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

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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.

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.

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...

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

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.

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

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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.

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

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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.

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

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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.

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

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 ...

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

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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.

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...

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

F/H Lab

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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...

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...

[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.

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

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

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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.

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

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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.

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

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.

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)

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

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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.

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.

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.

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.

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

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.

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

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

"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.

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.

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.

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)

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

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.

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...

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

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.

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

The aconitate hydratase family from Citrus

Directory of Open Access Journals (Sweden)

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

[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.

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

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.

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

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

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.

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.

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

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

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.

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

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

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

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

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.

[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.

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.

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).

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)

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.

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.

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

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....

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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

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

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.

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.

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.

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

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

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

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.

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.

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

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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".

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

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

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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.

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

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.

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.

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.

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

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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.

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.

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

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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.

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

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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.

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

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

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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

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.

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

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.

TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State

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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.

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

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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.

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

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.

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.

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

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...

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

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.

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

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 ...

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 ...

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.

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.

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.

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.

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.

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.

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

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

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% ...

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

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.

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.

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.

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.

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

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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.

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

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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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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

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

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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

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

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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.

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

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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.

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.

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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.

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

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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.

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

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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

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

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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.

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)

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

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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

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

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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

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

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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.

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

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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.

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)

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.

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.

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.

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.

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...

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.

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

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.

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)

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)

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

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.

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.

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.

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.

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.

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...

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.

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)

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

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

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.

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

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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.

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.

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.

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

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....

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

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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.

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

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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.

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

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.

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

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

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.

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

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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.

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

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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.

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.

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.

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

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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.

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.

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.

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

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

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...

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.

Elevated factor H-related protein 1 and factor H pathogenic variants decrease complement regulation in IgA nephropathy.

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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.

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.

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

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

Human regulatory B cells control the TFH cell response.

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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.

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

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

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.

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.

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.

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.

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.

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

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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.

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

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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.

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.

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.

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.

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.

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

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

[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.

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.

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...

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.

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.

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

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

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...

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.

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 ...

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.

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.

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.

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.

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.

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)

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)

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).

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.

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

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.

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.

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

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

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

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

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.

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

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.).

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.

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.

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

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.

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.

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.

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

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.

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.

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...

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

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...

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

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...

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.

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.

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.

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.

[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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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

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

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

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.

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.

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.

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

On Analog of Fourier Transform in Interior of the Light Cone

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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.

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

GenBank blastx search result: AK287540 [KOME

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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 ...

GenBank blastx search result: AK243510 [KOME

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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 ...

GenBank blastx search result: AK243527 [KOME

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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 ...

GenBank blastx search result: AK241214 [KOME

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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 ...

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

Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials.

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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.

Mesenchymal Stem Cells Control Complement C5 Activation by Factor H in Lupus Nephritis

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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

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

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.

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.

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.

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.

Polymorphisms of the low-density lipoprotein receptor gene in Brazilian individuals with heterozygous familial hypercholesterolemia

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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.

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.

Zero tillage: A potential technology to improve cotton yield

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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.

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.

The effect of human factor H on immunogenicity of meningococcal native outer membrane vesicle vaccines with over-expressed factor H binding protein.

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Peter T Beernink

Full Text Available The binding of human complement inhibitors to vaccine antigens in vivo could diminish their immunogenicity. A meningococcal ligand for the complement down-regulator, factor H (fH, is fH-binding protein (fHbp, which is specific for human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles (NOMV from mutant strains with over-expressed fHbp are in clinical development. In a previous study in transgenic mice, the presence of human fH impaired the immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001 and 4-fold higher complement-mediated bactericidal titers against a PorA-heterologous strain than the NOMV with the mutant fHbp (P = 0.003. By adsorption, the bactericidal antibodies were shown to be directed at fHbp. In transgenic mice in which human fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002, and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp (P = 0.001. Thus, in mice that differed only by the presence of human fH, the respective results with the two vaccines were opposite. The enhanced bactericidal activity elicited by the mutant fHbp vaccine in the presence of human fH far outweighed the loss of immunogenicity of the mutant protein in wild-type animals. Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may increase vaccine immunogenicity in humans.

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.

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.

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.

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.

Examination of chromosome 7p22 candidate genes RBaK, PMS2 and GNA12 in familial hyperaldosteronism type II.

