. Möller Pilát. Primera cita en España

    Directory of Open Access Journals (Sweden)

    ARRILLAGA, P., PARRA, L.A.

    1998-01-01

    Full Text Available Se aporta una descripción macro y microscópica completa de A. aestivalis, así como comentarios en relación con su posición taxonómica, considerando A. estivalis var. flavotacta (F.H. Möller F.H. Möller como sinónimo de A. aestivalis

  4. Antibacterial efficacy of nisin, pediocin 34 and enterocin FH99 against L. monocytogenes, E. faecium and E. faecalis and bacteriocin cross resistance and antibiotic susceptibility of their bacteriocin resistant variants.

    Science.gov (United States)

    Kaur, Gurpreet; Singh, Tejinder Pal; Malik, Ravinder Kumar; Bhardwaj, Arun; De, Sachinandan

    2014-02-01

    The bacteriocin susceptibility of Listeria monocytogenes MTCC 657, Enterococcus faecium DSMZ 20477, E. faecium VRE, and E. faecalis ATCC 29212 and their corresponding bacteriocin resistant variants was assessed. The single and combined effect of nisin and pediocin 34 and enterocin FH99 bacteriocins produced by Pediococcus pentosaceus 34, and E. faecium FH99, respectively, was determined. Pediocin34 proved to be more effective in inhibiting L. monocytogenes MTCC 657. A greater antibacterial effect was observed against E. faecium DSMZ 20477 and E. faecium (VRE) when the a combination of nisin, pediocin 34 and enterocin FH99 were used whereas in case of L. monocytogenes MTCC 657 a combination of pediocin 34 and enterocin FH99 was more effective in reducing the survival of pathogen. Bacteriocin cross-resistance and the antibiotic susceptibility of wild type and their corresponding resistant variants were assessed and results showed that resistance to a bacteriocin may extend to other bacteriocins within the same class and also the acquired resistance to bacteriocins can modify the antibiotic susceptibility/resistance profile of the bacterial species used in the study. According to the hydrophobicity nisin resistant variant of L. monocytogenes was more hydrophobic (p enterocin FH99 resistant variants were less hydrophobic than the wild type strain. Nisin, pediocin 34 and enterocin FH99 resistant variants of E. faecium DSMZ 20477 and E. faecium VRE were less hydrophobic than their wild type counterparts. Nisin resistant E. faecalis ATCC 29212 was less hydrophobic than its wild type counterpart.

  5. Suppressor screen and phenotype analyses revealed an emerging role of the Monofunctional peroxisomal enoyl-CoA hydratase 2 in compensated cell enlargement

    Directory of Open Access Journals (Sweden)

    Mana eKatano

    2016-02-01

    Full Text Available Efficient use of seed nutrient reserves is crucial for germination and establishment of plant seedlings. Mobilizing seed oil reserves in Arabidopsis involves β-oxidation, the glyoxylate cycle, and gluconeogenesis, which provide essential energy and the carbon skeletons needed to sustain seedling growth until photoautotrophy is acquired. We demonstrated that H+-PPase activity is required for gluconeogenesis. Lack of H+-PPase in fugu5 mutants increases cytosolic pyrophosphate (PPi levels, which partially reduces sucrose synthesis de novo and inhibits cell division. In contrast, post-mitotic cell expansion in cotyledons was unusually enhanced, a phenotype called compensation. Therefore, it appears that PPi inhibits several cellular functions, including cell cycling, to trigger compensated cell enlargement (CCE. Here, we mutagenized fugu5-1 seeds with 12C6+ heavy-ion irradiation and screened mutations that restrain CCE to gain insight into the genetic pathway(s involved in CCE. We isolated A#3-1, in which cell size was severely reduced, but cell number remained similar to that of original fugu5-1. Moreover, cell number decreased in A#3-1 single mutant (A#3-1sm, similar to that of fugu5-1, but cell size was almost equal to that of the wild type. Surprisingly, A#3-1 mutation did not affect CCE in other compensation exhibiting mutant backgrounds, such as an3-4 and fugu2-1/fas1-6. Subsequent map-based cloning combined with genome sequencing and HRM curve analysis identified enoyl-CoA hydratase 2 (ECH2 as the causal gene of A#3-1. The above phenotypes were consistently observed in the ech2-1 allele and supplying sucrose restored the morphological and cellular phenotypes in fugu5-1, ech2-1, A#3-1sm, fugu5-1 ech2-1 and A#3-1;fugu5-1. Taken together, these results suggest that defects in either H+-PPase or ECH2 compromise cell proliferation due to defects in mobilizing stored lipids. In contrast, ECH2 alone likely promotes CCE during the post-mitotic cell

  6. GC-MS characterization of n-hexane soluble fraction from dandelion (Taraxacum officinale Weber ex F.H. Wigg.) aerial parts and its antioxidant and antimicrobial properties.

    Science.gov (United States)

    Ivanov, Ivan; Petkova, Nadezhda; Tumbarski, Julian; Dincheva, Ivayla; Badjakov, Ilian; Denev, Panteley; Pavlov, Atanas

    2018-01-26

    A comparative investigation of n-hexane soluble compounds from aerial parts of dandelion (Taraxacum officinale Weber ex F.H. Wigg.) collected during different vegetative stages was carried out. The GC-MS analysis of the n-hexane (unpolar) fraction showed the presence of 30 biologically active compounds. Phytol [14.7% of total ion current (TIC)], lupeol (14.5% of TIC), taraxasteryl acetate (11.4% of TIC), β-sitosterol (10.3% of TIC), α-amyrin (9.0% of TIC), β-amyrin (8.3% of TIC), and cycloartenol acetate (5.8% of TIC) were identified as the major components in n-hexane fraction. The unpolar fraction exhibited promising antioxidant activity - 46.7 mmol Trolox equivalents/g extract (determined by 1,1-diphenyl-2-picrylhydrazyl method). This fraction demonstrated insignificant antimicrobial activity and can be used in cosmetic and pharmaceutical industries.

  7. Radical nephrectomy and regional lymph node dissection for locally advanced type 2 papillary renal cell carcinoma in an at-risk individual from a family with hereditary leiomyomatosis and renal cell cancer: a case report

    International Nuclear Information System (INIS)

    Kamai, Takao; Abe, Hideyuki; Arai, Kyoko; Murakami, Satoshi; Sakamoto, Setsu; Kaji, Yasushi; Yoshida, Ken-Ichiro

    2016-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant tumor susceptibility syndrome, and the disease-related gene has been identified as fumarate hydratase (fumarase, FH). HLRCC-associated kidney cancer is an aggressive tumor characterized by early metastasis to regional lymph nodes and distant organs. Since early diagnosis and provision of definitive therapy is thought to be the best way to reduce the tumor burden, it is widely accepted that germline testing and active surveillance for an at-risk individual from a family with HLRCC is very important. However, it still remains controversial how we should treat HLRCC-associated kidney cancer. We successfully treated the patient with locally advanced HLRCC-associated kidney cancer, who has received active surveillance because of at-risk individual, by radical nephrectomy and extended retroperitoneal lymph node dissection, and examined surgically resected samples from a molecular point of view. We recommended that 13 at-risk individuals from a family with HLRCC should receive active surveillance for early detection of renal cancer. A 48-year-old woman with a left renal tumor and involvement of multiple regional lymph nodes with high accumulation of fluorine-18-deoxyglucose on positron emission tomography was treated with axitinib as a neoadjuvant therapy. Preoperative axitinib induced the shrinkage of the tumor with decreased fluorine-18-deoxyglucose accumulation. Resected samples showed two thirds tumor tissue necrosis as well as high expression of serine/threonine kinase Akt and low expression of nuclear factor E2-related factor 2 (Nrf2) which activates anti-oxidant response and protects against oxidative stress in viable cancer cells. Targeted next-generation sequencing revealed that FH mutation and loss of the second allele were completely identical between blood and tumor samples, suggesting that FH mutation plays a direct role in FH-deficient RCC. She has remained well after radical

  8. F and H Area Effluent Treatment Facility (F/H ETF): ultrafiltration and hyperfiltration systems testing at Carre, Inc. with simulated F and H area effluents

    International Nuclear Information System (INIS)

    Ryan, J.P.

    1984-01-01

    The F and H Area Effluent Treatment Facility is essentially a four-stage process that will decontaminate the waste water that is currently being discharged to seepage basins in the Separations Areas. The stages include pretreatment, reverse osmosis, ion exchange, and evaporation. A series of tests were performed at Carre, Inc. (Seneca, SC) from March 5 through March 13, to determine the usefulness of ultrafiltration (UF) in the pretreatment stage of the ETF. The results of that testing program indicate that UF would be an excellent means of removing entrained activity from the 200 Area process effluents. Hyperfiltration (HF) was also tested as a means of providing an improved concentration factor from the reverse osmosis stage. The results show that the membranes that were tested would not reject salt well enough at high salt concentrations to be useful in the final reverse osmosis stage. However, there are several membranes which are commercially available that would provide the needed rejection if they could be applied (dynamically) on the Carre support structure. This avenue is still being explored, as theoretically, it could eliminate the need for the F/H ETF evaporator

  9. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.

    Science.gov (United States)

    Tamayo, Joel V; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M Tanaka; Gavis, Elizabeth R

    2017-04-04

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo's functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

    Directory of Open Access Journals (Sweden)

    Joel V. Tamayo

    2017-04-01

    Full Text Available The Drosophila hnRNP F/H homolog, Glorund (Glo, regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3′ untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.

  11. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

    Energy Technology Data Exchange (ETDEWEB)

    Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M. Tanaka; Gavis, Elizabeth R. (Princeton); (NIH)

    2017-04-01

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.

  12. Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age : implications for surveillance

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Badeloe, Sadhanna; Oosting, Sjoukje F.; Hovenga, Sjoerd; Semmelink, Harry J. F.; van Moorselaar, R. Jeroen A.; van Waesberghe, Jan Hein; Mensenkamp, Arjen R.; Menko, Fred H.

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation

  13. Analytic Morse/long-range potential energy surfaces and "adiabatic-hindered-rotor" treatment for a symmetric top-linear molecule dimer: A case study of CH3F-H2

    Science.gov (United States)

    Zhang, Xiao-Long; Ma, Yong-Tao; Zhai, Yu; Li, Hui

    2018-03-01

    A first effective six-dimensional ab initio potential energy surface (PES) for CH3F-H2 which explicitly includes the intramolecular Q3 stretching normal mode of the CH3F monomer is presented. The electronic structure computations have been carried out at the explicitly correlated coupled cluster level of theory [CCSD(T)-F12a] with an augmented correlation-consistent triple zeta basis set. Five-dimensional analytical intermolecular PESs for ν3(CH3F) = 0 and 1 are then obtained by fitting the vibrationally averaged potentials to the Morse/Long-Range (MLR) potential function form. The MLR function form is applied to the nonlinear molecule-linear molecule case for the first time. These fits to 25 015 points have root-mean-square deviations of 0.74 cm-1 and 0.082 cm-1 for interaction energies less than 0.0 cm-1. Using the adiabatic hindered-rotor approximation, three-dimensional PESs for CH3F-paraH2 are generated from the 5D PESs over all possible orientations of the hydrogen monomer. The infrared and microwave spectra for CH3F-paraH2 dimer are predicted for the first time. These analytic PESs can be used for modeling the dynamical behavior in CH3F-(H2)N clusters, including the possible appearance of microscopic superfluidity.

  14. SAJAA JA Marfan' (Converte.fh9

    African Journals Online (AJOL)

    Studio G5

    MFS is a multisystem disorder with a prevalence of 1/3000-. 1/5000 ... (Fig 2) and high-arched palate with secondary dental overcrowding .... Anaesthetic considerations. Patients may present for elective orthopaedic, cardiovascular or.

  15. 一株海绵放线菌的分离培养、发酵条件优化及其抑制弧菌效果%Isolation, optimization of fermentation conditions and inhibition of Vibrio in a sponge-associated actinobacterium FH

    Institute of Scientific and Technical Information of China (English)

    杜英侠; 付晚涛; 李晶莹; 傅敏; 张鑫; 曲春强; 李小艺; 张菊林; 顾颖; 王选骏

    2017-01-01

    为研究放线菌对海水养殖病原弧菌(哈维弧菌Vibrio harveyi和灿烂弧菌Vibrio splendidus)的抑制效果,从繁茂膜海绵Hymeniacidon perlevis中分离筛选出了一株具有抑菌活性的放线菌(FH),并采用16S rD-NA基因序列进行分析,初步鉴定为球孢链霉菌Streptomyces globisporus;以抑菌活性为导向对放线菌FH菌株的发酵条件进行优化,并通过测量发酵沉淀菌丝体干质量,获得了FH菌株生长曲线,同时研究了发酵产物保存温度及时间对抑菌效果的影响,以及FH发酵产物在灭菌海水中对弧菌的抑制作用.结果表明:对FH菌株生长曲线测定结果显示,0~15 h为适应期,15~72 h为指数生长期,72~120 h为稳定期,120 h后为衰亡期;抑制弧菌效果试验显示,FH菌株发酵正交试验的最优条件为温度25℃、pH 7.5、 装液量30 mL(250 mL三角瓶);在正交试验最优条件下,FH菌株发酵培养72 h获得的粗提物抑制哈维弧菌和灿烂弧菌的效果最好;FH菌株发酵粗提物在4℃和-20℃下保存60 d和在室温保存7 d,其抑菌效果无显著性差异(P>0.05);在100 mL灭菌海水中,FH菌株发酵产物2 mL可有效抑制哈维弧菌和灿烂弧菌的繁殖.研究表明,海绵放线菌及其发酵产物在海水养殖领域具有潜在应用价值.%A sponge-associated actinobacterium FH with strong bioactivity was isolated from marine sponge Hy-meniacidon perlevis, and identified by 16S rDNA gene sequence analysis as Streptomyces globisporus. The inhibition of Vibrio harveyi and Vibrio splendidus by FH strain was studied and the fermentation condition of FH strain was op-timized, including influence of preservation temperature and time on the antibacterial effect of fermented product. The dry weight of mycelium revealed that the growth curve of FH strain showed a lag phase in 0-15 h, log phase in 15-72 h, stationary phase in 72-120 h and decline phase after 120 h. The optimal fermentation of FH strain was observed under

  16. Storage compounds, ABA and fumarase in Fagus sylvatica embryos during stratification

    Czech Academy of Sciences Publication Activity Database

    Eliášová, Kateřina; Pešek, Bedřich; Vondráková, Zuzana

    2015-01-01

    Roč. 74, 10 March (2015), s. 25-33 ISSN 1641-1307 R&D Projects: GA MZe QI102A256 Institutional support: RVO:61389030 Keywords : Embryonic axis * Fagus sylvatica * Seed dormancy Subject RIV: EF - Botanics Impact factor: 0.643, year: 2015

  17. Abnormalities in succinylpurines in fumarase deficiency: Possible role in pathogenesis of CNS impairment

    Czech Academy of Sciences Publication Activity Database

    Zeman, J.; Krijt, J.; Stratilová, L.; Hansíková, H.; Wenchich, L.; Kmoch, S.; Chrastina, P.; Houštěk, Josef

    2000-01-01

    Roč. 23, - (2000), s. 371-374 R&D Projects: GA MŠk VS96127; GA ČR GA302/99/0648; GA MZd IZ4179 Grant - others:GA UK(XC) 65/1999 Institutional research plan: CEZ:AV0Z5011922 Subject RIV: ED - Physiology

  18. Characterisation of nitrilase and nitrile hydratase biocatalytic systems

    CSIR Research Space (South Africa)

    Brady, D

    2004-03-01

    Full Text Available (Faber 1992; Vogel 1989; Weiner and Chaplin 2000). Other nitrile compounds Many nitrile substrates were available from the laboratory com- pound inventory. All other substrates were obtained from Acros or Sigma. Analytical methods A Chromolith... regioselectivity for converting aromatic nitriles to the corresponding acid, but was also capable of hydrolys- ing aliphatic nitriles (Cohen et al. 1990). This catalytic capacity of Rhodococcus Novo SP361 for a broad substrate range was also observed...

  19. F/H area high level waste tank status report

    International Nuclear Information System (INIS)

    Hayes, C.R. Jr.; Wells, M.N.

    1997-03-01

    Section IX.E.3 of the SRS Federal Facility Agreement requires the DOE to submit to EPA and SCDHEC, an annual report on the status of tanks being removed from service. Tanks that are slated for removal from service either do not meet secondary containment standards or have leak sites. The attached document is intended to meet this annual report requirement. An updated status of relevant portions of the Waste Removal Plan and Schedule is also included

  20. http://www.aulamedica.es/fh/pdf/8547.pdf

    Directory of Open Access Journals (Sweden)

    Rosa María Damas Fuentes

    2015-01-01

    Full Text Available Objetive: To analyze the latex content of drugs in hospital formulary and establish possible therapeutic alternatives. Methods: All drugs susceptible of having latex were selected and written information was obtained from manufacturers. A therapeutic alternative was found for each of them, if possible. Results: Written information from manufacturer was obtained for 605 (97.9% and from label information for 8 of 632 selected drugs. For 43.9% of not safe drugs (total 57 on patients with latex allergy, a therapeutic alternative was found in hospital formulary. Conclusions: Knowing drugs having latex improve the prescription security, while the therapeutic alternatives chart eases the validation. The published data updates the scarce and variable information for patients and healthcare professionals.

  1. http://www.aulamedica.es/fh/pdf/10689.pdf

    Directory of Open Access Journals (Sweden)

    Marta García-Queiruga

    2017-03-01

    Full Text Available p>Purpose: To present the requirements, development, structure and results of an electronic interconsultation platform (e-Interconsultation for communication between primary and hospital care. Method: A working group was created and set out its purposes, working schedule, software requirements, the structure of the electronic platform, validation procedure, and its implementation. Once the software had been developed and validated and training sessions were conducted, the electronicplatform was launched in June 2015. Results: After 1 year of operation, a total of 321 electronic interconsultations had been made, 110 of which were referrals from hospital care to primary care in addition to 211 from primary to hospital care. The validation of prescriptions and the need for drug monitoring in primary care are among main reasons for consultation. Conclusions: The e-Interconsultation platform is a valid, efficient and user-friendly mean of consultation or patient referrals between both healthcare levels.

  2. Pursuit of excellence in F/H operator performance

    International Nuclear Information System (INIS)

    Keelan, B.; Curle, B.

    1996-01-01

    Performance of any fuel handling system is heavily dependent on the performance of the system operators. Sadly, this topic often receives little attention until incidents occur. Darlington has taken a proactive approach designed to reach and maintain excellent operator performance. Expectations and Standards are generated and published. A detailed, goal-oriented, auditable training program, which includes hands-on training modules, ensures operators reach the standards before qualifications are granted. Refresher courses maintain current skills. A depersonalized, computerized reporting system ensures training and standards are updated to match current situations. (author). 1 fig

  3. F/H effluent treatment facility. Technical data summary

    International Nuclear Information System (INIS)

    Ryan, J.P.; Stimson, R.E.

    1984-12-01

    This document provides the technical basis for the design of the facility. Some of the sections are described with options to permit simplification of the process, depending on the effluent quality criteria that the facility will have to meet. Each part of the F/HETF process is reviewed with respect to decontamination and concentration efficiency, operability, additional waste generation, energy efficiency, and compatability with the rest of the process

  4. Pursuit of excellence in F/H operator performance

    Energy Technology Data Exchange (ETDEWEB)

    Keelan, B; Curle, B [Ontario Hydro, Bowmanville (Canada). Darlington Nuclear Generating Station

    1997-12-31

    Performance of any fuel handling system is heavily dependent on the performance of the system operators. Sadly, this topic often receives little attention until incidents occur. Darlington has taken a proactive approach designed to reach and maintain excellent operator performance. Expectations and Standards are generated and published. A detailed, goal-oriented, auditable training program, which includes hands-on training modules, ensures operators reach the standards before qualifications are granted. Refresher courses maintain current skills. A depersonalized, computerized reporting system ensures training and standards are updated to match current situations. (author). 1 fig.

  5. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    Science.gov (United States)

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  6. Production of D-malate by maleate hydratase from Pseudomonas pseudoalcaligenes

    NARCIS (Netherlands)

    Werf, van der M.J.

    1994-01-01

    The biological activity of a chiral compound with respect to its pharmaceutical and agrochemical activity, flavour and taste can vary dramatically for the different enantiomers. Especially when using chiral compounds for pharmaceutical or agrochemical applications, the presence of the

  7. Dose-response relationship of rat aryl hydrocarbon hydroxylase and epoxide hydratase induction

    Energy Technology Data Exchange (ETDEWEB)

    Gielen, J.E.; Goujon, F.M.; Sele-Doyen, J.; Van Cantfort, J.

    1980-01-01

    This paper summarizes our recent results supporting the hypothesis that different regulation mechanisms are involved in the control of AHH and EH activity and that the AHH induction in the extrahepatic tissues might also be affected by liver specific inducers. In the rat, lung and kidney AHH is highly sensitive to the inducers present in cigarette smoke and cigarette smoke condensate, the EH activity not being affected by the same agents. Phenobarbital is also able to protentiate the inducing action of low doses of benzo(a)pyrene on the lung AHH activity. In primary rat liver cells in culture, AHH and EH can be selectivly induced. Low doses of benz(a)anthracene preferentially enhance the AHH activity while trans-stilbene oxide an various antioxidants modify only the EH activity. Phenobarbital, which also induces the AHH activity in cell culture, produces a more than additive effect when added to the culture medium in a mixture with benz(a)anthracene. Trans-stilbene oxide prevents the AHH induction by phenobarbital and not by benz(a)anthracene. Our results suggest that, in addition to its own induction capacity, phenobarbital is also able to potentiate the action of chemicals belonging to a different class of inducers.

  8. Biotransformation of benzonitrile herbicides via the nitrile hydratase-amidase pathway in rhodococci.

    Science.gov (United States)

    Veselá, Alicja B; Pelantová, Helena; Sulc, Miroslav; Macková, Martina; Lovecká, Petra; Thimová, Markéta; Pasquarelli, Fabrizia; Pičmanová, Martina; Pátek, Miroslav; Bhalla, Tek Chand; Martínková, Ludmila

    2012-12-01

    The aim of this work was to determine the ability of rhodococci to transform 3,5-dichloro-4-hydroxybenzonitrile (chloroxynil), 3,5-dibromo-4-hydroxybenzonitrile (bromoxynil), 3,5-diiodo-4-hydroxybenzonitrile (ioxynil) and 2,6-dichlorobenzonitrile (dichlobenil); to identify the products and determine their acute toxicities. Rhodococcus erythropolis A4 and Rhodococcus rhodochrous PA-34 converted benzonitrile herbicides into amides, but only the former strain was able to hydrolyze 2,6-dichlorobenzamide into 2,6-dichlorobenzoic acid, and produced also more of the carboxylic acids from the other herbicides compared to strain PA-34. Transformation of nitriles into amides decreased acute toxicities for chloroxynil and dichlobenil, but increased them for bromoxynil and ioxynil. The amides inhibited root growth in Lactuca sativa less than the nitriles but more than the acids. The conversion of the nitrile group may be the first step in the mineralization of benzonitrile herbicides but cannot be itself considered to be a detoxification.

  9. Purification and characterization of the enantioselective nitrile hydratase from Rhodococcus equi A4

    Czech Academy of Sciences Publication Activity Database

    Přepechalová, Irena; Martínková, Ludmila; Stolz, A.; Ovesná, M.; Bezouška, Karel; Kopecký, Jan; Křen, Vladimír

    2001-01-01

    Roč. 55, - (2001), s. 150-156 ISSN 0175-7598 R&D Projects: GA AV ČR IAA4020802 Institutional research plan: CEZ:A53/98:Z5-020-9ii Subject RIV: EE - Microbiology, Virology Impact factor: 1.754, year: 2001

  10. Analysis of a MULE-cyanide hydratase gene fusion in Verticillium dahliae

    Science.gov (United States)

    The genome of the phytopathogenic fungus Verticillium dahliae encodes numerous Class II “cut-and-paste” transposable elements, including those of a small group of MULE transposons. We have previously identified a fusion event between a MULE transposon sequence and sequence encoding a cyanide hydrata...

  11. Revisiting the TCA cycle: signaling to tumor formation.

    Science.gov (United States)

    Raimundo, Nuno; Baysal, Bora E; Shadel, Gerald S

    2011-11-01

    A role for mitochondria in tumor formation is suggested by mutations in enzymes of the TCA cycle: isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH) and fumarate hydratase (FH). Although they are all components of the TCA cycle, the resulting clinical presentations do not overlap. Activation of the hypoxia pathway can explain SDH phenotypes, but recent data suggest that FH and IDH mutations lead to tumor formation by repressing cellular differentiation. In this review, we discuss recent findings in the context of both mitochondrial and cytoplasmic components of the TCA cycle, and we propose that extrametabolic roles of TCA cycle metabolites result in reduced cellular differentiation. Furthermore, activation of the pseudohypoxia pathway likely promotes the growth of these neoplasias into tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. F/H Area Effluent Treatment Facility. Phase II. CAC basic data

    International Nuclear Information System (INIS)

    Collins, W.W.; O'Leary, C.D.

    1984-01-01

    Project objectives and requirements are listed for both Phase I and II. Schedule is listed with startup targeted for 1989. Storage facilities will be provided for both chemical and radioactive effluents. 8 figs., 19 tabs

  13. Surface Water Transport for the F/H Area Seepage Basins Groundwater Program

    International Nuclear Information System (INIS)

    Chen, Kuo-Fu.

    1995-01-01

    The contribution of the F- and H-Area Seepage Basins (FHSBs) tritium releases to the tritium concentration in the Savannah River are presented in this report. WASP5 was used to simulate surface water transport for tritium releases from the FHSBs. The WASP5 model was qualified with the 1993 tritium measurements at US Highway 301. The tritium concentrations in Fourmile Branch and the Savannah River were calculated for tritium releases from FHSBs. The calculated tritium concentrations above normal environmental background in the Savannah River, resulting from FHSBs releases, drop from 1.25 pCi/ml (<10% of EPA Drinking Water Guide) in 1995 to 0.0056 pCi/ml in 2045

  14. SAJAA MarApr 40-4 Con.fh9

    African Journals Online (AJOL)

    Studio G5

    both ventilation and oxygenation became increasingly difficult. Close to completion of .... shifts as the patient changes position.57 These clinical signs may be difficult to elicit in .... to advance the safety of anaesthesia practice.87. References. 1.

  15. FLUOR HANFORD (FH) MAKES CLEANUP A REALITY IN NEARLY 11 YEARS AT HANFORD

    Energy Technology Data Exchange (ETDEWEB)

    GERBER, M.S.

    2007-05-24

    For nearly 11 years, Fluor Hanford has been busy cleaning up the legacy of nuclear weapons production at one of the Department of Energy's (DOE'S) major sites in the United States. As prime nuclear waste cleanup contractor at the vast Hanford Site in southeastern Washington state, Fluor Hanford has changed the face of cleanup. Fluor beginning on October 1, 1996, Hanford Site cleanup was primarily a ''paper exercise.'' The Tri-Party Agreement, officially called the Hanford Federal Facility Agreement and Consent Order - the edict governing cleanup among the DOE, U.S. Environmental Protection Agency (EPA) and Washington state - was just seven years old. Milestones mandated in the agreement up until then had required mainly waste characterization, reporting, and planning, with actual waste remediation activities off in the future. Real work, accessing waste ''in the field'' - or more literally in huge underground tanks, decaying spent fuel POO{approx}{approx}S, groundwater, hundreds of contaminated facilities, solid waste burial grounds, and liquid waste disposal sites -began in earnest under Fluor Hanford. The fruits of labors initiated, completed and/or underway by Fluor Hanford can today be seen across the site. Spent nuclear fuel is buttoned up in secure, dry containers stored away from regional water resources, reactive plutonium scraps are packaged in approved containers, transuranic (TRU) solid waste is being retrieved from burial trenches and shipped offsite for permanent disposal, contaminated facilities are being demolished, contaminated groundwater is being pumped out of aquifers at record rates, and many other inventive solutions are being applied to Hanford's most intransigent nuclear wastes. (TRU) waste contains more than 100 nanocuries per gram, and contains isotopes higher than uranium on the Periodic Table of the Elements. (A nanocurie is one-billionth of a curie.) At the same time, Fluor Hanford has dramatically improved safety records, and cost effectively maintained and streamlined infrastructure and equipment that is impossibly old and in many cases ''extinct'' in terms of spare parts and vendor support. The story of Fluor's achievements at the Hanford Site - the oldest and most productive plutonium site in the world - is both inspiring and instructive.

  16. Roots of angiosperm formins: The evolutionary history of plant FH2 domain-containing proteins

    Czech Academy of Sciences Publication Activity Database

    Grunt, M.; Žárský, Viktor; Cvrčková, F.

    2008-01-01

    Roč. 8, Art_115 (2008), s. 1-19 ISSN 1471-2148 R&D Projects: GA ČR GA204/05/0268; GA MŠk(CZ) LC06004 Institutional research plan: CEZ:AV0Z50380511 Keywords : MULTIPLE SEQUENCE ALIGNMENT * TYROSINE-PHOSPHATASE * SWISS-MODEL Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.050, year: 2008

  17. Arabidopsis FH1 Formin Affects Cotyledon Pavement Cell Shape by Modulating Cytoskeleton Dynamics

    Czech Academy of Sciences Publication Activity Database

    Rosero, A.; Oulehlová, Denisa; Stillerová, L.; Schiebertová, P.; Gunt, M.; Žárský, Viktor; Cvrčková, F.

    2016-01-01

    Roč. 57, č. 3 (2016), s. 488-504 ISSN 0032-0781 Institutional support: RVO:61389030 Keywords : Arabidopsis thaliana * Confocal microscopy * Cotyledon pavement cells Subject RIV: ED - Physiology Impact factor: 4.760, year: 2016

  18. Growth performance of FH male calves fed milk replacer made of local ingredients for veal production

    Directory of Open Access Journals (Sweden)

    Elizabeth Wina

    1996-06-01

    Full Text Available The research was designed to evaluate the local feedstuff to be used in milk replacer (MP and its utilization for veal production . Fifteen male calves of the Friesian Holstein breed, 5-6 weeks old were used in the experiment lasting for 8 weeks. The treatments were (i commercial milk replacer (SPK, (ii local (SPL-1 and (iii mixture ofSPK and SPL-1 (SPKL. The amount of dry matter offerred is 3 % of live weight each and was given twice daily (in the morning and late afternoon . Elephant grass (0 .5 kg was offerred at noon . The observed parameters were average daily gain (ADG, dry matter (DM and crude protein (CP intake, carcass percentage, weight of carcass components, physical and chemical characteristics of meat. The results show that feed consumptions were 1,981, 1,613 and 1,050 g1day and ADGs were 897,496 and 73 g for treatments SPK, SPKL and SPL, respectively . Carcass percentage was 56.84 and 58 .76% with protein content was 87 .47 and 84 .78% for treatments SPK and SPKL, respectively . The benefit per head of calf was higher when fed mixture of local and commercial MP than fed only commercial MP but the benefit per day was higher when fed commercial MP than mixture of local and commercial. In conclusion, a cheaper milk replacer with less milk protein content resulting in a lower gain but higher benefit per head of calf than a commercial milk replacer containing high milk protein content

  19. SAJAA MarApr 19-24 Con.fh9

    African Journals Online (AJOL)

    Studio G5

    J Clinical Anesth 2003 Aug;15(5):328–33. 5 Romano E. Anestesia generale e speciale; UTET Editori, Torino 1997:173–174. 6 Amici M, Eusebi F, Miledi R. Effects of the antibiotic gentamicin on nicotinic acetylcholine receptors. Neuropharmacology 2005 Oct 18, 102(42)15219–23. 7 Maidatsi PG, Zaralidou AT, Gorgias NK, ...

  20. AtFH1 formin mutation affects actin filament and microtubule dynamics in Arabidopsis thaliana

    Czech Academy of Sciences Publication Activity Database

    Rosero, A.; Žárský, Viktor; Cvrčková, F.

    2013-01-01

    Roč. 64, č. 2 (2013), s. 585-597 ISSN 0022-0957 R&D Projects: GA ČR GAP305/10/0433 Institutional research plan: CEZ:AV0Z50380511 Keywords : Actin * Arabidopsis * At5g25500 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.794, year: 2013

  1. Moessbauer, electron paramagnetic resonance and magnetic susceptibility studies of photosensitive nitrile hydratase from Rhodococcus sp. N-771

    International Nuclear Information System (INIS)

    Nagamune, Teruyuki; Honda, Jun; Kobayashi, Yoshio; Sasabe, Hiroyuki; Endo, Isao; Ambe, Fumitoshi; Teratani, Yoshitaka; Hirata, Akira

    1992-01-01

    Moessbauer, magnetic susceptibility and electron paramagnetic resonance (EPR) studies of inactive and photoactivated NHase enzymes were performed to elucidate the electronic change of non-heme two-iron atom center of the enzyme by photoactivation. These spectroscopic investigations revealed that both the two iron atoms of the active NHase could be assigned to low-spin ferric state, and those of the inactive NHase could each be assigned to low-spin ferric and low-spin ferrous ones. From these results, it was concluded that one of the non-heme iron atoms is oxidized in the inactive NHase during photoactivation. (orig.)

  2. ДОСЛІДЖЕННЯ ХІМІЧНИХ ПЕРЕТВОРЕНЬ У ВУГЛЕВОДНЕВОМУ СКЛАДІ РОБОЧОЇ РІДИНИ «ГІДРОНІКОЙЛ» FH-51

    Directory of Open Access Journals (Sweden)

    А.М. Соловйов

    2007-02-01

    Full Text Available  Подано результати дослідження структурно-групового складу зразків товарної і після нальоту 3600 год авіаційної гідравлічної рідини «Гідронікойл» FH-51 методами дистиляції та рідинної хроматографії. Отримані результати досліджень показали наявність перебігу процесів термоокиснювальної деструкції вуглеводнів, що спричиняє суттєве зниження якості робочої рідини і погіршення її експлуатаційних властивостей. Підтверджено, що наявну систему контролю якості гідравлічних рідин науково не обґрунтовано і вона не забезпечує сучасних високих вимог до збереження експлуатаційної якості робочої рідини для гідравлічної системи літака. Актуальним постає завдання удосконалення існуючої системи  контролю якості гідравлічних рідин під час експлуатації.

  3. Degree of intraspecific genetic divergence and variability in three Sciaenid species

    Digital Repository Service at National Institute of Oceanography (India)

    Menezes, M.R.; Taniguchi, N.; Seki, S.

    .1.1.8); AAT: aspartate aminotransferase (2.6. I.1); FH, fumarate hydratase (4.2.1.2); GPI, glucose-phosphate isomerase (5.3.1.9); HEM, hemo- globin; IDH, isocitrate dehydrogenase (1.1.1.42); LDH, lactate dehydrogenase (1.1.1.27); MOH, malate dehydrogenase (1... GPI Gpi-J OM p* P P M P P* P* p* p* p* p* Gpi-2 OM P P P M P P P P M p* P HEM Hem-] H M M M M M M M M M M M Hem-2 H M M M M M M M M M M M IDH Idll-J L M p* P M M P M M M M P Idh-2 H p* P P p* M M M M M M M LOH Ldh-J H M M M M M M M M M P M Ldh-2 SM M M...

  4. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State.

    Science.gov (United States)

    Cardaci, Simone; Ciriolo, Maria Rosa

    2012-01-01

    Inborn defects of the tricarboxylic acid (TCA) cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

  5. A systems approach to predict oncometabolites via context-specific genome-scale metabolic networks.

    Directory of Open Access Journals (Sweden)

    Hojung Nam

    2014-09-01

    Full Text Available Altered metabolism in cancer cells has been viewed as a passive response required for a malignant transformation. However, this view has changed through the recently described metabolic oncogenic factors: mutated isocitrate dehydrogenases (IDH, succinate dehydrogenase (SDH, and fumarate hydratase (FH that produce oncometabolites that competitively inhibit epigenetic regulation. In this study, we demonstrate in silico predictions of oncometabolites that have the potential to dysregulate epigenetic controls in nine types of cancer by incorporating massive scale genetic mutation information (collected from more than 1,700 cancer genomes, expression profiling data, and deploying Recon 2 to reconstruct context-specific genome-scale metabolic models. Our analysis predicted 15 compounds and 24 substructures of potential oncometabolites that could result from the loss-of-function and gain-of-function mutations of metabolic enzymes, respectively. These results suggest a substantial potential for discovering unidentified oncometabolites in various forms of cancers.

  6. The Metabolic Basis of Kidney Cancer

    Science.gov (United States)

    Linehan, W. Marston; Ricketts, Christopher J.

    2012-01-01

    Kidney cancer is not a single disease; it is made up of a number of different types of cancer that occur in the kidney. Each of these different types of kidney cancer can have a different histology, have a different clinical course, can respond differently to therapy and is caused by a different gene. Kidney cancer is essentially a metabolic disease; each of the known genes for kidney cancer, VHL, MET, FLCN, TSC1, TSC2, TFE3, TFEB, MITF, fumarate hydratase (FH), succinate dehydrogenase B (SDHB), succinate dehydrogenase D (SDHD), and PTEN genes is involved in the cells ability to sense oxygen, iron, nutrients or energy. Understanding the metabolic basis of kidney cancer will hopefully provide the foundation for the development of effective forms of therapy for this disease. PMID:22705279

  7. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State

    Directory of Open Access Journals (Sweden)

    Simone Cardaci

    2012-01-01

    Full Text Available Inborn defects of the tricarboxylic acid (TCA cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH, fumarate hydratase (FH, and isocitrate dehydrogenase (IDH, pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

  8. Fishery Household (FH) database and cultivation areas in Indramayu regency to develop Shrimp and Milkfish farming based on GIS

    Science.gov (United States)

    Rostika, Rita; Purba, Noir P.; Iskandar; Paradhita Dewanti, Lantun; Mahdiana Apriliani, Izza

    2018-05-01

    With a coastline length of 114 km, the utilization of the coastline areas is potential for especially shrimp and milkfish cultivations, which have a higher economic value. However, appropriate development strategies are highly required. The purpose of this research is to examine the existing conditions and organize integrated information for fishery household as well as the areas utilized for shrimp and milkfish cultivations, especially in coastal areas. The methods used include an analysis from Landsat 8 imaginary, field survey, and interviews with various sources. This research conducted in June-November 2015. Data from remote sensing were digitized and utilized as mark point to survey area of cultivation. The results show that the distributions of RTP data cover Windu and Vaname shrimp polycultures by 1,727 RTP, milkfish by 1,551 RTP, Vaname shrimp by 2,953 RTP, and Windu Shrimp by 88 RTP. The area, which may be utilized as ponds, is 9,854.1 ha. The area for milkfish ponds is 12,065.08 ha, while the digitation result is 10,801.92 ha. It shows that Indramayu coastal areas still have numerous and various potentials, which may be utilized for shrimp and milkfish cultivations.

  9. Potential genetic anticipation in hereditary leiomyomatosis-renal cell cancer (HLRCC).

    Science.gov (United States)

    Wong, Mei Hua; Tan, Chuen Seng; Lee, Soo Chin; Yong, Yvonne; Ooi, Aik Seng; Ngeow, Joanne; Tan, Min Han

    2014-06-01

    Hereditary leiomyomatosis-renal cell cancer (HLRCC) is an autosomal dominant disorder characterised by cutaneous leiomyomas, symptomatic uterine leiomyomas and aggressive type II papillary renal cell carcinoma. It is caused by heterozygous mutations in the fumarate hydratase (FH) gene on chromosome 1q43. We present evidence of genetic anticipation in HLRCC syndrome. A comprehensive literature review was performed to determine the potential for genetic anticipation in HLRCC syndrome. The normal random effects model was used to evaluate for genetic anticipation to ensure reduction in bias. A total of 11 FH kindreds with available multi-generational data were identified for analysis. The mean difference in age at diagnosis of RCC between the first and second generation was -18.6 years (95 % CI -26.6 to -10.6, p anticipation for uterine leiomyomas was observed (p = 0.349). We report preliminary evidence of genetic anticipation of RCC in HLRCC syndrome. Additional clinical validation is important to confirm this observation, which may have practical implications on counseling and timing of surveillance initiation. Exploration of the underlying mechanisms of anticipation in HLRCC would be of considerable biological interest.

  10. The emerging role of fumarate as an oncometabolite

    International Nuclear Information System (INIS)

    Yang, Ming; Soga, Tomoyoshi; Pollard, Patrick J.; Adam, Julie

    2012-01-01

    The drive to understand how altered cellular metabolism and cancer are linked has caused a paradigm shift in the focus of cancer research. The discovery of a mutated metabolic enzyme, isocitrate dehydrogenase 1, that leads to accumulation of the oncometabolite 2-hydroxyglutarate, provided significant direct evidence that dysfunctional metabolism plays an important role in oncogenesis. Striking parallels exist with the Krebs cycle enzyme fumarate hydratase (FH), a tumor suppressor, whose mutation is associated with the development of leiomyomata, renal cysts, and tumors. Loss of FH enzymatic activity results in accumulation of intracellular fumarate which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways. Interestingly, our studies have questioned the role of HIF and have highlighted other candidate mechanisms, in particular the non-enzymatic modification of cysteine residues (succination) that could lead to disruption or loss of protein functions, dysfunctional cell metabolism and cell signaling. Here, we discuss the evidence for proposing fumarate as an onco-metabolite.

  11. Metabolic reconstructions identify plant 3-methylglutaconyl-CoA hydratase that is crucial for branched-chain amino acid catabolism in mitochondria

    Science.gov (United States)

    The proteinogenic branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are essential nutrients for mammals. In plants, they double as alternative energy sources when carbohydrates become limiting, the catabolism of BCAAs providing electrons to the respiratory chain and intermediates...

  12. Nitrile, amide and temperature effects on amidase-kinetics during acrylonitrile bioconversion by nitrile-hydratase/amidase in situ cascade system.

    Science.gov (United States)

    Cantarella, Laura; Gallifuoco, Alberto; Spera, Agata; Cantarella, Maria

    2013-08-01

    In this study the amidase kinetics of an in situ NHase/AMase cascade system was explored as a function of operational parameters such as temperature, substrate concentration and product formation. The results indicated that controlling amidase inactivation, during acrylonitrile bioconversion, makes it possible to recover the intermediate product of the two-step reaction in almost a pure form, without using purified enzyme. It has been demonstrated, in long-term experiments performed in continuous stirred UF-membrane bioreactors, that amidase is kinetically controlled by its proper substrate, depending on the structure, and by acrylonitrile. Using acrylamide, AMase-stability is temperature dependent (5°C, kd=0.008 h(-1); 30°C kd=0.023 h(-1)). Using benzamide, amidase is thermally stable up to 50°C and no substrate inhibition/inactivation occurs. With acrylonitrile, AMase-activity and -stability remain unchanged at concentrations <200 mM but at 200 mM, 35°C, after 70 h process, 90% irreversible inactivation occurs as no AMase-activity on benzamide revives. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Peroxisomal multifunctional enzyme type 2 from the fruitfly: dehydrogenase and hydratase act as separate entities, as revealed by structure and kinetics.

    Science.gov (United States)

    Haataja, Tatu J K; Koski, M Kristian; Hiltunen, J Kalervo; Glumoff, Tuomo

    2011-05-01

    All of the peroxisomal β-oxidation pathways characterized thus far house at least one MFE (multifunctional enzyme) catalysing two out of four reactions of the spiral. MFE type 2 proteins from various species display great variation in domain composition and predicted substrate preference. The gene CG3415 encodes for Drosophila melanogaster MFE-2 (DmMFE-2), complements the Saccharomyces cerevisiae MFE-2 deletion strain, and the recombinant protein displays both MFE-2 enzymatic activities in vitro. The resolved crystal structure is the first one for a full-length MFE-2 revealing the assembly of domains, and the data can also be transferred to structure-function studies for other MFE-2 proteins. The structure explains the necessity of dimerization. The lack of substrate channelling is proposed based on both the structural features, as well as by the fact that hydration and dehydrogenation activities of MFE-2, if produced as separate enzymes, are equally efficient in catalysis as the full-length MFE-2.

  14. Dynamics of Ebola epidemics in West Africa 2014 [v2; ref status: indexed, http://f1000r.es/5fh

    Directory of Open Access Journals (Sweden)

    Robin J. Evans

    2015-05-01

    Full Text Available This paper investigates the dynamics of Ebola virus transmission in West Africa during 2014. The reproduction numbers for the total period of epidemic and for different consequent time intervals are estimated based on a simple linear model. It contains one major parameter - the average infectious period that defines the dynamics of epidemics. Numerical implementations are carried out on data collected from three countries Guinea, Sierra Leone and Liberia as well as the total data collected worldwide. Predictions are provided by considering different scenarios involving the average times of infectiousness for the next few months and the end of the current epidemic is estimated according to each scenario.

  15. Structures and Spectroscopic Properties of F-(H2O) n with n = 1-10 Clusters from a Global Search Based On Density Functional Theory.

    Science.gov (United States)

    Shi, Ruili; Wang, Pengju; Tang, Lingli; Huang, Xiaoming; Chen, Yonggang; Su, Yan; Zhao, Jijun

    2018-04-05

    Using a genetic algorithm incorporated in density functional theory, we explore the ground state structures of fluoride anion-water clusters F - (H 2 O) n with n = 1-10. The F - (H 2 O) n clusters prefer structures in which the F - anion remains at the surface of the structure and coordinates with four water molecules, as the F - (H 2 O) n clusters have strong F - -H 2 O interactions as well as strong hydrogen bonds between H 2 O molecules. The strong interaction between the F - anion and adjacent H 2 O molecule leads to a longer O-H distance in the adjacent molecule than in an individual water molecule. The simulated infrared (IR) spectra of the F - (H 2 O) 1-5 clusters obtained via second-order vibrational perturbation theory (VPT2) and including anharmonic effects reproduce the experimental results quite well. The strong interaction between the F - anion and water molecules results in a large redshift (600-2300 cm -1 ) of the adjacent O-H stretching mode. Natural bond orbital (NBO) analysis of the lowest-energy structures of the F - (H 2 O) 1-10 clusters illustrates that charge transfer from the lone pair electron orbital of F - to the antibonding orbital of the adjacent O-H is mainly responsible for the strong interaction between the F - anion and water molecules, which leads to distinctly different geometric and vibrational properties compared with neutral water clusters.

  16. The plant formin AtFH4 interacts with both actin and microtubules, and contains a newly identified microtubule-binding domain

    Czech Academy of Sciences Publication Activity Database

    Deeks, M.J.; Fendrych, Matyáš; Smertenko, A.; Bell, K.S.; Oparka, K.; Cvrčková, F.; Žárský, Viktor; Hussey, P.J.