Science.gov (United States)

Jeske, Y W A; So, A; Kelemen, L; Sukor, N; Willys, C; Bulmer, B; Gordon, R D; Duffy, D; Stowasser, M

2008-04-01

1. There are two types of familial hyperaldosteronism (FH): FH-I and FH-II. FH-I is caused by a hybrid CYP11B1/CYP11B2 gene mutation. The genetic cause of FH-II, which is more common, is unknown. Adrenal hyperplasia and adenomas are features. We previously reported linkage of FH-II to a approximately 5 Mb region on chromosome 7p22. We subsequently reported finding no causative mutations in the retinoblastoma-associated Kruppel-associated box gene (RBaK), a candidate at 7p22 involved in tumorigenesis and cell cycle control. 2. In the current study we investigated RBaK regulatory regions and two other candidate genes: postmeiotic segregation increased 2 (PMS2, involved in DNA mismatch repair and tumour predisposition) and guanine nucleotide-binding protein alpha-12 (GNA12, a transforming oncogene). 3. The GNA12 and PMS2 genes were examined in two affected (A1, A2) and two unaffected (U1, U2) subjects from a large 7p22-linked FH-II family (family 1). No mutations were found. 4. The RBaK and PMS2 distal promoters were sequenced to -2150 bp from the transcription start site for RBaK and-2800 bp for PMS2. Five unreported single nucleotide polymorphisms (SNPs) were found in subjects A1, A2 but not in U1 or U2; A(-2031 bp)T, T(-2030 bp)G, G(-834 bp)C, C(-821 bp)G in RBaK and A(-876 bp)G in PMS2. Additional affected and unaffected subjects from family 1 and from two other 7p22-linked FH-II families and 58 unrelated normotensive control subjects were genotyped for these SNPs. 5. The five novel SNPs were found to be present in a significant proportion of normotensive controls. The four RBaK promoter SNPs were found to be in linkage disequilibrium in the normal population. The RBaK promoter (-)2031T/2030G/834C/821T allele was found to be in linkage disequilibrium with the causative mutation in FH-II family 1, but not in families 2 and 3. The PMS2 promoter (-)876G allele was also found to be linked to affected phenotypes in family 1. 6. The RBaK and PMS2 promoter SNPs alter the

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.

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 ...

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

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...

Portuguese Familial Hypercholesterolemia Study: presentation of the study and preliminary results.

Science.gov (United States)

Bourbon, Mafalda; Rato, Quitéria

2006-11-01

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder caused, in the majority of cases, by a partial or total lack of functional low density lipoprotein receptors (LDLR). Mutations in the LDLR gene lead to increased plasma cholesterol levels, resulting in cholesterol deposition in the arteries, thereby increasing the risk of premature coronary heart disease. The homozygous form of FH is rare but heterozygous FH is common, although underdiagnosed in many populations, including the Portuguese. In 1999 the Portuguese Familial Hypercholesterolemia Study was begun at the National Institute of Health. The aim of the Portuguese Familial H ypercholesterolemia Study is to perform an epidemiological study to determine the prevalence and distribution of FH in Portugal and to better understand the pathophysiology of coronary heart disease in these patients. The aim of the present work is to present the study's criteria and organization as well as its preliminary results. The study population consists of individuals of both sexes and all ages with a clinical diagnosis of FH, with biochemical and molecular characterization being performed. The clinical criteria used for the diagnosis of FH were adapted from those of the Simon Broome Heart Research Trust. The study is organized in five stages: 1. selection of individuals with a clinical diagnosis of FH; 2. completion of a clinical questionnaire and declaration of informed consent; 3. collection of blood samples; 4. biochemical characterization; 5. molecular study of three genes associated with the FH phenotype: LDLR, apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). Between 1999 and June 2006 the LDLR gene and the APOB gene of 141 index cases (38 children and 103 adults) were studied. In 78 of these index cases (76 heterozygotes and two homozygotes) 50 different mutations in the LDLR gene were identified, and two unrelated individuals were found to have the ApoB3500 mutation

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.

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.

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.

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

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

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.

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

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.

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.

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.

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.

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.

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...

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

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

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

Monoclonal antibodies to meningococcal factor H binding protein with overlapping epitopes and discordant functional activity.

Science.gov (United States)

Giuntini, Serena; Beernink, Peter T; Reason, Donald C; Granoff, Dan M

2012-01-01

Meningococcal factor H binding protein (fHbp) is a promising vaccine candidate. Anti-fHbp antibodies can bind to meningococci and elicit complement-mediated bactericidal activity directly. The antibodies also can block binding of the human complement down-regulator, factor H (fH). Without bound fH, the organism would be expected to have increased susceptibility to bacteriolysis. Here we describe bactericidal activity of two anti-fHbp mAbs with overlapping epitopes in relation to their different effects on fH binding and bactericidal activity. Both mAbs recognized prevalent fHbp sequence variants in variant group 1. Using yeast display and site-specific mutagenesis, binding of one of the mAbs (JAR 1, IgG3) to fHbp was eliminated by a single amino acid substitution, R204A, and was decreased by K143A but not by R204H or D142A. The JAR 1 epitope overlapped that of previously described mAb (mAb502, IgG2a) whose binding to fHbp was eliminated by R204A or R204H substitutions, and was decreased by D142A but not by K143A. Although JAR 1 and mAb502 appeared to have overlapping epitopes, only JAR 1 inhibited binding of fH to fHbp and had human complement-mediated bactericidal activity. mAb502 enhanced fH binding and lacked human complement-mediated bactericidal activity. To control for confounding effects of different mouse IgG subclasses on complement activation, we created chimeric mAbs in which the mouse mAb502 or JAR 1 paratopes were paired with human IgG1 constant regions. While both chimeric mAbs showed similar binding to fHbp, only JAR 1, which inhibited fH binding, had human complement-mediated bactericidal activity. The lack of human complement-mediated bactericidal activity by anti-fHbp mAb502 appeared to result from an inability to inhibit binding of fH. These results underscore the importance of inhibition of fH binding for anti-fHbp mAb bactericidal activity.

Ambulatory 24-hour multichannel intraluminal impedance-pH monitoring and high resolution endoscopy distinguish patients with non-erosive reflux disease from those with functional heartburn.

Directory of Open Access Journals (Sweden)

Chuanlian Chu

Full Text Available To assess the contribution of 24-h esophageal multichannel intraluminal impedance and pH (MII-pH monitoring and high resolution endoscopy (HRE with i-scan imaging in differentiating non erosive reflux disease (NERD from functional heartburn (FH.This is a retrospective cohort study of patients with heartburn from the Endoscopy Unit. NERD patients and FH patients were defined by 24-h MII-pH monitoring and white light endoscopy. Minimal mucosal changes were assessed by HRE with i-scan imaging.Total of 156 consecutive patients with heartburn but without esophageal mucosal erosions were studied. Forty-eight of these subjects had NERD, with increased acid exposure time (AET and positive SAP and/or SI. Eighteen had FH with normal AET and negative SAP and SI. When compared to FH patients and healthy controls, NERD patients had significantly increased number of total acid reflux episodes, as well as increased number of weakly acidic reflux episodes (p<0.01. The rate of proximal reflux episodes in NERD patients was higher than that of FH patients and healthy controls (p<0.01. Irregular or blurring of the Z-line (58.3% and white mucosal turbidity (47.9% were the most common endoscopic findings of minimal mucosal changes observed in this study. NERD patients had more prevalent minimal changes than FH patients and the controls (87.5%vs. 66.6%vs. 61.9%; p = 0.004 with sensitivity of 87.5%. Histopathological evaluation showed that NERD patients had significantly higher average scores of intercellular spaces dilation (2.82±0.9 vs. 1.2±0.6, p = 0.005 and papillae elongation (2.65±1.0 vs. 1.5±0.8, p = 0.014, but not for basal cell proliferation (1.6±1.3 vs. 1.0±0.9, p = 0.070. The histological scores of the NERD patients were 7.1±1.2, which were higher than those of FH patients (3.4±1.0, p = 0.004.Minimal mucosal changes could be useful markers to support clinical diagnosis of NERD. Combination of 24-h MII-pH monitoring and i-scan high resolution

Ambulatory 24-hour multichannel intraluminal impedance-pH monitoring and high resolution endoscopy distinguish patients with non-erosive reflux disease from those with functional heartburn.

Science.gov (United States)

Chu, Chuanlian; Du, Quanlin; Li, Changqing; Zhang, Linlu; Zhou, Xiaoyan; Zuo, Fang; Zhang, Yanmin; Li, Fang; Xie, Guofeng; Li, Yanqing