    2010-01-01

    Roč. 123, č. 8 (2010), s. 1209-1215 ISSN 0021-9533 R&D Projects: GA MŠk(CZ) LC06004; GA ČR GAP305/10/0433 Institutional research plan: CEZ:AV0Z50380511 Keywords : Actin regulating proteins * Membrane * Microtubule Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.290, year: 2010

  17. The Leishmania donovani complex: Genotypes of five metabolic enzymes (ICD, ME, MPI, G6PDH and FH), new targets for multilocus sequence typing

    Czech Academy of Sciences Publication Activity Database

    Zemanová, Eva; Jirků, Milan; Mauricio, I. L.; Horák, Aleš; Miles, M. A.; Lukeš, Julius

    2007-01-01

    Roč. 37, č. 2 (2007), s. 149-160 ISSN 0020-7519 R&D Projects: GA MŠk 2B06129 Grant - others:EU(EU) QLK2-CT-2001-01810 Institutional research plan: CEZ:AV0Z60220518 Source of funding: R - rámcový projekt EK Keywords : Leishmania donovani complex * zymodeme * multilocus sequence typing * Leishmania * phylogenetic network Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.392, year: 2007

  18. The influence of relative humidity on the dust measurement with the FH 62 I-N [1 m3.h-1

    International Nuclear Information System (INIS)

    Krasenbrink, A.

    1990-01-01

    The influence of relative humidity (rh) can be noticed evidently at continuous dust measurements if humidity increases rapidly up to more than 90%. This work investigated the possibilities to reduce the resulting error of taking up humidity by using two different types of glass fibre filters, the usual GF10 and its hydrophobic version GF10 HY. Compared with the results of the GF10 it could be shown that the GF10 HY takes up only 63% of humidity per time, yielding a concentration peak with an amount of 66% of the GF10 value. The total amount of absorbed humidity in mass units of the dust monitor differed between 30 μg and 50 μg for the GF10, and between 20 μg and 40 μg for the GF10 HY filter. (orig.) [de

  19. State-to-state and state-to-all-states reactive scattering angular distributions: F+H 2→HF+H

    International Nuclear Information System (INIS)

    Emmons, R.W.; Suck, S.H.

    1983-01-01

    How each state-to-state reactive transition determines nonundulatory ''state-to-all-states'' angular distribution has not yet been investigated. Here we present a complete exposure of state-to-state distorted-wave Born-approximation angular distributions in order to examine how the nonoscillatory and backward-peaked state-to-all-states reactive scattering angular distribution occurs

  20. F/H Area high level waste removal plan ampersand schedule as required by the Federal Facility Agreement for the Savannah River Site

    International Nuclear Information System (INIS)

    Hunter, M.A.

    1993-11-01

    The F and H-area HLW Tank Farms are one component of a larger integrated waste treatment system consisting of facilities designed for the overall processing of several radioactive waste streams resulting from nuclear material processing. Section IX.E of the SRS Federal Facility Agreement requires the DOE to submit to the EPA and SCDHEC for review and approval, a plan(s) and schedule(s) for the removal from service of waste tank systems(s)/component(s) that do not meet secondary containment standards, or that leak or have leaked. The Plan and Schedule for removal from service of these waste tanks is shown in Appendices A and B, respectively. Other portions of this package which include schedule dates are provided for information only. The SRS intends to remove systems from service as opposed to providing secondary containment for non-compliant systems. The systems that do not meet secondary containment requirements or that have leaked (as determined by tank assessment reports) include High Level Waste Tanks No. 1--24 along with corresponding ancillary equipment

  1. Intensive archaeological survey of the F/H Surface Enhancement Project Area, Savannah River Site, Aiken and Barnwell Counties, South Carolina

    Energy Technology Data Exchange (ETDEWEB)

    Sassaman, K.E.; Gillam, J.C.

    1993-08-01

    Twelve archaeological sites and four artifact occurrences were located by intensive survey of two tracts of land for the F and H Surface Enhancement Project on the Savannah River Site, Aiken and Barnwell Counties, South Carolina. Fieldwork in the 480-acre project area included surface reconnaissance of 3.6 linear kilometers of transects, 140 shovel tests along 4.2 linear kilometers of transects, an additional 162 shovel tests at sites and occurrences, and the excavation of six l {times} 2 m test units. All but one of the sites contained artifacts of the prehistoric era; the twelfth site consists of the remains of a twentieth-century home place. The historic site and six of the prehistoric sites consist of limited and/or disturbed contexts of archaeological deposits that have little research potential and are therefore considered ineligible for nomination to the National Register of Historic Places (NRHP). The remaining five sites have sufficient content and integrity to yield information important to ongoing investigations into upland site use. These sites (38AK146, 38AK535, 38AK539, 38AK541, and 38AK543) are thus deemed eligible for nomination to the NRHP and the Savannah River Archaeological Research Program (SRARP) recommends that they be preserved through avoidance or data recovery.

  2. GenBank blastx search result: AK059236 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059236 001-024-F01 AB016078.1 Rhodococcus sp. N-771 genes for nitrile hydratase r...egulator 2 and 1, amidase, nitrile hydratase alpha and beta subunits and nitrile hydratase activator, complete cds.|BCT BCT 8e-18 +3 ...

  3. GenBank blastx search result: AK243402 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243402 J100064O18 AB016078.1 AB016078 Rhodococcus sp. N-771 genes for nitrile hyd...ratase regulator 2 and 1, amidase, nitrile hydratase alpha and beta subunits and nitrile hydratase activator, complete cds. BCT 1e-27 1 ...

  4. Proteomic analysis in nitrogen-deprived Isochrysis galbana during lipid accumulation.

    Directory of Open Access Journals (Sweden)

    Pingping Song

    Full Text Available The differentially co-expressed proteins in N-deprived and N-enriched I. galbana were comparatively analyzed by using two dimensional electrophoresis (2-DE and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight-mass spectrometry (MALDI-TOF/TOF-MS with the aim of better understanding lipid metabolism in this oleaginous microalga. Forty-five of the 900 protein spots showed dramatic changes in N-deprived I. galbana compared with the N-enriched cells. Of these, 36 protein spots were analyzed and 27 proteins were successfully identified. The identified proteins were classified into seven groups by their molecular functions, including the proteins related to energy production and transformation, substance metabolism, signal transduction, molecular chaperone, transcription and translation, immune defense and cytoskeleton. These altered proteins slowed cell growth and photosynthesis of I. galbana directly or indirectly, but at the same time increased lipid accumulation. Eight key enzymes involved in lipid metabolism via different pathways were identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH, phosphoglycerate kinase (PGK, enolase, aspartate aminotransferase (AST, fumarate hydratase (FH, citrate synthase (CS, O-acetyl-serine lyase (OAS-L and ATP sulfurylase (ATPS. The results suggested that the glycolytic pathway and citrate transport system might be the main routes for lipid anabolism in N-deprived I. galbana, and that the tricarboxylic acid (TCA cycle, glyoxylate cycle and sulfur assimilation system might be the major pathways involved in lipid catabolism.

  5. Pre-sowing Seed Treatment with 24-Epibrassinolide Ameliorates Pesticide Stress in Brassica juncea L. through the Modulation of Stress Markers

    Directory of Open Access Journals (Sweden)

    Parvaiz Ahmad

    2016-11-01

    Full Text Available The present experiment was designed to assess the effects of seed soaking with 24-epibrassinolide (EBR on the physiology of Brassica juncea L. seedlings grown under imidacloprid (IMI toxicity. Application of EBR increased the length of seedlings, dry weight, and pigment contents, polyphenols, total phenols and organic acids under IMI toxicity. The expression of genes coding key enzymes of pigment, phenols, polyphenols and organic acid biosynthetic pathways was also studied including CHLASE (chlorophyllase, PSY (phytoene synthase, CHS (chalcone synthase and PAL (phenylalanine ammonialyase, CS (citrate synthase, SUCLG1 (succinyl Co-A ligase,, SDH (succinate dehydrogenase, FH (fumarate hydratase, MS (malate synthase. Multiple linear regression analysis revealed that IMI application regressed negatively on seedling length, dry weight and total chlorophyll content. However, EBR seed treatment regressed positively on all of the parameters studied. Moreover, interaction between IMI and EBR showed positive regression for growth parameters, content of pigments, total polyphenol, total phenol and malate, and expression of PSY and PAL. Negative interactions were noticed for the contents of fumarate, succinate and citrate, and expression of CHS and all genes studied related to organic acid metabolism. In conclusion, EBR enhanced the growth and contents of all studied metabolites by regulating the gene expression of B. juncea seedlings under IMI stress.

  6. Two-year efficacy and safety of Simvastatin 80 mg in familial hypercholesterolemia (The examination of probands and relatives in statin studies with familial hypercholesterolemia [ExPRESS FH])

    NARCIS (Netherlands)

    de Sauvage Nolting, Pernette R. W.; Buirma, Rudolf J. A.; Hutten, Barbara A.; Kastelein, John J. P.

    2002-01-01

    High-dose (80 mg) simvastatin is efficacious in both reducing low-density lipoprotein cholesterol (-48%) and triglyceride (-26%) levels and in elevating high-density lipoprotein cholesterol (+ 13%) levels in a large cohort of patients with familial hypercholesterolemia. No tachyphylaxis was seen

  7. Evaluation of potential severe accidents during low power and shutdown operations at Surry, Unit-1: Analysis of core damage frequency from internal events during mid-loop operations. Appendices F-H, Volume 2, Part 4

    International Nuclear Information System (INIS)

    Chu, T.L.; Musicki, Z.; Kohut, P.; Yang, J.; Bozoki, G.; Hsu, C.J.; Diamond, D.J.; Bley, D.; Johnson, D.; Holmes, B.

    1994-06-01

    Traditionally, probabilistic risk assessments (PRA) of severe accidents in nuclear power plants have considered initiating events potentially occurring only during full power operation. Some previous screening analyses that were performed for other modes of operation suggested that risks during those modes were small relative to full power operation. However, more recent studies and operational experience have implied that accidents during low power and shutdown could be significant contributors to risk. Two plants, Surry (pressurized water reactor) and Grand Gulf (boiling water reactor), were selected as the plants to be studied. The objectives of the program are to assess the risks of severe accidents initiated during plant operational states other than full power operation and to compare the estimated core damage frequencies, important accident sequences and other qualitative and quantitative results with those accidents initiated during full power operation as assessed in NUREG-1150. The scope of the program includes that of a level-3 PRA. In phase 2, mid-loop operation was selected as the plant configuration to be analyzed based on the results of the phase 1 study. The objective of the phase 2 study is to perform a detailed analysis of the potential accident scenarios that may occur during mid-loop operation, and compare the results with those of NUREG-1150. The scope of the level-1 study includes plant damage state analysis, and uncertainty analysis. Volume 1 summarizes the results of the study. Internal events analysis is documented in Volume 2. It also contains an appendix that documents the part of the phase 1 study that has to do with POSs other than mid-loop operation. Internal fire and internal flood analyses are documented in Volumes 3 and 4. A separate study on seismic analysis, documented in Volume 5, was performed for the NRC by Future Resources Associates, Inc. Volume 6 documents the accident progression, source terms, and consequence analysis

  8. iTRAQ-based proteomic profile analysis of ISKNV-infected CPB cells with emphasizing on glucose metabolism, apoptosis and autophagy pathways.

    Science.gov (United States)

    Wu, Shiwei; Yu, Lujun; Fu, Xiaozhe; Yan, Xi; Lin, Qiang; Liu, Lihui; Liang, Hongru; Li, Ningqiu

    2018-05-04

    Infectious spleen and kidney necrosis virus (ISKNV) has caused significant losses in the cultured mandarin fish (Siniperca chuatsi) industry. The molecular mechanisms that underlie interaction between ISKNV and hosts are not fully understood. In this study, the proteomic profile of CPB cells at progressive time points after ISKNV infection was analyzed by isobaric tags for relative and absolute quantitation (iTRAQ). A total of 2731 proteins corresponding to 6363 novel peptides (false discovery rate analysis of several proteins as G6PDH, β-tubulin and RPL11 were done to validate iTRAQ data. Among those differentially expressed proteins, several glucose metabolism-related enzymes, including glucose-6-phosphate dehydrogenase (G6PDH), pyruvate dehydrogenase phosphatase (PDP) and fumarate hydratase (FH), were up-regulated, while pyruvate dehydrogenase kinase (PDK) and enolase (ENO) were down-regulated at 24 h poi, suggesting that ISKNV enhanced glucose metabolism in CPB cells in early-stage infection. Simultaneously, expression of apoptosis-related proteins including Caspase 8, phosphoinositide 3-kinases (PI3Ks), and regulatory-associated protein of mTOR-like isoform X3 changed upon ISKNV infection, indicating that ISKNV induced apoptosis of CPB cells. Autophagy-related proteins including LC3 and PI3Ks were up-regulated at 24 h poi, indicating that ISKNV induced autophagy of CPB cells in early-stage infection. These findings may improve the understanding of ISKNV and host interaction and help clarify its pathogenesis mechanisms. Copyright © 2018. Published by Elsevier Ltd.

  9. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    Science.gov (United States)

    Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  10. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  11. Development of an Amperometric Biosensor Platform for the Combined Determination of L-Malic, Fumaric, and L-Aspartic Acid.

    Science.gov (United States)

    Röhlen, Désirée L; Pilas, Johanna; Schöning, Michael J; Selmer, Thorsten

    2017-10-01

    Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD + ) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM -1 (L-malate biosensor) and 0.4 μA mM -1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0-10.0 mM with a sensitivity of 0.09 μA mM -1 . The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.

  12. Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior.

    Science.gov (United States)

    Wang, Yue; Dong, Li; Cui, Heng; Shen, Dan-hua; Wang, Ying; Chang, Xiao-hong; Fu, Tian-yun; Ye, Xue; Yao, Yuan-yang

    2011-05-01

    Recently, a high frequency of mutations in mitochondrial DNA (mtDNA) has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines (SKOV3/SKOV3.ip1) with different metastatic potentials was examined. Cancer cells SKOV3.ip1 were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. SKOV3.ip1 exhibited a higher degree of migration potential than its paired cell line SKOV3. The proteins in the mitochondria of these two cells were isolated and separated by 2-D gel electrophoresis. The differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight (MALDI-TOF/TOF), and finally a selected protein candidate was further investigated by immunohistochemistry (IHC) method in nude mice bearing tumor tissues of these two cells. A total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis (PAGE) approach. Among them, 17 spots were detected only in either SKOV3 or SKOV3.ip1 cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 (SOD2), fumarate hydratase (FH), mitochondrial ribosomal protein L38 (MRPL38), and mRNA turnover 4 homolog (MRTO4). An increased staining of SOD2 was observed in SKOV3.ip1 over that of SKOV3 in IHC analysis. Our results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. The underlying mechanism warrants further study.

  13. Effects of CD44 Ligation on Signaling and Metabolic Pathways in Acute Myeloid Leukemia

    KAUST Repository

    Madhoun, Nour Y.

    2017-04-01

    Acute myeloid leukemia (AML) is characterized by a blockage in the differentiation of myeloid cells at different stages. CD44-ligation using anti-CD44 monoclonal antibodies (mAbs) has been shown to reverse the blockage of differentiation and to inhibit the proliferation of blasts in most AML-subtypes. However, the molecular mechanisms underlying this property have not been fully elucidated. Here, we sought to I) analyze the effects of anti-CD44 mAbs on downstream signaling pathways, including the ERK1/2 (extracellular signal-regulated kinase 1 and 2) and mTOR (mammalian target of rapamycin) pathways and II) use state-of-the-art Nuclear Magnetic Resonance (NMR) technology to determine the global metabolic changes during differentiation induction of AML cells using anti-CD44 mAbs and other two previously reported differentiation agents. In the first objective (Chapter 4), our studies provide evidence that CD44-ligation with specific mAbs in AML cells induced an increase in ERK1/2 phosphorylation. The use of the MEK inhibitor (U0126) significantly inhibited the CD44-induced differentiation of HL60 cells, suggesting that ERK1/2 is critical for the CD44-triggered differentiation in AML. In addition, this was accompanied by a marked decrease in the phosphorylation of the mTORC1 and mTORC2 complexes, which are strongly correlated with the inhibition of the PI3K/Akt pathway. In the second objective (Chapter 5), 1H NMR experiments demonstrated that considerable changes in the metabolic profiles of HL60 cells were induced in response to each differentiation agent. These most notable metabolites that significantly changed upon CD44 ligation were involved in the tricarboxylic acid (TCA) cycle and glycolysis such as, succinate, fumarate and lactate. Therefore, we sought to analyze the mechanisms underlying their alterations. Our results revealed that anti-CD44 mAbs treatment induced upregulation in fumarate hydratase (FH) expression and its activity which was accompanied by a

  14. NCBI nr-aa BLAST: CBRC-CREM-01-1371 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CREM-01-1371 ref|YP_926913.1| Phosphopyruvate hydratase [Shewanella amazonensi...s SB2B] gb|ABL99243.1| Phosphopyruvate hydratase [Shewanella amazonensis SB2B] YP_926913.1 6e-90 71% ...

  15. Familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Versmissen, Jorie; Vongpromek, Ranitha; Yahya, Reyhana

    2016-01-01

    cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM). RESULTS: Seven FH patients were asymptomatic and six had...... in asymptomatic FH patients may play a role in their apparent protection from premature CHD....

  16. CT findings of subarachnoid hemorrhage due to ruptured cerebral aneurysm with fundal hemorrhage

    International Nuclear Information System (INIS)

    Kashihara, Kengo; Yamashima, Tetsumori; Hasegawa, Takeshi; Kida, Shinya; Nitta, Hisashi; Yamamoto, Shinjiro

    1985-01-01

    CT scan and fundus oculi of subarachnoid hemorrhage due to ruptured cerebral aneurysm were investigated in 42 patients who were admitted between January, 1980, and August, 1984. Fundal hemorrhage (FH) was observed in 22 patients. The patients with FH showed a worse clinical grade (Hunt Kosnik) on admission than those without FH. The mortality rate of patients with FH was 64 %, much higher than the 5 % rate of those without FH. Moreover, the patients with FH showed more trouble in daily living than those without FH. CT scans of patients with FH usually showed severe subarachnoid hemorrhage (SAH), whereas those of patients without FH showed only mild hemorrhage. These findings suggest that fundal hemorrhage is caused by acute intracranial hypertension following subarachnoid hemorrhage due to a ruptured cerebral aneurysm. However, no significant correlation between the laterality of FH and the hemispheric dominancy of SAH could be demonstrated. (author)

  17. Phytochemicals and nutritional composition in accessions of Kei-apple (Dovyalis caffra): Southern African indigenous fruit.

    Science.gov (United States)

    Mpai, Semkaleng; du Preez, Rosemary; Sultanbawa, Yasmina; Sivakumar, Dharini

    2018-07-01

    Current study was initiated to identify the phytochemicals and the nutritional profile of eleven Kei-apple fruit accessions. Accession FH29 showed the highest level (492.45 mg 100 g -1 fresh weight) of total phenolic content, higher than the referral fruit, blueberry. Pyrogallol was identified as the predominant phenolic compound in all accessions. Accession FH 29 showed the highest (49.75 µmol TEAC g -1 fresh weight) antioxidant capacity. Catechin content was higher in accessions; FH151, FH15, FH14, FH29, FH243, FH 239 and FH 231. Accessions, FH14 and FH232 exhibited higher levels of β-carotene than the referral fruit apples (cv. Top red) and peaches (cv. Excellence). The total sugar (glucose and fructose) was highest (50 mg g -1 fresh weight) in accession FH240. Asparagine (3122.18 mg L -1 ) and gamma-aminobutyric (1688.87 mg L -1 ) were higher in accessions FH239 and FH243 respectively. Overall, the accession Kei-apple FH236 can be regarded as a good source of essential amino acids. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Collagenolytic activities of the major secreted cathepsin L peptidases involved in the virulence of the helminth pathogen, Fasciola hepatica.

    Directory of Open Access Journals (Sweden)

    Mark W Robinson

    Full Text Available BACKGROUND: The temporal expression and secretion of distinct members of a family of virulence-associated cathepsin L cysteine peptidases (FhCL correlates with the entry and migration of the helminth pathogen Fasciola hepatica in the host. Thus, infective larvae traversing the gut wall secrete cathepsin L3 (FhCL3, liver migrating juvenile parasites secrete both FhCL1 and FhCL2 while the mature bile duct parasites, which are obligate blood feeders, secrete predominantly FhCL1 but also FhCL2. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that FhCL1, FhCL2 and FhCL3 exhibit differences in their kinetic parameters towards a range of peptide substrates. Uniquely, FhCL2 and FhCL3 readily cleave substrates with Pro in the P2 position and peptide substrates mimicking the repeating Gly-Pro-Xaa motifs that occur within the primary sequence of collagen. FhCL1, FhCL2 and FhCL3 hydrolysed native type I and II collagen at neutral pH but while FhCL1 cleaved only non-collagenous (NC, non-Gly-X-Y domains FhCL2 and FhCL3 exhibited collagenase activity by cleaving at multiple sites within the α1 and α2 triple helix regions (Col domains. Molecular simulations created for FhCL1, FhCL2 and FhCL3 complexed to various seven-residue peptides supports the idea that Trp67 and Tyr67 in the S2 subsite of the active sites of FhCL3 and FhCL2, respectively, are critical to conferring the unique collagenase-like activity to these enzymes by accommodating either Gly or Pro residues at P2 in the substrate. The data also suggests that FhCL3 accommodates hydroxyproline (Hyp-Gly at P3-P2 better than FhCL2 explaining the observed greater ability of FhCL3 to digest type I and II collagens compared to FhCL2 and why these enzymes cleave at different positions within the Col domains. CONCLUSIONS/SIGNIFICANCE: These studies further our understanding of how this helminth parasite regulates peptidase expression to ensure infection, migration and establishment in host tissues.

  19. Characterisation of the nitrile biocatalytic activity of rhodococcus rhodochrous ATCC BAA-870

    CSIR Research Space (South Africa)

    Frederick, J

    2006-10-01

    Full Text Available rhodochrous ATCC BAA-870, was explored. The biocatalyst expressed a two enzyme system with sequential nitrile-converting activity: nitrile hydratase and amidase. This biocatalytic nitrile hydrolysis affords valuable applications in industry, including...

  20. Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy.

    Science.gov (United States)

    Piccinini, M; Mostert, M; Seardo, M A; Bussolino, S; Alberto, G; Lupino, E; Ramondetti, C; Buccinnà, B; Rinaudo, M T

    2009-01-01

    In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH-). Ten FH+ and 10 FH- were evaluated during pregnancy (12-14, 24-26, and 37-39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH- and 20 FH+ non-pregnant women served as controls. All FH+ and FH- controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH- and FH+ pregnant women at 12-14 weeks clinical parameters were normal; from 24-26 weeks, with unvaried glucose, insulin and BMI rose more in FH- and only in the latter recovered the 12-14 weeks values at follow-up. In all FH-, the cohort of PDH alterations was incomplete at 24-26 weeks, complete at 37-39 weeks, and absent at follow-up but complete from 12-14 weeks including follow-up in all FH+. In FH-, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.

  1. Quantification of fumarate and investigation of endogenous and exogenous fumarate stability in rat plasma by LC-MS/MS.

    Science.gov (United States)

    Shi, Yao; Tse, Susanna; Rago, Brian; Yapa, Udeni; Li, Fumin; Fast, Douglas M

    2016-04-01

    Fumaric acid is a commonly used excipient in pharmaceutical products. It is not known if its presence may lead to fluctuation of endogenous fumarate levels. An LC-MS/MS method was developed and validated to quantify fumarate in support of a toxicokinetics study. Stability evaluation showed that endogenous fumarate was stable for 6 h at room temperature, while exogenously added fumaric acid was converted to malate within 1 h due to the presence of fumarase. Citric acid, a fumarase inhibitor, prevented the conversion of added fumaric acid in rat plasma. The method was validated in citric acid stabilized rat plasma using a surrogate matrix approach. A discrepancy in stability was observed between endogenous fumarate and exogenously added fumaric acid.

  2. Suitability of teriparatide and level of acceptance of pharmacotherapeutic recommendations in a healthcare management areaSuitability of teriparatide and level of acceptance of pharmacotherapeutic recommendations in a healthcare management area DOI:\t10.7399/fh.2016.40.4.9953

    Directory of Open Access Journals (Sweden)

    Maria Rosa Cantudo-Cuenca

    2016-07-01

    Full Text Available Objective: To analyse the suitability of teriparatide prescriptions for osteoporosis treatment in a health management area, as well as the level of acceptance of pharmacotherapeutic recommendations made to physicians. Design: A prospective interventional study conducted from february 2015 to june 2015. Setting: South Seville Health Management Area. Participants: Patients receiving teriparatide. Main measurements: Suitability of teriparatide prescriptions according to Clinical Practice Guidelines and level of acceptance of pharmacotherapeutic recommendations. Results: Teriparatide prescriptions were unsuitable in 45 patients (68.2%; 11 due to no indication, 17 patients did not have previous treatments with first-line drugs, 6 due to contraindications and 9 patients were treated for more than 24 months with the drug. Besides, 4 prescriptions were unsuitable because of combination with other therapies. The acceptance of pharmacotherapeutic recommendations was 64.4%, leading to teriparatide discontinuation in 21 patients (72.4%, and a switch to alendronate or ibandronate in another 8 patients. Conclusions: A high percentage of teriparatide prescriptions is unsuitable in our health care management area, but it has decreased after pharmacist intervention.

  3. Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn

    NARCIS (Netherlands)

    Weijenborg, P. W.; Smout, A. J. P. M.; Bredenoord, A. J.

    2016-01-01

    Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity.

  4. Familial hypercholesterolaemia

    African Journals Online (AJOL)

    Familial hypercholesterolaemia (FH) is a monogenic disorder of low-density lipoprotein (LDL) metabolism. It is characterised .... Figure 2: Cumulative prevalence of physical signs in adult FH patients at the. GSH Lipid .... microvascular trauma.

  5. The prevalence and prognostic importance of possible familial hypercholesterolemia in patients with myocardial infarction

    DEFF Research Database (Denmark)

    Rerup, Sofie Aagaard; Bang, Lia E; Mogensen, Ulrik M

    2016-01-01

    AIMS: Familial hypercholesterolemia (FH) is a common genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease. The aim of this study was to examine the prevalence and prognostic significance of possible FH in patients with myocardial infarction (MI). METHODS...

  6. Opaque Communities: A Framework for Assessing Potential Homeland Security Threats from Voids on the Map

    Science.gov (United States)

    2014-09-01

    and the amount of undiscovered clandestine activity mounts.39 Although this rubric is interchangeable between actors, it does not adequately...public assistance. The FLDS twin communities at Short Creek exhibit the highest global prevalence of fumarase deficiency, a rare genetic disorder that...Physician Finds Rare Disease in FLDS Kids; Genetic Disorder: About 20 Cases Have Been Discovered in 15 Years in Two Polygamous Towns; Rare Disorder Not

  7. Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine.

    Science.gov (United States)

    Giuntini, Serena; Beernink, Peter T; Granoff, Dan M

    2015-12-16

    FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FH(high)), and six with FH(low) baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FH(low) baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FH(high) phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (pb deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FH(low) baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FH(high), the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Factor H Binds to the Hypervariable Region of Many Streptococcus pyogenes M Proteins but Does Not Promote Phagocytosis Resistance or Acute Virulence

    Science.gov (United States)

    Kristensen, Bodil M.; Olsen, John E.; Harris, Claire L.; Ufret-Vincenty, Rafael L.; Stålhammar-Carlemalm, Margaretha; Lindahl, Gunnar

    2013-01-01

    Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems. PMID:23637608

  9. Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence.

    Directory of Open Access Journals (Sweden)

    Mattias C U Gustafsson

    Full Text Available Many pathogens express a surface protein that binds the human complement regulator factor H (FH, as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems.

  10. Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.

    Science.gov (United States)

    Thedrez, Aurélie; Blom, Dirk J; Ramin-Mangata, Stéphane; Blanchard, Valentin; Croyal, Mikaël; Chemello, Kévin; Nativel, Brice; Pichelin, Matthieu; Cariou, Bertrand; Bourane, Steeve; Tang, Lihua; Farnier, Michel; Raal, Frederick J; Lambert, Gilles

    2018-03-01

    Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment. Residual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab. © 2017 American Heart Association

  11. Effects of Video Weather Training Products, Web-Based Preflight Weather Briefing, and Local Versus Non-Local Pilots on General Aviation Pilot Weather Knowledge and Flight Behavior. Phase 2

    Science.gov (United States)

    2010-03-01

    homa pilots are representative of u.S. pilots in general. Presumably, they are similar but, so far, this has not been directly investigated. Since...1 Training Product 2 Control Combined group n Age FH % IR n Age FH % IR n Age FH % IR N Age FH % IR Phase 1 16 39 280 53 16 38 235.5 47 18 42 262.5 50 50

  12. Evaluation of the Chemical and Mechanical Properties of Hardening High-Calcium Fly Ash Blended Concrete.

    Science.gov (United States)

    Fan, Wei-Jie; Wang, Xiao-Yong; Park, Ki-Bong

    2015-09-07

    High-calcium fly ash (FH) is the combustion residue from electric power plants burning lignite or sub-bituminous coal. As a mineral admixture, FH can be used to produce high-strength concrete and high-performance concrete. The development of chemical and mechanical properties is a crucial factor for appropriately using FH in the concrete industry. To achieve sustainable development in the concrete industry, this paper presents a theoretical model to systematically evaluate the property developments of FH blended concrete. The proposed model analyzes the cement hydration, the reaction of free CaO in FH, and the reaction of phases in FH other than free CaO. The mutual interactions among cement hydration, the reaction of free CaO in FH, and the reaction of other phases in FH are also considered through the calcium hydroxide contents and the capillary water contents. Using the hydration degree of cement, the reaction degree of free CaO in FH, and the reaction degree of other phases in FH, the proposed model evaluates the calcium hydroxide contents, the reaction degree of FH, chemically bound water, porosity, and the compressive strength of hardening concrete with different water to binder ratios and FH replacement ratios. The evaluated results are compared to experimental results, and good consistencies are found.

  13. Familial hypercholesterolemia: Screening, treatment and follow-up from pregnancy into young adulthood

    NARCIS (Netherlands)

    Kusters, D.M.

    2016-01-01

    In part 1, the consequences of familial hypercholesterolemia (FH) during pregnancy for the unborn child are explored. Part II comprises several studies on the screening, diagnosis and follow-up of children with FH. The treatment of children with FH is studied in part III, with the most important

  14. Final height after gonadotrophin releasing hormone agonist treatment for central precocious puberty : The Dutch experience

    NARCIS (Netherlands)

    Mul, D; Oostdijk, W; Otten, BJ; Rouwe, C; Jansen, M; Delemarre-van de Waal, HA; Waelkens, JJJ; Drop, SLS

    Final height (FH) data of 96 children (87 girls) treated with GnRH agonist for central precocious puberty were studied. In girls mean FH exceeded initial height prediction by 7.4 (5.7) cm (p <0.001); FH was significantly lower than target height, but still in the genetic target range. When treatment

  15. Formation, stability, and solubility of metal oxide nanoparticles: surface entropy, and free energy of ferrihydrite

    NARCIS (Netherlands)

    Hiemstra, T.

    2015-01-01

    Ferrihydrite (Fh) is an excellent model for understanding nanoparticle behavior in general. Moreover, Fh is one of the most important Fe (hydr) oxides in nature. Fh particles can be extremely small leading to a very high reactive surface area that changes its chemical potential, strongly affecting

  16. Structural studies of MFE-1: the 1.9 A crystal structure of the dehydrogenase part of rat peroxisomal MFE-1.

    Science.gov (United States)

    Taskinen, Jukka P; Kiema, Tiila R; Hiltunen, J Kalervo; Wierenga, Rik K

    2006-01-27

    The 1.9 A structure of the C-terminal dehydrogenase part of the rat peroxisomal monomeric multifunctional enzyme type 1 (MFE-1) has been determined. In this construct (residues 260-722 and referred to as MFE1-DH) the N-terminal hydratase part of MFE-1 has been deleted. The structure of MFE1-DH shows that it consists of an N-terminal helix, followed by a Rossmann-fold domain (domain C), followed by two tightly associated helical domains (domains D and E), which have similar topology. The structure of MFE1-DH is compared with the two known homologous structures: human mitochondrial 3-hydroxyacyl-CoA dehydrogenase (HAD; sequence identity is 33%) (which is dimeric and monofunctional) and with the dimeric multifunctional alpha-chain (alphaFOM; sequence identity is 28%) of the bacterial fatty acid beta-oxidation alpha2beta2-multienzyme complex. Like MFE-1, alphaFOM has an N-terminal hydratase part and a C-terminal dehydrogenase part, and the structure comparisons show that the N-terminal helix of MFE1-DH corresponds to the alphaFOM linker helix, located between its hydratase and dehydrogenase part. It is also shown that this helix corresponds to the C-terminal helix-10 of the hydratase/isomerase superfamily, suggesting that functionally it belongs to the N-terminal hydratase part of MFE-1.

  17. Medication adherence, cascade screening, and lifestyle patterns among women with hypercholesterolemia: Results from the WomenHeart survey.

    Science.gov (United States)

    Benson, Gretchen; Witt, Dawn R; VanWormer, Jeffrey J; Campbell, Susan M; Sillah, Arthur; Hayes, Sharonne N; Lui, Matt; Gulati, Martha

    2016-01-01

    Hypercholesterolemia is a major risk factor for cardiovascular disease. Women with hypercholesterolemia and familial hypercholesterolemia (FH) are a high-risk group often underdiagnosed, undertreated, and unaware of the need for cascade screening. The objectives were to identify the prevalence of hypercholesterolemia and FH in 2 national databases, explore lifestyle/medication adherence, and examine rates of cascade screening (lipid testing in all first-degree relatives) among those with FH. This was a cross-sectional study of women who completed an online survey in 2014. Outcomes were examined for 3 groups: diagnosed, probable, and no FH. For FH, multivariable logistic regression was used to examine the association between family member screening for FH and sociodemographic and/or clinical characteristics. There were 761 respondents with a mean (±standard deviation) age of 59 ± 10.1 years; 26% reported FH, 22% probable FH, and 51% no FH. Eighty-three percent of the total sample and 95% with FH take a statin. In those with hypercholesterolemia and FH, 65% and 58% reported high medication adherence, respectively. Women with probable FH consumed significantly fewer fruits/vegetables and were less active. FH cascade screening was: siblings 54%, parents 37%, and children 34%. Marital status, annual household income, and diabetes were significantly associated with cascade screening. In a survey of informed women with hypercholesterolemia and FH, cascade screening is underused. Our findings warrant increased efforts to identify cascade screening barriers. Early detection and treatment of hypercholesterolemia/FH is a priority for women, and their first-degree relatives, as this may dramatically reduce cardiovascular disease impact. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  18. A computerized Stroop task to assess cancer-related cognitive biases.

    Science.gov (United States)

    DiBonaventura, Marco DaCosta; Erblich, Joel; Sloan, Richard P; Bovbjerg, Dana H

    2010-01-01

    Biases in processing information related to sources of stress have widely been demonstrated with the use of Stroop emotional color word tasks. One study reported such biases among women with histories of breast cancer in a first-degree relative (FH+) who were given a Stroop cancer word task. This study aimed to replicate and extend these findings with a computerized version of the task. Response latencies and errors were recorded during administration of the task to FH+ and FH- women. A cancer list and 5 comparison lists were administered. Results indicated that FH+ women exhibited longer response latencies for cancer words than did FH- women (p Stroop cancer word task.

  19. Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence

    DEFF Research Database (Denmark)

    Gustafsson, Caj Ulrik Mattias; Lannergård, Jonas; Nilsson, Olof Rickard

    2013-01-01

    Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against...... represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited...... to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed...

  20. Development of CANDU prototype fuel handling simulator - concept and some simulation results with physical network modeling approach

    Energy Technology Data Exchange (ETDEWEB)

    Xu, X.P. [Candu Energy Inc, Mississauga, Ontario (Canada)

    2012-07-01

    This paper reviewed the need for a fuel handling(FH) simulator in training operators and maintenance personnel, in FH design enhancement based on operating experience (OPEX), and the potential application of Virtual Reality (VR) based simulation technology. Modeling and simulation of the fuelling machine (FM) magazine drive plant (one of the CANDU FH sub-systems) was described. The work established the feasibility of modeling and simulating a physical FH drive system using the physical network approach and computer software tools. The concept and approach can be applied similarly to create the other FH subsystem plant models, which are expected to be integrated with control modules to develop a master FH control model and further to create a virtual FH system. (author)

  1. Development of CANDU prototype fuel handling simulator - concept and some simulation results with physical network modeling approach

    International Nuclear Information System (INIS)

    Xu, X.P.

    2012-01-01

    This paper reviewed the need for a fuel handling(FH) simulator in training operators and maintenance personnel, in FH design enhancement based on operating experience (OPEX), and the potential application of Virtual Reality (VR) based simulation technology. Modeling and simulation of the fuelling machine (FM) magazine drive plant (one of the CANDU FH sub-systems) was described. The work established the feasibility of modeling and simulating a physical FH drive system using the physical network approach and computer software tools. The concept and approach can be applied similarly to create the other FH subsystem plant models, which are expected to be integrated with control modules to develop a master FH control model and further to create a virtual FH system. (author)

  2. An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain.

    Science.gov (United States)

    Wilding, Birgit; Veselá, Alicja B; Perry, Justin J B; Black, Gary W; Zhang, Meng; Martínková, Ludmila; Klempier, Norbert

    2015-07-28

    Paclitaxel (taxol) is an antimicrotubule agent widely used in the treatment of cancer. Taxol is prepared in a semisynthetic route by coupling the N-benzoyl-(2R,3S)-3-phenylisoserine sidechain to the baccatin III core structure. Precursors of the taxol sidechain have previously been prepared in chemoenzymatic approaches using acylases, lipases, and reductases, mostly featuring the enantioselective, enzymatic step early in the reaction pathway. Here, nitrile hydrolysing enzymes, namely nitrile hydratases and nitrilases, are investigated for the enzymatic hydrolysis of two different sidechain precursors. Both sidechain precursors, an openchain α-hydroxy-β-amino nitrile and a cyanodihydrooxazole, are suitable for coupling to baccatin III directly after the enzymatic step. An extensive set of nitrilases and nitrile hydratases was screened towards their activity and selectivity in the hydrolysis of two taxol sidechain precursors and their epimers. A number of nitrilases and nitrile hydratases converted both sidechain precursors and their epimers.

  3. [Transformation of 2- and 4-cyanopyridines by free and immobilized cells of nitrile-hydrolyzing bacteria].

    Science.gov (United States)

    Maksimova, Iu G; Vasil'ev, D M; Ovechkina, G V; Maksimov, A Iu; Demakov, V A

    2013-01-01

    The transformation dynamics of 2- and 4-cyanopyridines by cells suspended and adsorbed on inorganic carriers has been studied in the Rhodococcus ruber gt 1 strain possessing nitrile hydratase activity and the Pseudomonas fluorescens C2 strain containing nitrilase. It was shown that both nitrile hydratase and nitrilase activities of immobilized cells against 2-cyanopyridine were 1.5-4 times lower compared to 4-cyanopyridine and 1.6-2 times lower than the activities of free cells against 2-cyanpopyridine. The possibility of obtaining isonicotinic acid during the combined conversion of 4-cyanopyridine by a mixed suspension of R. ruber gt 1 cells with a high level of nitrile hydratase activity and R. erythropolis 11-2 cells with a pronounced activity of amidase has been shown. Immobilization of Rhodococcus cells on raw coal and Pseudomonas cells on china clay was shown to yield a heterogeneous biocatalyst for the efficient transformation of cyanopyridines into respective amides and carbonic acids.

  4. Severity of cotton whitefly (bemisia tabaci genn.) population with special reference to abiotic factors

    International Nuclear Information System (INIS)

    Zia, K.; Bashir, M.H.; Khan, B.S.; Khan, R.R.; Hafeez, F.

    2013-01-01

    Bemisia tabaci is serious insect and constantly destabilizing the cotton production. The research was conducted to evaluate cotton cultivars (transgenic and non transgenic) for resistance against whitefly and further correlated with weather factors such as temperature, relative humidity and rainfall, during the cropping seasons 2010 and 2011. However, peak population (6.36 per leaf) was recorded from FH-113 followed FH-167 and FH-114, whereas minimum population was recorded from FH-4243 in transgenic group whereas peak population (5.24 per leaf) was recorded from FH- 941 followed by FH-100 and FH- 901 while minimum population was recorded from FH-207, in non transgenic group of cultivars in the year 2010. The incidence and abundance was much high and reaching towards two folds in the year 2011 but the trend of whitefly varied with peak population (11.03 per leaf) recorded from FH -167 followed by FH- 4243 and FH113 (from transgenic group of cultivars) whereas a peak of 10.77 per leaf population of whitefly, recorded followed by FH-901 and FH-941 (from non transgenic group of cultivars). FH-207 found more resistant from all ten cultivars studied in 2011. Correlation among weather factors and whitefly population showed that rainfall was negatively correlated while temperature and relative humidity were positively correlated with whitefly population. In addition to that situation is becoming worse because of shifting from conventional to more advanced transgenic cultivars that are susceptible and serve as host. Moreover, climatic conditions provide addition favor and helps in population buildup, abundance and incidence. (author)

  5. Environment and feeding change the ability of heart rate to predict metabolism in resting Steller sea lions (Eumetopias jubatus).

    Science.gov (United States)

    Young, Beth L; Rosen, David A S; Haulena, Martin; Hindle, Allyson G; Trites, Andrew W

    2011-01-01

    The ability to use heart rate (fh) to predict oxygen consumption rates ([Formula: see text]) in Steller sea lions and other pinnipeds has been investigated in fasting animals. However, it is unknown whether established fh:[Formula: see text] relationships hold under more complex physiological situations, such as when animals are feeding or digesting. We assessed whether fh could accurately predict [Formula: see text] in trained Steller sea lions while fasting and after being fed. Using linear mixed-effects models, we derived unique equations to describe the fh:[Formula: see text] relationship for fasted sea lions resting on land and in water. Feeding did not significantly change the fh:[Formula: see text] relationship on land. However, Steller sea lions in water displayed a different fh:[Formula: see text] relationship after consuming a 4-kg meal compared with the fasting condition. Incorporating comparable published fh:[Formula: see text] data from Steller sea lions showed a distinct effect of feeding after a 6-kg meal. Ultimately, our study illustrated that both feeding and physical environment are statistically relevant when deriving [Formula: see text] from telemetered fh, but that only environment affects the practical ability to predict metabolism from fh. Updating current bioenergetic models with data gathered using these predictive fh:[Formula: see text] equations will yield more accurate estimates of metabolic rates of free-ranging Steller sea lions under a variety of physiological, behavioral, and environmental states.

  6. Optic Disc Drusen and Family History of Glaucoma-Results of a Patient-directed Survey.

    Science.gov (United States)

    Gramer, Gwendolyn; Gramer, Eugen; Weisschuh, Nicole

    2017-10-01

    Prospective evaluation of family history (FH) of glaucoma and FH of optic disc drusen (ODD) in patients with sonographically confirmed ODD. A total of 87 patients with ODD interviewed all their first-degree and second-degree relatives using a detailed questionnaire on whether an ophthalmologist had diagnosed or excluded glaucoma or ocular hypertension (OH). Using a second questionnaire, 62 of these patients also provided information about ODD in their FH. Control groups for FH of glaucoma consisted of 2170 patients with glaucoma or OH evaluated with the same methods and identical questions for FH of glaucoma in a previous study, and of 176 healthy individuals without glaucoma or ODD who were interviewed on family history of glaucoma. Glaucoma in FH was significantly more frequent in patients with ODD with an incidence of 20.7% compared with healthy controls with an incidence of 2.8%, and half as frequent as in glaucoma patients with an incidence of 40%. ODD in FH were found in 9.7% of patients with ODD. As there is a high frequency of family history of glaucoma in patients with ODD, evaluation of FH of ODD and FH of glaucoma is essential in patients with ODD. Glaucoma in FH of ODD patients requires intraocular pressure monitoring and whenever deemed beneficial timely initiation of intraocular pressure-lowering therapy.

  7. Novel Genetic Variants of Hepatitis B Virus in Fulminant Hepatitis

    Directory of Open Access Journals (Sweden)

    Jack Bee Chook

    2017-01-01

    Full Text Available Fulminant hepatitis (FH is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV, A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%, T720 (83.0%, Y2131 (82.4%, T2013 (82.1%, K2048 (82.1%, and A2512 (82.1%. This model gave a high specificity (99.3%, positive predictive value (95.6%, and negative predictive value (92.1%, but only moderate sensitivity (64.2%. We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.

  8. Inhibition by methotrexate (MTX) polyglutamates (PGS) of folate-dependent biosyntheses in L1210 Leukemia cells

    International Nuclear Information System (INIS)

    Matherly, L.H.; Barlowe, C.K.; Goldman, I.D.

    1986-01-01

    The inhibition of folate-dependent pathways by MTX PGS was evaluated in folate-depleted L1210 cells incubated with (6S)5-formyl(CHO)tetrahydrofolate(FH 4 )(5μM). The accumulation of MTX PGS during exposure to MTX (10μM;3h) inhibited cell growth (>70%) under these conditions. In the presence of 5-CHO-FH 4 , carbon transfer from 14 C-formate or 3- 14 C-serine into purines, dTMP, and amino acids was suppressed following MTX-pretreatment, suggesting the formation of only low levels of FH 4 to drive these reactions. In cells treated with MTX (6S)5-CHO-[ 3 H]-FH 4 was metabolized predominantly to 10-CHO-[ 3 H]-FH 4 . While intracellular dihydrofolate (FH 2 ) increased 10-fold, indicating a block at FH 2 reductase by MTX PGS, FH 2 represented only 20% of the total metabolites of 5-CHO-FH 4 . The incorporation of 14 C from 5-[ 14 C]-CHO-FH 4 into serine and methionine was not affected by the presence of intracellular MTX PGS, however, carbon transfer into dTMP and purine nucleotides was reduced (50-60%). These findings demonstrate that MTX pretreatment inhibits de novo nucleotide and amino acid biosynthetic pathways even when high levels of reduced folates are present. The data suggest a suppression of dTMP synthase and the purine transformylase(s) by MTX and/or FH 2 PGS that accumulate in drug-treated cells. Inhibition of the purine biosynthetic steps appears to trap 10-CHO-FH 4 , limiting FH 4 for the synthesis of dTMP, serine, and methionine

  9. Lipid phenotype and heritage pattern in families with genetic hypercholesterolemia not related to LDLR, APOB, PCSK9, or APOE.