2017-01-01

To assess the contribution of 24-h esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring and high resolution endoscopy (HRE) with i-scan imaging in differentiating non erosive reflux disease (NERD) from functional heartburn (FH). This is a retrospective cohort study of patients with heartburn from the Endoscopy Unit. NERD patients and FH patients were defined by 24-h MII-pH monitoring and white light endoscopy. Minimal mucosal changes were assessed by HRE with i-scan imaging. Total of 156 consecutive patients with heartburn but without esophageal mucosal erosions were studied. Forty-eight of these subjects had NERD, with increased acid exposure time (AET) and positive SAP and/or SI. Eighteen had FH with normal AET and negative SAP and SI. When compared to FH patients and healthy controls, NERD patients had significantly increased number of total acid reflux episodes, as well as increased number of weakly acidic reflux episodes (p<0.01). The rate of proximal reflux episodes in NERD patients was higher than that of FH patients and healthy controls (p<0.01). Irregular or blurring of the Z-line (58.3%) and white mucosal turbidity (47.9%) were the most common endoscopic findings of minimal mucosal changes observed in this study. NERD patients had more prevalent minimal changes than FH patients and the controls (87.5%vs. 66.6%vs. 61.9%; p = 0.004) with sensitivity of 87.5%. Histopathological evaluation showed that NERD patients had significantly higher average scores of intercellular spaces dilation (2.82±0.9 vs. 1.2±0.6, p = 0.005) and papillae elongation (2.65±1.0 vs. 1.5±0.8, p = 0.014), but not for basal cell proliferation (1.6±1.3 vs. 1.0±0.9, p = 0.070). The histological scores of the NERD patients were 7.1±1.2, which were higher than those of FH patients (3.4±1.0, p = 0.004). Minimal mucosal changes could be useful markers to support clinical diagnosis of NERD. Combination of 24-h MII-pH monitoring and i-scan high resolution endoscopy

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

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

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

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...

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.

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.

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

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.

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

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

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

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.

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.

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

Advanced operator interface design for CANDU-3 fuel handling system

Energy Technology Data Exchange (ETDEWEB)

Arapakota, D [Atomic Energy of Canada Ltd., Saskatoon, SK (Canada)

1996-12-31

The Operator Interface for the CANDU 3 Fuel Handling (F/H) System incorporates several improvements over the existing designs. A functionally independent sit-down CRT (cathode-ray tube) based Control Console is provided for the Fuel Handling Operator in the Main Control Room. The Display System makes use of current technology and provides a user friendly operator interface. Regular and emergency control operations can be carried out from this control console. A stand-up control panel is provided as a back-up with limited functionality adequate to put the F/H System in a safe state in case of an unlikely non-availability of the Plant Display System or the F/H Control System`. The system design philosophy, hardware configuration and the advanced display system features are described in this paper The F/H Operator Interface System developed for CANDU 3 can be adapted to CANDU 9 as well as to the existing stations. (author).

Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

Science.gov (United States)

Cordes, Frank S; Kraiczy, Peter; Roversi, Pietro; Simon, Markus M; Brade, Volker; Jahraus, Oliver; Wallis, Russell; Goodstadt, Leo; Ponting, Chris P; Skerka, Christine; Zipfel, Peter F; Wallich, Reinhard; Lea, Susan M

2006-05-01

Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design.

Professional knowledge in primary health care of the person/family in mental distress: Le Boterf perspective

Directory of Open Access Journals (Sweden)

Roselma Lucchese

2014-12-01

Full Text Available Aim of this study was to identify knowing-doing actions constituted the practice of Family Health (FH, in view of nurses in relation to the person and family care in mental distress in terms of professional knowledge of Le Boterf. Method: Descriptive exploratory qualitative study, to deepen contruction of nurse in FH. The survey was conducted in 3 Units FH. Result: Doing a thematic analysis, came to the following categories: “Knowing how to act and react with relevance”; “Knowing how to combine resources and mobilize them in a professional context”; “Knowing how to interact with multiple knowledges”; “Knowing how to transpose”; “Knowing how to learn and knowing how to learn to learn”; “Knowing how to engage”. Final considerations: the greatest difficulty was "be able to transpose," and that the daily demand of the FH teams requires a lot of this knowledge. Little transposition of knowing-doing in real situations has been verified.

Homozygous familial hypercholesterolaemia

DEFF Research Database (Denmark)

Cuchel, Marina; Bruckert, Eric; Ginsberg, Henry N

2014-01-01

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the......AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights...... into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance...... 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and...

Advanced operator interface design for CANDU-3 fuel handling system

International Nuclear Information System (INIS)

Arapakota, D.

1995-01-01

The Operator Interface for the CANDU 3 Fuel Handling (F/H) System incorporates several improvements over the existing designs. A functionally independent sit-down CRT (cathode-ray tube) based Control Console is provided for the Fuel Handling Operator in the Main Control Room. The Display System makes use of current technology and provides a user friendly operator interface. Regular and emergency control operations can be carried out from this control console. A stand-up control panel is provided as a back-up with limited functionality adequate to put the F/H System in a safe state in case of an unlikely non-availability of the Plant Display System or the F/H Control System'. The system design philosophy, hardware configuration and the advanced display system features are described in this paper The F/H Operator Interface System developed for CANDU 3 can be adapted to CANDU 9 as well as to the existing stations. (author)

Daily life, experience and needs of persons suffering from homozygous familial hypercholesterolaemia: insights from a patient survey.

Science.gov (United States)

Bruckert, Eric; Saheb, Samir; Bonté, Juliette Roth; Coudray-Omnès, Carole

2014-09-01

Homozygous familial hypercholesterolaemia (HoFH) is a rare and severe hereditary lipid disorder that is typically associated with high serum levels of low-density lipoprotein cholesterol (LDL-C). Excessive exposure to high levels of LDL-C puts affected individuals at very high risk of premature onset coronary heart disease, and this considerably limits life expectancy. Although the clinical features and treatment of HoFH have been extensively researched, societal and socio-psychological impacts of the disease have not been reported to date. The current study was conducted to investigate the burden of disease and treatment from the patient's perspective by means of semi-structured interviews with 24 HoFH patients. The findings of the survey indicate that HoFH represents a considerable burden for patients, not only due to physical signs and limitations caused by the disease but also a number of psychosocial factors, treatment-related issues and impact on their education and employment situation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Physical capture and release of drug molecules, water and cations by a smectite clay

DEFF Research Database (Denmark)

Carvalho dos Santos, Éverton

-fluorohectorite (LiFh, Li1.2(Mg4.8Li1.2)Si8O20F4), a synthetic clay mineral from the smectite family, have been experimentally analyzed. By means of X-rays powder diffraction (XRD), using both an in-house instrument and synchrotron radiation, UV-Vis spectroscopy, Thermogravimetric Analysis coupled to an Infrared......-analysis and inelastic neutron scattering data we established that the drug presence into the interlayer space of Fh is weakening the water-clay interactions. Furthermore, CIPRO’s release from Fh in synthetic gastric acid juice (SGA) as a function of time and temperature was also carefully followed. Our studies showed...... and toxicological tests, we demonstrated that the effectiveness and toxicity of pure CIPRO is unaffected in the clay-drug complex. To conclude, the high drug adsorption capacity as well as the slow and gradual release from CIPRO when intercalated in Fh adds this synthetic smectite to the list of promising drug...

Pilot-scale ultrafiltration testing for the F and H area effluent treatment facility

International Nuclear Information System (INIS)

Kessler, J.L.

1984-01-01

An F and H Area Effluent Treatment Facility (F/H ETF) is being designed to treat low activity aqueous effluents which are produced from F and H Area daily operations. The treatment scheme for the F/H ETF will include pretreatment (pH adjustment and filtration) followed by Reverse Osmosis and/or Ion Exchange to remove dissolved species. Several alternative treatment processes are being considered for the F/H ETF. One of the alternatives in the pretreatment step is tubular Ultrafiltration (UF), using a dynamically formed zirconium oxide membrane supported on a porous stainless steel backing. Pilot-scale testing with a single membrane module (13 ft 2 area) and 200-Area effluent simulant has demonstrated that UF is a viable filtration option for the F/H ETF. UF testing at TNX has defined the operating conditions necessary for extended operation and also demonstrated excellent filtration performance (filtrate SDI 2 /day) flux and will provide excellent pretreatment for both reverse osmosis and ion exchange. 2 refs

Evaluation and Characterization of Fasciola hepatica Tegument Protein Extract for Serodiagnosis of Human Fascioliasis

Science.gov (United States)

Morales, Adelaida

2012-01-01

Tegument protein extract from Fasciola hepatica adult flukes (FhTA) was obtained and assessed for its potential as a diagnostic agent for the serological detection of human fascioliasis using an indirect enzyme-linked immunosorbent assay (ELISA). In an analysis of sera from 45 patients infected with F. hepatica, sera from 41 patients with other parasitic infections, and sera from 33 healthy controls, the FhTA-ELISA showed sensitivity, specificity, and accuracy of 91.1%, 97.3%, and 95%, respectively. Specific IgG1 and IgG4 were the antibody isotypes mainly detected in sera from patients with fascioliasis. Polypeptides of 52, 38, 24 to 26, and 12 to 14 kDa were identified by Western blotting as the most immunoreactive components of the FhTA. A proteomic approach led us to identify enolase, aldolase, glutathione S-transferase, and fatty acid binding protein as the major immunoreactive components of the FhTA. PMID:23015645

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)

How accurately can we estimate energetic costs in a marine top predator, the king penguin?