    Science.gov (United States)

    Jarauta, Estíbaliz; Pérez-Ruiz, María Rosario; Pérez-Calahorra, Sofia; Mateo-Gallego, Rocio; Cenarro, Ana; Cofán, Montserrat; Ros, Emilio; Civeira, Fernando; Tejedor, Maria Teresa

    A substantial proportion of individuals clinically diagnosed as familial hypercholesterolemia (FH) do not carry pathogenic mutations in candidate genes. Whether in them the high cholesterol trait is transmitted monogenically has not been studied. We assessed the inheritance pattern, penetrance, and expression of high low-density lipoprotein (LDL)-cholesterol (LDLc) in families with genetic hypercholesterolemia (GH) without known causative mutations (non-FH-GH). The study included probands with a clinical diagnosis of FH and their families attending 2 lipid clinics in Spain. Inclusion criteria for probands were LDLc >95th percentile, triglycerides 90th percentile, >5 points in the Dutch Lipid Clinic Network criteria score, and absence of mutations in LDLR, APOB, PCSK9 or APOE. Eleven FH families with a LDLR mutation were also examined for comparison. We analyzed 49 non-FH-GH probands and 277 first-and second-degree relatives. LDLc was >90th percentile in 37.8% of blood relatives, at concentrations similar to those of probands. LDLc had a normal distribution in non-FH-GH families, in contrast with a bimodal distribution in FH families. When a dominant model was tested, family-based association tests gave much lower heritability values for total cholesterol and LDLc in non-FH-GH (0.39 and 0.32, respectively) than in FH (0.78 and 0.61, respectively). Non-FH-GH families have a milder lipid phenotype than genetically defined FH. The heritage pattern of LDLc in non-FH-GH does not fit with a monogenic disorder. Our findings support the concept that most non-FH-GHs are polygenic hypercholesterolemias. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  10. Expression, purification, cocrystallization and preliminary crystallographic analysis of sucrose octasulfate/human complement regulator factor H SCRs 6–8

    Energy Technology Data Exchange (ETDEWEB)

    Prosser, Beverly E.; Johnson, Steven; Roversi, Pietro [The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Clark, Simon J. [Faculty of Life Sciences, Manchester University, Michael Smith Building, Oxford Road, Manchester M13 9PT (United Kingdom); Tarelli, Edward [Medical Biomics Centre, St George’s, University of London, Cranmer Terrace, London SW17 0RE (United Kingdom); Sim, Robert B. [The MRC Immunochemistry Unit, The University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Day, Antony J. [Faculty of Life Sciences, Manchester University, Michael Smith Building, Oxford Road, Manchester M13 9PT (United Kingdom); Lea, Susan M., E-mail: susan.lea@bnc.ox.ac.uk [The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom)

    2007-06-01

    The crystallization of human complement regulator FH-678{sub 402H} with a glycosaminoglycan analogue is described. Human plasma protein complement factor H (FH) is an inhibitor of the spontaneously activated alternative complement pathway. An allotypic variant of FH, 402His, has been associated with age-related macular degeneration, the leading cause of blindness in the elderly. Crystals of FH domains 6–8 (FH678) containing 402His have been grown in the presence of a polyanionic sucrose octasulfate ligand (an analogue of the natural glycosaminoglycan ligands of FH) using both native and selenomethionine-derivatized protein. Native data sets diffracting to 2.3 Å and SeMet data sets of up to 2.8 Å resolution have been collected. An anomalous difference Patterson map reveals self- and cross-peaks from two incorporated Se atoms. The corresponding selenium substructure has been solved.

  11. Functional characterization of the role of rpfA in Xylella fastidiosa

    Science.gov (United States)

    Xylella fastidiosa coordinates virulence in grapevines via quorum sensing signal molecules that are regulated and synthesized by the rpf gene cluster (regulation of pathogenicity factors). rpfA encodes aconitate hydratase and could play a regulator role involved in virulence. To elucidate the role o...

  12. 3-Methylglutaconic aciduria-lessons from 50 genes and 977 patients

    NARCIS (Netherlands)

    Wortmann, S.B.; Kluijtmans, L.A.J.; Rodenburg, R.J.T.; Sass, J.O.; Nouws, J.; Kaauwen, E.P. van; Kleefstra, T.; Tranebjaerg, L.; Vries, M.C. de; Isohanni, P.; Walter, K.; Alkuraya, F.S.; Smuts, I.; Reinecke, C.J.; Westhuizen, F.H. van der; Thorburn, D.; Smeitink, J.A.M.; Morava, E.; Wevers, R.A.

    2013-01-01

    Elevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder. In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine degradation. In all other disorders with 3-methylglutaconic aciduria the origin is

  13. Biotransformation of nitriles to hydroxamic acids via a nitrile hydratase–amidase cascade reaction

    Czech Academy of Sciences Publication Activity Database

    Vejvoda, Vojtěch; Martínková, Ludmila; Veselá, Alicja Barbara; Kaplan, Ondřej; Lutz-Wahl, S.; Fischer, L.; Uhnáková, Bronislava

    2011-01-01

    Roč. 71, 1-2 (2011), s. 51-55 ISSN 1381-1177 R&D Projects: GA MŠk(CZ) LC06010; GA MŠk OC09046 Institutional research plan: CEZ:AV0Z50200510 Keywords : Nitrile hydratase * Rhodococcus erythropolis * Amidase Subject RIV: EE - Microbiology, Virology Impact factor: 2.735, year: 2011

  14. 3-Methylglutaconic aciduria—lessons from 50 genes and 977 patients

    DEFF Research Database (Denmark)

    Wortmann, Saskia B; Kluijtmans, Leo A J; Rodenburg, Richard J

    2013-01-01

    Elevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder. In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine degradation. In all other disorders with 3-methylglutaconic aciduria the origin is unk...

  15. Modelling non-redox enzymes: Anaerobic and aerobic acetylene ...

    Indian Academy of Sciences (India)

    Administrator

    Modelling non-redox enzymes: Anaerobic and aerobic acetylene hydratase. SABYASACHI SARKAR. Department of Chemistry, Indian Institute of Technology, Kanpur 208 016,. India. Acetaldehyde is the first metabolite produced during acetylene degradation by bacteria either aerobically or anaerobically. Conversion of ...

  16. Dicty_cDB: VFO725 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available phosphopyruvate hydratase (EC 4.2.1.11) - liver f... 264 1e-69 AM279157_1( AM279157 |pid:none) Echinostoma capron...i mRNA for enola... 254 9e-67 DQ869009_1( DQ869009 |pid:none) Echinostoma caproni enolase mRNA, ... 25

  17. Biotransformation of 3-substituted methyl (R,S)-4-cyanobutanoates with nitrile- and amide-converting biocatalysts

    Czech Academy of Sciences Publication Activity Database

    Martínková, Ludmila; Klempier, N.; Bardakji, J.; Kandelbauer, A.; Ovesná, M.; Podařilová, T.; Kuzma, Marek; Přepechalová, Irena; Griengl, G.; Křen, Vladimír

    2001-01-01

    Roč. 14, - (2001), s. 95-99 ISSN 1381-1177 R&D Projects: GA AV ČR IAA4020802 Institutional research plan: CEZ:AV0Z5020903 Keywords : Rhodococcus equi * nitrile hydratase * amidase Subject RIV: EE - Microbiology, Virology Impact factor: 1.408, year: 2001

  18. Nicotinic acid bio-production by Microbacterium imperiale CBS 489-74. Effect of 3-cyanopyridine and temperature on amidase activity

    Czech Academy of Sciences Publication Activity Database

    Cantarella, M.; Cantarella, L.; Gallifuoco, A.; Spera, A.; Martínková, Ludmila

    2012-01-01

    Roč. 47, č. 7 (2012), s. 1192-1196 ISSN 1359-5113 R&D Projects: GA MŠk OC09046 Keywords : Nitrile hydratase-amidase cascade system * 3-Cyanopyridine inactivation * 3-Cyanopyridine inhibition Subject RIV: CE - Biochemistry Impact factor: 2.414, year: 2012

  19. Selective biotransformation of substituted alicyclic nitriles by Rhodococcus equi A4

    Czech Academy of Sciences Publication Activity Database

    Martínková, Ludmila; Klempier, N.; Preiml, M.; Ovesná, Mária; Kuzma, Marek; Mylerová, Veronika; Křen, Vladimír

    2002-01-01

    Roč. 80, - (2002), s. 724-727 ISSN 0008-4042 R&D Projects: GA ČR GA524/00/1275; GA AV ČR IAA4020802 Keywords : nitrile hydratase * substituted cyclohexanecarbonitriles * cyclopentanecarbonitriles Subject RIV: EE - Microbiology, Virology Impact factor: 1.260, year: 2002

  20. High-yield continuous production of nicotinic acid via nitrile hydratase–amidase cascade reactions using cascade CSMRs

    Czech Academy of Sciences Publication Activity Database

    Cantarella, L.; Gallifuoco, A.; Malandra, A.; Martínková, Ludmila; Spera, A.; Cantarella, M.

    2011-01-01

    Roč. 48, 4-5 (2011), 345-350 ISSN 0141-0229 R&D Projects: GA MŠk OC09046 Institutional research plan: CEZ:AV0Z50200510 Keywords : Nitrile hydratase-amidase cascade system * 3-Cyanopyridine bioconversion * Nicotinic acid Subject RIV: EE - Microbiology, Virology Impact factor: 2.367, year: 2011

  1. GenBank blastx search result: AK287540 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287540 J065011K01 AF013216.1 AF013216 Myxococcus xanthus Dog (dog), isocitrate lyase (icl), Mls (mls), Ufo... (ufo), fumarate hydratase (fhy), and proteosome major subunit (clpP) genes, complete cds; and acyl-CoA oxidase (aco) gene, partial cds. BCT 0.0 0 ...

  2. GenBank blastn search result: AK241214 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241214 J065122P06 AF013216.1 AF013216 Myxococcus xanthus Dog (dog), isocitrate lyase (icl), Mls (mls), Ufo... (ufo), fumarate hydratase (fhy), and proteosome major subunit (clpP) genes, complete cds; and acyl-CoA oxidase (aco) gene, partial cds. BCT 8e-18 1 -1 ...

  3. GenBank blastx search result: AK243510 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243510 J100075B22 AF013216.1 AF013216 Myxococcus xanthus Dog (dog), isocitrate lyase (icl), Mls (mls), Ufo... (ufo), fumarate hydratase (fhy), and proteosome major subunit (clpP) genes, complete cds; and acyl-CoA oxidase (aco) gene, partial cds. BCT 2e-87 1 ...

  4. GenBank blastx search result: AK243527 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK243527 J100075P16 AF013216.1 AF013216 Myxococcus xanthus Dog (dog), isocitrate lyase (icl), Mls (mls), Ufo... (ufo), fumarate hydratase (fhy), and proteosome major subunit (clpP) genes, complete cds; and acyl-CoA oxidase (aco) gene, partial cds. BCT 1e-143 1 ...

  5. GenBank blastx search result: AK241214 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241214 J065122P06 AF013216.1 AF013216 Myxococcus xanthus Dog (dog), isocitrate lyase (icl), Mls (mls), Ufo... (ufo), fumarate hydratase (fhy), and proteosome major subunit (clpP) genes, complete cds; and acyl-CoA oxidase (aco) gene, partial cds. BCT 1e-151 1 ...

  6. Application of continuous stirred membrane reactor to 3-cyanopyridine bioconversion using the nitrile hydratase–amidase cascade system of Microbacterium imperiale CBS 498-74

    Czech Academy of Sciences Publication Activity Database

    Cantarella, L.; Gallifuoco, A.; Malandra, A.; Martínková, Ludmila; Pasquarelli, F.; Spera, A.; Cantarella, M.

    2010-01-01

    Roč. 47, č. 3 (2010), s. 64-70 ISSN 0141-0229 R&D Projects: GA MŠk OC09046 Institutional research plan: CEZ:AV0Z50200510 Keywords : Nitrile hydratase-amidase cascade system * 3-Cyanopyridine bioconversion * Nicotinamide Subject RIV: EE - Microbiology, Virology Impact factor: 2.287, year: 2010

  7. Toward an improved definition of the genetic and tumor spectrum associated with SDH germ-line mutations

    NARCIS (Netherlands)

    Evenepoel, Lucie; Papathomas, Thomas G.; Krol, Niels; Korpershoek, Esther; De Krijger, Ronald R.; Persu, Alexandre; Dinjens, Winand N M

    2015-01-01

    The tricarboxylic acid, or Krebs, cycle is central to the cellular metabolism of sugars, lipids, and amino acids; it fuels the mitochondrial respiratory chain for energy generation. In the past decade, mutations in the Krebs-cycle enzymes succinate dehydrogenase, fumarate hydratase, and isocitrate

  8. Nitrile biotransformation by Aspergillus niger

    Czech Academy of Sciences Publication Activity Database

    Šnajdrová, Radka; Kristová, Veronika; Crestia, D.; Nikolaou, K.; Kuzma, Marek; Lemaire, M.; Gallienne, E.; Bolte, J.; Bezouška, K.; Křen, Vladimír; Martínková, Ludmila

    2004-01-01

    Roč. 29, - (2004), s. 227-232 ISSN 1381-1177 R&D Projects: GA MŠk OC D25.002; GA AV ČR IAA4020213 Institutional research plan: CEZ:AV0Z5020903 Keywords : aspergillus niger * nitrile-converting enzymes * nitrile hydratase Subject RIV: EE - Microbiology, Virology Impact factor: 1.547, year: 2004

  9. A Comparative Study of Nitrilases Identified by Genome Mining

    Czech Academy of Sciences Publication Activity Database

    Kaplan, Ondřej; Veselá, Alicja Barbara; Petříčková, Alena; Pasquarelli, F.; Pičmanová, Martina; Rinágelová, Anna; Bhalla, T. C.; Pátek, Miroslav; Martínková, Ludmila

    2013-01-01

    Roč. 54, č. 3 (2013), s. 996-1003 ISSN 1073-6085 R&D Projects: GA ČR(CZ) GAP504/11/0394; GA TA ČR TA01021368 Institutional support: RVO:61388971 Keywords : Nitrilase * Arylacetonitrilase * Cyanide hydratase Subject RIV: CE - Biochemistry Impact factor: 2.275, year: 2013

  10. Sex and family history of cardiovascular disease influence heart rate variability during stress among healthy adults.

    Science.gov (United States)

    Emery, Charles F; Stoney, Catherine M; Thayer, Julian F; Williams, DeWayne; Bodine, Andrew

    2018-07-01

    Studies of sex differences in heart rate variability (HRV) typically have not accounted for the influence of family history (FH) of cardiovascular disease (CVD). This study evaluated sex differences in HRV response to speech stress among men and women (age range 30-49 years) with and without a documented FH of CVD. Participants were 77 adults (mean age = 39.8 ± 6.2 years; range: 30-49 years; 52% female) with positive FH (FH+, n = 32) and negative FH (FH-, n = 45) of CVD, verified with relatives of participants. Cardiac activity for all participants was recorded via electrocardiogram during a standardized speech stress task with three phases: 5-minute rest, 5-minute speech, and 5-minute recovery. Outcomes included time domain and frequency domain indicators of HRV and heart rate (HR) at rest and during stress. Data were analyzed with repeated measures analysis of variance, with sex and FH as between subject variables and time/phase as a within subject variable. Women exhibited higher HR than did men and greater HR reactivity in response to the speech stress. However, women also exhibited greater HRV in both the time and frequency domains. FH+ women generally exhibited elevated HRV, despite the elevated risk of CVD associated with FH+. Although women participants exhibited higher HR at rest and during stress, women (both FH+ and FH-) also exhibited elevated HRV reactivity, reflecting greater autonomic control. Thus, enhanced autonomic function observed in prior studies of HRV among women is also evident among FH+ women during a standardized stress task. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. My Approach to the Patient With Familial Hypercholesterolemia

    Science.gov (United States)

    Safarova, Maya S.; Kullo, Iftikhar J.

    2017-01-01

    Familial hypercholesterolemia (FH), a relatively common Mendelian genetic disorder, is associated with a dramatically increased lifetime risk of premature atherosclerotic cardiovascular disease due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The diagnosis of FH is based on clinical presentation or genetic testing. Early identification of patients with FH is of great public health importance because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, low awareness, detection, and control of FH pose hurdles in the prevention of FH-related cardiovascular events. Of the estimated 0.65 million to 1 million patients with FH in the United States, less than 10% carry a diagnosis of FH. Based on registry data, a substantial proportion of patients with FH are receiving no or inadequate lipid-lowering therapy. Statins remain the mainstay of treatment for patients with FH. Lipoprotein apheresis and newly approved lipid-lowering drugs are valuable adjuncts to statin therapy, particularly when the LDL-C–lowering response is suboptimal. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 provide an additional approximately 60% lowering of LDL-C levels and are approved for use in patients with FH. For homozygous FH, 2 new drugs that work independent of the LDL receptor pathway are available: an apolipoprotein B antisense oligonucleotide (mipomersen) and a microsomal triglyceride transfer protein inhibitor (lomitapide). This review attempts to critically examine the available data to provide a summary of the current evidence for managing patients with FH, including screening, diagnosis, treatment, and surveillance. PMID:27261867

  12. On Analog of Fourier Transform in Interior of the Light Cone

    Directory of Open Access Journals (Sweden)

    Tatyana Shtepina

    2014-01-01

    Full Text Available We introduce an analog of Fourier transform Fhρ in interior of light cone that commutes with the action of the Lorentz group. We describe some properties of Fhρ, namely, its action on pseudoradial functions and functions being products of pseudoradial function and space hyperbolic harmonics. We prove that Fhρ-transform gives a one-to-one correspondence on each of the irreducible components of quasiregular representation. We calculate the inverse transform too.

  13. Familial hypercholesterolemia in the danish general population

    DEFF Research Database (Denmark)

    Benn, Marianne; Watts, Gerald F; Tybjaerg-Hansen, Anne

    2012-01-01

    .0-17.4) in definite/probable FH compared with non-FH subjects, after adjusting for age, gender, body mass index, hypertension, metabolic syndrome and diabetes, and smoking. The corresponding adjusted odds ratio for coronary artery disease in FH subjects on cholesterol-lowering medication was 10.3 (7......Context: The diagnosis of familial hypercholesterolemia (FH) can be made using the Dutch Lipid Clinic Network criteria. This employs the personal and family history of premature coronary artery disease and hypercholesterolemia and the presence of a pathogenic mutation in the low-density lipoprotein...

  14. The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    M. H. Nielsen

    2016-01-01

    Full Text Available Objective. Microvesicles (MVs are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH particularly when associated with Achilles tendon xanthomas (ATX predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs, erythrocytes (ErytMVs, monocytes (MMVs, and endothelial cells (EMVs, as well as tissue factor-positive cells (TF+ MVs, were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation.

  15. Affinity purification of human factor H on polypeptides derived from streptococcal m protein: enrichment of the Y402 variant.

    Directory of Open Access Journals (Sweden)

    O Rickard Nilsson

    Full Text Available Recent studies indicate that defective activity of complement factor H (FH is associated with several human diseases, suggesting that pure FH may be used for therapy. Here, we describe a simple method to isolate human FH, based on the specific interaction between FH and the hypervariable region (HVR of certain Streptococcus pyogenes M proteins. Special interest was focused on the FH polymorphism Y402H, which is associated with the common eye disease age-related macular degeneration (AMD and has also been implicated in the binding to M protein. Using a fusion protein containing two copies of the M5-HVR, we found that the Y402 and H402 variants of FH could be efficiently purified by single-step affinity chromatography from human serum containing the corresponding protein. Different M proteins vary in their binding properties, and the M6 and M5 proteins, but not the M18 protein, showed selective binding of the FH Y402 variant. Accordingly, chromatography on a fusion protein derived from the M6-HVR allowed enrichment of the Y402 protein from serum containing both variants. Thus, the exquisite binding specificity of a bacterial protein can be exploited to develop a simple and robust procedure to purify FH and to enrich for the FH variant that protects against AMD.

  16. Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome.

    Science.gov (United States)

    de Bortoli, Nicola; Martinucci, Irene; Bellini, Massimo; Savarino, Edoardo; Savarino, Vincenzo; Blandizzi, Corrado; Marchi, Santino

    2013-09-21

    Several studies indicate a significant degree of overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). Likewise, both functional heartburn (FH) and IBS are functional digestive disorders that may occur in the same patients. However, data establishing a solid link between FH and IBS are lacking, mainly because the clinical definition of FH has undergone substantial changes over the years. The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS. In particular, several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH (as defined by the Rome III criteria) from GERD via pathophysiological investigations. Independent of these critical issues, there is preliminary evidence supporting a significant degree of FH-IBS overlap. This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications, particularly to distinguish FH from GERD. This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

  17. Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: The heredity survey.

    Science.gov (United States)

    Faggiano, Pompilio; Pirillo, Angela; Griffo, Raffaele; Ambrosetti, Marco; Pedretti, Roberto; Scorcu, Giampaolo; Werren, Marika; Febo, Oreste; Malfatto, Gabriella; Favretto, Giuseppe; Sarullo, Filippo; Antonini-Canterin, Francesco; Zobbi, Gianni; Temporelli, Pierluigi; Catapano, Alberico L

    2018-02-01

    Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low density lipoprotein cholesterol (LDL-C) predisposing to premature cardiovascular disease. Its prevalence varies and has been estimated around 1 in 200-500. The Heredity survey evaluated the prevalence of potential FH and the therapeutic approaches among patients with established coronary artery disease (CAD) or peripheral artery disease (PAD) in which it is less well documented. Data were collected in patients admitted to programs of rehabilitation and secondary prevention in Italy. Potential FH was estimated using Dutch Lipid Clinic Network (DLCN) criteria. Potential FH was defined as having a total score≥6. Among the 1438 consecutive patients evaluated, the prevalence of potential FH was 3.7%. The prevalence was inversely related to age, with a putative prevalence of 1:10 in those with Definite FH (DLCN score>8) had the highest percentages of patients after an ACS (75% vs 52.5% in the whole study population). At discharge, most patients were on high intensity statin therapy, but despite this, potential FH group still had a higher percentage of patients with LDL-C levels not at target and having a distance from the target higher than 50%. Among patients with established coronary heart disease, the prevalence of potential FH is higher than in the general population; the results suggest that a correct identification of potential FH, especially in younger patients, may help to better manage their high cardiovascular risk. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  18. Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in flavonoid biosynthetic pathway.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available Chalcone synthase (CHS catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1 encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants.

  19. Structural and functional characterization of the product of disease-related factor H gene conversion.

    Science.gov (United States)

    Herbert, Andrew P; Kavanagh, David; Johansson, Conny; Morgan, Hugh P; Blaum, Bärbel S; Hannan, Jonathan P; Barlow, Paul N; Uhrín, Dušan

    2012-03-06

    Numerous complement factor H (FH) mutations predispose patients to atypical hemolytic uremic syndrome (aHUS) and other disorders arising from inadequately regulated complement activation. No unifying structural or mechanistic consequences have been ascribed to these mutants beyond impaired self-cell protection. The S1191L and V1197A mutations toward the C-terminus of FH, which occur in patients singly or together, arose from gene conversion between CFH encoding FH and CFHR1 encoding FH-related 1. We show that neither single nor double mutations structurally perturbed recombinant proteins consisting of the FH C-terminal modules, 19 and 20 (FH19-20), although all three FH19-20 mutants were poor, compared to wild-type FH19-20, at promoting hemolysis of C3b-coated erythrocytes through competition with full-length FH. Indeed, our new crystal structure of the S1191L mutant of FH19-20 complexed with an activation-specific complement fragment, C3d, was nearly identical to that of the wild-type FH19-20:C3d complex, consistent with mutants binding to C3b with wild-type-like affinity. The S1191L mutation enhanced thermal stability of module 20, whereas the V1197A mutation dramatically decreased it. Thus, although mutant proteins were folded at 37 °C, they differ in conformational rigidity. Neither single substitutions nor double substitutions increased measurably the extent of FH19-20 self-association, nor did these mutations significantly affect the affinity of FH19-20 for three glycosaminoglycans, despite critical roles of module 20 in recognizing polyanionic self-surface markers. Unexpectedly, FH19-20 mutants containing Leu1191 self-associated on a heparin-coated surface to a higher degree than on surfaces coated with dermatan or chondroitin sulfates. Thus, potentially disease-related functional distinctions between mutants, and between FH and FH-related 1, may manifest in the presence of specific glycosaminoglycans.

  20. Mutations causative of familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Benn, Marianne; Watts, Gerald F; Tybjærg-Hansen, Anne

    2016-01-01

    causing mutations in 98 098 participants from the general population, the Copenhagen General Population Study. METHODS AND RESULTS: We genotyped for LDLR[W23X;W66G;W556S] and APOB[R3500Q] accounting for 38.7% of pathogenic FH mutations in Copenhagen. Clinical FH assessment excluded mutation information......-cholesterol concentration to discriminate between mutation carriers and non-carriers was 4.4 mmol/L. CONCLUSION: Familial hypercholesterolaemia-causing mutations are estimated to occur in 1:217 in the general population and are best identified by a definite or probable phenotypic diagnosis of FH based on the DLCN criteria....... The prevalence of the four FH mutations was 0.18% (1:565), suggesting a total prevalence of FH mutations of 0.46% (1:217). Using the Dutch Lipid Clinic Network (DLCN) criteria, odds ratios for an FH mutation were 439 (95% CI: 170-1 138) for definite FH, 90 (53-152) for probable FH, and 18 (13-25) for possible FH...

  1. Protection against Schistosoma mansoni infection using a Fasciola hepatica-derived fatty acid binding protein from different delivery systems.

    Science.gov (United States)

    Vicente, Belén; López-Abán, Julio; Rojas-Caraballo, Jose; del Olmo, Esther; Fernández-Soto, Pedro; Muro, Antonio

    2016-04-18

    Schistosomiasis is a water-borne disease afflicting over 261 million people in many areas of the developing countries with high morbidity and mortality. The control relies mainly on treatment with praziquantel. Fatty acid binding proteins (FABP) have demonstrated high levels of immune-protection against trematode infections. This study reports the immunoprotection induced by cross-reacting Fasciola hepatica FABP, native (nFh12) and recombinantly expressed using two different expression systems Escherichia coli (rFh15) and baculovirus (rFh15b) against Schistosoma mansoni infection. BALB/c mice were vaccinated with native nFh12 or recombinant rFh15 and rFh15 FABP from F. hepatica formulated in adjuvant adaptation (ADAD) system with natural or chemical synthesised immunomodulators (PAL and AA0029) and then challenged with 150 cercariae of S. mansoni. Parasite burden, hepatic lesions and antibody response were studied in vaccination trials. Furthermore differences between rFh15 and rFh15b immunological responses (cytokine production, splenocyte population and antibody levels) were studied. Vaccination with nFh12 induced significant reductions in worm burden (83%), eggs in tissues (82-92%) and hepatic lesions (85%) compared to infected controls using PAL. Vaccination with rFh15 showed lower total worm burden (56-64%), eggs in the liver (21-61%), eggs in the gut (30-77%) and hepatic damage (67-69%) using PAL and AA0029 as immunomodulators. In contrast, mice vaccinated with rFh15b showed only reductions in eggs trapped in the liver and intestine (53 and 60%, respectively), and hepatic lesions (45%). We observed a significant rise in TNFα, IL-6, IL-2, IL-4 and high antibody response (IgG, IgG1, IgG2a, IgM and IgE) in mice immunised with either rFh15 or rFh15b. Moreover, mice immunised with rFh15b showed an increase in IFNγ and a decrease in B220 cells compared to untreated mice, and less production of IgG1 and IgM than in mice immunised by rFh15. Higher level of

  2. The meningococcal vaccine candidate neisserial surface protein A (NspA binds to factor H and enhances meningococcal resistance to complement.

    Directory of Open Access Journals (Sweden)

    Lisa A Lewis

    2010-07-01

    Full Text Available Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH to fH-binding protein (fHbp is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a approximately 17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA, a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep I chain of lipooligosaccharide (LOS, or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6-7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components.

  3. A Family History of Stroke Is Associated with Increased Intima-Media Thickness in Young Ischemic Stroke - The Norwegian Stroke in the Young Study (NOR-SYS).

    Science.gov (United States)

    Øygarden, Halvor; Fromm, Annette; Sand, Kristin Modalsli; Kvistad, Christopher Elnan; Eide, Geir Egil; Thomassen, Lars; Naess, Halvor; Waje-Andreassen, Ulrike

    2016-01-01

    Positive family history (FH+) of cardiovascular disease (CVD) is a risk factor for own CVD. We aimed to analyze the effect of different types of FH (stroke, coronary heart disease (CHD), peripheral artery disease (PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic stroke patients. First-degree FH of CVD was assessed in ischemic stroke patients ≤ 60y using a standardized interview. Carotid ultrasound was performed and far wall cIMT in three carotid artery segments was registered, representing the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative groups and stepwise backward regression analyses were performed to identify factors associated with increased cIMT. During the study period 382 patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH of CVD. Regression analyses adjusting for risk factors revealed age as the most important predictor of cIMT in all segments. The association between FH+ and cIMT was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+ was associated with increased ICA-IMT in patients aged stroke (p = 0.034), but not a FH+ of CHD or PAD. FH of stroke is associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of cardiovascular FH is important to investigate heredity in young ischemic stroke patients. ClinicalTrials.gov NCT01597453.

  4. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Meningococcal factor H-binding protein vaccines with decreased binding to human complement factor H have enhanced immunogenicity in human factor H transgenic mice.

    Science.gov (United States)

    Rossi, Raffaella; Granoff, Dan M; Beernink, Peter T

    2013-11-04

    Factor H-binding protein (fHbp) is a component of a meningococcal vaccine recently licensed in Europe for prevention of serogroup B disease, and a second vaccine in clinical development. The protein specifically binds human factor H (fH), which down-regulates complement activation and enhances resistance to bactericidal activity. There are conflicting data from studies in human fH transgenic mice on whether binding of human fH to fHbp vaccines decreases immunogenicity, and whether mutant fHbp vaccines with decreased fH binding have enhanced immunogenicity. fHbp can be classified into two sub-families based on sequence divergence and immunologic cross-reactivity. Previous studies of mutant fHbp vaccines with low fH binding were from sub-family B, which account for approximately 60% of serogroup B case isolates. In the present study, we evaluated the immunogenicity of two mutant sub-family A fHbp vaccines containing single substitutions, T221A or D211A, which resulted in 15- or 30-fold lower affinity for human fH, respectively, than the corresponding control wild-type fHbp vaccine. In transgenic mice with high serum concentrations of human fH, both mutant vaccines elicited significantly higher IgG titers and higher serum bactericidal antibody responses than the control fHbp vaccine that bound human fH. Thus, mutations introduced into a sub-family A fHbp antigen to decrease fH binding can increase protective antibody responses in human fH transgenic mice. Collectively the data suggest that mutant fHbp antigens with decreased fH binding will result in superior vaccines in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Interaction of polyhydroxy fullerenes with ferrihydrite: adsorption and aggregation.

    Science.gov (United States)

    Liu, Jing; Zhu, Runliang; Xu, Tianyuan; Laipan, Mingwang; Zhu, Yanping; Zhou, Qing; Zhu, Jianxi; He, Hongping

    2018-02-01

    The rapid development of nanoscience and nanotechnology, with thousands types of nanomaterials being produced, will lead to various environmental impacts. Thus, understanding the behaviors and fate of these nanomaterials is essential. This study focused on the interaction between polyhydroxy fullerenes (PHF) and ferrihydrite (Fh), a widespread iron (oxyhydr)oxide nanomineral and geosorbent. Our results showed that PHF were effectively adsorbed by Fh. The adsorption isotherm fitted the D-R model well, with an adsorption capacity of 67.1mg/g. The adsorption mean free energy of 10.72kJ/mol suggested that PHF were chemisorbed on Fh. An increase in the solution pH and a decrease of the Fh surface zeta potential were observed after the adsorption of PHF on Fh; moreover, increasing initial solution pH led to a reduction of adsorption. The Fourier transform infrared spectra detected a red shift of C-O stretching from 1075 to 1062cm -1 and a decrease of Fe-O bending, implying the interaction between PHF oxygenic functional groups and Fh surface hydroxyls. On the other hand, PHF affected the aggregation and reactivity of Fh by changing its surface physicochemical properties. Aggregation of PHF and Fh with individual particle sizes increasing from 2nm to larger than 5nm was measured by atomic force microscopy. The uniform distribution of C and Fe suggested that the aggregates of Fh were possibly bridged by PHF. Our results indicated that the interaction between PHF and Fh could evidently influence the migration of PHF, as well as the aggregation and reactivity of Fh. Copyright © 2017. Published by Elsevier B.V.

  7. Influence of family history of dementia in the development and progression of late-onset Alzheimer's disease.

    Science.gov (United States)

    Scarabino, Daniela; Gambina, Giuseppe; Broggio, Elisabetta; Pelliccia, Franca; Corbo, Rosa Maria

    2016-03-01

    Family history of dementia (FH) is a recognized risk factor for developing late-onset Alzheimer's disease (AD). We asked whether having FH increases AD risk and influences disease severity (age at onset and cognitive impairment) in 420 AD patients and 109 controls with (FH+) or without (FH-). The relationships of APOE and other AD risk genes with FH were analyzed as well. The proportion of APOE e4 allele carriers was higher among the FH+ than the FH- AD patients (49.6% vs. 38.9%; P = 0.04). The distribution of the risk genotypes of nine AD susceptibility genes previously examined (CHAT, CYP17, CYP19, ESR1, FSHR, P53, P73, P21, PPARG) did not differ between the FH+ and the FH- AD patients, indicating that none contributed significantly to familial clustering of disease. FH was associated with an increased AD risk (odds ratio [OR] 2.71, 95% confidence interval [CI] 1.44-5.09; P = 0.002) independent of carrying the APOE e4 allele (OR 2.61, 95%CI 1.53-4.44; P = 0.0004). Having a first-degree relative or a parent with dementia was significantly associated with AD risk (OR 2.9, 95%CI 1.3-6.4; P = 0.009 and OR 2.7, 95%CI 1.1-6.2; P = 0.02) but having a sibling with dementia was not (OR 1.7, 95%CI 0.2 to 14.7; P = 0.6). Among the FH+ AD patients, having one or both parents affected seemed to raise the risk of earlier onset age (P = 0.02) and greater cognitive impairment (P = 0.02) than having only an affected sibling, whereas having two or more affected relatives did not. © 2015 Wiley Periodicals, Inc.

  8. Efficient aspartic acid production by a psychrophile-based simple biocatalyst.

    Science.gov (United States)

    Tajima, Takahisa; Hamada, Mai; Nakashimada, Yutaka; Kato, Junichi

    2015-10-01

    We previously constructed a Psychrophile-based Simple bioCatalyst (PSCat) reaction system, in which psychrophilic metabolic enzymes are inactivated by heat treatment, and used it here to study the conversion of aspartic acid from fumaric acid mediated by the activity of aspartate ammonia-lyase (aspartase). In Escherichia coli, the biosynthesis of aspartic acid competes with that of L-malic acid produced from fumaric acid by fumarase. In this study, E. coli aspartase was expressed in psychrophilic Shewanella livingstonensis Ac10 heat treated at 50 °C for 15 min. The resultant PSCat could convert fumaric acid to aspartic acid without the formation of L-malic acid because of heat inactivation of psychrophilic fumarase activity. Furthermore, alginate-immobilized PSCat produced high yields of aspartic acid and could be re-used nine times. The results of our study suggest that PSCat can be applied in biotechnological production as a new approach to increase the yield of target compounds.

  9. Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country

    NARCIS (Netherlands)

    Khoo, Kah Lin; Page, Michael M.; Liew, Yin Mei; Defesche, Joep C.; Watts, Gerald F.

    2016-01-01

    Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this

  10. Towards RNAi based therapy of liver diseases : diversity and complexity of shRNA and miRNA processing and functions

    NARCIS (Netherlands)

    Maczuga, Piotr

    2013-01-01

    Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low density lipoprotein cholesterol (LDL-C) and increasing the risk of cardio vascular diseases. FH and many other liver diseases can possibly be treated with RNA interference (RNAi). RNAi is a natural process

  11. Family History of Type 2 Diabetes is Associated with Metabolic Syndrome in Obese Female Subjects

    Directory of Open Access Journals (Sweden)

    Ticiana Costa Rodrigues

    2008-08-01

    Full Text Available The aim of this study was to evaluate the association between the family history (FH of type 2 diabetes and metabolic syndrome (MetS in a group of non-diabetic obese female subjects. A cross-sectional study was conducted in 239 female patients with obesity, regularly attending the Internal Medicine Division’s outpatient clinic (Hospital de Clínicas de Porto Alegre, Brazil. The inclusion criteria were patients with body mass index ?30 kg/m2 and absence of type 2 diabetes. The FH was considered positive if a first degree relative had a diagnosis of diabetes. Seventy-four of 239 patients evaluated (30% had a positive FH for type 2 diabetes. Patients with positive FH had higher waist/hip ratio and MetS more often than patients with negative FH. FH of type 2 diabetes was associated with MetS in this sample of non-diabetic obese female patients. Waist/hip ratio and fasting plasma glucose, markers of insulin resistance, were also associated with FH of type 2 diabetes. The simple question: “Do you have a FH of type 2 diabetes?” may help to identify the obese patients that should be better evaluated and intensively treated with the objective of preventing type 2 diabetes.

  12. Impact of family history of alcoholism on glutamine/glutamate ratio in anterior cingulate cortex in substance-naïve adolescents.

    Science.gov (United States)

    Cohen-Gilbert, Julia E; Sneider, Jennifer T; Crowley, David J; Rosso, Isabelle M; Jensen, J Eric; Silveri, Marisa M

    2015-12-01

    Neuroimaging studies of individuals with family histories of alcoholism provide evidence suggesting neurobiological risk factors for alcoholism. Youth family history positive (FH+) for alcoholism exhibit increased impulsivity compared to family history negative (FH-) peers in conjunction with altered functional activation in prefrontal cortex, including anterior cingulate cortex (ACC). This study examined glutamate (Glu) and glutamine (Gln), amino acids vital to protein synthesis, cellular metabolism and neurotransmission, acquired from ACC and parieto-occipital cortex (POC) using magnetic resonance spectroscopy (MRS) at 4T. Participants were 28 adolescents (13 male, 12-14 yrs) and 31 emerging adults (16 male, 18-25 yrs), stratified into FH- and FH+ groups. Significantly higher ACC Gln/Glu was observed in emerging adults versus adolescents in FH- but not FH+ groups. In FH- adolescents, higher impulsivity was significantly associated with higher ACC Gln/Glu. In FH+ emerging adults, higher impulsivity was negatively associated with ACC Gln/Glu. No differences or associations were observed for POC. These findings provide preliminary evidence that family history of alcoholism is associated with a neurochemical profile that may influence normative age differences in glutamatergic metabolites and their association with impulse control, which together could confer greater genetic risk of addiction later in life. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. CRISPR Correction of a Homozygous Low-Density Lipoprotein Receptor Mutation in Familial Hypercholesterolemia Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Omer, Linda; Hudson, Elizabeth A; Zheng, Shirong; Hoying, James B; Shan, Yuan; Boyd, Nolan L

    2017-11-01

    Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans. However, demand for donated livers and high-quality hepatocytes overwhelm the supply. Human pluripotent stem cells can differentiate to hepatocyte-like cells (HLCs) with the potential for experimental and clinical use. To be of future clinical use as autologous cells, LDLR genetic mutations in derived FH-HLCs need to be corrected. Genome editing technology clustered-regularly-interspaced-short-palindromic-repeats/CRISPR-associated 9 (CRISPR/Cas9) can repair pathologic genetic mutations in human induced pluripotent stem cells. We used CRISPR/Cas9 genome editing to permanently correct a 3-base pair homozygous deletion in LDLR exon 4 of patient-derived HoFH induced pluripotent stem cells. The genetic correction restored LDLR-mediated endocytosis in FH-HLCs and demonstrates the proof-of-principle that CRISPR-mediated genetic modification can be successfully used to normalize HoFH cholesterol metabolism deficiency at the cellular level.

  14. Clinical phenotype in relation to the distance-to-index-patient in familial hypercholesterolemia

    NARCIS (Netherlands)

    Besseling, Joost; Huijgen, Roeland; Martin, Seth S.; Hutten, Barbara A.; Kastelein, John J. P.; Hovingh, G. Kees

    2016-01-01

    We evaluated whether the severity of the familial hypercholesterolemia (FH) phenotype, i.e. increased levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) risk, decreases in more distantly related patients within one family. We included heterozygous FH patients

  15. Carotid Atherosclerosis Progression in Familial Hypercholesterolemia Patients A Pooled Analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE Studies

    NARCIS (Netherlands)

    Vergeer, Menno; Zhou, Rong; Bots, Michiel L.; Duivenvoorden, Raphaël; Koglin, Joerg; Akdim, Fatima; Mitchel, Yale B.; Huijgen, Roeland; Sapre, Aditi; de Groot, Eric; Sijbrands, Eric J. G.; Pasternak, Richard C.; Gagné, Claude; Marais, A. David; Ballantyne, Christie M.; Isaacsohn, Jonathan L.; Stalenhoef, Anton F. H.; Kastelein, John J. P.

    2010-01-01

    Background-Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH

  16. Arsenic scavenging by aluminum-substituted ferrihydrites in a circumneutral pH river impacted by acid mine drainage.

    Science.gov (United States)

    Adra, Areej; Morin, Guillaume; Ona-Nguema, Georges; Menguy, Nicolas; Maillot, Fabien; Casiot, Corinne; Bruneel, Odile; Lebrun, Sophie; Juillot, Farid; Brest, Jessica

    2013-11-19

    Ferrihydrite (Fh) is a nanocrystalline ferric oxyhydroxide involved in the retention of pollutants in natural systems and in water-treatment processes. The status and properties of major chemical impurities in natural Fh is however still scarcely documented. Here we investigated the structure of aluminum-rich Fh, and their role in arsenic scavenging in river-bed sediments from a circumneutral river (pH 6-7) impacted by an arsenic-rich acid mine drainage (AMD). Extended X-ray absorption fine structure (EXAFS) spectroscopy at the Fe K-edge shows that Fh is the predominant mineral phase forming after neutralization of the AMD, in association with minor amount of schwertmannite transported from the AMD. TEM-EDXS elemental mapping and SEM-EDXS analyses combined with EXAFS analysis indicates that Al(3+) substitutes for Fe(3+) ions into the Fh structure in the natural sediment samples, with local aluminum concentration within the 25-30 ± 10 mol %Al range. Synthetic aluminous Fh prepared in the present study are found to be less Al-substituted (14-20 ± 5 mol %Al). Finally, EXAFS analysis at the arsenic K-edge indicates that As(V) form similar inner-sphere surface complexes on the natural and synthetic Al-substituted Fh studied. Our results provide direct evidence for the scavenging of arsenic by natural Al-Fh, which emphasize the possible implication of such material for scavenging pollutants in natural or engineered systems.

  17. Combining ability estimates for earliness in cotton leaf curl virus resistant inbred parents

    International Nuclear Information System (INIS)

    Baloch, M.J.; Baloch, Q.B.

    2005-01-01

    Four female cotton leaf curl virus-resistant resistant (cclv) parents consisting of advance strains and commercial varieties (VH-137, FH-901, CRIS-467 and Cyto-51) and four male parents, all clcv resistant Punjab varieties (FH-945, CIM-707, CIM-473 and FH-1000) were mated in a cross classification Design-II fashion. The results show that genetic variances due to additive genes were higher than the dominant variances, yet both types of variances were substantial, implying that significant improvement could reliably be made from segregating populations. The general combining ability (gca) estimates by and large suggested that for improvement in the appearance of first white flower and 1st sympodial branch node number, parents FH-945 and VH-137 whereas for 1st effective boll setting, parents FH-1000 and FH-901 and for percent of open bolls at 120 days after planting, parents CIM-707 and CRIS-467 may be given preference. However, for hybrid cotton development regarding earliness, hybrids CRIS-467 x CIM-707, VH-137 x FH-945 and Cyto-51 x FH-1000 may be chosen. (author)

  18. Extreme phenotypes in hypercholesterolemia : From genotype to therapy

    NARCIS (Netherlands)

    Sjouke, B.

    2017-01-01

    Familial hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism, resulting in increased LDL-cholesterol levels and, as a consequence, an increased risk for coronary heart disease. Recently, many causal FH mutations in different genes have been identified and advances in genetic

  19. Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Jensen, J M; Gerdes, Lars Ulrik; Jensen, H K

    2000-01-01

    OBJECTIVES: Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD: traditio...

  20. The Influence of an Educational Computer Game on Children's Cultural Identities

    Science.gov (United States)

    Chen, Hsiang-Ping; Lien, Chi-Jui; Annetta, Len; Lu, Yu-Ling

    2010-01-01

    This study develops an educational computer game, FORmosaHope (FH), to explore the influences that an educational computer game might have on children's cultural identities. FH is a role-playing game, in which children can actively explore a mini-world to learn about science, technology, and society. One hundred and thirty sixth-graders, about…

  1. Excretory/secretory products from two Fasciola hepatica isolates induce different transcriptional changes and IL-10 release in LPS-activated bovine "BOMA" macrophages.

    Science.gov (United States)

    Bąska, Piotr; Norbury, Luke James; Zawistowska-Deniziak, Anna; Wiśniewski, Marcin; Januszkiewicz, Kamil

    2017-10-01

    Fasciola hepatica are trematodes that reside in the bile ducts of mammals. Infection causes US$3 billion in losses annually in animal production and is considered a zoonosis of growing importance. An under-represented area in F. hepatica research has been the examination of the different immunomodulatory abilities of various parasite isolates on the host immune system. In this paper, this issue was explored, with the bovine macrophage cell line "BOMA". The cells were matured by LPS treatment and stimulated with excretory/secretory antigens (ES) from two Fasciola hepatica isolates: a laboratory isolate "Weybridge" (Fh-WeyES) and a wild isolate (Fh-WildES). As expected, stimulation with antigen mixtures with highly similar compositions resulted in mild transcriptomic differences. However, there were significant differences in cytokine levels. Compared to Fh-WeyES, exposure to Fh-WildES upregulated 27 and downregulated 30 genes. Fh-ES from both isolates diminished the release of TNF-α, whereas only Fh-WildES decreased IL-10 secretion. Neither Fh-WeyES nor Fh-WildES had an impact on IL-12 release. Our results indicate that various isolates can have different immunomodulatory abilities and impacts on the bovine immune system.