Science.gov (United States)

Halsey, Lewis G; Fahlman, Andreas; Handrich, Yves; Schmidt, Alexander; Woakes, Anthony J; Butler, Patrick J

2007-01-01

King penguins (Aptenodytes patagonicus) are one of the greatest consumers of marine resources. However, while their influence on the marine ecosystem is likely to be significant, only an accurate knowledge of their energy demands will indicate their true food requirements. Energy consumption has been estimated for many marine species using the heart rate-rate of oxygen consumption (f(H) - V(O2)) technique, and the technique has been applied successfully to answer eco-physiological questions. However, previous studies on the energetics of king penguins, based on developing or applying this technique, have raised a number of issues about the degree of validity of the technique for this species. These include the predictive validity of the present f(H) - V(O2) equations across different seasons and individuals and during different modes of locomotion. In many cases, these issues also apply to other species for which the f(H) - V(O2) technique has been applied. In the present study, the accuracy of three prediction equations for king penguins was investigated based on validity studies and on estimates of V(O2) from published, field f(H) data. The major conclusions from the present study are: (1) in contrast to that for walking, the f(H) - V(O2) relationship for swimming king penguins is not affected by body mass; (2) prediction equation (1), log(V(O2) = -0.279 + 1.24log(f(H) + 0.0237t - 0.0157log(f(H)t, derived in a previous study, is the most suitable equation presently available for estimating V(O2) in king penguins for all locomotory and nutritional states. A number of possible problems associated with producing an f(H) - V(O2) relationship are discussed in the present study. Finally, a statistical method to include easy-to-measure morphometric characteristics, which may improve the accuracy of f(H) - V(O2) prediction equations, is explained.

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

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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.

Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn.

Science.gov (United States)

Savarino, Edoardo; Zentilin, Patrizia; Mastracci, Luca; Dulbecco, Pietro; Marabotto, Elisa; Gemignani, Lorenzo; Bruzzone, Luca; de Bortoli, Nicola; Frigo, Anna Chiara; Fiocca, Roberto; Savarino, Vincenzo

2013-04-01

Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH). Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n = 5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was >0.35. The prevalence of ME was higher (p < 0.0001) in EE (95 %), pH-POS (77 %), and HE (65 %) NERD patients than in FH patients (13 %) and HVs (15 %). Also, basal cell hyperplasia (p < 0.0023), DIS (p < 0.0001), and papillae elongation (p < 0.0002) showed similar rates of prevalence in the above populations (p < 0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p = 0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p < 0.0001 and p < 0.0001, respectively). The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy.

AAV-mediated knock-down of HRC exacerbates transverse aorta constriction-induced heart failure.

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Chang Sik Park

Full Text Available Histidine-rich calcium binding protein (HRC is located in the lumen of sarcoplasmic reticulum (SR that binds to both triadin (TRN and SERCA affecting Ca(2+ cycling in the SR. Chronic overexpression of HRC that may disrupt intracellular Ca(2+ homeostasis is implicated in pathogenesis of cardiac hypertrophy. Ablation of HRC showed relatively normal phenotypes under basal condition, but exhibited a significantly increased susceptibility to isoproterenol-induced cardiac hypertrophy. In the present study, we characterized the functions of HRC related to Ca(2+ cycling and pathogenesis of cardiac hypertrophy using the in vitro siRNA- and the in vivo adeno-associated virus (AAV-mediated HRC knock-down (KD systems, respectively.AAV-mediated HRC-KD system was used with or without C57BL/6 mouse model of transverse aortic constriction-induced failing heart (TAC-FH to examine whether HRC-KD could enhance cardiac function in failing heart (FH. Initially we expected that HRC-KD could elicit cardiac functional recovery in failing heart (FH, since predesigned siRNA-mediated HRC-KD enhanced Ca(2+ cycling and increased activities of RyR2 and SERCA2 without change in SR Ca(2+ load in neonatal rat ventricular cells (NRVCs and HL-1 cells. However, AAV9-mediated HRC-KD in TAC-FH was associated with decreased fractional shortening and increased cardiac fibrosis compared with control. We found that phospho-RyR2, phospho-CaMKII, phospho-p38 MAPK, and phospho-PLB were significantly upregulated by HRC-KD in TAC-FH. A significantly increased level of cleaved caspase-3, a cardiac cell death marker was also found, consistent with the result of TUNEL assay.Increased Ca(2+ leak and cytosolic Ca(2+ concentration due to a partial KD of HRC could enhance activity of CaMKII and phosphorylation of p38 MAPK, causing the mitochondrial death pathway observed in TAC-FH. Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through

Lipoprotein metabolism in familial hypercholesterolemia: Serial assessment using a one-step ultracentrifugation method