  2. Usefulness of Genetic Polymorphisms and Conventional Risk Factors to Predict Coronary Heart Disease in Patients With Familial Hypercholesterolemia

    NARCIS (Netherlands)

    van der Net, Jeroen B.; Janssens, A. Cecile J. W.; Defesche, Joep C.; Kastelein, John J. P.; Sijbrands, Eric J. G.; Steyerberg, Ewout W.

    2009-01-01

    Familial hypercholesterolemia (FH) is an autosomal dominant disorder with an associated high risk of coronary heart disease (CHD). The considerable variation in age of onset of CHD in patients with FH is believed to arise from conventional risk factors, as well as genetic variation other than in the

  3. Weather data around the world for design of field hospital HVAC

    NARCIS (Netherlands)

    Forejt, L.; Hensen, J.L.M.; Drkal, F.; Barankova, P.

    2006-01-01

    Field hospital (FH) is a military mobile complex to be deployed in almost any climate around the world. Heating, ventilation and air-conditioning (HVAC) system for the Czech Republic FH units is being redesigned. Computer simulation software will be used for the design of HVAC under variety of

  4. Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn.

    Science.gov (United States)

    Weijenborg, P W; Smout, A J P M; Bredenoord, A J

    2016-11-01

    Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non-erosive reflux disease (NERD) patients. In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability. Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar. Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception. © 2016 John Wiley & Sons Ltd.

  5. Arsenic Scavenging by Al-Substituted Ferrihydrites in a Circumneutral pH River Impacted by the Acid Mine Drainage of Carnoulès, Gard, France

    Science.gov (United States)

    ADRA, A.; Morin, G.; ona-Nguema, G.; Maillot, F.; Casiot, C.; Bruneel, O.

    2013-12-01

    Ferrihydrite (Fh) is a nanocrystalline ferric oxyhydroxide involved in the retention of pollutants in natural systems and in water-treatment processes. The status and properties of major chemical impurities in natural Fh is however still scarcely documented. Here we investigated the structure and reactivity of aluminum-rich Fh from river-bed sediments collected in a circumneutral river (pH 6-7) impacted by an arsenic-rich acid mine drainage (AMD). Extended X-ray absorption fine structure (EXAFS) spectroscopy at the Fe K-edge shows that Fh is the predominant mineral phase forming after neutralization of the AMD, in association with minor amount of schwertmannite transported from the AMD. EXAFS analysis indicates that Al(III) substitutes for Fe(III) ions into the Fh structure in the natural sediment samples, with local aluminum concentration within the 20-37×7 mol%Al range, in agreement with bulk chemical compositions. Synthetic aluminous Fh analogues prepared in the present study are found to be less Al-substituted (14-18×4 mol%Al). Finally, EXAFS analysis at the arsenic K-edge indicates that As(V) form similar inner-sphere surface complexes on the natural and synthetic Al-substituted Fh studied. Our results provide direct evidences for the scavenging of arsenic by natural Al- Fh, with possible implications for other pollutants in natural or engineered systems.

  6. Quality of life, anxiety and concerns among statin-treated children with familial hypercholesterolaemia and their parents

    NARCIS (Netherlands)

    de Jongh, S.; Kerckhoffs, M. C.; Grootenhuis, M. A.; Bakker, H. D.; Heymans, H. S. A.; Last, B. F.

    2003-01-01

    Aim: To assess the quality of life, anxiety and concerns among statin-treated children with familial hypercholesterolaemia (FH) and their parents. Methods: 69 FH children on statin therapy and 87 parents (51 families) participated in this study. Quality of life of the children, and anxiety levels of

  7. AcEST: DK952686 [AcEST

    Lifescience Database Archive (English)

    Full Text Available _PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy ... 75 4e-12 tr|B7FH62|B7FH62_MEDTR Putative uncharacterized...R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy PE=4 SV=1 Length = 151 Score = 75.1 bits (183), E

  8. AcEST: DK963394 [AcEST

    Lifescience Database Archive (English)

    Full Text Available |Q4R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy ... 75 3e-12 tr|B7FH62|B7FH62_MEDTR Putative u...EDDU Plastocyanin OS=Pediastrum duplex GN=Pcy PE=4 SV=1 Length = 151 Score = 75.1

  9. AcEST: DK948452 [AcEST

    Lifescience Database Archive (English)

    Full Text Available U Plastocyanin OS=Pediastrum duplex GN=Pcy ... 75 3e-12 tr|B7FH62|B7FH62_MEDTR Putative uncharacterized prot...PH+ A MVGTI V+ Sbjct: 86 KGLAFSAGESFESTFSEPGTYTYYCEPHRGAGMVGTITVQ 125 >tr|Q4R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex

  10. AcEST: DK952613 [AcEST

    Lifescience Database Archive (English)

    Full Text Available tr|Q4R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy ... 75 3e-12 tr|B7FH62|B7FH62_MEDTR Putativ...7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy PE=4 SV=1 Length = 151 Score = 7

  11. AcEST: DK952097 [AcEST

    Lifescience Database Archive (English)

    Full Text Available PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy ... 75 3e-12 tr|B7FH62|B7FH62_MEDTR Putative uncharacterized ...YYC PH+ A MVGTI V+ Sbjct: 86 KGLAFSAGESFESTFSEPGTYTYYCEPHRGAGMVGTITVQ 125 >tr|Q4R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex

  12. Design of the Familial Hypercholesterolaemia Australasia Network Registry: Creating Opportunities for Greater International Collaboration.

    Science.gov (United States)

    Bellgard, Matthew I; Walker, Caroline E; Napier, Kathryn R; Lamont, Leanne; Hunter, Adam A; Render, Lee; Radochonski, Maciej; Pang, Jing; Pedrotti, Annette; Sullivan, David R; Kostner, Karam; Bishop, Warrick; George, Peter M; O'Brien, Richard C; Clifton, Peter M; Bockxmeer, Frank M Van; Nicholls, Stephen J; Hamilton-Craig, Ian; Dawkins, Hugh Js; Watts, Gerald F

    2017-10-01

    Familial Hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipoprotein metabolism that leads to premature coronary heart disease. There are over 65,000 people estimated to have FH in Australia, but many remain undiagnosed. Patients with FH are often under-treated, but with early detection, cascade family testing and adequate treatment, patient outcomes can improve. Patient registries are key tools for providing new information on FH and enhancing care worldwide. The development and design of the FH Australasia Network Registry is a crucial component in the comprehensive model of care for FH, which aims to provide a standardized, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. Informed by stakeholder engagement, the FH Australasia Network Registry was collaboratively developed by government, patient and clinical networks and research groups. The open-source, web-based Rare Disease Registry Framework was the architecture chosen for this registry owing to its open-source standards, modular design, interoperability, scalability and security features; all these are key components required to meet the ever changing clinical demands across regions. This paper provides a high level blueprint for other countries and jurisdictions to help inform and map out the critical features of an FH registry to meet their particular health system needs.

  13. Familial hypercholesterolaemia in children and adolescents

    DEFF Research Database (Denmark)

    Wiegman, Albert; Gidding, Samuel S; Watts, Gerald F

    2015-01-01

    . If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle......Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness...... of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis...

  14. Association of coronary heart disease with age-adjusted aortocoronary calcification in patients with familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Jensen, J M; Gerdes, Lars Ulrik; Jensen, H K

    2000-01-01

    OBJECTIVES: Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD: traditio......OBJECTIVES: Existing algorithms of risk of coronary heart disease (CHD) do not pertain to patients with familial hypercholesterolaemia (FH), whose arteries have been exposed to hypercholesterolaemia since birth. We studied a cohort of FH patients to compare four diagnostic models of CHD......: traditional risk factors of CHD (age, sex, cholesterol, hypertension, smoking and body mass index), cholesterol year score, and aortic as well as coronary calcium measured by spiral computed tomography (CT). SUBJECTS: We invited 88 individuals with molecularly defined FH of whom 80 (91%) decided...

  15. Fasciola hepatica saposin-like-2 protein based ELISA for the serodiagnosis of chronic human fascioliasis

    Science.gov (United States)

    Figueroa-Santiago, Olgary; Delgado, Bonnibel; Espino, Ana M.

    2011-01-01

    An indirect enzyme-linked immunosorbent assay (ELISA) was developed and evaluated for its diagnostic ability to detect human IgG antibodies against Fasciola hepatica saposin-like protein-2. The assay was compared with an indirect ELISA with excretory-secretory products (FhES) from adult F. hepatica. In an analysis of the sera of 37 patients infected with F. hepatica, 40 patients with other parasitic infections, and 50 healthy controls, the sensitivity of both ELISA assays was 100%. However, the FhSAP2-based ELISA was more specific (95.6%) than the FhES-ELISA (91.9%). These results demonstrated that FhSAP2 can be used in the serodiagnosis of chronic human fascioliasis with additional advantage that is relative cheap and easy to produce. Studies are in progress to evaluate this FhSAP2-ELISA assay in a large-scale prevalence surveys in endemic areas. PMID:21683266

  16. Frequency hopping signal detection based on wavelet decomposition and Hilbert-Huang transform

    Science.gov (United States)

    Zheng, Yang; Chen, Xihao; Zhu, Rui

    2017-07-01

    Frequency hopping (FH) signal is widely adopted by military communications as a kind of low probability interception signal. Therefore, it is very important to research the FH signal detection algorithm. The existing detection algorithm of FH signals based on the time-frequency analysis cannot satisfy the time and frequency resolution requirement at the same time due to the influence of window function. In order to solve this problem, an algorithm based on wavelet decomposition and Hilbert-Huang transform (HHT) was proposed. The proposed algorithm removes the noise of the received signals by wavelet decomposition and detects the FH signals by Hilbert-Huang transform. Simulation results show the proposed algorithm takes into account both the time resolution and the frequency resolution. Correspondingly, the accuracy of FH signals detection can be improved.

  17. Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4 defines a new subtype of D-bifunctional protein deficiency

    Directory of Open Access Journals (Sweden)

    McMillan Hugh J

    2012-11-01

    Full Text Available Abstract Background D-bifunctional protein (DBP deficiency is typically apparent within the first month of life with most infants demonstrating hypotonia, psychomotor delay and seizures. Few children survive beyond two years of age. Among patients with prolonged survival all demonstrate severe gross motor delay, absent language development, and severe hearing and visual impairment. DBP contains three catalytically active domains; an N-terminal dehydrogenase, a central hydratase and a C-terminal sterol carrier protein-2-like domain. Three subtypes of the disease are identified based upon the domain affected; DBP type I results from a combined deficiency of dehydrogenase and hydratase activity; DBP type II from isolated hydratase deficiency and DBP type III from isolated dehydrogenase deficiency. Here we report two brothers (16½ and 14 years old with DBP deficiency characterized by normal early childhood followed by sensorineural hearing loss, progressive cerebellar and sensory ataxia and subclinical retinitis pigmentosa. Methods and results Biochemical analysis revealed normal levels of plasma VLCFA, phytanic acid and pristanic acid, and normal bile acids in urine; based on these results no diagnosis was made. Exome analysis was performed using the Agilent SureSelect 50Mb All Exon Kit and the Illumina HiSeq 2000 next-generation-sequencing (NGS platform. Compound heterozygous mutations were identified by exome sequencing and confirmed by Sanger sequencing within the dehydrogenase domain (c.101C>T; p.Ala34Val and hydratase domain (c.1547T>C; p.Ile516Thr of the 17β-hydroxysteroid dehydrogenase type 4 gene (HSD17B4. These mutations have been previously reported in patients with severe-forms of DBP deficiency, however each mutation was reported in combination with another mutation affecting the same domain. Subsequent studies in fibroblasts revealed normal VLCFA levels, normal C26:0 but reduced pristanic acid beta-oxidation activity. Both DBP

  18. Endotoxin and dust at respirable and nonrespirable particle sizes are not consistent between cage- and floor-housed poultry operations.

    Science.gov (United States)

    Kirychuk, Shelley P; Reynolds, Stephen J; Koehncke, Niels K; Lawson, Joshua; Willson, Philip; Senthilselvan, Ambikaipakan; Marciniuk, Darcy; Classen, Henry L; Crowe, Trever; Just, Natasha; Schneberger, David; Dosman, James A

    2010-10-01

    Individuals engaged in work in intensive animal houses experience some of the highest rates of occupationally related respiratory symptoms. Organic dust and in particular endotoxin has been most closely associated with respiratory symptoms and lung function changes in workers. It has previously been shown that for intensive poultry operations, type of poultry housing [cage-housed (CH) versus floor-housed (FH)] can influence the levels of environmental contaminants. The goal of the study was to determine the differences in endotoxin and dust levels at different size fractions between CH and FH poultry operations. Fifteen CH and 15 FH poultry operations were sampled for stationary measurements (area) of dust and associated endotoxin. Fractioned samples were collected utilizing Marple cascade impactors. Gravimetric and endotoxin analysis were conducted on each of the filters. When assessed by individual Marple stage, there was significantly greater airborne endotoxin concentration (endotoxin units per cubic meter) in the size fraction >9.8 μm for the FH operations whereas at the size fraction 1.6-3.5 μm, the CH operations had significantly greater airborne endotoxin concentration than the FH operations. Endotoxin concentration in the dust mass (endotoxin units per milligram) was significantly greater in the CH operations as compared to the FH operations for all size fractions >1.6 μm. As such, endotoxin in the respirable fraction accounted for 24% of the total endotoxin in the CH operations whereas it accounted for only 11% in the FH operations. There was significantly more dust in all size fractions in the FH operations as compared to the CH poultry operations. There is more endotoxin in the presence of significantly lower dust levels in the respirable particle size fractions in CH poultry operations as compared to the FH poultry operations. This difference in respirable endotoxin may be important in relation to the differential respiratory response experienced by

  19. New Approaches in Detection and Treatment of Familial Hypercholesterolemia.

    Science.gov (United States)

    Hartgers, Merel L; Ray, Kausik K; Hovingh, G Kees

    2015-12-01

    Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that clinically leads to increased low density lipoprotein-cholesterol (LDL-C) levels. As a consequence, FH patients are at high risk for cardiovascular disease (CVD). Mutations are found in genes coding for the LDLR, apoB, and PCSK9, although FH cannot be ruled out in the absence of a mutation in one of these genes. It is pivotal to diagnose FH at an early age, since lipid lowering results in a decreased risk of cardiovascular complications especially if initiated early, but unfortunately FH is largely underdiagnosed. While a number of clinical criteria are available, identification of a pathogenic mutation in any of the three aforementioned genes is seen by many as a way to establish a definitive diagnosis of FH. It should be remembered that clinical treatment is based on LDL-C levels and not solely on presence or absence of genetic mutations as LDL-C is what drives risk. Traditionally, mutation detection has been done by means of dideoxy sequencing. However, novel molecular testing methods are gradually being introduced. These next generation sequencing-based methods are likely to be applied on broader scale once their efficacy and effect on cost are being established. Statins are the first-line therapy of choice for FH patients as they have been proven to reduce CVD risk across a range of conditions including hypercholesterolemia (though not specifically tested in FH). However, in a significant proportion of FH patients LDL-C goals are not met, despite the use of maximal statin doses and additional lipid-lowering therapies. This underlines the need for additional therapies, and inhibition of PCSK9 and CETP is among the most promising new therapeutic options. In this review, we aim to provide an overview of the latest information about the definition, diagnosis, screening, and current and novel therapies for FH.

  20. The Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement.

    Science.gov (United States)

    Caswell, Clayton C; Han, Runlin; Hovis, Kelley M; Ciborowski, Pawel; Keene, Douglas R; Marconi, Richard T; Lukomski, Slawomir

    2008-02-01

    Non-specific activation of the complement system is regulated by the plasma glycoprotein factor H (FH). Bacteria can avoid complement-mediated opsonization and phagocytosis through acquiring FH to the cell surface. Here, we characterize an interaction between the streptococcal collagen-like protein Scl1.6 of M6-type group A Streptococcus (GAS) and FH. Using affinity chromatography with immobilized recombinant Scl1.6 protein, we co-eluted human plasma proteins with molecular weight of 155 kDa, 43 kDa and 38 kDa. Mass spectrometry identified the 155 kDa band as FH and two other bands as isoforms of the FH-related protein-1. The identities of all three bands were confirmed by Western immunoblotting with specific antibodies. Structure-function relation studies determined that the globular domain of the Scl1.6 variant specifically binds FH while fused to collagenous tails of various lengths. This binding is not restricted to Scl1.6 as the phylogenetically linked Scl1.55 variant also binds FH. Functional analyses demonstrated the cofactor activity of the rScl1.6-bound FH for factor I-mediated cleavage of C3b. Finally, purified FH bound to the Scl1.6 protein present in the cell wall material obtained from M6-type GAS. In conclusion, we have identified a functional interaction between Scl1 and plasma FH, which may contribute to GAS evasion of complement-mediated opsonization and phagocytosis.

  1. Refractory heartburn: comparison of intercellular space diameter in documented GERD vs. functional heartburn.

    Science.gov (United States)

    Vela, Marcelo F; Craft, Brandon M; Sharma, Neeraj; Freeman, Janice; Hazen-Martin, Debra

    2011-05-01

    Refractory heartburn despite acid suppression may be explained by ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH), i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH) detects acid and nonacid reflux and is useful for evaluating acid-suppressed, refractory patients. Intercellular space diameter (ISD) of esophageal epithelium measured by transmission electron microscopy (TEM) is a marker of epithelial damage present in both erosive and nonerosive reflux disease. ISD has not been used to study refractory heartburn or FH. Our aim was to compare ISD in healthy controls and refractory heartburn patients with GERD and FH. In refractory heartburn patients (heartburn more than twice/week for at least 2 months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or abnormal impedance-pH (increased acid exposure or positive symptom index) defined GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH. Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each subject, determined by blinded TEM of esophageal biopsies, was the average of 100 measurements (10 measurements in each of 10 micrographs). In all, 11 healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was significantly higher in GERD compared with controls (0.87 vs. 0.32 μm, P=0.003) and FH (0.87 vs. 0.42 μm, P=0.012). Mean ISD was similar in FH and controls (0.42 vs. 0.32 μm, P=0.1). The proportion of patients with abnormal ISD was significantly higher for GERD compared with FH (60 vs. 9%, P=0.014). ISD is increased in refractory heartburn patients with GERD but not those with FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to distinguish GERD from FH in patients with refractory heartburn.

  2. An enquiry based on a standardised questionnaire into knowledge, awareness and preferences concerning the care of familial hypercholesterolaemia among primary care physicians in the Asia-Pacific region: the “Ten Countries Study”

    Science.gov (United States)

    Pang, Jing; Hu, Miao; Lin, Jie; Miida, Takashi; Nawawi, Hapizah M; Park, Jeong Euy; Wu, Xue; Ramli, Anis S; Kim, Ngoc Thanh; Kwok, See; Gonzalez-Santos, Lourdes E; Su, Ta-Chen; Truong, Thanh Huong; Soran, Handrean; Yamashita, Shizuya; Tomlinson, Brian; Watts, Gerald F

    2017-01-01

    Objective To determine physicians’ knowledge, awareness and preferences regarding the care of familial hypercholesterolaemia (FH) in the Asia-Pacific region. Setting A formal questionnaire was anonymously completed by physicians from different countries/regions in the Asia-Pacific. The survey sought responses relating to general familiarity, awareness of management guidelines, identification (clinical characteristics and lipid profile), prevalence and inheritance, extent of elevation in risk of cardiovascular disease (CVD) and practice on screening and treatment. Participants Practising community physicians from Australia, Japan, Malaysia, South Korea, Philippines, Hong Kong, China, Vietnam and Taiwan were recruited to complete the questionnaire, with the UK as the international benchmark. Primary outcome An assessment and comparison of the knowledge, awareness and preferences of FH among physicians in 10 different countries/regions. Results 1078 physicians completed the questionnaire from the Asia-Pacific region; only 34% considered themselves to be familiar with FH. 72% correctly described FH and 65% identified the typical lipid profile, with a higher proportion of physicians from Japan and China selecting the correct FH definition and lipid profile compared with those from Vietnam and Philippines. However, less than half of the physician were aware of national or international management guidelines; this was significantly worse than physicians from the UK (35% vs 61%, p<0.001). Knowledge of prevalence (24%), inheritability (41%) and CVD risk (9%) of FH were also suboptimal. The majority of the physicians considered laboratory interpretative commenting as being useful (81%) and statin therapy as an appropriate cholesterol-lowering therapy (89%) for FH management. Conclusions The study identified important gaps, which are readily addressable, in the awareness and knowledge of FH among physicians in the region. Implementation of country-specific guidelines and

  3. Production of biologically active recombinant human factor H in Physcomitrella.

    Science.gov (United States)

    Büttner-Mainik, Annette; Parsons, Juliana; Jérôme, Hanna; Hartmann, Andrea; Lamer, Stephanie; Schaaf, Andreas; Schlosser, Andreas; Zipfel, Peter F; Reski, Ralf; Decker, Eva L

    2011-04-01

    The human complement regulatory serum protein factor H (FH) is a promising future biopharmaceutical. Defects in the gene encoding FH are associated with human diseases like severe kidney and retinal disorders in the form of atypical haemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis II (MPGN II) or age-related macular degeneration (AMD). There is a current need to apply intact full-length FH for the therapy of patients with congenital or acquired defects of this protein. Application of purified or recombinant FH (rFH) to these patients is an important and promising approach for the treatment of these diseases. However, neither protein purified from plasma of healthy individuals nor recombinant protein is currently available on the market. Here, we report the first stable expression of the full-length human FH cDNA and the subsequent production of this glycoprotein in a plant system. The moss Physcomitrella patens perfectly suits the requirements for the production of complex biopharmaceuticals as this eukaryotic system not only offers an outstanding genetical accessibility, but moreover, proteins can be produced safely in scalable photobioreactors without the need for animal-derived medium compounds. Transgenic moss lines were created, which express the human FH cDNA and target the recombinant protein to the culture supernatant via a moss-derived secretion signal. Correct processing of the signal peptide and integrity of the moss-produced rFH were verified via peptide mapping by mass spectrometry. Ultimately, we show that the rFH displays complement regulatory activity comparable to FH purified from plasma. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  4. Relationship between family history of type 2 diabetes and serum FGF21.

    Science.gov (United States)

    Davis, Greggory R; Deville, Tiffany; Guillory, Joshua; Bellar, David; Nelson, Arnold G

    2017-11-01

    Determining predictive markers for the development of type 2 diabetes (T2D), particularly in young individuals, offers immense potential benefits in preventative medicine. Previous research examining serum fibroblast growth factor 21 (FGF21) in humans has revealed equivocal relationships with clinical markers of metabolic dysfunction. However, it is unknown to what extent, if any, first-degree family history of T2D (mother or father of the participant diagnosed with T2D) level affects serum FGF21 levels. The aim of this study was to determine whether in healthy individuals with FH+ (n = 18) and without FH- (n = 17) a family history of T2D affects serum FGF21. Fasting serum and clinical, metabolic and anthropometric measures were determined using a cross-sectional design. Differences between groups for FGF21 were not significant (FH+ = 266 pg/mL ± 51·4, FH = 180 pg/mL ± 29; Z = 0·97, P = 0·33). Adiponectin values were lower in FH+ (8·81 μg/mL ± 2·14) compared to FH- (10·65 μg/mL ± 1·44; F = 8·83, P = 0·01). Resistin was negatively correlated with FGF21 for all participants (r = -0·38, P = 0·03), but no other clinical, metabolic, or serum markers were predictive for serum FGF21 in FH+ or FH-. Serum FGF21 is not significantly different between FH+ and FH- in young, healthy individuals. Based upon the data of this pilot study, it is unclear whether serum FGF21 can be used as a stand-alone predictive marker for T2D in healthy subjects. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  5. Autonomic abnormalities demonstrable in young normotensive subjects who are children of hypertensive parents

    Directory of Open Access Journals (Sweden)

    Lopes H.F.

    2000-01-01

    Full Text Available Although a slightly elevated office blood pressure (BP has been reported in several studies, little is known about the prolonged resting blood pressure, heart rate (HR and baroreflex sensitivity (BRS of prehypertensive subjects with a family history of hypertension. Office blood pressure, prolonged resting (1 h BP and HR were measured in 25 young normotensives with a positive family history of hypertension (FH+ and 25 young normotensives with a negative family history of hypertension (FH-, matched for age, sex, and body mass index. After BP and HR measurements, blood samples were collected for the determination of norepinephrine, plasma renin activity and aldosterone levels, and baroreflex sensitivity was then tested. Casual BP, prolonged resting BP and heart rate were significantly higher in the FH+ group (119.9 ± 11.7/78.5 ± 8.6 mmHg, 137.3 ± 12.3/74.4 ± 7.9 mmHg, 68.5 ± 8.4 bpm compared to the FH- group (112.9 ± 11.4/71.2 ± 8.3 mmHg, 128.0 ± 11.8/66.5 ± 7.4 mmHg, 62.1 ± 6.0 bpm. Plasma norepinephrine level was significantly higher in the FH+ group (220.1 ± 104.5 pg/ml than in the FH- group (169.1 ± 63.3 pg/ml. Baroreflex sensitivity to tachycardia (0.7 ± 0.3 vs 1.0 ± 0.5 bpm/mmHg was depressed in the FH+ group (P<0.05. The FH+ group exhibited higher casual blood pressure, prolonged resting blood pressure, heart rate and plasma norepinephrine levels than the FH- group (P<0.05, suggesting an increased sympathetic tone in these subjects. The reflex tachycardia was depressed in the FH+ group.

  6. Diagnostic Yield of Sequencing Familial Hypercholesterolemia Genes in Severe Hypercholesterolemia

    Science.gov (United States)

    Khera, Amit V.; Won, Hong-Hee; Peloso, Gina M.; Lawson, Kim S.; Bartz, Traci M.; Deng, Xuan; van Leeuwen, Elisabeth M.; Natarajan, Pradeep; Emdin, Connor A.; Bick, Alexander G.; Morrison, Alanna C.; Brody, Jennifer A.; Gupta, Namrata; Nomura, Akihiro; Kessler, Thorsten; Duga, Stefano; Bis, Joshua C.; van Duijn, Cornelia M.; Cupples, L. Adrienne; Psaty, Bruce; Rader, Daniel J.; Danesh, John; Schunkert, Heribert; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Lander, Eric; Wilson, James G.; Correa, Adolfo; Boerwinkle, Eric; Merlini, Piera Angelica; Ardissino, Diego; Saleheen, Danish; Gabriel, Stacey; Kathiresan, Sekar

    2017-01-01

    Background About 7% of US adults have severe hypercholesterolemia (untreated LDL cholesterol ≥190 mg/dl). Such high LDL levels may be due to familial hypercholesterolemia (FH), a condition caused by a single mutation in any of three genes. Lifelong elevations in LDL cholesterol in FH mutation carriers may confer CAD risk beyond that captured by a single LDL cholesterol measurement. Objectives Assess the prevalence of a FH mutation among those with severe hypercholesterolemia and determine whether CAD risk varies according to mutation status beyond the observed LDL cholesterol. Methods Three genes causative for FH (LDLR, APOB, PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD cases, 8,577 CAD-free controls) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database. Results Among 8,577 CAD-free control participants, 430 had LDL cholesterol ≥190 mg/dl; of these, only eight (1.9%) carried a FH mutation. Similarly, among 11,908 participants from 5 prospective cohorts, 956 had LDL cholesterol ≥190 mg/dl and of these, only 16 (1.7%) carried a FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers when compared with non-carriers. When compared to a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had six-fold higher risk for CAD (OR 6.0; 95%CI 5.2–6.9) whereas those with LDL cholesterol ≥190 mg/dl as well as a FH mutation demonstrated twenty-two fold increased risk (OR 22.3; 95%CI 10.7–53.2). Conclusions Among individuals with LDL cholesterol ≥190 mg/dl, gene sequencing identified a FH mutation in <2%. However, for any given observed LDL cholesterol, FH mutation carriers are at substantially increased risk for CAD

  7. Biotransformation of nitriles by Rhodococcus equi A4 immobilized in LentiKats

    Czech Academy of Sciences Publication Activity Database

    Kubáč, David; Čejková, A.; Masák, J.; Jirků, V.; Lemaire, M.; Gallienne, E.; Bolte, J.; Stloukal, R.; Martínková, Ludmila

    2006-01-01

    Roč. 39, - (2006), s. 59-61 ISSN 1381-1177 R&D Projects: GA ČR GA203/05/2267; GA MŠk OC D25.001; GA AV ČR IAA4020213 Institutional research plan: CEZ:AV0Z50200510 Keywords : nitrile hydratase * amidase * nitriles Subject RIV: EE - Microbiology, Virology Impact factor: 2.149, year: 2006

  8. The Host Plant Metabolite Glucose Is the Precursor of Diffusible Signal Factor (DSF) Family Signals in Xanthomonas campestris

    OpenAIRE

    Deng, Yinyue; Liu, Xiaoling; Wu, Ji'en; Lee, Jasmine; Chen, Shaohua; Cheng, Yingying; Zhang, Chunyan; Zhang, Lian-Hui

    2015-01-01

    Plant pathogen Xanthomonas campestris pv. campestris produces cis-11-methyl-2-dodecenoic acid (diffusible signal factor [DSF]) as a cell-cell communication signal to regulate biofilm dispersal and virulence factor production. Previous studies have demonstrated that DSF biosynthesis is dependent on the presence of RpfF, an enoyl-coenzyme A (CoA) hydratase, but the DSF synthetic mechanism and the influence of the host plant on DSF biosynthesis are still not clear. We show here that exogenous ad...

  9. 生体触媒の化学工業への導入

    OpenAIRE

    長澤, 透

    1996-01-01

    Microbial processes for industrial production of commodity chemicals are rapidly gaining practical significance for preparation of high purity products, in an environmentally acceptable manner, while realizing energy savings. The use of bacterial nitrile hydratase for industrial production of the important chemical, acrylamide, was recently pioneered in Japan. We review here the enzymatic production of acrylamide and recent progress in the production of other commodity chemicals through micro...

  10. Selection and screening for enzymes of nitrile metabolism

    Czech Academy of Sciences Publication Activity Database

    Martínková, Ludmila; Vejvoda, Vojtěch; Křen, Vladimír

    2008-01-01

    Roč. 133, č. 3 (2008), s. 318-326 ISSN 0168-1656 R&D Projects: GA AV ČR IAA500200708; GA ČR GA203/05/2267; GA MŠk(CZ) LC06010; GA MŠk OC 171 Institutional research plan: CEZ:AV0Z50200510 Keywords : nitrilase * nitrile hydratase * amidase Subject RIV: CE - Biochemistry Impact factor: 2.748, year: 2008

  11. The Effect of Simulated Flash-Heat Pasteurization on Immune Components of Human Milk

    Directory of Open Access Journals (Sweden)

    Brodie Daniels

    2017-02-01

    Full Text Available A pasteurization temperature monitoring system has been designed using FoneAstra, a cellphone-based networked sensing system, to monitor simulated flash-heat (FH pasteurization. This study compared the effect of the FoneAstra FH (F-FH method with the Sterifeed Holder method currently used by human milk banks on human milk immune components (immunoglobulin A (IgA, lactoferrin activity, lysozyme activity, interleukin (IL-8 and IL-10. Donor milk samples (N = 50 were obtained from a human milk bank, and pasteurized. Concentrations of IgA, IL-8, IL-10, lysozyme activity and lactoferrin activity were compared to their controls using the Student’s t-test. Both methods demonstrated no destruction of interleukins. While the Holder method retained all lysozyme activity, the F-FH method only retained 78.4% activity (p < 0.0001, and both methods showed a decrease in lactoferrin activity (71.1% Holder vs. 38.6% F-FH; p < 0.0001 and a decrease in the retention of total IgA (78.9% Holder vs. 25.2% F-FH; p < 0.0001. Despite increased destruction of immune components compared to Holder pasteurization, the benefits of F-FH in terms of its low cost, feasibility, safety and retention of immune components make it a valuable resource in low-income countries for pasteurizing human milk, potentially saving infants’ lives.

  12. [Symptom overlaps between functional heartburn, functional dyspepsia, and irritable bowel syndrome].

    Science.gov (United States)

    2014-05-01

    To determine symptom overlaps between functional heartburn (FH), functional dyspepsia (FD), and irritable bowel syndrome (IBS). One hundred and ten patients with frequent heartburn but no mucosa breakage under endoscopy were enrolled consecutively. They were required to fill out a questionnaire. The overlapped symptoms of FD and IBS symptoms were screened using Rome ill criteria. The participants were also examined using Hamilton anxiety scale/Hamilton depression scale. All of the participants were followed with 24 h esophageal multichannel intra-luminal impedance monitoring with pH sensor (MII-pH) monitoring and proton pump inhibitor (PPI) trials. The participants were divided into non-erosive reflux disease (NERD) and FH groups. The prevalence of symptom overlaps FD and IBS, between NERD and FH groups was analyzed. Women were more likely to present with FH than with NERD (P heartburn symptom had FD symptoms; 31 (28.2%) had IBS symptoms, and 10 (9.09%) had both FD and IBS symptoms. Patients with FH were more likely to have symptom overlaps of FD and IBS than those with NERD (62% vs. 35%, 48% vs. 11.7%, respectively; P 0.05). IBS-diarrhea was also slightly more likely to have overlapped NERD and FH symptoms than IBS-constipation. Again, the difference was not significant (16.4% vs. 11.8%, P > 0.05). Female, higher prevalence of anxiety and depression, overlapped FD and IBS symptoms are more likely to appear in FH patients than in NERD patients.

  13. Comparison of Esophageal Function Tests in Chinese Patients with Functional Heartburn and Reflux Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Feng Gao

    2017-01-01

    Full Text Available Objective. To investigate the differences in the results of esophageal function tests for functional heartburn (FH and reflux hypersensitivity (RH. Methods. Patients with FH and RH and healthy volunteers (HVs from the Department of Gastroenterology, Beijing Anzhen Hospital and Beijing Chao-Yang hospital, who underwent high-resolution manometry and impedance (HRIM, and 24-hour multichannel intraluminal impedance and pH recording (MII/pH between 2014 and 2016, were enrolled in this study. Results. 36 HV, 147 FH patients, and 91 RH patients were enrolled. The postreflux swallow-induced peristaltic wave index (PSPW index and mean nocturnal baseline impedance (MNBI values were significantly lower in RH than in FH and HV. The ineffective esophageal motility (IEM, fragmented peristalsis rates, total bolus exposure, proximal total reflux events, and distal total reflux events were significantly greater in RH than in FH and HV. Conclusions. Compared to HV and FH patients, RH patients exhibited greater IEM and fragmented peristalsis rates, a greater total bolus exposure, more proximal total and distal total reflux events, and reduced chemical clearance and mucosal integrity. By using the above described parameters, HRIM and MII/pH assays could be used to correctly classify RH and FH and hence allow physicians to provide adequate relief from associated symptoms.

  14. Follicular helper T cells poise immune responses to the development of autoimmune pathology.

    Science.gov (United States)

    Gómez-Martín, Diana; Díaz-Zamudio, Mariana; Romo-Tena, Jorge; Ibarra-Sánchez, María J; Alcocer-Varela, Jorge

    2011-04-01

    Follicular helper T cells (T(FH)) have been implicated as a lineage that provides sufficient help to B cells in order to become professional antibody producers. This T helper subset is characterized by a distinctive cell-surface phenotype (CD4(+)CD57(+)CXCR5(+)) and cytokine profile (IL-21, IL-6, and IL-27) as well as transcriptional program (BCL-6, ICOS, and PD-1). Evidence supports the concept that T(FH) subset development, as well as for other lineages, is dependent on microenvironment cues that modulate a particular transcriptional program, susceptible to plasticity. Recently, it has been shown that BCL-6 and IL-21 act as master regulators for the development and function of T(FH) cells. Moreover, costimulation via ICOS, as well as signaling proteins such as SAP constitute required elements of the regulatory network that modulates T(FH) functions. T(FH) dysregulation has been implicated in the development of autoimmune pathology, such as SLE. Indeed, the Sanroque mice associated to the mutation of Roquin, a ubiquitin ligase, essential for the regulation of ICOS and germinal center responses, constitutes a model that shares features with human SLE. Recently, the expansion of "circulating T(FH) cells" (CD4(+)CXCR5(+)ICOS(high)PD1(high)) has been described for a subset of SLE patients that share T(FH) dependent features of disease with Sanroque mice, such as glomerulonephritis and cytopenias. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Parents' and caregivers' experiences and behaviours when eating out with children with a food hypersensitivity.

    Science.gov (United States)

    Begen, Fiona M; Barnett, Julie; Barber, Miriam; Payne, Ros; Gowland, M Hazel; Lucas, Jane S

    2017-07-20

    For parents and caregivers of food hypersensitive (FH) children, accommodating their child's dietary needs when eating out can be a challenging experience. This study explored caregivers' experiences and behaviours when eating out with their FH child in order to gain insights into how they support and prepare their child in negotiating safe eating out experiences. A cross-sectional, qualitative design was used. In depth, semi-structured interviews were carried out with 15 caregivers of children with FH. Interviews were analysed using framework analysis. Caregivers reported a number of issues relating to eating out with their FH child, or allowing their child to eat out without their supervision. Through themes of 'family context', 'child-focused concerns', and 'venue issues', caregivers described how they managed these and explained the limitations and sacrifices that FH imposed on their child, themselves, and family members. Through deeper understanding of the anxieties, negotiations and compromises experienced by caregivers of children with FH when they are eating out, clinicians and support charities can tailor their support to meet the needs of caregivers and children. Support and education provision should focus on providing caregivers of children with FH the tools and strategies to help enable safe eating out experiences.

  16. Acetylene as fast food: Implications for development of life on anoxic primordial earth and in the outer solar system

    Science.gov (United States)

    Oremland, R.S.; Voytek, M.A.

    2008-01-01

    Acetylene occurs, by photolysis of methane, in the atmospheres of jovian planets and Titan. In contrast, acetylene is only a trace component of Earth's current atmosphere. Nonetheless, a methane-rich atmosphere has been hypothesized for early Earth; this atmosphere would also have been rich in acetylene. This poses a paradox, because acetylene is a potent inhibitor of many key anaerobic microbial processes, including methanogenesis, anaerobic methane oxidation, nitrogen fixation, and hydrogen oxidation. Fermentation of acetylene was discovered 25 years ago, and Pelobacter acetylenicus was shown to grow on acetylene by virtue of acetylene hydratase, which results in the formation of acetaldehyde. Acetaldehyde subsequently dismutates to ethanol and acetate (plus some hydrogen). However, acetylene hydratase is specific for acetylene and does not react with any analogous compounds. We hypothesize that microbes with acetylene hydratase played a key role in the evolution of Earth's early biosphere by exploiting an available source of carbon from the atmosphere and in so doing formed protective niches that allowed for other microbial processes to flourish. Furthermore, the presence of acetylene in the atmosphere of a planet or planetoid could possibly represent evidence for an extraterrestrial anaerobic ecosystem. ?? Mary Ann Liebert, Inc.

  17. Degradation of the metal-cyano complex tetracyanonickelate (II) by Fusarium oxysporum N-10.

    Science.gov (United States)

    Yanase, H; Sakamoto, A; Okamoto, K; Kita, K; Sato, Y

    2000-03-01

    A fungus with the ability to utilize a metalcyano compound, tetracyanonickelate (II) ¿K2[Ni (CN)4]; TCN¿, as its sole source of nitrogen was isolated from soil and identified as Fusarium oxysporum N-10. Both intact mycelia and cell-free extract of the strain catalyzed hydrolysis of TCN to formate and ammonia and produced formamide as an intermediate, thereby indicating that a hydratase and an amidase sequentially participated in the degradation of TCN. The enzyme catalyzing the hydration of TCN was purified approximately ten-fold from the cell-free extract of strain N-10 with a yield of 29%. The molecular mass of the active enzyme was estimated to be 160 kDa. The enzyme appears to exist as a homotetramer, each subunit having a molecular mass of 40 kDa. The enzyme also catalyzed the hydration of KCN, with a cyanide-hydrating activity 2 x 10(4) times greater than for TCN. The kinetic parameters for TCN and KCN indicated that hydratase isolated from F. oxysporum was a cyanide hydratase able to utilize a broad range of cyano compounds and nitriles as substrates.

  18. Acetylene as fast food: implications for development of life on anoxic primordial Earth and in the outer solar system.

    Science.gov (United States)

    Oremland, Ronald S; Voytek, Mary A

    2008-02-01

    Acetylene occurs, by photolysis of methane, in the atmospheres of jovian planets and Titan. In contrast, acetylene is only a trace component of Earth's current atmosphere. Nonetheless, a methane-rich atmosphere has been hypothesized for early Earth; this atmosphere would also have been rich in acetylene. This poses a paradox, because acetylene is a potent inhibitor of many key anaerobic microbial processes, including methanogenesis, anaerobic methane oxidation, nitrogen fixation, and hydrogen oxidation. Fermentation of acetylene was discovered approximately 25 years ago, and Pelobacter acetylenicus was shown to grow on acetylene by virtue of acetylene hydratase, which results in the formation of acetaldehyde. Acetaldehyde subsequently dismutates to ethanol and acetate (plus some hydrogen). However, acetylene hydratase is specific for acetylene and does not react with any analogous compounds. We hypothesize that microbes with acetylene hydratase played a key role in the evolution of Earth's early biosphere by exploiting an available source of carbon from the atmosphere and in so doing formed protective niches that allowed for other microbial processes to flourish. Furthermore, the presence of acetylene in the atmosphere of a planet or planetoid could possibly represent evidence for an extraterrestrial anaerobic ecosystem.

  19. Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation

    Directory of Open Access Journals (Sweden)

    Adam Z. Blatt

    2017-11-01

    Full Text Available Platelet/granulocyte aggregates (PGAs increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP negative regulator, Factor H (FH. Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS, yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism. Utilizing recombinant fragments of FH spanning the entire length of the protein, we mapped the regions of FH most critical for limiting AP activity on the surface of isolated human platelets and neutrophils, as well as the regions most critical for regulating PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP. FH domains 19–20 were the most critical for limiting AP activity on platelets, neutrophils, and at the platelet/granulocyte interface. The role of FH in PGA formation was attributed to its ability to regulate AP-mediated C5a generation. AHUS-related mutations in domains 19–20 caused differential effects on control of PGA formation and AP activity on platelets and neutrophils. Our data indicate FH C-terminal domains are key for regulating PGA formation, thus increased FH protection may have a beneficial impact on diseases characterized by increased PGA formation, such as cardiovascular disease. Additionally, aHUS-related mutations in domains 19–20 have varying effects on control of TRAP-mediated PGA formation, suggesting that some, but not all, aHUS-related mutations may cause increased PGA formation that contributes to excessive thrombosis in patients with aHUS.

  20. Children with hypercholesterolemia of unknown cause: Value of genetic risk scores.

    Science.gov (United States)

    Sjouke, Barbara; Tanck, Michael W T; Fouchier, Sigrid W; Defesche, Joep C; Hutten, Barbara A; Wiegman, Albert; Kastelein, John J P; Hovingh, G Kees

    2016-01-01

    Familial hypercholesterolemia (FH) is caused by mutations in LDLR, APOB, or PCSK9, and in a previous study, we identified a causative mutation in these FH genes in 95% (255 of 269) of children with the FH phenotype. It has been hypothesized that a polygenic form of hypercholesterolemia is present in FH patients in whom no mutation is identified in the 3 FH genes. To address whether a polygenic form of hypercholesterolemia, defined as high-weighted effect of low-density lipoprotein cholesterol (LDL-C) raising SNPs expressed as the genetic risk score (GRS), is present in the remaining 14 children. On reassessment of the molecular diagnosis and clinical phenotype, 8 FH kindreds met the criteria for hypercholesterolemia of unknown cause and were included in this study. We calculated a weighted GRS comprising 10 established LDL-C-associated SNPs and the APOE genotype in these index cases and evaluated whether the index cases were characterized by an increased GRS compared to 26 first-degree relatives. Phenotypically affected and unaffected individuals could not be distinguished based on any of the risk scores. In this and our previous study, we show that a causal mutation in LDLR, APOB, and PCSK9 can be identified in almost all children with a definite clinical diagnosis of FH. In the small group of patients without a mutation, we did not observe a higher GRS compared with unaffected relatives, which suggests that the FH phenotype is not caused by the aggregate of LDL-C increasing SNPs. Our data imply that application of the GRS is not instrumental as a diagnostic tool to individually define clinically diagnosed FH patients with polygenic hypercholesterolemia in our study population. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  1. Prevalence, management, and outcomes of familial hypercholesterolemia in patients with acute coronary syndromes in the Arabian Gulf.

    Science.gov (United States)

    Al-Rasadi, Khalid; Al-Zakwani, Ibrahim; Alsheikh-Ali, Alawi A; Almahmeed, Wael; Rashed, Wafa; Ridha, Mustafa; Santos, Raul D; Zubaid, Mohammad

    2018-02-14

    Information on the epidemiology of familial hypercholesterolemia (FH) in the Arabian Gulf region, which has an elevated rate of consanguinity and type II diabetes, is scarce. To assess the prevalence of FH, its management, and impact on atherosclerotic cardiovascular disease (ASCVD) outcomes in a multicenter cohort of Arabian Gulf patients with acute coronary syndrome (ACS). Patients (N = 3224) hospitalized with ACS were studied. FH was diagnosed using the Dutch Lipid Clinic Network criteria. A composite endpoint of nonfatal myocardial infarction, stroke, transient ischemic attack, and mortality between the "probable/definite" and the "unlikely" FH patients was assessed after 1 year. Analyses were performed using univariate and multivariate statistical techniques. At admission, the proportion of "probable/definite", "possible", and "unlikely" FH in ACS patients was 3.7% (n = 119), 28% (n = 911), and 68% (n = 2194), respectively. Overall, 54% (n = 1730) of patients had diabetes, whereas 24% (n = 783) were current smokers. The "probable/definite" FH group was younger (50 vs 63 years; P definite" FH cohort had worse lipid control (13% vs 23%; P < .001) and presented with a greater association with the composite ASCVD endpoint when compared with the "unlikely" FH group (odds ratio: 1.85; 95% confidence interval: 1.01-3.38; P = .047) after multivariable adjustment. In Arabian Gulf citizens, FH was common in ACS patients, was undertreated, and was associated with a worse 1-year prognosis. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  2. Familial hypercholesterolaemia: a model of care for Australasia.

    Science.gov (United States)

    Watts, Gerald F; Sullivan, David R; Poplawski, Nicola; van Bockxmeer, Frank; Hamilton-Craig, Ian; Clifton, Peter M; O'Brien, Richard; Bishop, Warrick; George, Peter; Barter, Phillip J; Bates, Timothy; Burnett, John R; Coakley, John; Davidson, Patricia; Emery, Jon; Martin, Andrew; Farid, Waleed; Freeman, Lucinda; Geelhoed, Elizabeth; Juniper, Amanda; Kidd, Alexa; Kostner, Karam; Krass, Ines; Livingston, Michael; Maxwell, Suzy; O'Leary, Peter; Owaimrin, Amal; Redgrave, Trevor G; Reid, Nicola; Southwell, Lynda; Suthers, Graeme; Tonkin, Andrew; Towler, Simon; Trent, Ronald

    2011-10-01

    Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that causes marked elevation in plasma cholesterol and premature coronary heart disease. There are at least 45,000 people with FH in Australia and New Zealand, but the vast majority remains undetected and those diagnosed with the condition are inadequately treated. To bridge this major gap in coronary prevention the FH Australasia Network (Australian Atherosclerosis Society) has developed a consensus model of care (MoC) for FH. The MoC is based on clinical experience, expert opinion, published evidence and consultations with a wide spectrum of stakeholders, and has been developed for use primarily by specialist centres intending starting a clinical service for FH. This MoC aims to provide a standardised, high-quality and cost-effective system of care that is likely to have the highest impact on patient outcomes. The MoC for FH is presented as a series of recommendations and algorithms focusing on the standards required for the detection, diagnosis, assessment and management of FH in adults and children. The process involved in cascade screening and risk notification, the backbone for detecting new cases of FH, is detailed. Guidance on treatment is based on risk stratifying patients, management of non-cholesterol risk factors, safe and effective use of statins, and a rational approach to follow-up of patients. Clinical and laboratory recommendations are given for genetic testing. An integrative system for providing best clinical care is described. This MoC for FH is not prescriptive and needs to be complemented by good clinical judgment and adjusted for local needs and resources. After initial implementation, the MoC will require critical evaluation, development and appropriate modification. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Fasciola hepatica Surface Coat Glycoproteins Contain Mannosylated and Phosphorylated N-glycans and Exhibit Immune Modulatory Properties Independent of the Mannose Receptor.

    Directory of Open Access Journals (Sweden)

    Alessandra Ravidà

    2016-04-01

    Full Text Available Fascioliasis, caused by the liver fluke Fasciola hepatica, is a neglected tropical disease infecting over 1 million individuals annually with 17 million people at risk of infection. Like other helminths, F. hepatica employs mechanisms of immune suppression in order to evade its host immune system. In this study the N-glycosylation of F. hepatica's tegumental coat (FhTeg and its carbohydrate-dependent interactions with bone marrow derived dendritic cells (BMDCs were investigated. Mass spectrometric analysis demonstrated that FhTeg N-glycans comprised mainly of oligomannose and to a lesser extent truncated and complex type glycans, including a phosphorylated subset. The interaction of FhTeg with the mannose receptor (MR was investigated. Binding of FhTeg to MR-transfected CHO cells and BMDCs was blocked when pre-incubated with mannan. We further elucidated the role played by MR in the immunomodulatory mechanism of FhTeg and demonstrated that while FhTeg's binding was significantly reduced in BMDCs generated from MR knockout mice, the absence of MR did not alter FhTeg's ability to induce SOCS3 or suppress cytokine secretion from LPS activated BMDCs. A panel of negatively charged monosaccharides (i.e. GlcNAc-4P, Man-6P and GalNAc-4S were used in an attempt to inhibit the immunoregulatory properties of phosphorylated oligosaccharides. Notably, GalNAc-4S, a known inhibitor of the Cys-domain of MR, efficiently suppressed FhTeg binding to BMDCs and inhibited the expression of suppressor of cytokine signalling (SOCS 3, a negative regulator the TLR and STAT3 pathway. We conclude that F. hepatica contains high levels of mannose residues and phosphorylated glycoproteins that are crucial in modulating its host's immune system, however the role played by MR appears to be limited to the initial binding event suggesting that other C-type lectin receptors are involved in the immunomodulatory mechanism of FhTeg.

  4. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2011-09-01

    Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

  5. Behavioral Impulsivity and Risk-Taking Trajectories Across Early Adolescence in Youths With and Without Family Histories of Alcohol and Other Drug Use Disorders.

    Science.gov (United States)

    Dougherty, Donald M; Lake, Sarah L; Mathias, Charles W; Ryan, Stacy R; Bray, Bethany C; Charles, Nora E; Acheson, Ashley

    2015-08-01

    Youths with family histories of alcohol and other drug use disorders (FH+) are at increased susceptibility for developing substance use disorders relative to those without such histories (FH-). This vulnerability may be related to impaired adolescent development of impulse control and elevated risk-taking. However, no previous studies have prospectively examined impulse control and risk-taking in FH+ youth across adolescence. A total of 386 pre-adolescents (305 FH+, 81 FH-; aged 10 to 12) with no histories of regular alcohol or other drug use were compared on behavioral measures of impulsivity including delay discounting, response initiation (Immediate Memory Task), response inhibition impulsivity (GoStop Impulsivity Paradigm), and risk-taking (Balloon Analogue Risk Task-Youth). Youths completed these laboratory tasks every 6 months, allowing for the examination of 10- to 15-year-olds. Hierarchical linear modeling was used to characterize the development of impulse control and risk-taking as shown in performance of these tasks throughout adolescence. We found that (i) FH+ youths had increased levels of delay discounting and response inhibition impulsivity at study entry; (ii) regardless of FH status, all youths had relatively stable delay discounting across time, improvements in response inhibition and response initiation impulsivity, and increased risk-taking; and (iii) although FH+ youths had increased response inhibition impulsivity at pre-adolescence, these differences were negligible by mid-adolescence. Heightened delay discounting in FH+ pre-adolescents coupled with normal adolescent increases in risk-taking may contribute to their increased susceptibility toward problem substance use in adolescence. Copyright © 2015 by the Research Society on Alcoholism.

  6. 4. Identification of a novel nonsense variant C.1332DUP, P. (D445* in the LDLR gene that causes familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Faisal Al-Allaf

    2017-10-01

    Conclusion: The duplication variant results in the production of a defective LDL receptor containing the p. (D445* variant. This variant results in a premature stop codon at position 445 in exon 9 of the LDLR gene, which results in truncation of the protein. The segregation pattern of the variant is consistent with the lipid profile, suggesting a more severe FH phenotype when the variant is in the homozygous state. Finding of this study could be very useful in developing critical genetic screen for potential FH patients. In addition, these data contribute to the understanding of the molecular basis of FH in Saudis.

  7. Improving detection of familial hypercholesterolaemia in primary care using electronic audit and nurse‐led clinics

    Science.gov (United States)

    Neely, Dermot; Humphries, Steve E.; Saunders, Tanya; Gray, Val; Gordon, Louise; Payne, Jules; Carter, Slade; Neuwirth, Clare; Rees, Alan; Gallagher, Hazel

    2015-01-01

    Abstract Rationale, aims and objectives In the UK fewer than 15% of familial hypercholesterolemia (FH) cases are diagnosed, representing a major gap in coronary heart disease prevention. We wished to support primary care doctors within the Medway Clinical Commissioning Group (CCG) to implement NICE guidance (CG71) and consider the possibility of FH in adults who have raised total cholesterol concentrations, thereby improving the detection of people with FH. Methods Utilizing clinical decision support software (Audit+) we developed an FH Audit Tool and implemented a systematic audit of electronic medical records within GP practices, first identifying all patients diagnosed with FH or possible FH and next electronically flagging patients with a recorded total cholesterol of >7.5 mmol L−1 or LDL‐C > 4.9 mmol L−1 (in adults), for further assessment. After a 2‐year period, a nurse‐led clinic was introduced to screen more intensely for new FH index cases. We evaluated if these interventions increased the prevalence of FH closer to the expected prevalence from epidemiological studies. Results The baseline prevalence of FH within Medway CCG was 0.13% (1 in 750 persons). After 2 years, the recorded prevalence of diagnosed FH increased by 0.09% to 0.22% (1 in 450 persons). The nurse advisor programme ran for 9 months (October 2013–July 2014) and during this time, the recorded prevalence of patients diagnosed with FH increased to 0.28% (1 in 357 persons) and the prevalence of patients ‘at risk and unscreened’ reduced from 0.58% to 0.14%. Conclusions Our study shows that two simple interventions increased the detection of FH. This systematic yet simple electronic case‐finding programme with nurse‐led review allowed the identification of new index cases, more than doubling the recorded prevalence of detected disease to 1 in 357 (0.28%). This study shows that primary care has an important role in identifying patients with this condition. PMID

  8. On the convergence of nonlinear Beltrami type operators

    Directory of Open Access Journals (Sweden)

    Riccardo De Arcangelis

    1986-11-01

    Full Text Available One of the results proved is the following: if (fh is a sequence of K-quasiregular mappings, converging to f  in L1loc , whose jacobians verify a weak integrability condition, then the solutions of Dirichlet problems for the nonlinear Laplace-Beltrami operator associated to each fh converge to the solution of the Dirichlet problem for the nonlinear Laplace-Beltrami operator associated to f. Such result is deduced as a particular case of a more general theorem concerning nonlinear operators. The case of K-quasiconformal functions fh is also treated. A class of weighted Sobolev spaces associated to quasiconformal mappings is studied.

  9. Perbandingan Karkas Dari Beberapa Bangsa Sapi

    Directory of Open Access Journals (Sweden)

    Cut Aida Fitri

    2002-04-01

    Full Text Available ABSTRACT. The objective of this research was determined how far the comparisons of carcass of those three species. This research were used 57 fattening cow. Which consisting of 19 Aceh (SA cow. 19 Brahman cross (BX cow and 19 Friesian Holstein (FH, for 90 days observation time. The attributes that observed include: percentage of carcass weight, percentage of meat weight, percentage of added result, percentage of bone weight, percentage of fat. From each of those multi special of cow, considering each of their weight before cutter. The result of this research are: mean (± SE of their life weight are: SA 316.00  ± 9.68 kg, BX: 410.16 ± 9.53 kg and FH: 414.37 ± 10.12 kg. Mean (± SE of carcass percentage are: FH: 53.33 ± 0.83%, SA 55.75 ± 0.67% and BX: 56.28 ± 0.74. Mean (± SE of meat weight percentage : FH: 69.15 ± 0.74%, BX: 70.91 ± 1.18% and SA: 72.67 ± 1.08%. Mean (± SE of added result percentage: FH: 25.22  ± 0.57%, BX: 25.33 ± 0.47% and SA: 25.74 ± 0.74%. Mean (± SE of bone weight  percentage: SA: 16.75 ± 00.58%, BX: 19.24 ± 0.72% and FH: 20.91 ± 0.74%. Mean (±SE of fat percentage: SA: 6.94 ± 0.75% , BX: 17.84 ± 0.55%, and FH: 8.21 ± 0.49%. The result of ‘T’ test of SA carcass, meat and fat weight percentage were not significantly different with BX. SA added result percentage was not significantly different with BX and FH. SA bone weight percentage was signicantly different (P < 0.05 with BX. SA carcass, meats and fat weight percentage were significantly different (P < 0.05 with FH. SA bone weight percentage was not significantly different with FH. Carcass weight percentage of BX was signicantly different (P < 0.05 with FH. Meat, added result meat, bones and fat weight percentage of BX were not sifnificantly different with FH.

  10. Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.

    Science.gov (United States)

    Nanchen, David; Gencer, Baris; Auer, Reto; Räber, Lorenz; Stefanini, Giulio G; Klingenberg, Roland; Schmied, Christian M; Cornuz, Jacques; Muller, Olivier; Vogt, Pierre; Jüni, Peter; Matter, Christian M; Windecker, Stephan; Lüscher, Thomas F; Mach, François; Rodondi, Nicolas

    2015-09-21

    We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  11. Flying Height Measurement of Magnetic Disk Using Double Common-path Heterodyne Interferometer

    International Nuclear Information System (INIS)

    Lin, D J; Yue, Z Y; Song, N H; Meng, Y G; Yin, C Y

    2006-01-01

    The magnetic storage capacity depends significantly on the area density, which is close related to the flying-height (FH) of magnetic head. In this paper a double common-path heterodyne interferometer is proposed to measure the FH. The resolution of FH measurement reaches 0.1nm by means of phase measurement method. The influence of vibration of magnetic disk and work table is considered in the configuration design so as to reduce the system error. The experimental results show that the error compensation is better than 10nm when the vibration of disk is 1.2μm

  12. Improving detection of familial hypercholesterolaemia in primary care using electronic audit and nurse-led clinics.

    Science.gov (United States)

    Green, Peter; Neely, Dermot; Humphries, Steve E

    2016-06-01

    In the UK fewer than 15% of familial hypercholesterolemia (FH) cases are diagnosed, representing a major gap in coronary heart disease prevention. We wished to support primary care doctors within the Medway Clinical Commissioning Group (CCG) to implement NICE guidance (CG71) and consider the possibility of FH in adults who have raised total cholesterol concentrations, thereby improving the detection of people with FH. Utilizing clinical decision support software (Audit+) we developed an FH Audit Tool and implemented a systematic audit of electronic medical records within GP practices, first identifying all patients diagnosed with FH or possible FH and next electronically flagging patients with a recorded total cholesterol of >7.5 mmol L(-1) or LDL-C > 4.9 mmol L(-1) (in adults), for further assessment. After a 2-year period, a nurse-led clinic was introduced to screen more intensely for new FH index cases. We evaluated if these interventions increased the prevalence of FH closer to the expected prevalence from epidemiological studies. The baseline prevalence of FH within Medway CCG was 0.13% (1 in 750 persons). After 2 years, the recorded prevalence of diagnosed FH increased by 0.09% to 0.22% (1 in 450 persons). The nurse advisor programme ran for 9 months (October 2013-July 2014) and during this time, the recorded prevalence of patients diagnosed with FH increased to 0.28% (1 in 357 persons) and the prevalence of patients 'at risk and unscreened' reduced from 0.58% to 0.14%. Our study shows that two simple interventions increased the detection of FH. This systematic yet simple electronic case-finding programme with nurse-led review allowed the identification of new index cases, more than doubling the recorded prevalence of detected disease to 1 in 357 (0.28%). This study shows that primary care has an important role in identifying patients with this condition. © 2015 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley

  13. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes

    DEFF Research Database (Denmark)

    Vallejo-Vaz, Antonio J; Akram, Asif; Kondapally Seshasai, Sreenivasa Rao

    2016-01-01

    BACKGROUND: The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH...... to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH...

  14. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei

    DEFF Research Database (Denmark)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K.

    2015-01-01

    production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led......Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities...... of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact...

  15. Morphine Decreases Social Interaction of Adult Male Rats, While THC Does Not Affect It

    Czech Academy of Sciences Publication Activity Database

    Šlamberová, R.; Mikulecká, Anna; Macúchová, E.; Hrebíčková, I.; Ševčíková, M.; Nohejlová, K.; Pometlová, M.

    2016-01-01

    Roč. 65, Suppl.5 (2016), S547-S555 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : social behavior * opioids * morphine * cannabinoids * THC * male rats Subject RIV: FH - Neurology Impact factor: 1.461, year: 2016

  16. Acid-sensing ion channels in rat hypothalamic vasopressin neurons of the supraoptic nucleus

    Czech Academy of Sciences Publication Activity Database

    Ohbuchi, T.; Sato, K.; Suzuki, H.; Okada, Y.; Dayanithi, Govindan; Murphy, D.; Ueta, Y.

    2010-01-01

    Roč. 588, č. 12 (2010), s. 2147-2162 ISSN 0022-3751 Institutional research plan: CEZ:AV0Z50390703 Keywords : hypothalamus * ASIC * oxytocin Subject RIV: FH - Neurology Impact factor: 5.139, year: 2010

  17. GABA(B) receptor phosphorylation regulates KCTD12-induced K+ current desensitization

    Czech Academy of Sciences Publication Activity Database

    Adelfinger, L.; Tureček, Rostislav; Ivankova, K.; Jensen, A. A.; Moss, S. J.; Gassmann, M.; Bettler, B.

    2014-01-01

    Roč. 91, č. 3 (2014), s. 369-379 ISSN 0006-2952 Institutional support: RVO:68378041 Keywords : GABA-B * G-protein coupled receptor * GPCR Subject RIV: FH - Neurology Impact factor: 5.009, year: 2014

  18. Mechanism of increased mortality in hemodialysed patients with periodontitis

    Czech Academy of Sciences Publication Activity Database

    Šedý, Jiří; Horká, E.; Foltán, R.; Špačková, J.; Dušková, J.

    2010-01-01

    Roč. 74, č. 2 (2010), s. 374-376 ISSN 0306-9877 Institutional research plan: CEZ:AV0Z50390703 Keywords : hemodialysis * renal failure * periodontitis Subject RIV: FH - Neurology Impact factor: 1.389, year: 2010

  19. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

    NARCIS (Netherlands)

    Vallejo-Vaz, Antonio J.; Akram, Asif; Kondapally Seshasai, Sreenivasa Rao; Cole, Della; Watts, Gerald F.; Hovingh, G. Kees; Kastelein, John J. P.; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Freiberger, Tomas; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alnouri, Fahad; Alonso, Rodrigo; Al-Rasadi, Khalid; Banach, Maciej; Bogsrud, Martin P.; Bourbon, Mafalda; Bruckert, Eric; Car, Josip; Ceska, Richard; Corral, Pablo; Descamps, Olivier; Dieplinger, Hans; Do, Can T.; Durst, Ronen; Ezhov, Marat V.; Fras, Zlatko; Gaita, Dan; Gaspar, Isabel M.; Genest, Jaques; Harada-Shiba, Mariko; Jiang, Lixin; Kayikcioglu, Meral; Lam, Carolyn S. P.; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lin, Jie; Lin, Nan; Maher, Vincent; Majano, Nelson; Marais, A. David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nilsson, Lennart; Nordestgaard, Børge G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Reiner, Željko; Sahebkar, Amirhossein; Santos, Lourdes E.; Schunkert, Heribert; Shehab, Abdullah; Slimane, M. Naceur; Stoll, Mario; Su, Ta-Chen; Susekov, Andrey; Tilney, Myra; Tomlinson, Brian; Tselepis, Alexandros D.; Vohnout, Branislav; Widén, Elisabeth; Yamashita, Shizuya; Catapano, Alberico L.; Ray, Kausik K.

    2016-01-01

    Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European

  20. Molecular mechanisms of neuropathological changes in Alzheimer's disease: a review

    Czech Academy of Sciences Publication Activity Database

    Šerý, O.; Povová, J.; Míšek, Ivan; Pešák, L.; Janout, V.

    2013-01-01

    Roč. 51, č. 1 (2013), s. 1-9 ISSN 1641-4640 Institutional support: RVO:67985904 Keywords : amyloid precursor protein * tau protein * apolipoprotein E Subject RIV: FH - Neurology Impact factor: 1.667, year: 2013

  1. A categorical approach to neurodynamical modelling of musical tonality

    Czech Academy of Sciences Publication Activity Database

    Hadrava, Michal; Hlinka, Jaroslav

    2015-01-01

    Roč. 16, suppl. 1 (2015), P101 ISSN 1471-2202 R&D Projects: GA ČR GA13-23940S Institutional support: RVO:67985807 Keywords : neurodynamics * music * tonality * category theory Subject RIV: FH - Neurology

  2. Macrosomia - maternal and fetal risk factors

    African Journals Online (AJOL)

    developed world.4. Patients and methods ... mothers were booked patients, compared with 329 of the control mothers. .... Boyd ME, Usher R, McLean FH. ... Oliguria fo described compartm. Fietsam e abdomina ruptured syndrome direct abd.

  3. The importance of being subtle: small changes in calcium homeostasis control cognitive decline in normal aging

    Czech Academy of Sciences Publication Activity Database

    Toescu, E.C.; Verkhratsky, Alexei

    2007-01-01

    Roč. 6, - (2007), s. 267-273 ISSN 1474-9718 Institutional research plan: CEZ:AV0Z50390512 Keywords : Aging * Ca homeostasis * Cognitive decline Subject RIV: FH - Neurology Impact factor: 5.854, year: 2007

  4. Superior temporal sulcus and social cognition in dangerous drivers

    Czech Academy of Sciences Publication Activity Database

    Zelinková, J.; Shaw, D. J.; Mareček, R.; Mikl, M.; Urbánek, Tomáš; Peterková, L.; Zámečník, P.; Brázdil, M.

    2013-01-01

    Roč. 83, December (2013), s. 1024-1030 ISSN 1053-8119 Institutional support: RVO:68081740 Keywords : fMRI * antisocial behavior * social cognition * STS Subject RIV: FH - Neurology Impact factor: 6.132, year: 2013

  5. River water quality in the northern sugarcane-producing regions of ...

    African Journals Online (AJOL)

    2011-02-16

    Feb 16, 2011 ... Sugarcane production in South Africa occurs exclusively in the eastern regions of ... transboundary rivers, making their management internation- ...... KOEGELENBERG FH (2004) Irrigation User's Manual – Chapter 5: Water.

  6. Hippocampus-dependent retrieval and hippocampus-independent extinction of place avoidance navigation, and stress-induced out-of-context activation of a memory revealed by reversible lesion experiments in rats

    Czech Academy of Sciences Publication Activity Database

    Ježek, Karel; Wesierska, M.; Fenton, André Antonio

    2002-01-01

    Roč. 51, Suppl. 1 (2002), s. S35-S47 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z5011922 Keywords : memory * hippocampus * extinction Subject RIV: FH - Neurology Impact factor: 0.984, year: 2002

  7. Influence of convulsants on rat brain activities of alanine aminotransferase and aspartate aminotransferase

    Czech Academy of Sciences Publication Activity Database

    Netopilová, M.; Haugvicová, Renata; Kubová, Hana; Dršata, J.; Mareš, Pavel

    2001-01-01

    Roč. 26, č. 12 (2001), s. 1285-1291 ISSN 0364-3190 Institutional research plan: CEZ:AV0Z5011922 Keywords : alanine aminotransferase * aspartale aminotransferase Subject RIV: FH - Neurology Impact factor: 1.638, year: 2001

  8. Control of hypothalamic orexin neurons by acid and CO2

    Czech Academy of Sciences Publication Activity Database

    Williams, R.H.; Jensen, L.T.; Verkhratsky, Alexei; Fugger, L.; Burdakov, D.

    2007-01-01

    Roč. 104, č. 25 (2007), s. 10685-10690 ISSN 0027-8424 Institutional research plan: CEZ:AV0Z50390512 Keywords : Arousal * Hypocretin * Hypothalamus Subject RIV: FH - Neurology Impact factor: 9.598, year: 2007

  9. The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia

    DEFF Research Database (Denmark)

    Nielsen, M H; Irvine, H; Vedel, S

    2016-01-01

    Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate...

  10. Etiopathogenesis of neurogenic pulmonary edema

    Czech Academy of Sciences Publication Activity Database

    Šedý, Jiří

    2010-01-01

    Roč. 160, 5-6 (2010), s. 152-154 ISSN 0043-5341 Institutional research plan: CEZ:AV0Z50390512 Keywords : neurogenic pulmonary edema * intracranial pressure * sympathetic system Subject RIV: FH - Neurology

  11. Gonadal steroids, gonadotropins and DHEAS in young adults with familial hypercholesterolemia who had initiated statin therapy in childhood

    NARCIS (Netherlands)

    Braamskamp, Marjet J. A. M.; Kusters, D. Meeike; Wiegman, Albert; Avis, Hans J.; Wijburg, Frits A.; Kastelein, John J. P.; van Trotsenburg, A. S. Paul; Hutten, Barbara A.

    2015-01-01

    Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia (FH) with the aim to prevent premature cardiovascular disease (CVD). However, concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production. In

  12. Neural complexity, dissociation, and schizophrenia

    Czech Academy of Sciences Publication Activity Database

    Bob, P.; Šusta, M.; Chládek, Jan; Glaslová, K.; Fedor-Ferybergh, P.

    2007-01-01

    Roč. 13, č. 10 (2007), HY1-5 ISSN 1234-1010 Institutional research plan: CEZ:AV0Z20650511 Keywords : neural complexity * dissociation * schizophrenia Subject RIV: FH - Neurology Impact factor: 1.607, year: 2007

  13. Observation of dynamic interactions between fundamental and second-harmonic modes in a high-power sub-terahertz gyrotron operating in regimes of soft and hard self-excitation.

    Science.gov (United States)

    Saito, Teruo; Tatematsu, Yoshinori; Yamaguchi, Yuusuke; Ikeuchi, Shinji; Ogasawara, Shinya; Yamada, Naoki; Ikeda, Ryosuke; Ogawa, Isamu; Idehara, Toshitaka

    2012-10-12

    Dynamic mode interaction between fundamental and second-harmonic modes has been observed in high-power sub-terahertz gyrotrons [T. Notake et al., Phys. Rev. Lett. 103, 225002 (2009); T. Saito et al. Phys. Plasmas 19, 063106 (2012)]. Interaction takes place between a parasitic fundamental or first-harmonic (FH) mode and an operating second-harmonic (SH) mode, as well as among SH modes. In particular, nonlinear excitation of the parasitic FH mode in the hard self-excitation regime with assistance of a SH mode in the soft self-excitation regime was clearly observed. Moreover, both cases of stable two-mode oscillation and oscillation of the FH mode only were observed. These observations and theoretical analyses of the dynamic behavior of the mode interaction verify the nonlinear hard self-excitation of the FH mode.

  14. Homozygous familiar hypercholesterolemia in China: Case series from the national lipid clinics and literature review

    Directory of Open Access Journals (Sweden)

    Cheng-Gang Zhu

    2017-03-01

    Conclusion: In a conclusion, we found a relatively common recruitment of this type of patients in our hospital, which might have an important clinical implication for the identification and management of the patients with FH in China.

  15. Actieve opsporing van patiënten met familiaire hypercholesterolemie en verzekerbaarheid voor levens- en arbeidsongeschiktheidsverzekeringen

    NARCIS (Netherlands)

    Homsma, S. J.; Lansberg, P. J.; Kastelein, J. J.

    2004-01-01

    In the Netherlands, people with familial hypercholesterolaemia (FH) have been actively screened since 1994 by means of DNA analysis. Recently, the Stichting Opsporing Erfelijke Hypercholesterolemie (Foundation for the Detection of Familial Hypercholesterolaemia) initiated a large scale-screening

  16. Eyes - bulging

    Science.gov (United States)

    ... different ages. In: Lambert SR, Lyons CJ, eds. Taylor and Hoyt's Pediatric Ophthalmology and Strabismus . 5th ed. Philadelphia, PA: Elsevier; 2017:chap 96. Orge FH, Grigorian F. Examination and common problems of the neonatal eye. ...

  17. Hong et al., Afr J Tradit Complement Altern Med. (2013) 10(4):66-69 ...

    African Journals Online (AJOL)

    AJTCAM

    inflammation, annex inflammation, uterine prolapse, and neurasthenia. .... Research progress on pharmacological effects of Bidens bipinnata L. China Pharmacy. ... Clinic. 24 (3): 147-149. 8. Wang, Q., Zhang Y.N., Chen F.H. (2009). Research ...

  18. Parkinson's disease induced pluripotent stem cells with triplication of the alpha-synuclein locus

    Czech Academy of Sciences Publication Activity Database

    Devine, M.J.; Ryten, M.; Vodička, Petr; Thomson, A.J.; Burdon, T.; Houlden, H.; Cavaleri, F.; Nagano, M.; Drummond, N.J.; Taanman, J.W.; Schapira, A.H.; Gwinn, K.; Hardy, J.; Lewis, P.A.; Kunath, T.

    2011-01-01

    Roč. 2, č. 440 (2011), s. 1-1 ISSN 2041-1723 Institutional research plan: CEZ:AV0Z50450515 Keywords : gene duplication * dementia * association Subject RIV: FH - Neurology Impact factor: 7.396, year: 2011

  19. Pregnancy in a Woman with Homozygous Familial Hypercholesterolemia Not on Low-Density Lipoprotein Apheresis

    Directory of Open Access Journals (Sweden)

    Akl C. Fahed

    2012-11-01

    Full Text Available Pregnancy in women with homozygous familial hypercholesterolemia (FH has been rarely reported and might pose risks on the mother and her fetus. Although most reported cases remained on low-density lipoprotein (LDL apheresis, there are no clear guidelines regarding the management of this entity. We report the first case of an uncomplicated pregnancy in a 24-year-old homozygous FH woman who was not maintained on LDL apheresis. FH expresses a wide variability in the phenotype, and management of homozygous FH cases who desire to become pregnant should be individualized based on preconceptional assessment with frequent antenatal follow-up. Decisions on management should be made after weighing the risks versus benefits of LDL apheresis.

  20. Nonpharmacological lipoprotein apheresis reduces arterial inflammation in familial hypercholesterolemia

    NARCIS (Netherlands)

    van Wijk, Diederik F.; Sjouke, Barbara; Figueroa, Amparo; Emami, Hamed; van der Valk, Fleur M.; MacNabb, Megan H.; Hemphill, Linda C.; Schulte, Dominik M.; Koopman, Marion G.; Lobatto, Mark E.; Verberne, Hein J.; Fayad, Zahi A.; Kastelein, John J. P.; Mulder, Willem J. M.; Hovingh, G. Kees; Tawakol, Ahmed; Stroes, Erik S. G.

    2014-01-01

    Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which is associated with accelerated atherogenesis and increased cardiovascular risk. This study used (18)F-fluorodeoxyglucose

  1. Physiology of neuronal-glial networking

    Czech Academy of Sciences Publication Activity Database

    Verkhratsky, Alexei

    2010-01-01

    Roč. 57, č. 4 (2010), s. 332-343 ISSN 0197-0186 Institutional research plan: CEZ:AV0Z50390703 Keywords : Glia * Astrocytes * Glutamate receptors Subject RIV: FH - Neurology Impact factor: 3.601, year: 2010

  2. Concomitant Astroglial Atrophy and Astrogliosis in a Triple Transgenic Animal Model of Alzheimer's Disease

    Czech Academy of Sciences Publication Activity Database

    Olabarria, M.; Noristani, H. N.; Verkhratsky, Alexei; Rodríguez Arellano, Jose Julio

    2010-01-01

    Roč. 58, č. 7 (2010), s. 831-838 ISSN 0894-1491 Institutional research plan: CEZ:AV0Z50390703 Keywords : astroglia * Alzheimer's disease * hippocampus Subject RIV: FH - Neurology Impact factor: 5.186, year: 2010

  3. Glia: the fulcrum of brain diseases

    Czech Academy of Sciences Publication Activity Database

    Giaume, C.; Kirchhoff, F.; Matute, C.; Reichenbach, A.; Verkhratsky, Alexei

    2007-01-01

    Roč. 14, - (2007), s. 1324-1335 ISSN 1350-9047 Institutional research plan: CEZ:AV0Z50390512 Keywords : Glia * Astrocyte * Oligodendrocyte Subject RIV: FH - Neurology Impact factor: 8.254, year: 2007

  4. Purinergic signalling in the nervous system: an overview

    Czech Academy of Sciences Publication Activity Database

    Abbracchio, M. P.; Burnstock, G.; Verkhratsky, Alexei; Zimmermann, H.

    2009-01-01

    Roč. 32, č. 1 (2009), s. 19-29 ISSN 0166-2236 Institutional research plan: CEZ:AV0Z50390512 Keywords : extracellular hydrolysis * behaviour Subject RIV: FH - Neurology Impact factor: 12.794, year: 2009

  5. Behavioral phenotyping of minipigs transgenic for the Huntington gene

    Czech Academy of Sciences Publication Activity Database

    Schramke, S.; Schuldenzucker, V.; Schubert, R.; Frank, F.; Wirsig, M.; Ott, S.; Motlík, Jan; Fels, M.; Kemper, N.; Hölzner, E.; Reilmann, R.

    2016-01-01

    Roč. 265, S1 (2016), s. 34-45 ISSN 0165-0270 Institutional support: RVO:67985904 Keywords : animal models * minipig * phenotyping * behavioral * motor Subject RIV: FH - Neurology Impact factor: 2.554, year: 2016

  6. Neuroimaging of a minipig model of Huntington's disease: Feasibility of volumetric, diffusion-weighted and spectroscopic assessments

    Czech Academy of Sciences Publication Activity Database

    Schubert, R.; Frank, F.; Nagelmann, N.; Liebsch, L.; Schuldenzucker, V.; Schramke, S.; Wirsig, M.; Johnson, H.; Young Kim, E.; Ott, S.; Hölzner, E.; Demokritov, S. O.; Motlík, Jan; Faber, C.; Reilmann, R.

    2016-01-01

    Roč. 265, S1 (2016), s. 46-55 ISSN 0165-0270 Institutional support: RVO:67985904 Keywords : animal models * minipig * MRI * brain atlas * preclinical research Subject RIV: FH - Neurology Impact factor: 2.554, year: 2016

  7. Our experience in the treatment of idiopathic sensorineural hearing loss (ISNHL): Effect of combination therapy with HBO2 and vasodilator infusion therapy

    Czech Academy of Sciences Publication Activity Database

    Kratochvílová, B.; Profant, Oliver; Astl, J.; Holý, R.

    2016-01-01

    Roč. 43, č. 7 (2016), s. 771-780 ISSN 1066-2936 Institutional support: RVO:68378041 Keywords : idiopathic sensorineural hearing logs * vasodilator infusion * hyperbaric oxygen therapy Subject RIV: FH - Neurology Impact factor: 0.895, year: 2016

  8. BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury

    Czech Academy of Sciences Publication Activity Database

    Chumak, Tetyana; Rüttiger, L.; Lee, S.Ch.; Campanelli, D.; Zuccotti, A.; Singer, W.; Popelář, Jiří; Gutsche, K.; Geisler, H.S.; Schraven, S.P.; Jaumann, M.; Panford-Walsh, R.; Hu, J.; Schimmang, T.; Zimmermann, U.; Syka, Josef; Knipper, M.

    2016-01-01

    Roč. 53, č. 8 (2016), s. 5607-5627 ISSN 0893-7648 Institutional support: RVO:68378041 Keywords : BDNF * central hyperactivity * high-spontaneous rate Subject RIV: FH - Neurology Impact factor: 6.190, year: 2016

  9. Chronic Pyruvate Supplementation Increases Exploratory Activity and Brain Energy Reserves in Young and Middle-Aged Mice

    Czech Academy of Sciences Publication Activity Database

    Koivisto, H.; Leinonen, H.; Puurula, M.; Hafez, H. S.; Barrera Alquicer, Glenda; Stridh, M. L.; Waagepetersen, H. S.; Tiainen, M.; Soininen, P.; Zilberter, Y.; Tanila, H.

    2016-01-01

    Roč. 8, Mar 16 (2016), s. 41 ISSN 1663-4365 Institutional support: RVO:67985823 Keywords : Alzheimer’s disease * aging * memory * explorative activity * glycogen Subject RIV: FH - Neurology Impact factor: 4.504, year: 2016

  10. Funkce lícního nervu po mikrochirurgické léčbě\

    Czech Academy of Sciences Publication Activity Database

    Fík, Z.; Chovanec, M.; Zvěřina, E.; Kluh, J.; Profant, Oliver; Kraus, J.; Hrubá, S.; Čada, Z.; Procházková, K.; Plzák, J.; Betka, J.

    2017-01-01

    Roč. 80, č. 5 (2017), s. 545-551 ISSN 1210-7859 Institutional support: RVO:68378041 Keywords : facial nerve * vestibular schwannoma * microsurgery Subject RIV: FH - Neurology OBOR OECD: Otorhinolaryngology Impact factor: 0.368, year: 2016

  11. Ouick Reaction Report on Financial Reporting Procedures for the Defense Homeowners Assistance Fund

    National Research Council Canada - National Science Library

    1992-01-01

    ...) Financial Statements for FY 1992 (Project No. 2FH-2002). The objective of the audit is to determine whether the Fund's financial statements are presented fairly in accordance with generally -accepted accounting principles...

  12. Clinical and imaging characteristics of foraminal nerve root disorders of the lumbar spine

    International Nuclear Information System (INIS)

    Nishi, Tomio; Tani, Takayuki; Suzuki, Norio; Aonuma, Hiroshi

    2009-01-01

    We analyzed cases of lumbar nerve root compression at intervertebral foramina, by comparing 19 cases of foraminal stenosis (FS), and 38 cases of foraminal hernia (FH) with 21 cases of lumbar canal stenosis (LCS). Japan Orthopedic Association (JOA) scores, intervertebral disc degeneration, anatomical measurements of the nerve root foramina and the MRI findings were reviewed. The scores for pain in the lower extremities, and walking ability were both lowest in the FS group. The scores for low back pain, lower extremities, and sensory disturbances were lowest in the FH group. Anterior-posterior diameters of the nerve root foramina were smaller in the FS group and FH group than in the LCS group. More degenerated discs and short length of upper part of the nerve root foramina were seen in FS group than in the other groups. The MRI images of so-called black out nerve root foramina were positive in 63.6% of FS cases, 75% of FH cases. (author)

  13. Early programming of astrocyte organization in the mouse suprachiasmatic nuclei by light

    Czech Academy of Sciences Publication Activity Database

    Canal, M. M.; Mohammed, N. M.; Rodríguez Arellano, Jose Julio

    2009-01-01

    Roč. 26, č. 8 (2009), s. 1545-1558 ISSN 0742-0528 Institutional research plan: CEZ:AV0Z50390512 Keywords : Development * GFAP * Circadian rhythm Subject RIV: FH - Neurology Impact factor: 3.987, year: 2009

  14. Subdural infusion of dexamethasone inhibits leukomyelitis after acute spinal cord injury in a rat model

    Czech Academy of Sciences Publication Activity Database

    Kwiecien, J. M.; Jarocz, B.; Urdzíková, Lucia; Rola, R.; Dabrowski, W.

    2015-01-01

    Roč. 53, č. 1 (2015), s. 41-51 ISSN 1641-4640 Institutional support: RVO:68378041 Keywords : spinal cord injury * leukomyelitis * macrophage s * subdural infusion * dexamethasone Subject RIV: FH - Neurology Impact factor: 1.233, year: 2015

  15. Dicty_cDB: AFB514 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available TCACTGTTCATCCAAAATTCTTAACAACAAGAAGAAGCGGAACCAAGAACAAGAAGA ACA sequence update 2001. 6. 1 Translated Amino Acid sequence ---atsnnqlmip...skg*ihchrfshc*nq*treristsl rfirsnsreiclyf*fh*tnc*wycrqcfhlkii*cylsl*nhl*rchgyvqenhgkdlv ltvhpkflttrrsgtknkkn Frame B: ---atsnnqlmips

  16. Radiosurgical lesion of the rat hippocampus using the Leksell gamma knife: relation between radiation dose and functional and structural damage

    Czech Academy of Sciences Publication Activity Database

    Liščák, R.; Vladyka, V.; Novotný Jr., J.; Brožek, G.; Náměstková, Kateřina; Mareš, V.; Hájek, M.; Herynek, V.; Syková, Eva

    2002-01-01

    Roč. 97, č. 5 (2002), s. 666-673 ISSN 0022-3085 Institutional research plan: CEZ:AV0Z5039906 Keywords : radiosurgery * Leksell gamma knife Subject RIV: FH - Neurology Impact factor: 2.626, year: 2002

  17. Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index

    Czech Academy of Sciences Publication Activity Database

    Šerý, Omar; Hlinecká, L.; Povová, J.; Bonczek, Ondřej; Zeman, T.; Janout, V.; Ambrož, P.; Khan, N. A.; Balcar, V. J.

    2016-01-01

    Roč. 362, č. 1 (2016), s. 27-32 ISSN 0022-510X Institutional support: RVO:67985904 Keywords : Arachidonic acid * genetics * inflammation * leukotrienes * curcumin Subject RIV: FH - Neurology Impact factor: 2.295, year: 2016

  18. Effect Of Cognitive Stimulation On Hippocampal Ripples In Epileptic Patients

    Czech Academy of Sciences Publication Activity Database

    Brázdil, M.; Cimbálník, J.; Roman, R.; Stead, M.; Daniel, P.; Halámek, Josef; Jurák, Pavel

    2013-01-01

    Roč. 54, S3 (2013), s. 268-268 ISSN 0013-9580. [International Epilepsy Congress /30./. 23.06.2013-27.06.2013, Montreal] Institutional support: RVO:68081731 Keywords : Cognitive Stimulation * Epileptic Patients Subject RIV: FH - Neurology

  19. Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia

    NARCIS (Netherlands)

    de Jongh, Saskia; Lilien, Marc R.; Bakker, Henk D.; Hutten, Barbara A.; Kastelein, John J. P.; Stroes, Erik S. G.

    2002-01-01

    Objectives: in patients with familial hypercholesterolemia (FH), the propensity towards atherosclerosis may vary considerably. In the general population, a positive family history is associated with an increased risk for cardiovascular events. Since endothelial dysfunction is predictive for future

  20. Atherogenic lipoprotein particle size and concentrations and the effect of pravastatin in children with familial hypercholesterolemia

    NARCIS (Netherlands)

    van der Graaf, Anouk; Rodenburg, Jessica; Vissers, Maud N.; Hutten, Barbara A.; Wiegman, Albert; Trip, Mieke D.; Stroes, Erik S. G.; Wijburg, Frits A.; Otvos, James D.; Kastelein, John J. P.

    2008-01-01

    OBJECTIVE: To determine lipoprotein particle concentrations and size in children with familial hypercholesterolemia (FH) and investigate the effect of pravastatin therapy on these measures. STUDY DESIGN: Lipoprotein particle concentrations and sizes were examined by nuclear magnetic resonance (NMR)

  1. The effects of pattern shape, subliminal stimulation, and voluntary control on multistable visual perception

    Czech Academy of Sciences Publication Activity Database

    Taddei-Ferretti, C.; Radilová, Jiřina; Musio, C.; Santillo, S.; Cibelli, E.; Cotugno, A.; Radil, Tomáš

    2008-01-01

    Roč. 1225, - (2008), s. 163-170 ISSN 0006-8993 Institutional research plan: CEZ:AV0Z50110509 Keywords : visual perception * figure reversal Subject RIV: FH - Neurology Impact factor: 2.494, year: 2008

  2. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients

    NARCIS (Netherlands)

    Jansen, A. C. M.; van Aalst-Cohen, E. S.; Tanck, M. W.; Trip, M. D.; Lansberg, P. J.; Liem, A. H.; van Lennep, H. W. O. Roeters; Sijbrands, E. J. G.; Kastelein, J. J. P.

    2004-01-01

    Objective. To determine the contribution of classical risk factors to the development of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolaemia (FH). Design. A retrospective, multi-centre, cohort study. Extensive data were collected by scrutinizing medical records

  3. ARG3.1/ARC expression in hippocampal dentate gyrus astrocytes: ultrastructural evidence and co-localization with glial fibrillary acidic protein

    Czech Academy of Sciences Publication Activity Database

    Rodríguez, J.J.; Davies, H.A.; Errington, M.L.; Verkhratsky, Alexei; Bliss, T.V.P.; Stewart, M.G.

    2008-01-01

    Roč. 12, č. 2 (2008), s. 671-678 ISSN 1582-1838 Institutional research plan: CEZ:AV0Z50390512 Keywords : Hippocampus * Ultrastructure * Glia Subject RIV: FH - Neurology Impact factor: 5.114, year: 2008

  4. ISSN 2073-9990 East Cent. Afr. J. surg

    African Journals Online (AJOL)

    Hp 630 Dual Core

    and short term complications between FH and SH save for bleeding in the short term follow up which ..... suggested that these tags eventually regress in the long run and perhaps patients may be counseled to that effect ... Memorial Hospital.

  5. Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk

    Czech Academy of Sciences Publication Activity Database

    Rambousek, Lukáš; Kačer, P.; Syslová, K.; Bumba, J.; Bubeníková-Valešová, V.; Šlamberová, R.

    2014-01-01

    Roč. 139, JUN (2014), s. 138-144 ISSN 0376-8716 Institutional support: RVO:67985823 Keywords : methamphetamine * amphetamine * pharmacokinetics * sex differences * breast feeding milk * mass spectrometry Subject RIV: FH - Neurology Impact factor: 3.423, year: 2014

  6. Vnitřní časový systém

    Czech Academy of Sciences Publication Activity Database

    Illnerová, Helena; Sumová, Alena

    2011-01-01

    Roč. 8, č. 9 (2011), s. 374-378 ISSN 1214-8687 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian system * biological clock * clock genes * melatonin * circadian disorders Subject RIV: FH - Neurology

  7. African Review of Economics and Finance: Submissions

    African Journals Online (AJOL)

    The African Review of Economics and Finance is a peer-reviewed, scholarly ... financial markets and institutions, asset pricing, forecasting, impact of culture and ... In: Friedman BM, Hahn FH (Eds), Handbook of monetary economics, vol.1.

  8. CD36 gene polymorphism is associated with Alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

    Šerý, Omar; Janoutová, J.; Ewerlingová, Laura; Hálová, Alice; Lochman, J.; Janout, V.; Khan, N. A.; Balcar, Vladimír Josef

    2017-01-01

    Roč. 135, č. 1 (2017), s. 46-53 ISSN 0300-9084 Institutional support: RVO:67985904 Keywords : polymorphism * association * CD36 Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 3.112, year: 2016

  9. Malate and fumarate extend lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Clare B Edwards

    Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

  10. The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells.

    Science.gov (United States)

    Wangpaichitr, Medhi; Sullivan, Elizabeth J; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G; Lampidis, Theodore J; Kuo, Macus T; Savaraj, Niramol

    2012-03-01

    Elimination of cisplatin-resistant lung cancer cells remains a major obstacle. We have shown that cisplatin-resistant tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here, we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1 and contributed to higher ROS in cisplatin-resistant tumors in vivo and in vitro. By reconstituting TRX1 protein in cisplatin-resistant cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. Cisplatin-resistant cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase mRNA, which contributed to oxidative metabolism (OXMET) when compared with parental cells. Restoring intracellular TRX1 protein in cisplatin-resistant cells resulted in lowering ASS and fumarase mRNAs, which in turn sensitized them to arginine deprivation. Interestingly, cisplatin-resistant cells also had significantly higher basal levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Overexpressing TRX1 lowered ACC and FAS proteins expressions in cisplatin-resistant cells. Chemical inhibition and short interfering RNA of ACC resulted in significant cell death in cisplatin-resistant compared with parental cells. Conversely, TRX1 overexpressed cisplatin-resistant cells resisted 5-(tetradecyloxy)-2-furoic acid (TOFA)-induced death. Collectively, lowering TRX1 expression through increased secretion leads cisplatin-resistant cells to higher ROS production and increased dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin-resistant lung cancer.