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Hayato Tada

2015-04-01

Full Text Available Objectives: It is well known that familial hypercholesterolemia (FH is a common inherited disorder that can markedly elevate the level of plasma LDL cholesterol. However, little data exists regarding the clinical impact of the plasma triglyceride (TG-rich lipoprotein fraction, including VLDL and IDL, in FH. Thus, we assessed the hypothesis that the mutations in the LDL receptor modulate lipoprotein metabolism other than the LDL fraction. Design and methods: We investigated plasma lipoprotein with a one-step ultracentrifugation method for 146 controls (mean age=61.4±17.1 yr, mean LDL cholesterol=92.7±61.2 mg/dl, 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0 yr, mean LDL cholesterol=225.1±61.2 mg/dl, and 16 homozygous/compound heterozygous mutation-determined FH subjects (mean age=26.9±17.1 yr, mean LDL cholesterol=428.6±86.1 mg/dl. In addition, we evaluated cholesterol/TG ratio in each lipoprotein fraction separated by ultracentrifugation. Results: In addition to total cholesterol and LDL cholesterol levels, VLDL cholesterol (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively and IDL cholesterol (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively exhibited a tri-model distribution according to their status in LDL receptor mutation(s. Moreover, the ratios of cholesterol/TG of each lipoprotein fraction increased significantly in heterozygous FH and homozygous/compound heterozygous FH groups, compared with that of controls, suggesting that the abnormality in LDL receptor modulates the quality as well as the quantity of each lipoprotein fraction. Conclusions: Our results indicate that cholesterol in TG-rich lipoproteins, including VLDL and IDL, are significantly higher in FH subjects, revealing a tri-modal distribution according to the number of LDL receptor mutations. Keywords: LDL cholesterol, Familial hypercholesterolemia, Ultracentrifugation, Lipoprotein

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

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

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

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.

Family history of premature myocardial infarction, life course socioeconomic position and coronary heart disease mortality--A Cohort of Norway (CONOR) study.

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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.

Low-density lipoprotein apheresis: an evidence-based analysis.

Science.gov (United States)

2007-01-01

To assess the effectiveness and safety of low-density lipoprotein (LDL) apheresis performed with the heparin-induced extracorporeal LDL precipitation (HELP) system for the treatment of patients with refractory homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH). BACKGROUND ON FAMILIAL HYPERCHOLESTEROLEMIA: Familial hypercholesterolemia is a genetic autosomal dominant disorder that is caused by several mutations in the LDL-receptor gene. The reduced number or absence of functional LDL receptors results in impaired hepatic clearance of circulating low-density lipoprotein cholesterol (LDL-C) particles, which results in extremely high levels of LDL-C in the bloodstream. Familial hypercholesterolemia is characterized by excess LDL-C deposits in tendons and arterial walls, early onset of atherosclerotic disease, and premature cardiac death. Familial hypercholesterolemia occurs in both HTZ and HMZ forms. Heterozygous FH is one of the most common monogenic metabolic disorders in the general population, occurring in approximately 1 in 500 individuals. Nevertheless, HTZ FH is largely undiagnosed and an accurate diagnosis occurs in only about 15% of affected patients in Canada. Thus, it is estimated that there are approximately 3,800 diagnosed and 21,680 undiagnosed cases of HTZ FH in Ontario. In HTZ FH patients, half of the LDL receptors do not work properly or are absent, resulting in plasma LDL-C levels 2- to 3-fold higher than normal (range 7-15mmol/L or 300-500mg/dL). Most HTZ FH patients are not diagnosed until middle age when either they or one of their siblings present with symptomatic coronary artery disease (CAD). Without lipid-lowering treatment, 50% of males die before the age of 50 and 25% of females die before the age of 60, from myocardial infarction or sudden death. In contrast to the HTZ form, HMZ FH is rare (occurring in 1 case per million persons) and more severe, with a 6- to 8-fold elevation in plasma LDL-C levels (range 15-25mmol

Family history suggestive of an inherited susceptibility to breast cancer and treatment outcome in young women after breast-conserving therapy

International Nuclear Information System (INIS)

Chabner, E.; Nixon, A.J.; Garber, J.; Gelman, R.; Bornstein, B.; Connolly, J.; Hetelekidis, S.; Recht, A.; Schnitt, S.; Silver, B.; Harris, J.R.