  11. Endogenous superoxide is a key effector of the oxygen sensitivity of a model obligate anaerobe.

    Science.gov (United States)

    Lu, Zheng; Sethu, Ramakrishnan; Imlay, James A

    2018-04-03

    It has been unclear whether superoxide and/or hydrogen peroxide play important roles in the phenomenon of obligate anaerobiosis. This question was explored using Bacteroides thetaiotaomicron , a major fermentative bacterium in the human gastrointestinal tract. Aeration inactivated two enzyme families-[4Fe-4S] dehydratases and nonredox mononuclear iron enzymes-whose homologs, in contrast, remain active in aerobic Escherichia coli Inactivation-rate measurements of one such enzyme, B. thetaiotaomicron fumarase, showed that it is no more intrinsically sensitive to oxidants than is an E. coli fumarase. Indeed, when the E. coli enzymes were expressed in B. thetaiotaomicron , they no longer could tolerate aeration; conversely, the B. thetaiotaomicron enzymes maintained full activity when expressed in aerobic E. coli Thus, the aerobic inactivation of the B. thetaiotaomicron enzymes is a feature of their intracellular environment rather than of the enzymes themselves. B. thetaiotaomicron possesses superoxide dismutase and peroxidases, and it can repair damaged enzymes. However, measurements confirmed that the rate of reactive oxygen species production inside aerated B. thetaiotaomicron is far higher than in E. coli Analysis of the damaged enzymes recovered from aerated B. thetaiotaomicron suggested that they had been inactivated by superoxide rather than by hydrogen peroxide. Accordingly, overproduction of superoxide dismutase substantially protected the enzymes from aeration. We conclude that when this anaerobe encounters oxygen, its internal superoxide levels rise high enough to inactivate key catabolic and biosynthetic enzymes. Superoxide thus comprises a major element of the oxygen sensitivity of this anaerobe. The extent to which molecular oxygen exerts additional direct effects remains to be determined.

  12. First insight into CD59-like molecules of adult Fasciola hepatica.

    Science.gov (United States)

    Shi, Yunliang; Toet, Hayley; Rathinasamy, Vignesh; Young, Neil D; Gasser, Robin B; Beddoe, Travis; Huang, Weiyi; Spithill, Terry W

    2014-09-01

    The present study focussed on investigating CD59-like molecules of Fasciola hepatica. A cDNA encoding a CD59-like protein (termed FhCD59-1) identified previously in the membrane fraction of the F. hepatica tegument was isolated. This homologue was shown to encode a predicted open reading frame (ORF) of 122 amino acids (aa) orthologous to human CD59 with a 25 aa signal peptide, a mature protein containing 10 cysteines and a conserved CD59/Ly-6 family motif "CCXXXXCN". An analysis of cDNAs from two different adult specimens of F. hepatica revealed seven variable types of FhCD59-1 sequences, designated FhCD59-1.1 to FhCD59-1.7, which had 94.3-99.7% amino acid sequence identity upon pairwise comparison. Molecular modeling of FhCD59-1.1 with human CD59 confirmed the presence of the three-finger protein domain found in the CD59 family and predicted three disulphide bonds in the F. hepatica sequence. The interrogation of F. hepatica databases identified two additional sequences, designated FhCD59-2 and FhCD59-3, which had only 23.4-29.5% amino acid identity to FhCD59-1.1. Orthologues of the inferred CD59 protein sequences of F. hepatica were also identified in other flatworms, including Fasciola gigantica, Fascioloides magna, Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni, Clonorchis sinensis, Opisthorchis viverrini, Taenia solium, Echinococcus granulosus and the free living Schmidtea mediterannea. The results revealed a considerable degree of sequence complexity in the CD59-like sequence families in F. hepatica and flatworms. Phylogenetic analysis of CD59-like aa sequences from F. hepatica and flatworms showed that FhCD59-2 clustered with the known surface-associated protein SmCD59-2 of S. mansoni. Relatively well-supported clades specific to schistosomes, fasciolids and opisthorchiids were identified. The qPCR analysis of gene transcription showed that the relative expression of these 3 FhCD59-like sequences varied by 11-47-fold during fluke

  13. Elevated factor H-related protein 1 and factor H pathogenic variants decrease complement regulation in IgA nephropathy.

    Science.gov (United States)

    Tortajada, Agustín; Gutiérrez, Eduardo; Goicoechea de Jorge, Elena; Anter, Jaouad; Segarra, Alfons; Espinosa, Mario; Blasco, Miquel; Roman, Elena; Marco, Helena; Quintana, Luis F; Gutiérrez, Josué; Pinto, Sheila; Lopez-Trascasa, Margarita; Praga, Manuel; Rodriguez de Córdoba, Santiago

    2017-10-01

    IgA nephropathy (IgAN), a frequent cause of chronic kidney disease worldwide, is characterized by mesangial deposition of galactose-deficient IgA1-containing immune complexes. Complement involvement in IgAN pathogenesis is suggested by the glomerular deposition of complement components and the strong protection from IgAN development conferred by the deletion of the CFHR3 and CFHR1 genes (Δ CFHR3-CFHR1 ). Here we searched for correlations between clinical progression and levels of factor H (FH) and FH-related protein 1 (FHR-1) using well-characterized patient cohorts consisting of 112 patients with IgAN, 46 with non-complement-related autosomal dominant polycystic kidney disease (ADPKD), and 76 control individuals. Patients with either IgAN or ADPKD presented normal FH but abnormally elevated FHR-1 levels and FHR-1/FH ratios compared to control individuals. Highest FHR-1 levels and FHR-1/FH ratios are found in patients with IgAN with disease progression and in patients with ADPKD who have reached chronic kidney disease, suggesting that renal function impairment elevates the FHR-1/FH ratio, which may increase FHR-1/FH competition for activated C3 fragments. Interestingly, Δ CFHR3-CFHR1 homozygotes are protected from IgAN, but not from ADPKD, and we found five IgAN patients with low FH carrying CFH or CFI pathogenic variants. These data support a decreased FH activity in IgAN due to increased FHR-1/FH competition or pathogenic CFH variants. They also suggest that alternative pathway complement activation in patients with IgAN, initially triggered by galactose-deficient IgA1-containing immune complexes, may exacerbate in a vicious circle as renal function deterioration increase FHR-1 levels. Thus, a role of FHR-1 in IgAN pathogenesis is to compete with complement regulation by FH. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. White Matter Hyperintensities on T2-Weighted MRI Images among DNA-Verified Older Familial Hypercholesterolemia Patients

    International Nuclear Information System (INIS)

    Hyttinen, L.; Autti, T.; Soljanlahti, S.; Rauma, S.; Vuorio, A.F.; Strandberg, T.E.

    2009-01-01

    Background: Familial hypercholesterolemia (FH) is a genetic disorder, causing an increased risk of coronary heart disease (CHD) if untreated. Silent brain infarctions and white matter hyperintensities (WMHIs) observed on T2-weighted magnetic resonance images (MRI) are associated with increased risk for stroke and myocardial infarction. Age is a strong predictor of WMHIs. Purpose: To use MRI to assess the presence of clinically silent brain lesions in older FH patients, and to compare the occurrence and size of these lesions in older FH patients with middle-aged FH patients and healthy controls. Material and Methods: A total of 43 older (age = 65 years) FH patients with the same FH North Karelia mutation, living in Finland, were identified. In this comprehensive cohort, 1.5T brain MRI was available for 33 individuals (age 65-84 years, M/F 9/24, mean duration of statin treatment 15.3 years). This group was divided into two age categories: 65-74 years (FHe1 group, n=23) and 75-84 years (FHe2 group, n=10). Infarcts, including lacunas, and WMHIs on T2-weighted images were recorded. Data from brain MRI were compared to those of a group of middle-aged FH patients with CHD (n=19, age 48-64 years) and with middle-aged healthy controls (n=29, age 49-63 years). Results: Only two (6%) of the older FH patients had clinically silent brain infarcts detected by MRI. The amount of large WMHIs (>5 mm in diameter) was similar in the FHe1 group compared with the groups of middle-aged FH patients and healthy controls, even though the FHe1 group was 13 years older. The total amount of WMHIs and the amount of large WMHIs were greatest in the FHe2 group. Conclusion: FH patients aged 65 to 74 years receiving long-term statin treatment (15 years) did not have more WMHIs on brain MRI compared to middle-aged FH patients and healthy controls

  15. Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

    Science.gov (United States)

    de Bortoli, Nicola; Martinucci, Irene; Savarino, Edoardo; Tutuian, Radu; Frazzoni, Marzio; Piaggi, Paolo; Bertani, Lorenzo; Furnari, Manuele; Franchi, Riccardo; Russo, Salvatore; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino

    2015-06-01

    Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for

  16. White Matter Hyperintensities on T2-Weighted MRI Images among DNA-Verified Older Familial Hypercholesterolemia Patients

    Energy Technology Data Exchange (ETDEWEB)

    Hyttinen, L. (Dept. of Internal Medicine, North Karelia Central Hospital, Joensuu (Finland)); Autti, T.; Soljanlahti, S. (Medical Imaging Center, Helsinki Univ. Central Hospital, Helsinki (Finland)); Rauma, S. (Dept. of Radiology, North Karelia Central Hospital, Joensuu (Finland)); Vuorio, A.F. (Dept. of Medicine, Univ. of Helsinki, Helsinki (Finland)); Strandberg, T.E. (Dept. of Health Sciences/Geriatrics, Univ. of Oulu, Oulu (Finland))

    2009-04-15

    Background: Familial hypercholesterolemia (FH) is a genetic disorder, causing an increased risk of coronary heart disease (CHD) if untreated. Silent brain infarctions and white matter hyperintensities (WMHIs) observed on T2-weighted magnetic resonance images (MRI) are associated with increased risk for stroke and myocardial infarction. Age is a strong predictor of WMHIs. Purpose: To use MRI to assess the presence of clinically silent brain lesions in older FH patients, and to compare the occurrence and size of these lesions in older FH patients with middle-aged FH patients and healthy controls. Material and Methods: A total of 43 older (age = 65 years) FH patients with the same FH North Karelia mutation, living in Finland, were identified. In this comprehensive cohort, 1.5T brain MRI was available for 33 individuals (age 65-84 years, M/F 9/24, mean duration of statin treatment 15.3 years). This group was divided into two age categories: 65-74 years (FHe1 group, n=23) and 75-84 years (FHe2 group, n=10). Infarcts, including lacunas, and WMHIs on T2-weighted images were recorded. Data from brain MRI were compared to those of a group of middle-aged FH patients with CHD (n=19, age 48-64 years) and with middle-aged healthy controls (n=29, age 49-63 years). Results: Only two (6%) of the older FH patients had clinically silent brain infarcts detected by MRI. The amount of large WMHIs (>5 mm in diameter) was similar in the FHe1 group compared with the groups of middle-aged FH patients and healthy controls, even though the FHe1 group was 13 years older. The total amount of WMHIs and the amount of large WMHIs were greatest in the FHe2 group. Conclusion: FH patients aged 65 to 74 years receiving long-term statin treatment (15 years) did not have more WMHIs on brain MRI compared to middle-aged FH patients and healthy controls.

  17. The detection of heterozygous familial hypercholesterolemia in Ireland.

    LENUS (Irish Health Repository)

    O'Kane, Maurice J

    2012-05-01

    Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant condition with a population prevalence of 1 in 500, and is associated with significant cardiovascular morbidity and mortality. It may be caused by mutations in the low-density lipoprotein (LDL) receptor, apolipoprotein B100 (Apo B100), or proprotein convertase subtilisin\\/kexin type 9 (PCSK9) genes, with over 1,000 causative mutations described. Statin therapy in HeFH is considered effective and safe. Audit data suggest that approximately 80% of the putative HeFH population remains unidentified and, therefore, there is a need to develop a strategy for the identification of affected individuals so that early lipid-lowering treatment may be offered. There is good evidence showing the effectiveness and acceptability of HeFH screening programs in Europe. The authors describe a protocol for an all island approach to HeFH detection in the Republic of Ireland\\/Northern Ireland. Index cases will be identified by opportunistic screening using the Simon Broome, or Make Early Diagnosis to Prevent Early Death (MedPed) and World Health Organization (WHO) criteria. Patients identified as "definite," "probable," or "possible" HeFH criteria will be offered genetic testing. The authors expect causative mutations to be identified in approximately 80% of patients with "definite" HeFH but in only approximately 20% of patients with "possible" HeFH. Cascade screening will be undertaken in first-degree relatives of the index case using genetic testing (where a causative mutation has been identified), or otherwise using LDL cholesterol concentration. The establishment of a HeFH screening program on an all-island basis will require: expansion of the existing molecular genetics diagnostic services, the establishment of a cohort of nurses\\/genetic counselors, a HeFH database to support cascade testing, the development of a network of lipid clinics (in a primary or secondary care setting), and an educational

  18. The relationship between heart rate and rate of oxygen consumption in Galapagos marine iguanas (Amblyrhynchus cristatus) at two different temperatures.

    Science.gov (United States)

    Butler, Patrick J; Frappell, Peter B; Wang, Tobias; Wikelski, Martin

    2002-07-01

    To enable the use of heart rate (fH) for estimating field metabolic rate (FMR) in free-ranging Galapagos marine iguanas Amblyrhynchus cristatus, we determined the relationships between fH and mass-specific rate of oxygen consumption (sVO2) in seven iguanas before and during exercise on a treadmill and during the post-exercise period. The experiments were conducted at 27 and 35 degrees C, which are the temperatures that represent the lowest and highest average body temperatures of these animals in the field during summer. There were linear and significant relationships between fH and sVO2 at both temperatures (r(2)=0.86 and 0.91 at 27 degrees C and 36 degrees C, respectively). The slopes of the two regression lines did not differ, but there were significant differences in their intercepts. Thus, while heart rate can be used to predict FMR, the effects of temperature on the intercept of the regression must be taken into account when converting fH to sVO2. On the basis of our data, this can be achieved by applying the following formula: sVO2=0.0113fH-0.2983Q(10)((T(b)-27)/10). The increase in sVO2 with elevated body temperature results from an increase in fH, with no significant change in mass-specific oxygen pulse (sO(2) pulse; cardiac stroke volume times the difference in oxygen content between arterial and mixed venous blood). However, during exercise at both temperatures, increases in fH are insufficient to provide all of the additional O(2) required and there are also significant increases in the sO(2) pulses. This creates the situation whereby the same fH at the two temperatures can represent different values of sVO2.

  19. Understanding Forest Health with Remote Sensing -Part I—A Review of Spectral Traits, Processes and Remote-Sensing Characteristics

    Directory of Open Access Journals (Sweden)

    Angela Lausch

    2016-12-01

    Full Text Available Anthropogenic stress and disturbance of forest ecosystems (FES has been increasing at all scales from local to global. In rapidly changing environments, in-situ terrestrial FES monitoring approaches have made tremendous progress but they are intensive and often integrate subjective indicators for forest health (FH. Remote sensing (RS bridges the gaps of these limitations, by monitoring indicators of FH on different spatio-temporal scales, and in a cost-effective, rapid, repetitive and objective manner. In this paper, we provide an overview of the definitions of FH, discussing the drivers, processes, stress and adaptation mechanisms of forest plants, and how we can observe FH with RS. We introduce the concept of spectral traits (ST and spectral trait variations (STV in the context of FH monitoring and discuss the prospects, limitations and constraints. Stress, disturbances and resource limitations can cause changes in FES taxonomic, structural and functional diversity; we provide examples how the ST/STV approach can be used for monitoring these FES characteristics. We show that RS based assessments of FH indicators using the ST/STV approach is a competent, affordable, repetitive and objective technique for monitoring. Even though the possibilities for observing the taxonomic diversity of animal species is limited with RS, the taxonomy of forest tree species can be recorded with RS, even though its accuracy is subject to certain constraints. RS has proved successful for monitoring the impacts from stress on structural and functional diversity. In particular, it has proven to be very suitable for recording the short-term dynamics of stress on FH, which cannot be cost-effectively recorded using in-situ methods. This paper gives an overview of the ST/STV approach, whereas the second paper of this series concentrates on discussing in-situ terrestrial monitoring, in-situ RS approaches and RS sensors and techniques for measuring ST/STV for FH.

  20. Investigating the effect of ascorbate on the Fe(II)-catalyzed transformation of the poorly crystalline iron mineral ferrihydrite.

    Science.gov (United States)

    Xiao, Wei; Jones, Adele M; Collins, Richard N; Waite, T David

    2018-05-09

    The inorganic core of the iron storage protein, ferritin, is recognized as being analogous to the poorly crystalline iron mineral, ferrihydrite (Fh). Fh is also abundant in soils where it is central to the redox cycling of particular soil contaminants and trace elements. In geochemical circles, it is recognized that Fh can undergo Fe(II)-catalyzed transformation to form more crystalline iron minerals, vastly altering the reactivity of the iron oxide and, in some cases, the redox poise of the system. Of relevance to both geochemical and biological systems, we investigate here if the naturally occurring reducing agent, ascorbate, can effect such an Fe(II)-catalyzed transformation of Fh at 25 °C and circumneutral pH. The transformation of ferrihydrite to possible secondary Fe(III) mineralization products was quantified using Fourier transform infrared (FTIR) spectroscopy, with supporting data obtained using X-ray absorbance spectroscopy (XAS) and X-ray diffraction (XRD). Whilst the amount of Fe(II) formed in the presence of ascorbate has resulted in Fh transformation in previous studies, no transformation of Fh to more crystalline Fe(III) (oxyhydr)oxides was observed in this study. Further experiments indicated this was due to the ability of ascorbate to inhibit the formation of goethite, lepidocrocite and magnetite. The manner in which ascorbate associated with Fh was investigated using FTIR and total organic carbon (TOC) analysis. The majority of ascorbate was found to adsorb to the Fh surface under anoxic conditions but, under oxic conditions, ascorbate was initially adsorbed then became incorporated within the Fe(III) (oxyhydr)oxide structure (i.e., co-precipitated) over time. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Prediction of facial height, width, and ratio from thumbprints ridge count and its possible applications

    Directory of Open Access Journals (Sweden)

    Lawan Hassan Adamu

    2017-01-01

    Full Text Available The fingerprints and face recognition are two biometric processes that comprise methods for uniquely recognizing humans based on certain number of intrinsic physical or behavioral traits. The objectives of the study were to predict the facial height (FH, facial width, and ratios from thumbprints ridge count and its possible applications. This was a cross-sectional study. A total of 457 participants were recruited. A fingerprint live scanner was used to capture the plain thumbprint. The facial photograph was captured using a digital camera. Pearson's correlation analysis was used for the relationship between thumbprint ridge density and facial linear dimensions. Step-wise linear multiple regression analysis was used to predict facial distances from thumbprint ridge density. The result showed that in males the right ulnar ridge count correlates negatively with lower facial width (LFW, upper facial width/upper FH (UFW/UFH, lower FH/FH (LFH/FH, and positively with UFH and UFW/LFW. The right and left proximal ridge counts correlate with LFW and UFH, respectively. In males, the right ulnar ridge count predicts LFW, UFW/LFW, UFW/UFH, and LFH/FH. Special upper face height I, LFW, height of lower third of the face, UFW/LFW was predicted by right radial ridge counts. LFH, height of lower third of the face, and LFH/FH were predicted from left ulnar ridge count whereas left proximal ridge count predicted LFW. In females only, the special upper face height I was predicted by right ulnar ridge count. In conclusion, thumbprint ridge counts can be used to predict FH, width, ratios among Hausa population. The possible application of fingerprints in facial characterization for used in human biology, paleodemography, and forensic science was demonstrated.

  2. Thermal and electronic charge transport in bulk nanostructured Zr0.25Hf0.75NiSn composites with full-Heusler inclusions

    International Nuclear Information System (INIS)

    Makongo, Julien P.A.; Misra, Dinesh K.; Salvador, James R.; Takas, Nathan J.; Wang, Guoyu; Shabetai, Michael R.; Pant, Aditya; Paudel, Pravin; Uher, Ctirad; Stokes, Kevin L.; Poudeu, Pierre F.P.

    2011-01-01

    Bulk Zr 0.25 Hf 075 NiSn half-Heusler (HH) nanocomposites containing various mole fractions of full-Heusler (FH) inclusions were prepared by solid state reaction of pre-synthesized HH alloy with elemental Ni at 1073 K. The microstructures of spark plasma sintered specimens of the HH/FH nanocomposites were investigated using transmission electron microscopy and their thermoelectric properties were measured from 300 K to 775 K. The formation of coherent FH inclusions into the HH matrix arises from solid-state Ni diffusion into vacant sites of the HH structure. HH(1-y)/FH(y) composites with mole fraction of FH inclusions below the percolation threshold, y∼0.2, show increased electrical conductivity, reduced Seebeck coefficient and increased total thermal conductivity arising from gradual increase in the carrier concentration for composites. A drastic reduction (∼55%) in κ l was observed for the composite with y=0.6 and is attributed to enhanced phonon scattering due to mass fluctuations between FH and HH, and high density of HH/FH interfaces. - Graphical abstract: Large reduction in the lattice thermal conductivity of bulk nanostructured half-Heusler/full-Heusler (Zr 0.25 Hf 075 NiSn/ Zr 0.25 Hf 075 Ni 2 Sn) composites, obtained by solid-state diffusion at 1073 K of elemental Ni into vacant sites of the half-Heusler structure, arising from the formation of regions of spinodally decomposed HH and FH phases with a spatial composition modulation of ∼2 nm. Highlights: → Bulk composites from solid state transformation of half-Heusler matrix through Ni diffusion. → Formation of coherent phase boundaries between half-Heusler matrix and full-Heusler inclusion. → Alteration of thermal and electronic transports with increasing full-Heusler inclusion. → Enhanced phonon scattering at half-Heusler/ full-Heusler phase boundaries.

  3. Assessment of physicians' awareness and knowledge of familial hypercholesterolemia in Saudi Arabia: Is there a gap?

    Science.gov (United States)

    Batais, Mohammed Ali; Almigbal, Turky H; Bin Abdulhak, Aref A; Altaradi, Hani B; AlHabib, Khalid F

    2017-01-01

    The scarcity of familial hypercholesterolemia (FH) cases reported in Saudi Arabia might be indicative of a lack of awareness of this common genetic disease among physicians. To assess physicians' awareness, practice, and knowledge of FH in Saudi Arabia. This is a cross-sectional study conducted among physicians at four tertiary hospitals in Riyadh, Saudi Arabia between March 2016 and May 2016 using a self-administered questionnaire. A total of 294 physicians completed the survey (response rate 90.1%). Overall, 92.9% of the participants have poor knowledge of FH while only 7.1% have acceptable knowledge. The majority (68.7%) of physicians rated their familiarity with FH as average or above average, and these had higher mean knowledge scores than participants with self-reported below average familiarity (mean 3.4 versus 2.6) (P knowledge scores compared to those without FH patients in their care (3.5 versus 2.9) (P = 0.006). In addition, there were statistically significant differences between physicians' mean knowledge scores and their ages, levels of training, and years in practice. Moreover, a substantial deficit was identified in the awareness of various clinical algorithms to diagnose patients with FH, cascade screening, specialist lipid services, and the existence of statin alternatives, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. A substantial deficit was found in the awareness, knowledge, practice, and detection of FH among physicians in Saudi Arabia. Extensive educational programs are required to raise physician awareness and implement best practices; only then can the impact of these interventions on FH management and patient outcome be assessed.

  4. Test of two heat-pump systems, Fre-Heater Type B and Fre-Heater Type C, made by Mueller. Installations for the cooling of milk and the heating of water on farms. Beproeving van twee warmtepompsystemen, type Fre-Heater, modellen B en C, fabrikaat Mueller. Installaties voor het koelen van melk en het verwarmen van water op de boerderij

    Energy Technology Data Exchange (ETDEWEB)

    Bouman, S; Verheij, C P; de Vries, J

    1980-01-01

    At the request of Meko Holland BV, Assen (the Netherlands), two heat-pump systems, Fre-Heater Type B and Fre-Heater Type C (FH-B and FH-C), were tested for their suitability for the simultaneous cooling of milk and heating of water on farms. The main purpose of the tests was to provide information about the technical properties of the systems, and about the possibilities they offer for the saving of energy. The test was carried out according to the directives laid down in the 'Beproevingsmethoden voor warmtepompsystemen ten behoeve van het verwarmen van water op de boerderij' (Test methods for heat-pump systems for the heating of water on farms), issued by the Netherlands Institute for Dairy Research, 1980. Both systems were compared with a conventional air-cooled refrigerated farm milk tank with a COPR (coefficient of performance of refrigeration) of 2.5. The FH-B was found to have a COPR of 2.25, and the FH-C a COPR of 2.52. The net savings of energy that could be achieved with the FH-B were 16.8 kWh per m3 cooled 'milk', and with the FH-C 17.2 kWh per m3 cooled 'milk'. Based on a pay-back period of five years and a price of electrical energy of Dfl 0.20 per kWh, the FH-B appeared to be economically justified at a farm with 38 cows and the FH-C at a farm with 48 cows (milk production 5.5 m3 per cow per year).

  5. Understanding Forest Health with Remote Sensing-Part II—A Review of Approaches and Data Models

    Directory of Open Access Journals (Sweden)

    Angela Lausch

    2017-02-01

    Full Text Available Stress in forest ecosystems (FES occurs as a result of land-use intensification, disturbances, resource limitations or unsustainable management, causing changes in forest health (FH at various scales from the local to the global scale. Reactions to such stress depend on the phylogeny of forest species or communities and the characteristics of their impacting drivers and processes. There are many approaches to monitor indicators of FH using in-situ forest inventory and experimental studies, but they are generally limited to sample points or small areas, as well as being time- and labour-intensive. Long-term monitoring based on forest inventories provides valuable information about changes and trends of FH. However, abrupt short-term changes cannot sufficiently be assessed through in-situ forest inventories as they usually have repetition periods of multiple years. Furthermore, numerous FH indicators monitored in in-situ surveys are based on expert judgement. Remote sensing (RS technologies offer means to monitor FH indicators in an effective, repetitive and comparative way. This paper reviews techniques that are currently used for monitoring, including close-range RS, airborne and satellite approaches. The implementation of optical, RADAR and LiDAR RS-techniques to assess spectral traits/spectral trait variations (ST/STV is described in detail. We found that ST/STV can be used to record indicators of FH based on RS. Therefore, the ST/STV approach provides a framework to develop a standardized monitoring concept for FH indicators using RS techniques that is applicable to future monitoring programs. It is only through linking in-situ and RS approaches that we will be able to improve our understanding of the relationship between stressors, and the associated spectral responses in order to develop robust FH indicators.

  6. Binding of Cd by ferrihydrite organo-mineral composites: Implications for Cd mobility and fate in natural and contaminated environments.

    Science.gov (United States)

    Du, Huihui; Peacock, Caroline L; Chen, Wenli; Huang, Qiaoyun

    2018-09-01

    Adsorption and coprecipitation of organic matter with iron (hydr)oxides can alter iron (hydr)oxide surface properties and their reactivity towards nutrient elements and heavy metals. Organo-mineral composites were synthesized using humic acid (HA) and iron oxide, during coprecipitation with ferrihydrite (Fh) and adsorption to pre-formed Fh with two C loadings. The Fh-HA coprecipitated composites have a higher C content and smaller surface area compared to the equivalent adsorbed composites. NanoSIMS shows there is a high degree of spatial correlation between Fe and C for both composites, but C distribution is more uniform in the coprecipitated composites. The C 1s NEXAFS reveals a similar C composition between the Fh-HA coprecipitated and adsorbed composites. However composites at high carbon loading are more enriched in aromatic C, likely due to preferential binding of carboxyl functional groups on aromatic rings in the HA. The amount of Cd sorbed is independent of the composite type, either coprecipitated or adsorbed, but is a function of the C loading. Composites with low C loading show Cd sorption that is almost identical to pure Fh, while composites with high C loading show Cd sorption that is intermediate between pure Fh and pure HA, with sorption significantly enhanced over pure Fh at pH < 6.5. A bidentate edge-sharing binding was identified for Cd on pure Fh and Cd-carboxyl binding on pure HA. These findings have significant implications not only for the sequestration of Cd in contaminated environments but also the coupled biogeochemical cycling of Cd, Fe and C in the critical zone. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  7. [Research on etiological aspects of dual pathology].

    Science.gov (United States)

    Barea, Juan; Benito, Ana; Mateu, César; Martín, Eva; López, Nuria; Haro, Gonzalo

    2010-01-01

    It is important to assess the interaction between family psychopathologic history (FH), family dynamics (FD), behavior disorders, substance-use disorders and personality disorders (PD). Cross-sectional design. The sample was made up of 350 subjects with substance-use disorders who were assessed for FH including alcoholism and substance-use disorders through an interview; for substance use via a questionnaire; for FD; for PD using the International Personality Disorder Examination (IPDE); for behavior problems in adolescence; and for disocial disorder. Correlated variables were included in logistic regression models. Early age of onset for substance use is related to FH of substance use disorders and poorer FD. FH of alcoholism, substance-use disorders and psychiatric disorders are related to poorer FD. Early age of onset for substance use, FH and a disruptive FD are related to behavior problems and disocial disorder. Early age of onset for substance use, FH, disruptive FD, behavior problems and disocial disorder are related to presence of PD. Logistic regression predicted the presence of PD by age of onset for use of methadone (CI(95):1.005/3.222; p=0.048) and of other opiates (CI(95):0.864/0.992;p=0.028). FH score in alcoholism predicted Borderline Personality Disorder (CI(95):1.137- 2.942; p=0.013), and age of onset of cocaine use predicted Antisocial Personality Disorder (CI(95):0.864/0.992; p=0.028). FH of substance use and own use predict the presence of some PDs.

  8. Autofluorescence imaging endoscopy can distinguish non-erosive reflux disease from functional heartburn: A pilot study.

    Science.gov (United States)

    Luo, Xi; Guo, Xiao-Xu; Wang, Wei-Feng; Peng, Li-Hua; Yang, Yun-Sheng; Uedo, Noriya

    2016-04-14

    To investigate whether autofluorescence imaging (AFI) endoscopy can distinguish non-erosive reflux disease (NERD) from functional heartburn (FH). In this prospective observational trial, 127 patients presenting with typical reflux symptoms for > 6 mo were screened. All the participants underwent endoscopy, during which white light imaging (WLI) was followed by AFI. Finally 84 patients with normal esophageal appearance on WLI were enrolled. It was defined as being suggestive of NERD if one or more longitudinal purple lines longer than one centimeter were visualized in the distal part of the esophagus during AFI endoscopy. Ambulatory 24-h multichannel intraluminal impedance and pH monitoring was also performed. After standard proton-pump inhibitor (PPI) tests, subjects were divided into an NERD group and an FH group and the diagnostic performance of AFI endoscopy to differentiate NERD from FH was evaluated. Of 84 endoscopy-negative patients, 36 (42.9%) had a normal pH/impedance test. Of these, 26 patients with favorable responses to PPI tests were classified as having NERD. Finally 10 patients were diagnosed with FH and the others with NERD. Altogether, 68 (81.0%) of the 84 patients were positive on AFI endoscopy. In the NERD group, there were 67 (90.5%) patients with abnormal esophageal findings on AFI endoscopy while only 1 (10%) patient was positive on AFI endoscopy in the FH group. The sensitivity and specificity of AFI in differentiating NERD from FH were 90.5% (95%CI: 81.5%-96.1%) and 90.0% (95%CI: 55.5%-99.7%), respectively. Meanwhile, the accuracy, positive predictive value and negative predictive value of AFI in differentiating between NERD and FH were 90.5% (95%CI: 84.2%-96.8%), 98.5% (95%CI: 92.1%-99.9%) and 56.3% (95%CI: 30.0%-80.2%), respectively. Autofluorescence imaging may serve as a complementary method in evaluating patients with NERD and FH.

  9. Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

    Science.gov (United States)

    Kandulski, A; Jechorek, D; Caro, C; Weigt, J; Wex, T; Mönkemüller, K; Malfertheiner, P

    2013-09-01

    Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH. © 2013 John Wiley & Sons Ltd.

  10. Model cerebrálních vazospasmů a metabolomické mapování

    Czech Academy of Sciences Publication Activity Database

    Hejčl, Aleš; Vondráková, Kateřina; Kelbich, P.; Sameš, M.; Tsenov, Grygoriy; Kačer, P.

    2017-01-01

    Roč. 111, č. 1 (2017), s. 56-61 ISSN 0009-2770 R&D Projects: GA ČR(CZ) GA14-20613S Institutional support: RVO:67985823 ; RVO:68378041 Keywords : cerebral vasospasm * microdialysis * endothelin-1 * HPLC * MS Subject RIV: FH - Neurology; FH - Neurology (UEM-P) OBOR OECD: Neuroscience s (including psychophysiology; Clinical neurology (UEM-P) Impact factor: 0.387, year: 2016

  11. Analysis of Multiple B-Value Diffusion-Weighted Imaging in Pediatric Acute Encephalopathy

    Science.gov (United States)

    Tachibana, Yasuhiko; Aida, Noriko; Niwa, Tetsu; Nozawa, Kumiko; Kusagiri, Kouki; Mori, Kana; Endo, Kazuo; Obata, Takayuki; Inoue, Tomio

    2013-01-01

    Acute encephalopathy is a disease group more commonly seen in children. It is often severe and has neurological sequelae. Imaging is important for early diagnosis and prompt treatment to ameliorate an unfavorable outcome, but insufficient sensitivity/specificity is a problem. To overcome this, a new value (fraction of high b-pair (FH)) that could be processed from clinically acceptable MR diffusion-weighted imaging (DWI) with three different b-values was designed on the basis of a two-compartment model of water diffusion signal attenuation. The purpose of this study is to compare FH with the apparent diffusion coefficient (ADC) regarding the detectability of pediatric acute encephalopathy. We retrospectively compared the clinical DWI of 15 children (1–10 years old, mean 2.34, 8 boys, 7 girls) of acute encephalopathy with another 16 children (1–11 years old, mean 4.89, 9 boys, 7 girls) as control. A comparison was first made visually by mapping FH on the brain images, and then a second comparison was made on the basis of 10 regions of interest (ROIs) set on cortical and subcortical areas of each child. FH map visually revealed diffusely elevated FH in cortical and subcortical areas of the patients with acute encephalopathy; the changes seemed more diffuse in FH compared to DWI. The comparison based on ROI revealed elevated mean FH in the cortical and subcortical areas of the acute encephalopathy patients compared to control with significant difference (Pencephalopathy may be superior in FH compared to ADC. PMID:23755112

  12. Familial hypercholesterolaemia reduces the quality of life of patients not reaching treatment targets

    DEFF Research Database (Denmark)

    Mortensen, Gitte Lee; Madsen, Ivan Bredbjerg; Kruse, Charlotte

    2016-01-01

    are only met in approximately 50% of patients. This comparative study examined the quality of life (QoL) impact of FH in patients who had and had not reached the target of treatment. METHODS: Two qualitative focus group interviews were carried out with a total of ten FH patients. A semi...... of treatment. FUNDING: The study was funded by a research grant from Amgen. TRIAL REGISTRATION: not relevant....

  13. Development of Two Antibody Detection Enzyme-Linked Immunosorbent Assays for Serodiagnosis of Human Chronic Fascioliasis

    Science.gov (United States)

    Cabán-Hernández, Kimberly; Gaudier, José F.; Ruiz-Jiménez, Caleb

    2014-01-01

    Coprological examination based on egg detection in stool samples is currently used as the gold standard for the diagnosis of human fascioliasis. However, this method is not effective during the acute phase of the disease and has poor sensitivity during the chronic phase. Serodiagnosis has become an excellent alternative to coprological examination in efforts to combat the effects of fascioliasis on human and animal health. Two novel recombinant Fasciola hepatica proteins, i.e., a ferritin (FhFtn-1) and a tegument-associated protein (FhTP16.5), were used as antigens to develop in-house enzyme-linked immunosorbent assay (ELISA) methods. The assays were optimized and validated using 152 serum samples from humans with a known infection status, including healthy subjects, patients with chronic fascioliasis, and patients with other parasitic diseases. The FhFtn-1 ELISA was shown to be 96.6% sensitive and 95.7% specific; the respective parameters for the FhTP16.5 ELISA were 91.4% and 92.4%. The performances of the FhFtn-1 and FhTP16.5 ELISAs were compared with that of an available commercial test (the DRG test) using a subset of serum samples. Our in-house tests were slightly more sensitive than the DRG test in detecting antibodies against F. hepatica, but the differences were not statistically significant. In conclusion, the present study provides evidence for the potential of the FhFtn-1 and FhTP16.5 ELISAs as diagnostic tools for human fascioliasis, as might be implemented in conjunction with standard assays for large-scale screenings in areas where the disease is endemic and for the detection of occasional cases in clinical laboratories. PMID:24353000

  14. Development of two antibody detection enzyme-linked immunosorbent assays for serodiagnosis of human chronic fascioliasis.

    Science.gov (United States)

    Cabán-Hernández, Kimberly; Gaudier, José F; Ruiz-Jiménez, Caleb; Espino, Ana M

    2014-03-01

    Coprological examination based on egg detection in stool samples is currently used as the gold standard for the diagnosis of human fascioliasis. However, this method is not effective during the acute phase of the disease and has poor sensitivity during the chronic phase. Serodiagnosis has become an excellent alternative to coprological examination in efforts to combat the effects of fascioliasis on human and animal health. Two novel recombinant Fasciola hepatica proteins, i.e., a ferritin (FhFtn-1) and a tegument-associated protein (FhTP16.5), were used as antigens to develop in-house enzyme-linked immunosorbent assay (ELISA) methods. The assays were optimized and validated using 152 serum samples from humans with a known infection status, including healthy subjects, patients with chronic fascioliasis, and patients with other parasitic diseases. The FhFtn-1 ELISA was shown to be 96.6% sensitive and 95.7% specific; the respective parameters for the FhTP16.5 ELISA were 91.4% and 92.4%. The performances of the FhFtn-1 and FhTP16.5 ELISAs were compared with that of an available commercial test (the DRG test) using a subset of serum samples. Our in-house tests were slightly more sensitive than the DRG test in detecting antibodies against F. hepatica, but the differences were not statistically significant. In conclusion, the present study provides evidence for the potential of the FhFtn-1 and FhTP16.5 ELISAs as diagnostic tools for human fascioliasis, as might be implemented in conjunction with standard assays for large-scale screenings in areas where the disease is endemic and for the detection of occasional cases in clinical laboratories.

  15. Reviewing reactor engineering and fuel handling

    International Nuclear Information System (INIS)

    1991-12-01

    Experience has shown that the better operating nuclear power plants have well defined and effectively administered policies and procedures for governing reactor engineering and fuel handling (RE and FH) activities. This document provides supplementary guidance to OSART experts for evaluating the RE and FH programmes and activities at a nuclear power plant and assessing their effectiveness and adequacy. It is in no way intended to conflict with existing regulations and rules, but rather to exemplify those characteristics and features that are desirable for an effective, well structured RE and FH programme. This supplementary guidance addresses those aspects of RE and FH activities that are required in order to ensure optimum core operation for a nuclear reactor without compromising the limits imposed by the design, safety considerations of the nuclear fuel. In the context of this document, reactor engineering refers to those activities associated with in-core fuel and reactivity management, whereas fuel handling refers to the movement, storage, control and accountability of unirradiated and irradiated fuel. The document comprises five main sections and several appendices. In Section 2 of this guide, the essential aspects of an effective RE and FH programme are discussed. In Section 3, the various types of documents and reference materials needed for the preparatory work and investigation are listed. In Section 4, specific guidelines for investigation of RE and FH programmes are presented. In Section 5, the essential attributes of an excellent RE and FH programme are listed. The supplementary guidance is concluded with a series of appendices exemplifying the various qualities and attributes of a sound, well defined RE and FH programme

  16. AcEST: BP916672 [AcEST

    Lifescience Database Archive (English)

    Full Text Available A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy ... 45 0.003 tr|B7FH62|B7FH62_MEDTR Putative unchar...GEAIEFINNAGFPHNIVFDEDEVPAGVDADAIS 98 >tr|Q4R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy PE=4 S

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    Lifescience Database Archive (English)

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  18. Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Soufi Muhidien

    2008-11-01

    Full Text Available Abstract Background Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH with those from healthy individuals. Methods Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p Results Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Conclusion Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

  19. Building bridges: formin1 of Arabidopsis forms a connection between the cell wall and the actin cytoskeleton.

    Science.gov (United States)

    Martinière, Alexandre; Gayral, Philippe; Hawes, Chris; Runions, John

    2011-04-01

    Actin microfilament (MF) organization and remodelling is critical to cell function. The formin family of actin binding proteins are involved in nucleating MFs in Arabidopsis thaliana. They all contain formin homology domains in the intracellular, C-terminal half of the protein that interacts with MFs. Formins in class I are usually targeted to the plasma membrane and this is true of Formin1 (AtFH1) of A. thaliana. In this study, we have investigated the extracellular domain of AtFH1 and we demonstrate that AtFH1 forms a bridge from the actin cytoskeleton, across the plasma membrane and is anchored within the cell wall. AtFH1 has a large, extracellular domain that is maintained by purifying selection and that contains four conserved regions, one of which is responsible for immobilising the protein. Protein anchoring within the cell wall is reduced in constructs that express truncations of the extracellular domain and in experiments in protoplasts without primary cell walls. The 18 amino acid proline-rich extracellular domain that is responsible for AtFH1 anchoring has homology with cell-wall extensins. We also have shown that anchoring of AtFH1 in the cell wall promotes actin bundling within the cell and that overexpression of AtFH1 has an inhibitory effect on organelle actin-dependant dynamics. Thus, the AtFH1 bridge provides stable anchor points for the actin cytoskeleton and is probably a crucial component of the signalling response and actin-remodelling mechanisms. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  20. Predicting Self-Management Behaviors in Familial Hypercholesterolemia Using an Integrated Theoretical Model: the Impact of Beliefs About Illnesses and Beliefs About Behaviors.

    Science.gov (United States)

    Hagger, Martin S; Hardcastle, Sarah J; Hingley, Catherine; Strickland, Ella; Pang, Jing; Watts, Gerald F

    2016-06-01

    Patients with familial hypercholesterolemia (FH) are at markedly increased risk of coronary artery disease. Regular participation in three self-management behaviors, physical activity, healthy eating, and adherence to medication, can significantly reduce this risk in FH patients. We aimed to predict intentions to engage in these self-management behaviors in FH patients using a multi-theory, integrated model that makes the distinction between beliefs about illness and beliefs about self-management behaviors. Using a cross-sectional, correlational design, patients (N = 110) diagnosed with FH from a clinic in Perth, Western Australia, self-completed a questionnaire that measured constructs from three health behavior theories: the common sense model of illness representations (serious consequences, timeline, personal control, treatment control, illness coherence, emotional representations); theory of planned behavior (attitudes, subjective norms, perceived behavioral control); and social cognitive theory (self-efficacy). Structural equation models for each self-management behavior revealed consistent and statistically significant effects of attitudes on intentions across the three behaviors. Subjective norms predicted intentions for health eating only and self-efficacy predicted intentions for physical activity only. There were no effects for the perceived behavioral control and common sense model constructs in any model. Attitudes feature prominently in determining intentions to engage in self-management behaviors in FH patients. The prominence of these attitudinal beliefs about self-management behaviors, as opposed to illness beliefs, suggest that addressing these beliefs may be a priority in the management of FH.

  1. Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemia[S

    Science.gov (United States)

    Medeiros, Ana Margarida; Alves, Ana Catarina; Aguiar, Pedro; Bourbon, Mafalda

    2014-01-01

    The distinction between a monogenic dyslipidemia and a polygenic/environmental dyslipidemia is important for the cardiovascular risk assessment, counseling, and treatment of these patients. The present work aims to perform the cardiovascular risk assessment of dyslipidemic children to identify useful biomarkers for clinical criteria improvement in clinical settings. Main cardiovascular risk factors were analyzed in a cohort of 237 unrelated children with clinical diagnosis of familial hypercholesterolemia (FH). About 40% carried at least two cardiovascular risk factors and 37.6% had FH, presenting mutations in LDLR and APOB. FH children showed significant elevated atherogenic markers and lower concentration of antiatherogenic particles. Children without a molecular diagnosis of FH had higher levels of TGs, apoC2, apoC3, and higher frequency of BMI and overweight/obesity, suggesting that environmental factors can be the underlying cause of their hypercholesterolem≥ia. An apoB/apoA1 ratio ≥0.68 was identified as the best biomarker (area under the curve = 0.835) to differentiate FH from other dyslipidemias. The inclusion in clinical criteria of a higher cut-off point for LDL cholesterol or an apoB/apoA1 ratio ≥0.68 optimized the criteria sensitivity and specificity. The correct identification, at an early age, of all children at-risk is of great importance so that specific interventions can be implemented. apoB/apoA1 can improve the identification of FH patients. PMID:24627126

  2. Behavioral and physiological significance of minimum resting metabolic rate in king penguins.

    Science.gov (United States)

    Halsey, L G; Butler, P J; Fahlman, A; Woakes, A J; Handrich, Y

    2008-01-01

    Because fasting king penguins (Aptenodytes patagonicus) need to conserve energy, it is possible that they exhibit particularly low metabolic rates during periods of rest. We investigated the behavioral and physiological aspects of periods of minimum metabolic rate in king penguins under different circumstances. Heart rate (f(H)) measurements were recorded to estimate rate of oxygen consumption during periods of rest. Furthermore, apparent respiratory sinus arrhythmia (RSA) was calculated from the f(H) data to determine probable breathing frequency in resting penguins. The most pertinent results were that minimum f(H) achieved (over 5 min) was higher during respirometry experiments in air than during periods ashore in the field; that minimum f(H) during respirometry experiments on water was similar to that while at sea; and that RSA was apparent in many of the f(H) traces during periods of minimum f(H) and provides accurate estimates of breathing rates of king penguins resting in specific situations in the field. Inferences made from the results include that king penguins do not have the capacity to reduce their metabolism to a particularly low level on land; that they can, however, achieve surprisingly low metabolic rates at sea while resting in cold water; and that during respirometry experiments king penguins are stressed to some degree, exhibiting an elevated metabolism even when resting.

  3. Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

    International Nuclear Information System (INIS)

    Pereira, Carolina; Miname, Marcio; Makdisse, Marcia; Kalil, Roberto Filho; Santos, Raul D.

    2014-01-01

    Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients

  4. Radiation effects on the fluoxetine hydrochloride toxicity in the presence of domestic sewage

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Vanessa H. Ogihara; Borrely, Sueli I., E-mail: vanessa.ogihara@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Campos, Fabio; Piveli, Roque P. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Escola Politecnica. Centro Tecnologico de Hidraulica

    2013-07-01

    The sanitation field is directly related to environmental quality and health. The improvements in wastewater treatment systems provide benefits to the environment and their population. It is clearly understood that the conventional wastewater treatment does not remove many micropollutants, including some medicinal products, and that these products can be toxic to living organisms. The goal of this research was the assessment of toxicity of fluoxetine hydrochloride (FH) as well as the irradiation application to remove FH from waters. The FH was irradiated in water solutions and also contained in domestic sewage. Both types of samples were irradiated at a Dynamitron® Electron Beam Accelerator (EBA). The Vibrio fischeri bacteria was applied as biological assay to the samples (water solution of FH; untreated sewage and the mixture of untreated sewage + FH). The efficiency was 1.44% to 26.21% less toxic after treatments. UV-Vis Spectrometry showed the degradation of FH by radiation. 2.5 kGy was a suitable dose that could be suggested for environmental application of Electron Beam Technology. (author)

  5. Two Years after Molecular Diagnosis of Familial Hypercholesterolemia: Majority on Cholesterol-Lowering Treatment but a Minority Reaches Treatment Goal

    Science.gov (United States)

    Huijgen, Roeland; Kindt, Iris; Verhoeven, Sjoerd B. J.; Sijbrands, Eric J. G.; Vissers, Maud N.; Kastelein, John J. P.; Hutten, Barbara A.

    2010-01-01

    Background The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed. Methodology/Principal Findings In 2008, we sent questionnaires to all subjects (aged 18–65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L. Conclusions/Significance The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through genetic cascade screening. The attained LDL-C levels were lower than those reported in previous surveys on medication use in FH, which could reflect the effect of more stringent lipid target levels. However, only a minority of the medication users reached the LDL-C target. PMID:20169164

  6. Detecting familial hypercholesterolemia by serum lipid profile screening in a hospital setting: Clinical, genetic and atherosclerotic burden profile.

    Science.gov (United States)

    Scicali, R; Di Pino, A; Platania, R; Purrazzo, G; Ferrara, V; Giannone, A; Urbano, F; Filippello, A; Rapisarda, V; Farruggia, E; Piro, S; Rabuazzo, A M; Purrello, F

    2018-01-01

    Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT). We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides 160 mg/dL and triglycerides 8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61-0.83] vs 0.71 [0.60-0.75] mm, p 190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively). A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  7. Functional Heartburn Overlaps With Irritable Bowel Syndrome More Often than GERD.

    Science.gov (United States)

    de Bortoli, Nicola; Frazzoni, Leonardo; Savarino, Edoardo V; Frazzoni, Marzio; Martinucci, Irene; Jania, Aleksandra; Tolone, Salvatore; Scagliarini, Michele; Bellini, Massimo; Marabotto, Elisa; Furnari, Manuele; Bodini, Giorgia; Russo, Salvatore; Bertani, Lorenzo; Natali, Veronica; Fuccio, Lorenzo; Savarino, Vincenzo; Blandizzi, Corrado; Marchi, Santino

    2016-12-01

    We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn. Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH. Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (Pheartburn (GERD+HE). IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.

  8. Radiation effects on the fluoxetine hydrochloride toxicity in the presence of domestic sewage

    International Nuclear Information System (INIS)

    Silva, Vanessa H. Ogihara; Borrely, Sueli I.; Campos, Fabio; Piveli, Roque P.

    2013-01-01

    The sanitation field is directly related to environmental quality and health. The improvements in wastewater treatment systems provide benefits to the environment and their population. It is clearly understood that the conventional wastewater treatment does not remove many micropollutants, including some medicinal products, and that these products can be toxic to living organisms. The goal of this research was the assessment of toxicity of fluoxetine hydrochloride (FH) as well as the irradiation application to remove FH from waters. The FH was irradiated in water solutions and also contained in domestic sewage. Both types of samples were irradiated at a Dynamitron® Electron Beam Accelerator (EBA). The Vibrio fischeri bacteria was applied as biological assay to the samples (water solution of FH; untreated sewage and the mixture of untreated sewage + FH). The efficiency was 1.44% to 26.21% less toxic after treatments. UV-Vis Spectrometry showed the degradation of FH by radiation. 2.5 kGy was a suitable dose that could be suggested for environmental application of Electron Beam Technology. (author)

  9. Family history of hypertension and left ventricular mass in youth: possible mediating parameters.

    Science.gov (United States)

    Cook, B B; Treiber, F A; Mensah, G; Jindal, M; Davis, H C; Kapuku, G K

    2001-04-01

    Whether positive family history (FH) of essential hypertension (EH) in normotensive youth is associated with increased left ventricular mass (LVM) and hemodynamic, anthropometric, and demographic parameters previously associated with increased LVM in adults is unknown. To examine these issues, 323 healthy youth (mean age, 13.6 +/- 1.3 years), 194 with positive FH of EH (61% African Americans, 39% whites) and 129 with negative FH of EH (33% African Americans, 67% whites) were evaluated. Hemodynamics were measured at rest and during four stressors (ie, postural change, car driving simulation, video game, forehead cold). Echocardiographic-derived measures of LVM were indexed separately to body surface area and height(2.7). Controlling for age and race differences (ie, 74% of African Americans v 47% of whites had positive FH), the positive FH group exhibited greater LVM/height(2.7), LVM/body surface area, higher systolic (SBP) and diastolic blood pressures (DBP), and total peripheral resistance index (TPRI) and lower cardiac index at rest (P men), general adiposity, resting cardiac index and blood pressure (BP), and TPRI responsivity to video game and cold stimulation (P < .05 for all). Thus, greater LVM index in positive FH of EH youth appears in part related to their greater BP and TPRI at rest and during stress.

  10. Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Carolina Pereira

    2014-08-01

    Full Text Available Background: Familial hypercholesterolemia (FH is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c. Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD. Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD, such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI values ≤ 0.90. This study assessed 202 patients (35% of men with heterozygous FH (90.6% with LDL receptor mutations, mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049. Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

  11. Common Patterns of Congenital Lower Extremity Shortening: Diagnosis, Classification, and Follow-up.

    Science.gov (United States)

    Bedoya, Maria A; Chauvin, Nancy A; Jaramillo, Diego; Davidson, Richard; Horn, B David; Ho-Fung, Victor

    2015-01-01

    Congenital lower limb shortening is a group of relatively rare, heterogeneous disorders. Proximal focal femoral deficiency (PFFD) and fibular hemimelia (FH) are the most common pathologic entities in this disease spectrum. PFFD is characterized by variable degrees of shortening or absence of the femoral head, with associated dysplasia of the acetabulum and femoral shaft. FH ranges from mild hypoplasia to complete absence of the fibula with variable shortening of the tibia. The development of the lower limb requires complex and precise gene interactions. Although the etiologies of PFFD and FH remain unknown, there is a strong association between the two disorders. Associated congenital defects in the lower extremity are found in more than 50% of patients with PFFD, ipsilateral FH being the most common. FH also has a strong association with shortening and bowing of the tibia and with foot deformities such as absence of the lateral rays of the foot. Early diagnosis and radiologic classification of these abnormalities are imperative for appropriate management and surgical planning. Plain radiography remains the main diagnostic imaging modality for both PFFD and FH, and appropriate description of the osseous abnormalities seen on radiographs allows accurate classification, prognostic evaluation, and surgical planning. Minor malformations may commonly be misdiagnosed. ©RSNA, 2015.

  12. Preparation and dielectric properties of novel composites based on oxidized styrene-butadienestyrene copolymer and polyaniline modified exfoliated graphite nanoplates

    Science.gov (United States)

    Lv, Qun-Chen; Li, Ying; Zhong, Zhi-Kui; Wu, Hui-Jun; He, Fu-An; Lam, Kwok-Ho

    2018-05-01

    To improve the dielectric performance of high-dielectric-constant conductive filler/polymer composites, polyaniline was deposited on exfoliated graphite nanoplates (xGNPs) by in-situ polymerization method to form polyaniline (PANI) coated xGNPs (xGNPs@PANI) as the conductive filler for the oxidized styrene-butadienestyrene copolymer (SBS-FH) containing both hydroxyl and formyloxy groups. The results of TEM, SEM, FTIR, TGA, Raman spectrum, XPS, and WAXD showed that PANI had been coated onto the surface of xGNPs successfully. The xGNPs@PANI/SBS-FH composites were prepared by a simple solution-blending method and the homogenous distribution of xGNPs@PANI in the SBS-FH matrix was confirmed by SEM. The presence of xGNPs@PANI was found to significantly improve the dielectric properties of resultant composite compared to the unmodified xGNPs. For example, the xGNPs@PANI/SBS-FH composite near percolation threshold filled with 9.38 vol.% xGNPs@PANI showed a dielectric constant of 56.8 and a dielectric loss factor of 0.51 at 1000 Hz, while the corresponding values of xGNPs (1.19 vol.%)/SBS composite were 15.96 and 2.91 at 1000 Hz, respectively. In addition, the incorporation of xGNPs@PANI into SBS-FH could effectively enhance the thermal conductivity of resultant xGNPs@PANI/SBS-FH composite.

  13. Risk factors for alcoholism in the Oklahoma Family Health Patterns project: impact of early life adversity and family history on affect regulation and personality.

    Science.gov (United States)

    Sorocco, Kristen H; Carnes, Nathan C; Cohoon, Andrew J; Vincent, Andrea S; Lovallo, William R

    2015-05-01

    This study examined the impact of early lifetime adversity (ELA) on affect regulation and personality in persons with family history (FH+) and without (FH-) a family history of alcoholism. We examined the impact of early life adversity in healthy young adults, 18-30 years of age enrolled in a long-term study on risk for alcohol and other substance abuse. ELA was assessed by a composite score of low socioeconomic status and personal experience of physical or sexual abuse and/or separation from parents before age 16, resulting in a score of 0, 1-2, or >3 adverse events. Unstable affect regulation and personality variables were obtained via self-report measures. Higher ELA scores were seen in FH+ (χ(2)=109.2, paffect regulation, negative moods, and have risky drinking and drug abuse tendencies independent of ELA level. ELA predicts reduced stress reactivity and poorer cognitive control over impulsive behaviors as shown elsewhere. The present work shows that FH+ have poor mood regulation and antisocial characteristics. The greater prevalence of ELA in FH+ persons indicates that life experience and FH+ work in tandem to result in risky patterns of alcohol and drug experimentation to elevate risk for alcoholism. Further studies of genetic and environmental contributions to alcoholism are called for. Published by Elsevier Ireland Ltd.

  14. Automatic classification of 6-month-old infants at familial risk for language-based learning disorder using a support vector machine.

    Science.gov (United States)

    Zare, Marzieh; Rezvani, Zahra; Benasich, April A

    2016-07-01

    This study assesses the ability of a novel, "automatic classification" approach to facilitate identification of infants at highest familial risk for language-learning disorders (LLD) and to provide converging assessments to enable earlier detection of developmental disorders that disrupt language acquisition. Network connectivity measures derived from 62-channel electroencephalogram (EEG) recording were used to identify selected features within two infant groups who differed on LLD risk: infants with a family history of LLD (FH+) and typically-developing infants without such a history (FH-). A support vector machine was deployed; global efficiency and global and local clustering coefficients were computed. A novel minimum spanning tree (MST) approach was also applied. Cross-validation was employed to assess the resultant classification. Infants were classified with about 80% accuracy into FH+ and FH- groups with 89% specificity and precision of 92%. Clustering patterns differed by risk group and MST network analysis suggests that FH+ infants' EEG complexity patterns were significantly different from FH- infants. The automatic classification techniques used here were shown to be both robust and reliable and should provide valuable information when applied to early identification of risk or clinical groups. The ability to identify infants at highest risk for LLD using "automatic classification" strategies is a novel convergent approach that may facilitate earlier diagnosis and remediation. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Carolina [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Miname, Marcio [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Makdisse, Marcia [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Kalil, Roberto Filho [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Santos, Raul D., E-mail: rdsf@cardiol.br [Instituto do Coração HCFMUSP, São Paulo, SP (Brazil); Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2014-08-15

    Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

  16. Rapid onset pressor response to exercise in young women with a family history of hypertension.

    Science.gov (United States)

    Matthews, Evan L; Greaney, Jody L; Wenner, Megan M

    2017-09-01

    What is the central question of this study? Alterations in blood pressure control at exercise onset are apparent in older adults with established cardiovascular disease. It is currently not known whether these alterations are evident in young adults with a family history of hypertension. What is the main finding and its importance? We demonstrate that young women with a family history of hypertension display a larger change in blood pressure within the first 10 s of isometric exercise. These data suggest altered blood pressure control in young women with a family history of hypertension. Hypertensive adults demonstrate atypical increases in blood pressure (BP) and muscle sympathetic nerve activity (MSNA) at the immediate onset of static muscle contraction. However, it is unknown whether these abnormal responses occur in young, otherwise healthy adults at risk for developing future disease, such as those with a family history of hypertension (+FH). We tested the hypothesis that +FH young women have exaggerated increases in BP and MSNA at the onset of static muscle contraction compared with those without a family history of hypertension (-FH). We retrospectively examined beat-by-beat BP and MSNA during the initial 30 s of isometric handgrip exercise (30% of maximal voluntary contraction) in 16 +FH (22 ± 2 years old, 22 ± 3 kg m -2 ) and 16 -FH (22 ± 3 years old, 22 ± 3 kg m -2 ) women. Resting mean arterial pressure (+FH 80 ± 11 mmHg versus -FH 84 ± 13 mmHg), MSNA burst frequency (+FH 7 ± 3 bursts min -1 versus -FH 9 ± 5 bursts min -1 ) and burst incidence [+FH 12 ± 4 bursts (100 heart beats) -1 versus -FH 12 ± 8 bursts (100 heart beats) -1 ] were similar between groups (all P > 0.05). Within the first 10 s of exercise, changes in mean arterial pressure (+FH Δ8 ± 6 mmHg versus -FH Δ3 ± 2 mmHg, P exercise was not different between groups (-FH 7 ± 5 bursts min -1 versus +FH 9 ± 3 bursts min -1

  17. A Trematode Parasite Derived Growth Factor Binds and Exerts Influences on Host Immune Functions via Host Cytokine Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Azad A Sulaiman

    2016-11-01

    Full Text Available The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally. Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived. We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite. Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion. FhTLM can bind to receptor members of the Transforming Growth Factor (TGF superfamily, with a greater affinity for TGF-β RII. Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages. The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity. In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM. When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype. They express high levels interleukin (IL-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide. Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor. Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1. Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs in their evasion of antibody-dependent cell cytotoxicity (ADCC by reducing the NO response of macrophages-again dependent on TGF-β RI kinase. FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages. The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration. Furthermore, the adoption of a regulatory macrophage phenotype would allow

  18. Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-year Results of the Newborn Eye Screen Test (NEST) Study

    Science.gov (United States)

    Callaway, Natalia F.; Ludwig, Cassie A.; Blumenkranz, Mark S.; Jones, Jennifer Michelle; Fredrick, Douglas R.; Moshfeghi, Darius M.

    2016-01-01

    Purpose To report the birth prevalence, risk factors, characteristics and location of fundus hemorrhages (FH) of the retina and optic nerve present in newborns at birth. Design Prospective cohort study at Stanford University School of Medicine. Participants All infants who were 37 weeks postmenstrual age or older and were deemed stable by their pediatrician were eligible for screening. Infants who were anophthalmic or had known or suspected infectious conjunctivitis were excluded. Methods Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013 through July 25, 2014 were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test (NEST) study. Maternal, obstetric, and neonatal factors were obtained by reviewing hospital records prior to discharge. The location, retinal layer, and laterality of FH were recorded by one pediatric vitreoretinal specialist. Main Outcome Measures Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics and adverse events. Results The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self

  19. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study.

    Science.gov (United States)

    Criado-García, Juan; Fuentes, Francisco; Cruz-Teno, Cristina; García-Rios, Antonio; Jiménez-Morales, Anabel; Delgado-Lista, Javier; Mata, Pedro; Alonso, Rodrigo; López-Miranda, José; Pérez-Jiménez, Francisco

    2011-04-09

    Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  20. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Pérez-Jiménez Francisco

    2011-04-01

    Full Text Available Abstract Background Heterozygous Familial Hypercholesterolemia (FH is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls. We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag and whether they could be predictive factors for cardiovascular risk. 75% (410 of the patients with FH were RR, 23% (127 RQ and 1.6% (9 QQ; in the control group 75.3% (131 were RR, 21.3% (37 RQ and 3.4% (6 QQ (p = 0.32. No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease, either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96. In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97. Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  1. Human thermal physiological and psychological responses under different heating environments.

    Science.gov (United States)

    Wang, Zhaojun; Ning, Haoran; Ji, Yuchen; Hou, Juan; He, Yanan

    2015-08-01

    Anecdotal evidence suggests that many residents of severely cold areas of China who use floor heating (FH) systems feel warmer but drier compared to those using radiant heating (RH) systems. However, this phenomenon has not been verified experimentally. In order to validate the empirical hypothesis, and research the differences of human physiological and psychological responses in these two asymmetrical heating environments, an experiment was designed to mimic FH and RH systems. The subjects participating in the experiment were volunteer college-students. During the experiment, the indoor air temperature, air speed, relative humidity, globe temperature, and inner surface temperatures were measured, and subjects' heart rate, blood pressure and skin temperatures were recorded. The subjects were required to fill in questionnaires about their thermal responses during testing. The results showed that the subjects' skin temperatures, heart rate and blood pressure were significantly affected by the type of heating environment. Ankle temperature had greatest impact on overall thermal comfort relative to other body parts, and a slightly cool FH condition was the most pleasurable environment for sedentary subjects. The overall thermal sensation, comfort and acceptability of FH were higher than that of RH. However, the subjects of FH felt drier than that of RH, although the relative humidity in FH environments was higher than that of the RH environment. In future environmental design, the thermal comfort of the ankles should be scrutinized, and a FH cool condition is recommended as the most comfortable thermal environment for office workers. Consequently, large amounts of heating energy could be saved in this area in the winter. The results of this study may lead to more efficient energy use for office or home heating systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. An enquiry based on a standardised questionnaire into knowledge, awareness and preferences concerning the care of familial hypercholesterolaemia among primary care physicians in the Asia-Pacific region: the "Ten Countries Study".

    Science.gov (United States)

    Pang, Jing; Hu, Miao; Lin, Jie; Miida, Takashi; Nawawi, Hapizah M; Park, Jeong Euy; Wu, Xue; Ramli, Anis S; Kim, Ngoc Thanh; Kwok, See; Gonzalez-Santos, Lourdes E; Su, Ta-Chen; Truong, Thanh Huong; Soran, Handrean; Yamashita, Shizuya; Tomlinson, Brian; Watts, Gerald F

    2017-10-25

    To determine physicians' knowledge, awareness and preferences regarding the care of familial hypercholesterolaemia (FH) in the Asia-Pacific region. A formal questionnaire was anonymously completed by physicians from different countries/regions in the Asia-Pacific. The survey sought responses relating to general familiarity, awareness of management guidelines, identification (clinical characteristics and lipid profile), prevalence and inheritance, extent of elevation in risk of cardiovascular disease (CVD) and practice on screening and treatment. Practising community physicians from Australia, Japan, Malaysia, South Korea, Philippines, Hong Kong, China, Vietnam and Taiwan were recruited to complete the questionnaire, with the UK as the international benchmark. An assessment and comparison of the knowledge, awareness and preferences of FH among physicians in 10 different countries/regions. 1078 physicians completed the questionnaire from the Asia-Pacific region; only 34% considered themselves to be familiar with FH. 72% correctly described FH and 65% identified the typical lipid profile, with a higher proportion of physicians from Japan and China selecting the correct FH definition and lipid profile compared with those from Vietnam and Philippines. However, less than half of the physician were aware of national or international management guidelines; this was significantly worse than physicians from the UK (35% vs 61%, pcountry-specific guidelines and extensive work in FH education and awareness programmes are imperative to improve the care of FH in the region. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Functional heartburn: clinical characteristics and outcome.

    Science.gov (United States)

    Surdea Blaga, Teodora; Dumitrascu, Dan; Galmiche, Jean-Paul; Bruley des Varannes, Stanislas

    2013-03-01

    Patients with heartburn and normal upper gastrointestinal endoscopy, normal oesophageal acid exposure, no symptom-reflux association and who fail to respond to a proton-pump inhibitor are classified as having functional heartburn (FH). This study aimed (i) to characterize the symptoms and functional abnormalities of patients with FH and (ii) to describe their clinical outcome. Among all patients referred for 24 h multichannel intraluminal impedance-pH (MII-pH), patients with FH were identified. The clinical characteristics and high-resolution oesophageal pressure topography recordings of FH patients were analyzed at the time of the 24-h MII-pH test. A symptom-related and health-related quality-of-life questionnaire was then sent to FH patients to assess the long-term outcome. Forty patients fulfilled the criteria for FH, representing 8.5% of the referred population. Twenty-two months after initial testing, 66% of patients still suffered from heartburn. The rate of mixed reflux (liquid/gas) was higher in patients with persisting heartburn at the final evaluation (63 vs. 50%, P=0.04). Sixty-six per cent of patients had one or more manometric abnormalities. Acid clearance time in MII-pH was significantly higher in patients with weak peristalsis than patients with normal peristalsis (60 ± 45 vs. 31 ± 19 s, P=0.03). A high rate of mixed reflux and/or a manometric abnormality were associated with a higher risk of persistent heartburn. FH is a chronic disorder with persisting symptoms in two-thirds of patients. An increased rate of mixed reflux and/or the presence of manometric abnormalities are associated with a higher risk of persisting symptoms and may help to identify the population with unmet therapeutic needs.

  4. Zero tillage: A potential technology to improve cotton yield

    Directory of Open Access Journals (Sweden)

    Abbas Hafiz Ghazanfar

    2016-01-01

    Full Text Available Zero tillage technology revealed with no use of any soil inverting technique to grow crops. The crop plant seed is planted in the soil directly after irrigation to make the soil soft without any replenishing in soil layers. A study was conducted to evaluate cotton genotypes FH-114 and FH-142 for the consecutive three years of growing seasons from 2013-15. The seed of both genotypes was sown with two date of sowing, 1 March and 1 May of each three years of sowing under three tillage treatments (zero tillage, minimum tillage and conventional tillage in triplicate completely randomized split-split plot design. It was found from results that significant differences were recorded for tillage treatments, date of sowing, genotypes and their interactions. Multivariate analysis was performed to evaluate the yield and it attributed traits for potential of FH-114 and FH-142 cotton genotypes. The genotype FH-142 was found with higher and batter performance as compared to FH-114 under zero tillage, minimum tillage and conventional tillage techniques. The traits bolls per plant, boll weight, fibre fineness, fibre strength, plant height, cotton yield per plant and sympodial branches per plant were found as most contributing traits towards cotton yield and production. It was also found that FH-142 gives higher output in terms of economic gain under zero tillage with 54% increase as compared to conventional tillage technique. It was suggested that zero tillage technology should be adopted to improve cotton yield and quality. It was also recommended that further study to evaluate zero tillage as potential technology should be performed with different regions, climate and timing throughout the world.

  5. Polymorphisms of the low-density lipoprotein receptor gene in Brazilian individuals with heterozygous familial hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    L.A. Salazar

    2000-11-01

    Full Text Available Familial hypercholesterolemia (FH is a metabolic disorder inherited as an autosomal dominant trait characterized by an increased plasma low-density lipoprotein (LDL level. The disease is caused by several different mutations in the LDL receptor gene. Although early identification of individuals carrying the defective gene could be useful in reducing the risk of atherosclerosis and myocardial infarction, the techniques available for determining the number of the functional LDL receptor molecules are difficult to carry out and expensive. Polymorphisms associated with this gene may be used for unequivocal diagnosis of FH in several populations. The aim of our study was to evaluate the genotype distribution and relative allele frequencies of three polymorphisms of the LDL receptor gene, HincII1773 (exon 12, AvaII (exon 13 and PvuII (intron 15, in 50 unrelated Brazilian individuals with a diagnosis of heterozygous FH and in 130 normolipidemic controls. Genomic DNA was extracted from blood leukocytes by a modified salting-out method. The polymorphisms were detected by PCR-RFLP. The FH subjects showed a higher frequency of A+A+ (AvaII, H+H+ (HincII1773 and P1P1 (PvuII homozygous genotypes when compared to the control group (P<0.05. In addition, FH probands presented a high frequency of A+ (0.58, H+ (0.61 and P1 (0.78 alleles when compared to normolipidemic individuals (0.45, 0.45 and 0.64, respectively. The strong association observed between these alleles and FH suggests that AvaII, HincII1773 and PvuII polymorphisms could be useful to monitor the inheritance of FH in Brazilian families.

  6. The predictive power of family history measures of alcohol and drug problems and internalizing disorders in a college population.

    Science.gov (United States)

    Kendler, Kenneth S; Edwards, Alexis; Myers, John; Cho, Seung Bin; Adkins, Amy; Dick, Danielle

    2015-07-01

    A family history (FH) of psychiatric and substance use problems is a potent risk factor for common internalizing and externalizing disorders. In a large web-based assessment of mental health in college students, we developed a brief set of screening questions for a FH of alcohol problems (AP), drug problems (DP) and depression-anxiety in four classes of relatives (father, mother, aunts/uncles/grandparents, and siblings) as reported by the student. Positive reports of a history of AP, DP, and depression-anxiety were substantially correlated within relatives. These FH measures predicted in the student, in an expected pattern, dimensions of personality and impulsivity, alcohol consumption and problems, smoking and nicotine dependence, use of illicit drugs, and symptoms of depression and anxiety. Using the mean score from the four classes of relatives was more predictive than using a familial/sporadic dichotomy. Interactions were seen between the FH of AP, DP, and depression-anxiety and peer deviance in predicting symptoms of alcohol and tobacco dependence. As the students aged, the FH of AP became a stronger predictor of alcohol problems. While we cannot directly assess the validity of these FH reports, the pattern of findings suggest that our brief screening items were able to assess, with some accuracy, the FH of substance misuse and internalizing psychiatric disorders in relatives. If correct, these measures can play an important role in the creation of developmental etiologic models for substance and internalizing psychiatric disorders which constitute one of the central goals of the overall project. © 2015 Wiley Periodicals, Inc.

  7. Parentally-adjusted deficit of height as a prognostic factor of the effectiveness of growth hormone (GH) therapy in children with GH deficiency.

    Science.gov (United States)

    Hilczer, Maciej; Smyczyńska, Joanna; Lewiński, Andrzej

    2006-01-01

    Parental height is the most important identifiable factor influencing final height (FH) of children with growth hormone (GH) deficiency (GHD), treated with GH. Assessment of FH of patients with GHD--classified into familial short stature (FSS) and non-familial short stature (non-FSS) according to parentally adjusted deficit of height. The analysis comprised 101 patients (76 boys) with childhood-onset GHD. Final height was compared with patients' height before GH therapy, predicted adult height (PAH) and target height (TH). Both GH peak in stimulating tests and height standard deviation score (SDS) before the therapy were significantly lower in non-FSS than in FSS. Target height was significantly lower in FSS than in non-FSS. Parentally-adjusted deficit of height was significantly more profound in non-FSS than in FSS. The prognosis of adult height was very similar in both groups of patients, being significantly worse in non-FSS than in FSS while corrected by TH. The absolute FH was similar in FSS and non-FSS, being, however, significantly lower in non-FSS than in FSS while corrected by TH. Improvement of height was significantly better in non-FSS than in FSS. In both groups, FH SDS was significantly better than height SDS before the therapy (H0SDS). In FSS group, PAH was similar to TH, moreover, FH corresponded to both PAH and TH. In non-FSS group FH was significantly higher than PAH, but both FH and PAH were significantly lower than TH. 1) Growth hormone therapy was more effective in the patients with non-FSS than in those with FSS. 2) Parentally-adjusted deficit of height is an important prognostic factor of GH therapy effectiveness.

  8. Attainment of LDL Cholesterol Treatment Goals in Children and Adolescents With Familial Hypercholesterolemia. The SAFEHEART Follow-up Registry.

    Science.gov (United States)

    Saltijeral, Adriana; Pérez de Isla, Leopoldo; Alonso, Rodrigo; Muñiz, Ovidio; Díaz-Díaz, José Luis; Fuentes, Francisco; Mata, Nelva; de Andrés, Raimundo; Díaz-Soto, Gonzalo; Pastor, José; Pinilla, José Miguel; Zambón, Daniel; Pinto, Xavier; Badimón, Lina; Mata, Pedro

    2017-06-01

    Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Vanillin formation from ferulic acid in Vanilla planifolia is catalysed by a single enzyme

    DEFF Research Database (Denmark)

    Gallage, Nethaji J; Hansen, Esben H; Kannangara, Rubini

    2014-01-01

    Vanillin is a popular and valuable flavour compound. It is the key constituent of the natural vanilla flavour obtained from cured vanilla pods. Here we show that a single hydratase/lyase type enzyme designated vanillin synthase (VpVAN) catalyses direct conversion of ferulic acid and its glucoside...... to the inner part of the vanilla pod and high transcript levels are found in single cells located a few cell layers from the inner epidermis. Transient expression of VpVAN in tobacco and stable expression in barley in combination with the action of endogenous alcohol dehydrogenases and UDP...

  10. Production of vanillin by metabolically engineered Escherichia coli.

    Science.gov (United States)

    Yoon, Sang-Hwal; Li, Cui; Kim, Ju-Eun; Lee, Sook-Hee; Yoon, Ji-Young; Choi, Myung-Suk; Seo, Weon-Taek; Yang, Jae-Kyung; Kim, Jae-Yeon; Kim, Seon-Won

    2005-11-01

    E. coli was metabolically engineered to produce vanillin by expression of the fcs and ech genes from Amycolatopsis sp. encoding feruloyl-CoA synthetase and enoyl-CoA hydratase/aldolase, respectively. Vanillin production was optimized by leaky expression of the genes, under the IPTG-inducible trc promoter, in complex 2YT medium. Supplementation with glucose, fructose, galactose, arabinose or glycerol severely decreased vanillin production. The highest vanillin production of 1.1 g l(-1) was obtained with cultivation for 48 h in 2YT medium with 0.2% (w/v) ferulate, without IPTG and no supplementation of carbon sources.

  11. Carbohydrates as efficient catalysts for the hydration of α-amino nitriles.

    Science.gov (United States)

    Chitale, Sampada; Derasp, Joshua S; Hussain, Bashir; Tanveer, Kashif; Beauchemin, André M

    2016-11-01

    Directed hydration of α-amino nitriles was achieved under mild conditions using simple carbohydrates as catalysts exploiting temporary intramolecularity. A broadly applicable procedure using both formaldehyde and NaOH as catalysts efficiently hydrated a variety of primary and secondary susbtrates, and allowed the hydration of enantiopure substrates to proceed without racemization. This work also provides a rare comparison of the catalytic activity of carbohydrates, and shows that the simple aldehydes at the basis of chemical evolution are efficient organocatalysts mimicking the function of hydratase enzymes. Optimal catalytic efficiency was observed with destabilized aldehydes, and with difficult substrates only simple carbohydrates such as formaldehyde and glycolaldehyde proved reliable.

  12. Cells and methods for producing fatty alcohols

    Science.gov (United States)

    Pfleger, Brian F.; Youngquist, Tyler J.

    2017-07-18

    Recombinant cells and methods for improved yield of fatty alcohols. The recombinant cells harbor a recombinant thioesterase gene, a recombinant acyl-CoA synthetase gene, and a recombinant acyl-CoA reductase gene. In addition, a gene product from one or more of an acyl-CoA dehydrogenase gene, an enoyl-CoA hydratase gene, a 3-hydroxyacyl-CoA dehydrogenase gene, and a 3-ketoacyl-CoA thiolase gene in the recombinant cells is functionally deleted. Culturing the recombinant cells produces fatty alcohols at high yields.

  13. Phenotypic heterogeneity in two siblings with 3-methylglutaconic aciduria type I caused by a novel intragenic deletion.

    Science.gov (United States)

    Mercimek-Mahmutoglu, Saadet; Tucker, Tracy; Casey, Brett

    2011-11-01

    We describe two siblings with 3-methylglutaconic aciduria type I with phenotypic heterogeneity. The index case was a 14-year-old female with learning disability, attention deficit-hyperactivity and early onset subclinical leukoencephalopathy. Her 9-year-old brother had severe expressive speech delay and delay in speech sound development with normal cognitive functions. The diagnosis was confirmed by a demonstration of 3-methylglutaconyl-CoA hydratase enzyme deficiency in the cultured skin fibroblasts and homozygous deletion of exons 1-3 within the AUH gene. Copyright © 2011. Published by Elsevier Inc.

  14. Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

    Science.gov (United States)

    Molina-Montes, E; Gomez-Rubio, P; Márquez, M; Rava, M; Löhr, M; Michalski, C W; Molero, X; Farré, A; Perea, J; Greenhalf, W; Ilzarbe, L; O'Rorke, M; Tardón, A; Gress, T; Barberà, V M; Crnogorac-Jurcevic, T; Domínguez-Muñoz, E; Muñoz-Bellvís, L; Balsells, J; Costello, E; Huang, J; Iglesias, M; Kleeff, J; Kong, Bo; Mora, J; Murray, L; O'Driscoll, D; Poves, I; Scarpa, A; Ye, W; Hidalgo, M; Sharp, L; Carrato, A; Real, F X; Malats, N

    2018-04-01

    Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

  15. Winter metabolic depression does not change arterial baroreflex control of heart rate in the tegu lizard Salvator merianae.

    Science.gov (United States)

    Zena, Lucas A; Dantonio, Valter; Gargaglioni, Luciane H; Andrade, Denis V; Abe, Augusto S; Bícego, Kênia C

    2016-03-01

    Baroreflex regulation of blood pressure is important for maintaining appropriate tissue perfusion. Although temperature affects heart rate (fH) reflex regulation in some reptiles and toads, no data are available on the influence of temperature-independent metabolic states on baroreflex. The South American tegu lizard Salvator merianae exhibits a clear seasonal cycle of activity decreasing fH along with winter metabolic downregulation, independent of body temperature. Through pharmacological interventions (phenylephrine and sodium nitroprusside), the baroreflex control of fH was studied at ∼ 25 °C in spring-summer- and winter-acclimated tegus. In winter lizards, resting and minimum fH were lower than in spring-summer animals (respectively, 13.3 ± 0.82 versus 10.3 ± 0.81 and 11.2 ± 0.65 versus 7.97 ± 0.88 beats min(-1)), while no acclimation differences occurred in resting blood pressure (5.14 ± 0.38 versus 5.06 ± 0.56 kPa), baroreflex gain (94.3 ± 10.7 versus 138.7 ± 30.3% kPa(-1)) or rate-pressure product (an index of myocardial activity). Vagal tone exceeded the sympathetic tone of fH, especially in the winter group. Therefore, despite the lower fH, winter acclimation does not diminish the fH baroreflex responses or rate-pressure product, possibly because of increased stroke volume that may arise because of heart hypertrophy. Independent of acclimation, fH responded more to hypotension than to hypertension. This should imply that tegus, which have no pressure separation within the single heart ventricle, must have other protection mechanisms against pulmonary hypertension or oedema, presumably through lymphatic drainage and/or vagal vasoconstriction of pulmonary artery. Such a predominant fH reflex response to hypotension, previously observed in anurans, crocodilians and mammals, may be a common feature of tetrapods. © 2016. Published by The Company of Biologists Ltd.

  16. Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-Year Results of the Newborn Eye Screen Test Study.

    Science.gov (United States)

    Callaway, Natalia F; Ludwig, Cassie A; Blumenkranz, Mark S; Jones, Jennifer Michelle; Fredrick, Douglas R; Moshfeghi, Darius M

    2016-05-01

    To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth. Prospective cohort study at Stanford University School of Medicine. All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded. Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist. Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events. The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant. Fundus

  17. Lysosomal acid lipase deficiency: A hidden disease among cohorts of familial hypercholesterolemia?

    Science.gov (United States)

    Chora, Joana Rita; Alves, Ana Catarina; Medeiros, Ana Margarida; Mariano, Cibelle; Lobarinhas, Goreti; Guerra, António; Mansilha, Helena; Cortez-Pinto, Helena; Bourbon, Mafalda

    Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  18. Does family history of metabolic syndrome affect the metabolic profile phenotype in young healthy individuals?

    Science.gov (United States)

    Lipińska, Anna; Koczaj-Bremer, Magdalena; Jankowski, Krzysztof; Kaźmierczak, Agnieszka; Ciurzyński, Michał; Ou-Pokrzewińska, Aisha; Mikocka, Ewelina; Lewandowski, Zbigniew; Demkow, Urszula; Pruszczyk, Piotr

    2014-01-01

    Early identification of high-risk individuals is key for the prevention of cardiovascular disease (CVD). The aim of this study was to assess the potential impact of a family history of metabolic syndrome (fhMetS) on the risk of metabolic disorders (abnormal body mass, lipid profile, glucose metabolism, insulin resistance, and blood pressure) in healthy young individuals. We studied CVD risk factors in 90 healthy volunteers, aged 27-39 years; of these, 78 had fhMetS and 12 were without fhMetS (control group). Fasting serum lipids, glucose, and insulin levels were assayed, and anthropometric parameters and blood pressure using, an ambulatory blood pressure monitoring system, were measured. Nutritional and physical activity habits were assessed. Despite similar nutritional and physical activity habits, abnormal body mass was found in 53.2% of the fhMetS participants and 46.1% of the control participants (p = 0.54). The occurrence of obesity was 19.4% and 0%, respectively (p = 0.69). Compared to the control participants, fhMetS was associated with significantly higher total cholesterol (5.46 mmol/L vs. 4.69 mmol/L, p family history of MetS.

  19. An improved method on stimulated T-lymphocytes to functionally characterize novel and known LDLR mutations[S

    Science.gov (United States)

    Romano, Maria; Di Taranto, Maria Donata; Mirabelli, Peppino; D'Agostino, Maria Nicoletta; Iannuzzi, Arcangelo; Marotta, Gennaro; Gentile, Marco; Raia, Maddalena; Di Noto, Rosa; Del Vecchio, Luigi; Rubba, Paolo; Fortunato, Giuliana

    2011-01-01

    The main causes of familial hypercholesterolemia (FH) are mutations in LDL receptor (LDLR) gene. Functional studies are necessary to demonstrate the LDLR function impairment caused by mutations and would be useful as a diagnostic tool if they allow discrimination between FH patients and controls. In order to identify the best method to detect LDLR activity, we compared continuous Epstein-Barr virus (EBV)-transformed B-lymphocytes and mitogen stimulated T-lymphocytes. In addition, we characterized both novel and known mutations in the LDLR gene. T-lymphocytes and EBV-transformed B-lymphocytes were obtained from peripheral blood of 24 FH patients and 24 control subjects. Functional assays were performed by incubation with fluorescent LDL followed by flow cytometry analysis. Residual LDLR activity was calculated normalizing fluorescence for the mean fluorescence of controls. With stimulated T-lymphocytes we obtained a better discrimination capacity between controls and FH patients compared with EBV-transformed B-lymphocytes as demonstrated by receiver operating characteristic (ROC) curve analysis (the areas under the curve are 1.000 and 0.984 respectively; P < 0.0001 both). The characterization of LDLR activity through T-lymphocytes is more simple and faster than the use of EBV-transformed B-lymphocytes and allows a complete discrimination between controls and FH patients. Therefore the evaluation of residual LDLR activity could be helpful not only for mutation characterization but also for diagnostic purposes. PMID:21865347

  20. The mTORC1-4E-BP-eIF4E axis controls de novo Bcl6 protein synthesis in T cells and systemic autoimmunity.

    Science.gov (United States)

    Yi, Woelsung; Gupta, Sanjay; Ricker, Edd; Manni, Michela; Jessberger, Rolf; Chinenov, Yurii; Molina, Henrik; Pernis, Alessandra B

    2017-08-15

    Post-transcriptional modifications can control protein abundance, but the extent to which these alterations contribute to the expression of T helper (T H ) lineage-defining factors is unknown. Tight regulation of Bcl6 expression, an essential transcription factor for T follicular helper (T FH ) cells, is critical as aberrant T FH cell expansion is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we show that lack of the SLE risk variant Def6 results in deregulation of Bcl6 protein synthesis in T cells as a result of enhanced activation of the mTORC1-4E-BP-eIF4E axis, secondary to aberrant assembly of a raptor-p62-TRAF6 complex. Proteomic analysis reveals that this pathway selectively controls the abundance of a subset of proteins. Rapamycin or raptor deletion ameliorates the aberrant T FH cell expansion in mice lacking Def6. Thus deregulation of mTORC1-dependent pathways controlling protein synthesis can result in T-cell dysfunction, indicating a mechanism by which mTORC1 can promote autoimmunity.Excessive expansion of the T follicular helper (T FH ) cell pool is associated with autoimmune disease and Def6 has been identified as an SLE risk variant. Here the authors show that Def6 limits proliferation of T FH cells in mice via alteration of mTORC1 signaling and inhibition of Bcl6 expression.

  1. Fouling effects of tri-n-butylphosphate on reverse osmosis performance and techniques for performance recovery

    International Nuclear Information System (INIS)

    Poy, F.L.

    1987-01-01

    The F/H Effluent Treatment Facility (F/H ETF) must be on-line by November 1988 to treat the low level activity wastes presently being discharged to the F- and H- areas' seepage basins. The three main processes of the F/H ETF are filtration, reverse osmosis, and ion exchange. Any dissolved organics present in the F/H ETF's feed have the potential to affect operation of the reverse osmosis system. Earlier studies with F/H ETF feed simulant and 70 volume percent kerosene and 30 volume percent tri-n-butylphosphate (TBP) additions showed that the kerosene/TBP mixture results in partial fouling of reverse osmosis membranes. A more detailed analysis of the seepage basin feed has shown that TBP is the major dissolved organic compound. Since it is dissolved (soluble to about 400 ppM at 25 degree C), TBP will be present in the reverse osmosis feed unless removed by a means other than filtration. Thus the fouling effect of TBP (without kerosene) on reverse osmosis performance was investigated. 4 refs., 8 figs., 2 tabs

  2. Intraoperative 3-D imaging improves sentinel lymph node biopsy in oral cancer

    International Nuclear Information System (INIS)

    Bluemel, Christina; Herrmann, Ken; Buck, Andreas K.; Lapa, Constantin; Kuebler, Alexander; Hartmann, Stefan; Linz, Christian; Mueller-Richter, Urs; Geissinger, Eva; Wild, Vanessa

    2014-01-01

    The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer. Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used. All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98 %), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22 % of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100 %). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients. FhSPECT is a feasible technology that allows the accurate identification of SLNs in oral cancer. FhSPECT overcomes the shine-through phenomenon, one of the most important limitations of SLNB, thereby confirming the importance of SLNB in patients with cN0 oral cancer. (orig.)

  3. Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia.

    Science.gov (United States)

    Fahed, Akl C; Shibbani, Kamel; Andary, Rabih R; Arabi, Mariam T; Habib, Robert H; Nguyen, Denis D; Haddad, Fady F; Moubarak, Elie; Nemer, Georges; Azar, Sami T; Bitar, Fadi F

    2017-01-01

    Valvular heart disease frequently occurs as a consequence of premature atherosclerosis in individuals with familial hypercholesterolemia (FH). Studies have primarily focused on aortic valve calcification in heterozygous FH, but there is paucity of data on the incidence of valvular disease in homozygous FH. We performed echocardiographic studies in 33 relatively young patients (mean age: 26 years) with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis) to look for subclinical valvulopathy. Twenty-one patients had evidence of valvulopathy of the aortic or mitral valves, while seven subjects showed notable mitral regurgitation. Older patients were more likely to have aortic valve calcification (>21 versus ≤21 years: 59% versus 12.5%; p = 0.01) despite lower LDL levels at the time of the study (385 versus 513 mg/dL; p = 0.016). Patients with valvulopathy were older and had comparable LDL levels and a lower carotid intima-media thickness. Our data suggests that, in homozygous FH patients, valvulopathy (1) is present across a wide age spectrum and LDL levels and (2) is less likely to be influenced by lipid-lowering treatment. Echocardiographic studies that focused on aortic root thickening and stenosis and regurgitation are thus likely an effective modality for serial follow-up of subclinical valvular heart disease.

  4. Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Akl C. Fahed

    2017-01-01

    Full Text Available Valvular heart disease frequently occurs as a consequence of premature atherosclerosis in individuals with familial hypercholesterolemia (FH. Studies have primarily focused on aortic valve calcification in heterozygous FH, but there is paucity of data on the incidence of valvular disease in homozygous FH. We performed echocardiographic studies in 33 relatively young patients (mean age: 26 years with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis to look for subclinical valvulopathy. Twenty-one patients had evidence of valvulopathy of the aortic or mitral valves, while seven subjects showed notable mitral regurgitation. Older patients were more likely to have aortic valve calcification (>21 versus ≤21 years: 59% versus 12.5%; p = 0.01 despite lower LDL levels at the time of the study (385 versus 513 mg/dL; p = 0.016. Patients with valvulopathy were older and had comparable LDL levels and a lower carotid intima-media thickness. Our data suggests that, in homozygous FH patients, valvulopathy (1 is present across a wide age spectrum and LDL levels and (2 is less likely to be influenced by lipid-lowering treatment. Echocardiographic studies that focused on aortic root thickening and stenosis and regurgitation are thus likely an effective modality for serial follow-up of subclinical valvular heart disease.

  5. Frost hardiness of mycorrhizal (Hebeloma sp.) and non-mycorrhizal Scots pine roots.

    Science.gov (United States)

    Korhonen, Anna; Lehto, Tarja; Repo, Tapani

    2013-10-01

    The frost hardiness (FH) of mycorrhizal [ectomycorrhizal (ECM)] and non-mycorrhizal (NM) Scots pine (Pinus sylvestris) seedlings was studied to assess whether mycorrhizal symbiosis affected the roots' tolerance of below-zero temperatures. ECM (Hebeloma sp.) and NM seedlings were cultivated in a growth chamber for 18 weeks. After 13 weeks' growth in long-day and high-temperature (LDHT) conditions, a half of the ECM and NM seedlings were moved into a chamber with short-day and low-temperature (SDLT) conditions to cold acclimate. After exposures to a range of below-zero temperatures, the FH of the roots was assessed by means of the relative electrolyte leakage test. The FH was determined as the inflection point of the temperature-response curve. No significant difference was found between the FH of mycorrhizal and non-mycorrhizal roots in LDHT (-8.9 and -9.8 °C) or SDLT (-7.5 and -6.8 °C). The mycorrhizal treatment had no significant effect on the total dry mass, the allocation of dry mass among the roots and needles or nutrient accumulation. The mycorrhizal treatment with Hebeloma sp. did not affect the FH of Scots pine in this experimental setup. More information is needed on the extent to which mycorrhizas tolerate low temperatures, especially with different nutrient contents and different mycorrhiza fungi.

  6. Use of next-generation sequencing to detect LDLR gene copy number variation in familial hypercholesterolemia.

    Science.gov (United States)

    Iacocca, Michael A; Wang, Jian; Dron, Jacqueline S; Robinson, John F; McIntyre, Adam D; Cao, Henian; Hegele, Robert A

    2017-11-01

    Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, caused predominantly by autosomal codominant mutations in the LDL receptor gene ( LDLR ). In providing a molecular diagnosis for FH, the current procedure often includes targeted next-generation sequencing (NGS) panels for the detection of small-scale DNA variants, followed by multiplex ligation-dependent probe amplification (MLPA) in LDLR for the detection of whole-exon copy number variants (CNVs). The latter is essential because ∼10% of FH cases are attributed to CNVs in LDLR ; accounting for them decreases false negative findings. Here, we determined the potential of replacing MLPA with bioinformatic analysis applied to NGS data, which uses depth-of-coverage analysis as its principal method to identify whole-exon CNV events. In analysis of 388 FH patient samples, there was 100% concordance in LDLR CNV detection between these two methods: 38 reported CNVs identified by MLPA were also successfully detected by our NGS method, while 350 samples negative for CNVs by MLPA were also negative by NGS. This result suggests that MLPA can be removed from the routine diagnostic screening for FH, significantly reducing associated costs, resources, and analysis time, while promoting more widespread assessment of this important class of mutations across diagnostic laboratories. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  7. Use of next-generation sequencing to detect LDLR gene copy number variation in familial hypercholesterolemia[S

    Science.gov (United States)

    Iacocca, Michael A.; Wang, Jian; Dron, Jacqueline S.; Robinson, John F.; McIntyre, Adam D.; Cao, Henian

    2017-01-01

    Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, caused predominantly by autosomal codominant mutations in the LDL receptor gene (LDLR). In providing a molecular diagnosis for FH, the current procedure often includes targeted next-generation sequencing (NGS) panels for the detection of small-scale DNA variants, followed by multiplex ligation-dependent probe amplification (MLPA) in LDLR for the detection of whole-exon copy number variants (CNVs). The latter is essential because ∼10% of FH cases are attributed to CNVs in LDLR; accounting for them decreases false negative findings. Here, we determined the potential of replacing MLPA with bioinformatic analysis applied to NGS data, which uses depth-of-coverage analysis as its principal method to identify whole-exon CNV events. In analysis of 388 FH patient samples, there was 100% concordance in LDLR CNV detection between these two methods: 38 reported CNVs identified by MLPA were also successfully detected by our NGS method, while 350 samples negative for CNVs by MLPA were also negative by NGS. This result suggests that MLPA can be removed from the routine diagnostic screening for FH, significantly reducing associated costs, resources, and analysis time, while promoting more widespread assessment of this important class of mutations across diagnostic laboratories. PMID:28874442

  8. Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials.

    Directory of Open Access Journals (Sweden)

    Hushan Yuan

    Full Text Available A key advantage of nanomaterials for biomedical applications is their ability to feature multiple small reporter groups (multimodality, or combinations of reporter groups and therapeutic agents (multifunctionality, while being targeted to cell surface receptors. Here a facile combination of techniques for the syntheses of multimodal, targeted nanoparticles (NPs is presented, whereby heat-induced-radiolabeling (HIR labels NPs with radiometals and so-called click chemistry is used to attach bioactive groups to the NP surface. Click-reactive alkyne or azide groups were first attached to the nonradioactive clinical Feraheme (FH NPs. Resulting "Alkyne-FH" and "Azide-FH" intermediates, like the parent NP, tolerated 89Zr labeling by the HIR method previously described. Subsequently, biomolecules were quickly conjugated to the radioactive NPs by either copper-catalyzed or copper-free click reactions with high efficiency. Synthesis of the Alkyne-FH or Azide-FH intermediates, followed by HIR and then by click reactions for biomolecule attachment, provides a simple and potentially general path for the synthesis of multimodal, multifunctional, and targeted NPs for biomedical applications.

  9. Complement Factor H as a potential atherogenic marker in chronic Chagas disease.

    Science.gov (United States)

    Lidani, Kárita Cláudia Freitas; Sandri, Thaisa Lucas; Andrade, Fabiana Antunes; Bavia, Lorena; Nisihara, Renato; Reason, Iara J Messias

    2018-05-19

    We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas disease (CD). FH plasmatic levels were determined in 80 chronic CD patients. Glycemic index, lipidogram (high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, triglycerides and total cholesterol), and Ultrasensitive C-Reactive Protein (uCRP) values were obtained from medical records. Height, weight, body mass index (BMI) blood pressure and left ventricular ejection fraction (LVEF) were obtained from echocardiography exams. Comparisons between chronic CD clinical forms were performed using Mann-Whitney test and correlation Spearman test. FH levels were correlated positively with triglycerides (p=0.001, r=0.39), LDL-C (p=0.009, r=0.3), cholesterol (p=0.02, r=0.28), uCRP (p=0.029, r=0.31) and BMI (p=0.008, r=0.34); and negatively with HDL-C (p=0.03, r=-0.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels were observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Systematic review and metaanalysis of statins for heterozygous familial hypercholesterolemia in children: evaluation of cholesterol changes and side effects.

    LENUS (Irish Health Repository)

    O'Gorman, Clodagh S

    2012-02-01

    Heterozygous familial hypercholesterolemia (heFH) affects 1 in 500 individuals. Evidence supports the low-density lipoprotein (LDL)-lowering effect of statins for adults with heFH. However, there are concerns regarding the treatment children with heFH. By performing a systematic review and metaanalysis of the published literature, this study aimed to evaluate the efficacy and safety of statins used for children with heFH. A systematic review was performed by searching multiple medical databases and citations to identify reports of randomized controlled trials of statins used to treat children with heFH. The trials were retrieved, reviewed, and subjected to metaanalysis. The search yielded 2,174 titles. Of the 63 studies retrieved and reviewed, 56 were excluded, 7 were included in the systematic review, and 4 were included in the metaanalysis. Significant heterogeneity was detected. The metaanalysis showed significant LDL lowering, high-density lipoprotein (HDL) cholesterol elevation, and increases in height and weight with statins. The metaanalysis could not be performed for many side effects of statins, but individual trials showed no significant side effects. Quality assessment showed methodologic concerns, with potential for bias. For example, six trials analyzed statin effects without intention to treat despite such a stated intention. Metaanalysis shows significant LDL lowering with statin treatment. Further studies, including epidemiologic and multicenter studies, are required.

  11. Mesenchymal Stem Cells Control Complement C5 Activation by Factor H in Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Haijun Ma

    2018-06-01

    Full Text Available Lupus nephritis (LN is one of the most severe complications of systemic lupus erythematosus (SLE caused by uncontrolled activation of the complement system. Mesenchymal stem cells (MSCs exhibit clinical efficacy for severe LN in our previous studies, but the underlying mechanisms of MSCs regulating complement activation remain largely unknown. Here we show that significantly elevated C5a and C5b-9 were found in patients with LN, which were notably correlated with proteinuria and different renal pathological indexes of LN. MSCs suppressed systemic and intrarenal activation of C5, increased the plasma levels of factor H (FH, and ameliorated renal disease in lupus mice. Importantly, MSCs transplantation up-regulated the decreased FH in patients with LN. Mechanistically, interferon-α enhanced the secretion of FH by MSCs. These data demonstrate that MSCs inhibit the activation of pathogenic C5 via up-regulation of FH, which improves our understanding of the immunomodulatory mechanisms of MSCs in the treatment of lupus nephritis. Keywords: Lupus nephritis, C5, MSCs, FH

  12. The Effect of Simulated Flash-Heat Pasteurization on Immune Components of Human Milk.

    Science.gov (United States)

    Daniels, Brodie; Schmidt, Stefan; King, Tracy; Israel-Ballard, Kiersten; Amundson Mansen, Kimberly; Coutsoudis, Anna

    2017-02-22

    A pasteurization temperature monitoring system has been designed using FoneAstra, a cellphone-based networked sensing system, to monitor simulated flash-heat (FH) pasteurization. This study compared the effect of the FoneAstra FH (F-FH) method with the Sterifeed Holder method currently used by human milk banks on human milk immune components (immunoglobulin A (IgA), lactoferrin activity, lysozyme activity, interleukin (IL)-8 and IL-10). Donor milk samples ( N = 50) were obtained from a human milk bank, and pasteurized. Concentrations of IgA, IL-8, IL-10, lysozyme activity and lactoferrin activity were compared to their controls using the Student's t -test. Both methods demonstrated no destruction of interleukins. While the Holder method retained all lysozyme activity, the F-FH method only retained 78.4% activity ( p pasteurization, the benefits of F-FH in terms of its low cost, feasibility, safety and retention of immune components make it a valuable resource in low-income countries for pasteurizing human milk, potentially saving infants' lives.

  13. Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function

    Directory of Open Access Journals (Sweden)

    Onda Kisara

    2011-11-01

    Full Text Available Abstract Background Glomerular damage in IgA nephropathy (IgAN is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis. Methods Membrane attack complex (MAC, properdin (P, factor H (fH and Complement receptor type 1 (CR1 were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. Glomerular deposition of C5, fH and P was assessed using an immunofluorescence technique and correlated with histological severity of IgAN and clinical parameters. Fibrotic changes and glomerular sclerosis were evaluated in renal biopsy specimens. Results Immunofluorescence studies revealed glomerular depositions of C5, fH and P in patients with IgAN. Urinary MAC, fH and P levels in IgAN patients were significantly higher than those in healthy controls (p Conclusions Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN.

  14. Intraoperative 3-D imaging improves sentinel lymph node biopsy in oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bluemel, Christina; Herrmann, Ken; Buck, Andreas K.; Lapa, Constantin [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Kuebler, Alexander; Hartmann, Stefan; Linz, Christian; Mueller-Richter, Urs [University Hospital Wuerzburg, Department of Oral and Maxillofacial Plastic Surgery, Wuerzburg (Germany); Geissinger, Eva; Wild, Vanessa [University Wuerzburg, Institute of Pathology, Wuerzburg (Germany)

    2014-12-15

    The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer. Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used. All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98 %), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22 % of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100 %). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients. FhSPECT is a feasible technology that allows the accurate identification of SLNs in oral cancer. FhSPECT overcomes the shine-through phenomenon, one of the most important limitations of SLNB, thereby confirming the importance of SLNB in patients with cN0 oral cancer. (orig.)

  15. Using early standardized language measures to predict later language and early reading outcomes in children at high risk for language-learning impairments.

    Science.gov (United States)

    Flax, Judy F; Realpe-Bonilla, Teresa; Roesler, Cynthia; Choudhury, Naseem; Benasich, April

    2009-01-01

    The aim of the study was to examine the profiles of children with a family history (FH+) of language-learning impairments (LLI) and a control group of children with no reported family history of LLI (FH-) and identify which language constructs (receptive or expressive) and which ages (2 or 3 years) are related to expressive and receptive language abilities, phonological awareness, and reading abilities at ages 5 and 7 years. Participants included 99 children (40 FH+ and 59 FH-) who received a standardized neuropsychological battery at 2, 3, 5, and 7 years of age. As a group, the FH+ children had significantly lower scores on all language measures at 2 and 3 years, on selected language and phonological awareness measures at 5 years, and on phonological awareness and nonword reading at 7 years. Language comprehension at 3 years was the best predictor of later language and early reading for both groups. These results support past work suggesting that children with a positive family history of LLI are at greater risk for future language and reading problems through their preschool and early school-age years. Furthermore, language comprehension in the early years is a strong predictor of future language-learning status.

  16. Program planning for large-scale control system upgrades

    International Nuclear Information System (INIS)

    Madani, M.; Giajnorio, J.; Richard, T.; Ho, D.; Volk, W.; Ertel, A.

    2011-01-01

    Bruce Power has been planning to replace the Bruce A Fuel Handling (FH) computer systems including the Controller and Protective computers for many years. This is a complex project, requiring an extended FH outage. To minimize operational disruption and fully identify associated project risks, Bruce Power is executing the project in phases starting with the Protective Computer replacement. GEH-C is collaborating with Bruce Power in a Preliminary Engineering (PE) phase to generate a project plan including specifications, budgetary cost, schedule, risks for the Protective computer replacement project. To assist Bruce Power in its evaluation, GEH-C's is using 6-Sigma methodologies to identify and rank Critical to Quality (CTQ) requirements in collaboration with Bruce Power Maintenance, Operations, Plant Design and FH Engineering teams. PE phase established the project scope, hardware and software specifications, material requirements and finally concluded with a recommended hardware platform and approved controls architecture.

  17. Evaluation of eating habits and lifestyle in patients with obesity before and after bariatric surgery: a single Italian center experience.

    Science.gov (United States)

    Cena, Hellas; De Giuseppe, Rachele; Biino, Ginevra; Persico, Francesca; Ciliberto, Ambra; Giovanelli, Alessandro; Stanford, Fatima Cody

    2016-01-01

    The study evaluated and compared the eating habits and lifestyle of patients with moderate to severe obesity who have undergone Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG). Food frequency (FF), food habits (FH), physical activity and life style (PA) as well as smoking habits (SH) were analyzed in 50 RYGB (25 M; aged: 24-64) and 50 SG patients (25 M; aged: 22-63) by means of a validated questionnaire, before (T0) and 6 months (T1) post bariatric surgery. A score for each section (FF, FH, PA, SH) was calculated. ANOVA analysis (age/sex adjusted): FF and FH scores improved at T1 (RYGB and SG: p habits improved, patients did not change their physical activity level or their smoking habits. Patients should receive adequate lifestyle counseling to ensure the maximal benefit from bariatric surgery.

  18. F + H/sub 2/ potential energy surface: the ecstasy and the agony

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, H.F. III

    1985-12-05

    This account surveys 14 years of more or less continuing theoretical research on the FH/sub 2/ potential energy hypersurface. Early encouragement concerning the ability of theory to reliably characterize the entrance barrier for F + H/sub 2/ ..-->.. FH + H has more recently been sobered by the realization that very high levels of theory are required for this task. The importance of zero-point vibrational corrections and tunneling corrections in reliable predictions of the same activation energy is discussed. In contrast, the barrier height of H + FH ..-->.. HF + H three-center exchange stands as a prominent early success of ab initio molecular electronic structure theory. 90 references, 4 figures, 6 tables.

  19. Measurement of intima-media thickness of common carotid arteries using ultrasound in patients with familial and non-familial hypercholesterolaemia and correlation of intima-media thickness to obesity.

    Science.gov (United States)

    Nafikudin, M; Nawawi, H; Muid, S; Annuar, R; Yusoff, K; Khalid, B A

    2003-12-01

    Ultrasonographic measurements of the intima-media thickness (IMT) of common carotid arteries (CCA) were taken in 50 patients with familial hypercholesterolaemia (FH) and 57 patients with non-familial hypercholesterolemia (NFH). The lipid profile, body mass index (BMI) and waist-hip ratio (WHR) of each patient were recorded. In FH patients, the IMT was significantly higher in overweight and elevated WHR subgroups compared to the normal with significant correlations between BMI and WHR to the IMT. In NFH patients, the IMT was significantly higher in the elevated WHR compared to the normal subgroup but the correlations between either BMI or WHR to IMT were insignificant. These suggest that the environmentally modified anthropometric indices may have an effect on atherosclerosis in genetically determined hypercholesterolaemia in FH patients.

  20. Feasibility and acceptability of esophageal-directed hypnotherapy for functional heartburn.

    Science.gov (United States)

    Riehl, M E; Pandolfino, J E; Palsson, O S; Keefer, L

    2016-07-01

    Functional heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) and could be applied to FH. The objective of this study was to determine the feasibility, acceptability, and clinical utility of 7 weekly sessions of esophageal-directed HYP (EHYP) on heartburn symptoms, quality of life, and EHv. Similar to other work in FGIDs and regardless of hypnotizability, there were consistent and significant changes in heartburn symptoms, visceral anxiety, and quality of life and a trend for improvement in catastrophizing. We would recommend EHYP in FH patients who are either non-responsive to medications or who would prefer a lifestyle intervention. © 2015 International Society for Diseases of the Esophagus.

  1. The feasibility and acceptability of esophageal-directed hypnotherapy for functional heartburn

    Science.gov (United States)

    Riehl, M. E.; Pandolfino, J. E.; Palsson, O. S.; Keefer, L.

    2015-01-01

    SUMMARY Functional Heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) and could be applied to FH. The objective of this study was to determine the feasibility, acceptability and clinical utility of 7 weekly sessions of esophageal-directed hypnotherapy (EHYP) on heartburn symptoms, quality of life and EHv. Similar to other work in FGIDs and regardless of hypnotizability, there were consistent and significant changes in heartburn symptoms, visceral anxiety and quality of life and a trend for improvement in catastrophizing. We would recommend EHYP in FH patients who are either non-responsive to medications or who would prefer a lifestyle intervention. PMID:25824436

  2. Type 2 diabetes family histories, body composition and fasting glucose levels: a cross-section analysis in healthy sedentary male and female.

    Science.gov (United States)

    Bianco, Antonino; Pomara, Francesco; Thomas, Ewan; Paoli, Antonio; Battaglia, Giuseppe; Petrucci, Marco; Proia, Patrizia; Bellafiore, Marianna; Palma, Antonio

    2013-01-01

    Diabetes type 2 is a world wide spread disease with a multifactorial pathogenetic evolution. Various factors like obesity, physical inactivity and poor lifestyle habits contribute to its development. The aim of this study was to verify if in young healthy sedentary male and female there is positive correlation between family history to type 2 diabetes and an increase in body weight and fat mass, or alterations in basal glycemia values. Totally183 male and 237 female healthy sedentary subjects were analysed in 2012, in Italy. They were divided in three groups: FH(+) with first degree family history, FH(++) with second degree family history and FH(-) with no family history. Anthropometrics, body composition and blood parameters were assessed. Male had the highest BMI values (Plife-style changes, such as increased physical activity and controlled quantity and quality of food intake.

  3. Self-Reported Questionnaire of Functional Health of Home-Dwelling Elderly People Living in Austria: Based on the Patient Questionnaire of the Standardized Assessment of Elderly People in Primary Care.

    Science.gov (United States)

    Schulc, Eva; Gothe, Raffaella Matteucci; Them, Christa; Tufan, İsmail; Mueller, Gerhard

    2017-08-01

    The aim was to review the construct validity and reliability of a functional health assessment questionnaire (Questionnaire on Functional Health 2 [Q-FH2]). The Q-FH2 was used to assess 344 elderly people in a home setting. A polychoric correlation matrix was applied to conduct a principal axis factor analysis with oblique rotation. The number of factors was determined using various procedures and calculated using theta coefficients to estimate ordinal reliability. The exploratory factor analysis supported a 4-factor solution with an explained total variance of 82%. The internal consistency showed  coefficients ranging from 0.758 to 0.854. The Q-FH2 appears to be a useful instrument to assess the multidimensionality of functional health as defined by the International Classification of Functioning, Disability and Health to determine the resources and deficits regarding the independent living of older adults and to derive appropriate consulting measures.

  4. Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation

    Czech Academy of Sciences Publication Activity Database

    Bohuslavová, Romana; Dodd, Nicole; Mácová, Iva; Chumak, Tetyana; Horák, Martin; Syka, Josef; Fritzsch, B.; Pavlínková, Gabriela

    2017-01-01

    Roč. 54, č. 2 (2017), s. 1352-1368 ISSN 0893-7648 R&D Projects: GA ČR(CZ) GA13-07996S; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) EE2.3.30.0020 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:86652036 ; RVO:68378041 ; RVO:67985823 Keywords : Islet1 transcription factor * Cerebellum * Vestibular system Subject RIV: FH - Neurology; FH - Neurology (UEM-P); FH - Neurology (FGU-C) OBOR OECD: Neuroscience s (including psychophysiology; Neuroscience s (including psychophysiology (FGU-C); Developmental biology (UEM-P) Impact factor: 6.190, year: 2016

  5. A study on determination methods of fueling machine heavy water supply setpressure for Wolsong nuclear power plant unit 1

    International Nuclear Information System (INIS)

    Kim, J. M.; Jeong, B. Y.; Baek, S. J.; Noh, T. S.; Kim, Y. H.; Park, W. K.

    2001-01-01

    The present Wolsong 1 Fuel Handling (F/H)D 2 O Supply Pressure Control System, based on an analog cascaded Proportional-Integral-Differential (PID) control, is less accurate and requires more labor for test and maintenance in comparison with up-to-data digital controllers. Furthermore, F/H operator and technical staff have recently encountered difficulties in operation and maintenance because of frequent occurrences of system instability and failure, and obsolescence of hardware. However the analysis and design review of F/H D 2 O Supply Pressure Control System have not been performed appropriately. Therefore, the design review of F/H D 2 O Supply Pressure Control System has been thoroughly reviewed and analyzed. Based on the analysis results, the optimum pressure setpoints and its determination methods have been proposed for Wolsong Nuclear Power Plant Unit 1

  6. Differences in [14C]glycerol utilization in normal and familial hypercholesterolemic fibroblasts

    International Nuclear Information System (INIS)

    Shireman, R.B.; Durieux, J.

    1991-01-01

    It is known that cultured fibroblasts from familial hypercholesterolemia (FH) patients lack the normal cell receptor for low density lipoprotein (LDL) and that the absence of receptor-mediated transport of LDL cholesterol into these cells results in increased cellular synthesis of cholesterol. After 20 h perincubation in lipid-free medium, cultured FH fibroblasts incorporated significantly greater amounts of [ 14 C]glycerol into cellular lipids than did normal fibroblasts. Relative to the control medium which contained only bovine serum albumin (BSA), preincubation with 5% fetal bovine serum or 50 micrograms LDL/ml decreased [ 14 C]glycerol incorporation by both cell types. FH cells utilized more [ 14 C]glycerol for phospholipid synthesis and less for triglyceride synthesis than normal cells. This study indicates that LDL may be important in the transport of glycerides, as well as cholesterol, to cells

  7. Partitioning of uranyl between ferrihydrite and humic substances at acidic and circum-neutral pH

    Science.gov (United States)

    Dublet, Gabrielle; Lezama Pacheco, Juan; Bargar, John R.; Fendorf, Scott; Kumar, Naresh; Lowry, Gregory V.; Brown, Gordon E.

    2017-10-01

    As part of a larger study of the reactivity and mobility of uranyl (U(VI)O22+) cations in subsurface environments containing natural organic matter (NOM) and hydrous ferric oxides, we have examined the effect of reference humic and fulvic substances on the sorption of uranyl on 2-line ferrihydrite (Fh), a common, naturally occurring nano-Fe(III)-hydroxide. Uranyl was reacted with Fh at pH 4.6 and 7.0 in the presence and absence of Elliott Soil Humic Acid (ESHA) (0-835 ppm) or Suwanee River Fulvic Acid (SRFA) (0-955 ppm). No evidence was found for reduction of uranyl by either form of NOM after 24 h of exposure. The following three size fractions were considered in this study: (1) ≥0.2 μm (Fh-NOM aggregates), (2) 0.02-0.2 μm (dispersed Fh nanoparticles and NOM macro-molecules), and (3) <0.02 μm (dissolved). The extent to which U(VI) is sorbed in aggregates or dispersed as colloids was assessed by comparing U, Fe, and NOM concentrations in these three size fractions. Partitioning of uranyl between Fh and NOM was determined in size fraction (1) using X-ray absorption spectroscopy (XAS). Uranyl sorption on Fh-NOM aggregates was affected by the presence of NOM in different ways depending on pH and type of NOM (ESHA vs. SRFA). The presence of ESHA in the uranyl-Fh-NOM ternary system at pH 4.6 enhanced uranyl uptake more than the presence of SRFA. In contrast, neither form of NOM affected uranyl sorption at pH 7.0 over most of the NOM concentration range examined (0-500 ppm); at the highest NOM concentrations (500-955 ppm) uranyl uptake in the aggregates was slightly inhibited at pH 7.0, which is interpreted as being due to the dispersion of Fh aggregates. XAS at the U LIII-edge was used to characterize molecular-level changes in uranyl complexation as a result of sorption to the Fh-NOM aggregates. In the absence of NOM, uranyl formed dominantly inner-sphere, mononuclear, bidentate sorption complexes on Fh. However, when NOM concentration was increased at pH 4.6, the

  8. An efficient fermentation method for the degradation of cyanogenic glycosides in flaxseed.

    Science.gov (United States)

    Wu, C-F; Xu, X-M; Huang, S-H; Deng, M-C; Feng, A-J; Peng, J; Yuan, J-P; Wang, J-H

    2012-01-01

    Recently, flaxseed has become increasingly popular in the health food market because it contains a considerable amount of specific beneficial nutrients such as lignans and omega-3 fatty acids. However, the presence of cyanogenic glycosides (CGs) in flaxseed severely limits the exploitation of its health benefits and nutritive value. We, therefore, developed an effective fermentation method, optimised by response surface methodology (RSM), for degrading CGs with an enzymatic preparation that includes 12.5% β-glucosidase and 8.9% cyanide hydratase. These optimised conditions resulted in a maximum CG degradation level of 99.3%, reducing the concentration of cyanide in the flaxseed power from 1.156 to 0.015 mg g(-1) after 48 h of fermentation. The avoidance of steam heat to evaporate hydrocyanic acid (HCN) results in lower energy consumption and no environmental pollution. In addition, the detoxified flaxseed retained the beneficial nutrients, lignans and fatty acids at the same level as untreated flaxseed, and this method could provide a new means of removing CGs from other edible plants, such as cassava, almond and sorghum by simultaneously expressing cyanide hydratase and β-glucosidase.

  9. Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country.

    Science.gov (United States)

    Khoo, Kah Lin; Page, Michael M; Liew, Yin Mei; Defesche, Joep C; Watts, Gerald F

    2016-01-01

    Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014. We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH. We treated 13 women and 2 men aged 6 to 59 years, 10 with homozygous and 5 with heterozygous FH, all on maximally tolerated cholesterol-lowering drug therapy, for a total of 65 patient-years. Acute lowering of low-density lipoprotein cholesterol post apheresis was 56.3 ± 7.2%, with time-averaged mean lowering of 34.9 ± 13.9%. No patients experienced any cardiovascular events during the period of receiving LA. Patients receiving LA experienced few side effects and enjoyed reasonable quality of life, but inability to continue treatment was frequent because of cost. LA for severe FH can be delivered effectively in the short term in developing nations, but costs are a major barrier to sustaining this mode of treatment for this high-risk group of patients. New drug therapies for FH, such as the proprotein convertase subtilisin/kexin type 9 inhibitors, microsomal triglyceride transfer protein inhibitors, and apolipoprotein-B100 antisense oligonucleotides may allow improved care for these patients, but costs and long-term safety remain as issues to be addressed. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  10. Carotid atherosclerosis progression in familial hypercholesterolemia patients: a pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies.

    Science.gov (United States)

    Vergeer, Menno; Zhou, Rong; Bots, Michiel L; Duivenvoorden, Raphaël; Koglin, Joerg; Akdim, Fatima; Mitchel, Yale B; Huijgen, Roeland; Sapre, Aditi; de Groot, Eric; Sijbrands, Eric J G; Pasternak, Richard C; Gagné, Claude; Marais, A David; Ballantyne, Christie M; Isaacsohn, Jonathan L; Stalenhoef, Anton F; Kastelein, John J P

    2010-07-01

    Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH patients still show accelerated cIMT increase and to assess the impact of statin treatment, before and after random assignment, on atherosclerosis progression. We retrospectively evaluated cIMT change, and prior statin treatment and postbaseline LDL-C change as predictors of cIMT change, in 1513 HeFH patients who were randomly assigned to the statin arms of the early ASAP and more recent RADIANCE 1, CAPTIVATE, and ENHANCE studies. In the 3 recent studies combined, mean cIMT increased at only 33%of the rate of the simvastatin-treated patients in the ASAP study (0.014 mm/2 years [95% confidence interval, -0.0003-0.028] versus 0.041 mm/2 years [95% confidence interval, 0.020-0.061]; P<0.05). Patients whose statin therapy could be intensified, as evidenced by an LDL-C decrease after the initiation of on-trial statin therapy, showed cIMT decrease in the first 6 to 12 months and a much lower cIMT increase measured over the full 2 years. In line with this, previously statin-naive HeFH patients showed a lower overall cIMT increase. Over the years, intensification of statin therapy in HeFH patients has resulted in an impressive decrease in carotid atherosclerosis progression. In studies that assess other antiatherosclerotic modalities, statin therapy may still induce rapid changes in cIMT. For future cIMT studies, our analyses suggest that patient populations other than intensively pretreated HeFH patients should be selected and that the statin regimen should not be changed on study initiation.

  11. Contemporary Trends in the Management and Outcomes of Patients With Familial Hypercholesterolemia in Canada: A Prospective Observational Study.

    Science.gov (United States)

    Brunham, Liam R; Cermakova, Lubomira; Lee, Terry; Priecelova, Ida; Alloul, Karine; de Chantal, Marilyn; Francis, Gordon A; Frohlich, Jiri

    2017-03-01

    Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic diseases in the world and an important cause of premature cardiovascular (CV) disease. The purpose of this study was to characterize the clinical features, current treatment patterns, and CV outcomes of patients with HeFH in British Columbia, Canada. We conducted a longitudinal observational study of patients with HeFH attending a specialized lipid clinic. We collected data on lipid levels, medication use, and CV events at baseline and last follow-up. We recruited 339 patients with clinically diagnosed HeFH, with a total of 3700 person-years of follow-up. The mean low-density lipoprotein cholesterol (LDL-C) level was 5.9 mmol/L at baseline and 3.7 mmol/L at last follow-up. Use of lipid-lowering therapy (LLT) increased from 35.7% at baseline to 84.7% at last follow-up. A ≥ 50% reduction in LDL-C level was achieved in 34.5% of patients, and an LDL-C level ≤ 2 mmol/L was seen in 8.3%. The overall CV event rate in this cohort was 33.5/1000 person-years. Among patients who had a CV event during follow-up, 59% experienced a recurrent event within 5 years. These data contribute to our understanding of contemporary trends in the management of patients with HeFH in Canada. Despite a majority of patients receiving LLT, few patients reached high-risk lipid targets. These data highlight important opportunities to improve the care of patients with HeFH. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Lead Speciation and In Vitro Bioaccessibility of Compost-Amended Urban Garden Soils

    Energy Technology Data Exchange (ETDEWEB)

    Attanayake, Chammi P.; Hettiarachchi, Ganga M.; Ma, Qing; Pierzynski, Gary M.; Ransom, Michel D. (NWU); (KSU)

    2017-01-01

    In situ soil amendments can modify the Pb bioavailability by changing soil Pb speciation. Urban soils from three vegetable gardens containing different total Pb concentrations were used. The study evaluated how compost amendment and aging of soil-compost mixture in situ affected the following: (i) soil Pb speciation in the field and (ii) change of soil Pb speciation during an in vitro bioaccessibility extraction mimicking gastric phase dissolution at pH 2.5. X-ray absorption fine structure spectroscopy was used to determine Pb speciation in amended and nonamended soils and residues left after in vitro bioaccessibility extraction of those soils. Compost amendment and aging of compost in the field had a negligible effect on Pb bioaccessibility in the soils. Major Pb species in the soils were Pb sorbed to Fe oxy(hydr)oxide (Pb-Fh) and to soil organic C (Pb-Org). The fraction of Pb-Org was increased as soil-compost mixture aged in the field. During the in vitro extraction, the fraction of Pb-Fh was decreased, the fraction of Pb-Org was increased, and hydroxypyromorphite was formed in both amended and nonamended soils. Freshly incorporated compost enhanced the dissolution of Pb-Fh during the extraction. As soil-compost mixture aged in the field, the dissolution of Pb-Fh was low, demonstrating more stability of the Pb-Fh during the extraction. Compost amendment showed potential to contribute to reduced bioaccessibility of Pb as compost aged in the soil by increasing Pb-Org fraction in the field and stability of Pb-Fh during the in vitro bioaccessibility extraction.

  13. Susceptibility to gastric cancer and polymorphisms of insertion/deletion at the intron 3 of the XRCC4 and VNTR at the promoter region of the XRCC5.

    Science.gov (United States)

    Saadat, Mostafa; Pashaei, Samira; Amerizade, Foroozan

    2015-07-01

    The genes encoding X-ray repair cross-complementing group 4 (XRCC4; OMIM: 194363) and 5 (XRCC5; OMIM: 194364) are involved in repair of DNA double-strand breaks. To investigating the associations between polymorphisms of Insertion/Deletion (I/D, rs28360071) in the intron 3 of the XRCC4 and VNTR in the promoter region of the XRCC5 and risk of gastric cancer, the present study was carried out. We included 159 (56 females, 103 males) with gastric cancer and 242 (75 females, 167 males) healthy blood donors frequency matched for age and gender. Using PCR-based methods, the genotypes of the study polymorphisms were determined. The alleles of VNTR XRCC5 polymorphism divided into two groups: L (0 and 1 repeats) and H (2 and 3 repeats) alleles. For the I/D XRCC4 polymorphism, after stratification of the subjects according to their family history (FH) of cancer, either the ID (OR = 3.19, 95%CI: 1.35-7.50, P = 0.008) or the DD genotypes (OR = 4.62, 95%CI: 1.63-13.0, P = 0.004) among positive FH persons, increased the risk of gastric cancer compared with the reference group (persons who have negative FH and II genotype). For the VNTR XRCC5 polymorphism, the LH + HH genotypes among positive FH persons, increased the risk of gastric cancer compared with the reference group (persons who have negative FH and LL genotype) (OR = 2.88, 95%CI: 1.34-6.18, P = 0.006). Sensitivity analysis showed that the above mentioned associations were not occurred due to the maldistribution of the genotypes among missing data. The present study suggests that both polymorphisms of the XRCC4 and XRCC5 might be risk factors for gastric cancer development especially among persons with positive FH.

  14. GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial.

    Science.gov (United States)

    Blum, Werner F; Ross, Judith L; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Kalifa, Gabriel; Deal, Cheri; Drop, Stenvert L S; Rappold, Gudrun; Cutler, Gordon B

    2013-08-01

    Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency. Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome. A prospective, multinational, open-label, randomized 3-arm study consisting of a 2-year control period and a subsequent extension period to FH. The treatment groups were 1) SHOX-D-C/GH (untreated during the control period, GH-treated during the extension), 2) SHOX-D-GH/GH, and 3) Turner-GH/GH (GH-treated during both study periods). Short-statured prepubertal patients with genetically confirmed SHOX deficiency (n = 49) or Turner syndrome (n = 24) who participated in the extension. Depending on the study arm, patients received a daily sc injection of 0.05 mg/kg recombinant human GH from start of the study or start of the extension until attainment of FH or study closure. Height SD score gain from start of GH treatment to FH was similar between the combined SHOX-deficient groups (n = 28, 1.34 ± 0.18 [least-squares mean ± SE]) and the Turner group (n = 19, 1.32 ± 0.22). In this FH population, 57% of the patients with SHOX deficiency and 32% of the patients with Turner syndrome achieved a FH greater than -2 SD score. GH treatment in short children with SHOX deficiency showed similar long-term efficacy as seen in girls with Turner syndrome.

  15. The relationship between body temperature, heart rate, breathing rate, and rate of oxygen consumption, in the tegu lizard (Tupinambis merianae) at various levels of activity.

    Science.gov (United States)

    Piercy, Joanna; Rogers, Kip; Reichert, Michelle; Andrade, Denis V; Abe, Augusto S; Tattersall, Glenn J; Milsom, William K

    2015-12-01

    The present study determined whether EEG and/or EMG recordings could be used to reliably define activity states in the Brazilian black and white tegu lizard (Tupinambis merianae) and then examined the interactive effects of temperature and activity states on strategies for matching O2 supply and demand. In a first series of experiments, the rate of oxygen consumption (VO2), breathing frequency (fR), heart rate (fH), and EEG and EMG (neck muscle) activity were measured in different sleep/wake states (sleeping, awake but quiet, alert, or moving). In general, metabolic and cardio-respiratory changes were better indictors of the transition from sleep to wake than were changes in the EEG and EMG. In a second series of experiments, the interactive effects of temperature (17, 27 and 37 °C) and activity states on fR, tidal volume (VT), the fraction of oxygen extracted from the lung per breath (FIO2-FEO2), fH, and the cardiac O2 pulse were quantified to determine the relative roles of each of these variables in accommodating changes in VO2. The increases in oxygen supply to meet temperature- and activity-induced increases in oxygen demand were produced almost exclusively by increases in fH and fR. Regression analysis showed that the effects of temperature and activity state on the relationships between fH, fR and VO2 was to extend a common relationship along a single curve, rather than separate relationships for each metabolic state. For these lizards, the predictive powers of fR and fH were maximized when the effects of changes in temperature, digestive state and activity were pooled. However, the best r(2) values obtained were 0.63 and 0.74 using fR and fH as predictors of metabolic rate, respectively.

  16. Family history of premature myocardial infarction, life course socioeconomic position and coronary heart disease mortality--A Cohort of Norway (CONOR) study.

    Science.gov (United States)

    Fiskå, Bendik S; Ariansen, Inger; Graff-Iversen, Sidsel; Tell, Grethe S; Egeland, Grace M; Næss, Øyvind

    2015-01-01

    To investigate self-reported family history (FH) of premature myocardial infarction (MI) in first-degree relatives as a risk factor for coronary heart disease (CHD) mortality, and assess whether any observed effect could be explained by current or life course socioeconomic position. 130,066 participants from Cohort of Norway were examined during 1994-2003. A subgroup (n=84,631) had additional life course socioeconomic data. Using Cox proportional hazard analyses, we calculated hazard ratios (HR) for CHD mortality, assessed by linkages to the Norwegian Cause of Death Registry through 2009. For subgroup analyses, we created an index of life course socioeconomic position, and assessed its role as a potential confounder in the association of FH with CHD. For men, MI in parents and siblings were both a significant risk factor for CHD mortality after adjusting for established risk factors and current socioeconomic conditions; the highest risk was with MI in siblings (HR: 1.44 [1.19-1.75]). For women, FH constituted significant risk after similar adjustment only for those with MI in parents plus siblings (HR: 1.78 [1.16-2.73]). Adjusting for current and life course socioeconomic conditions only marginally lowered the estimates, and those with FH did not have worse life course socioeconomic position than those without. FH of premature MI is an independent risk factor for CHD mortality that differs in magnitude of effect by the sex of the index person and type of familial relationship. Life course socioeconomic position has little impact on the association between FH and CHD, suggesting the effect is not confounded by this. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Barriers and promoters of home-based pasteurization of breastmilk among HIV-infected mothers in greater Dar es Salaam, Tanzania.

    Science.gov (United States)

    Young, Sera; Leshabari, Sebalda; Arkfeld, Chaele; Singler, Jennifer; Dantzer, Emily; Israel-Ballard, Kiersten; Mashio, Clara; Maternowska, Catherine; Chantry, Caroline

    2013-06-01

    For the past decade, heat-treating breastmilk has been an infant feeding option recommended by the World Health Organization as a strategy to reduce vertical transmission. However, little is known about field experiences with it. Our primary objective was to explore the barriers and promoters of the implementation of breastmilk pasteurization, "flash-heating" (FH), in the real-world setting of Dar es Salaam, Tanzania. Nineteen in-depth interviews were conducted with participants in a home-based infant feeding counseling intervention in which FH was promoted after 6 months of exclusive breastfeeding. Additionally, three focus group discussions were conducted with peer counselors. Interviews were transcribed, translated, and coded independently using NVivo 8 software (QSR International). Data were analyzed using the socioecological framework. Information and support provided by peer counselors were the most important promoters of initiation and continuation of FH; this impacted individual-, interpersonal-, and institutional-level promoters of success. Other promoters included perceived successful breastmilk expression, infant health after initiation of FH, and the inability to pay for replacement milks. Stigma was the most important barrier and cut across all levels of the framework. Other barriers included doubt about the safety or importance of pasteurized breastmilk, difficulties with expressing milk (often attributed to poor diet), and competing responsibilities. The most common suggestion for improving the uptake and duration of FH was community education. Given the acknowledged role of breastmilk pasteurization in the prevention of vertical transmission, further implementation research is needed. A multilevel intervention addressing barriers to FH would likely improve uptake.

  18. The oxidative TCA cycle operates during methanotrophic growth of the Type I methanotroph Methylomicrobium buryatense 5GB1.

    Science.gov (United States)

    Fu, Yanfen; Li, Yi; Lidstrom, Mary

    2017-07-01

    Methanotrophs are a group of bacteria that use methane as sole carbon and energy source. Type I methanotrophs are gamma-proteobacterial methanotrophs using the ribulose monophosphate cycle (RuMP) cycle for methane assimilation. In order to facilitate metabolic engineering in the industrially promising Type I methanotroph Methylomicrobium buryatense 5GB1, flux analysis of cellular metabolism is needed and 13 C tracer analysis is a foundational tool for such work. This biological system has a single-carbon input and a special network topology that together pose challenges to the current well-established methodology for 13 C tracer analysis using a multi-carbon input such as glucose, and to date, no 13 C tracer analysis of flux in a Type I methanotroph has been reported. In this study, we showed that by monitoring labeling patterns of several key intermediate metabolites in core metabolism, it is possible to quantitate the relative flux ratios for important branch points, such as the malate node. In addition, it is possible to assess the operation of the TCA cycle, which has been thought to be incomplete in Type I methanotrophs. Surprisingly, our analysis provides direct evidence of a complete, oxidative TCA cycle operating in M. buryatense 5GB1 using methane as sole carbon and energy substrate, contributing about 45% of the total flux for de novo malate production. Combined with mutant analysis, this method was able to identify fumA (METBUDRAFT_1453/MBURv2__60244) as the primary fumarase involved in the oxidative TCA cycle, among 2 predicted fumarases, supported by 13 C tracer analysis on both fumA and fumC single knockouts. Interrupting the oxidative TCA cycle leads to a severe growth defect, suggesting that the oxidative TCA cycle functions to not only provide precursors for de novo biomass synthesis, but also to provide reducing power to the system. This information provides new opportunities for metabolic engineering of M. buryatense for the production of

  19. Vaccination against Fasciola hepatica using cathepsin L3 and B3 proteases delivered alone or in combination.

    Science.gov (United States)

    Wesołowska, Agnieszka; Basałaj, Katarzyna; Norbury, Luke J; Sielicka, Alicja; Wędrychowicz, Halina; Zawistowska-Deniziak, Anna

    2018-01-30

    No licensed vaccine is currently available for prevention of Fasciola hepatica infections. However, considering the alarming increase in drug resistance, there is an urgent need for a safe and fully effective vaccine against fasciolosis. Here, we tested if cathepsins L (FhCL3-1, FhCL3-2) and B (FhCB3) secreted by juvenile liver flukes are viable vaccine targets when delivered alone or in combination in a rat model. Since control over the early immune response is crucial for parasite's establishment in its host, it was hypothesised that targeting fluke juvenile stages may prove beneficial. Moreover, it was assumed that selected antigens will act in a cumulative manner to interfere with liver fluke migration and thereby will reduce F. hepatica infection. Recombinant FhCL3-1 and FhCL3-2 delivered alone reduced liver fluke burdens by 47 % and 63 %, respectively. A trivalent vaccine containing rFhCL3-1/CL3-2/CB3 did not increase the protective vaccine efficacy compared to the rFhCL3-2 vaccinated group (53 %), although, reductions in liver fluke wet weight (statistically significant) and liver damage score were most pronounced. Further, the highest IgG1 and IgG2a levels were seen in rFhCL3-2 vaccinated rats, the group for which the highest reduction in worm burden was demonstrated. Moreover, IgG1 and IgG2a levels in vaccinated rats were significantly elevated compared to those reported for control groups up to 4 week post-infection. While the mechanism of protection remains unknown, it appears that it depends on vaccine-induced antibodies directed against cathepsins. The obtained results imply that F. hepatica juvenile-specific cathepsins are promising vaccine candidates that induce responses that successfully target early migratory liver fluke stages. Now, the challenge is to evaluate these juvenile-specific cathepsins for use in livestock. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Distribution of impurity states and charge transport in Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yuanfeng; Makongo, Julien P.A. [Laboratory for Emerging Energy and Electronic Materials, Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Page, Alexander [Department of Physics, University of Michigan, Ann Arbor, MI 48109 (United States); Sahoo, Pranati [Laboratory for Emerging Energy and Electronic Materials, Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Uher, Ctirad [Department of Physics, University of Michigan, Ann Arbor, MI 48109 (United States); Stokes, Kevin [The Advanced Materials Research Institute, Department of Physics, University of New Orleans, New Orleans, LA 70148 (United States); Poudeu, Pierre F.P., E-mail: ppoudeup@umich.edu [Laboratory for Emerging Energy and Electronic Materials, Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2016-02-15

    Energy filtering of charge carriers in a semiconducting matrix using atomically coherent nanostructures can lead to a significant improvement of the thermoelectric figure of merit of the resulting composite. In this work, several half-Heusler/full-Heusler (HH/FH) nanocomposites with general compositions Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} (0≤x≤0.15 and y=0.005, 0.01 and 0.025) were synthesized in order to investigate the behavior of extrinsic carriers at the HH/FH interfaces. Electronic transport data showed that energy filtering of carriers at the HH/FH interfaces in Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} samples strongly depends on the doping level (y value) as well as the energy levels occupied by impurity states in the samples. For example, it was found that carrier filtering at HH/FH interfaces is negligible in Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 1−y}Sb{sub y} (y=0.01 and 0.025) composites where donor states originating from Sb dopant dominate electronic conduction. However, we observed a drastic decrease in the effective carrier density upon introduction of HH/FH interfaces for the mechanically alloyed Zr{sub 0.25}Hf{sub 0.75}Ni{sub 1+x}Sn{sub 0.995}Sb{sub 0.005} samples where donor states from unintentional Fe impurities contribute the largest fraction of conduction electrons. This work demonstrates the ability to synergistically integrate the concepts of doping and energy filtering through nanostructuring for the optimization of electronic transport in semiconductors. - Graphical abstract: Electronic transport in semiconducting half-Heusler (HH) matrices containing full-Heusler (FH) nanoinclusions strongly depends on the energy distribution of impurity states within the HH matrix with respect to the magnitude of the potential energy barrier at the HH/FH interfaces. - Highlights: • Coherent nanostructures enhanced thermoelectric behavior of half-Heusler alloys. • Nanostructures act as energy filter of