1997-01-01

PURPOSE: To determine whether outcome after conservative surgery and radiation therapy for young women is affected by having a family history (FH) suggestive of an inherited susceptibility to breast cancer. MATERIALS AND METHODS: Between 1968 and 1986, 205 patients 36 years of age or younger at diagnosis were treated with breast-conserving surgery and radiation therapy for clinical stage I or II invasive breast cancer. Three patients were not evaluable for FH; the remainder constitute the study population. At the time of diagnosis, 34 patients (17%; 95% CI 12-29%) had a mother or sister who had breast cancer diagnosed before age 50 years or who had ovarian cancer (2 cases) and were recorded as having a positive FH. This definition was chosen for clinical utility and to maximize the probability of inherited breast cancer within this sub-group (average 40-50%). Without genetic testing, the possibility of misclassification exists in both groups. The median age at diagnosis of the 34 patients with a positive FH was 33 years and was the same as the median age of the 168 patients in whom the FH was negative. All but 2 patients (99%) had a potential follow-up time of at least 5 years; 173 patients (86%) had a potential follow-up time of at least 10 years. RESULTS: Distributions of tumor size, pathologic nodal involvement, histologic type, histologic grade, the presence of an extensive intraductal component or lymphatic vascular invasion, volume of tissue excised, and use of adjuvant chemotherapy did not differ significantly by FH. The distribution of the sites of first failure within the first 5 years of follow-up is shown. The overall pattern of failure was significantly different (p=0.03) between patients with a positive FH and those with a negative FH; however, there was no statistically significant difference (Fisher Exact Test) in percentage of patients with no evidence of disease or local failure. At 5 years follow-up, the development of an opposite breast cancer

On the convergence of nonlinear Beltrami type operators

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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.

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.

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.)

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

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.

Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia

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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.

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.

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.

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.

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.

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.)

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.

AcEST: DK948452 [AcEST

Lifescience Database Archive (English)

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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

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...

Preliminary antigenic characterisation of an adult worm vomit preparation of Fasciola hepatica by infected human sera Caracterização antigênica preliminar de preparação de vômito de verme adulto de Fasciola hepatica por soros humanos infectados

Directory of Open Access Journals (Sweden)

María Alejandra De Almeida

2007-02-01

Full Text Available Fascioliasis is an emerging/re-emerging vector-borne disease with the widest known distribution. Approximately 17 million people are infected around the world, being the Andean region the most affected area. There is an important necessity to develop sensitive and specific diagnostic tools to treat patients early and to avoid complications. In this paper we evaluated the immune response of infected humans against two antigenic preparations: the total soluble extract (FhTSE and the adult worm vomit (FhAWV in order to identify antigenic fractions specific for Fasciola hepatica. Both preparations were processed by SDS-PAGE and Western blot with human sera with fascioliasis (F, other parasitosis and healthy individuals. In the immunoblot of FhTSE, sera F recognised 16 bands with MW between eight and 110 kDa, from which those of 8, 9, 10, 38, 45 and 57 kDa were specific. In the preparation FhAWV, sera F recognised nine bands with MW from eight to 85 kDa, from which those of 8, 12, 15 and 24 kDa were specific. Some bands of cross-reaction were evident with sera from patients with other parasitoses, more frequent with the FhTSE. Bands within the MW mentioned, particularly that of eight kDa, have been shown to be specific by others, and deserve additional characterisation for their potential use in immunodiagnosis.Fasciolíase é uma doença emergente/re-emergente transmitida por vetores com a distribuição sabidamente mais ampla. Existem aproximadamente 17 milhões de pessoas infectadas em todo mundo, sendo a região andina a área mais afetada. Há uma necessidade importante para desenvolver ferramentas diagnósticas sensíveis e específicas para tratar cedo os pacientes e para evitar complicações. Neste trabalho avaliamos a resposta imune de seres humanos infectados comparando a duas preparações antigênicas: o extrato solúvel total (FhTSE e o vômito (FhAWV do verme adulto a fim de identificar as frações antigênicas específicas para

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...

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.

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.

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.

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.

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.

Impact of arterial input function selection on the accuracy of dynamic contrast-enhanced MRI quantitative analysis for the diagnosis of clinically significant prostate cancer.

Science.gov (United States)

Azahaf, Mustapha; Haberley, Marc; Betrouni, Nacim; Ernst, Olivier; Behal, Hélène; Duhamel, Alain; Ouzzane, Adil; Puech, Philippe

2016-03-01

Using a limited temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) dataset to assess the impact of the arterial input function (AIF) choice on the transfer constant (K(trans) ) to distinguish prostate carcinoma (PCa) from benign tissue. Thirty-eight patients with clinically important peripheral PCa (≥0.5 cc) were retrospectively studied. These patients underwent 1.5T multiparametric prostate MR with PCa and benign regions of interest (ROIs) selected using a visual registration with morphometric reconstruction obtained from radical prostatectomy. Using three pharmacokinetic (PK) analysis software programs, the mean K(trans) of ROIs was computed using three AIFs: an individual AIF (Ind-AIF) and two literature population average AIFs of Weinmann (W-AIF) and of Fritz-Hansen (FH-AIF). A pairwise comparison of the area under the receiver operating characteristic curves (AUROCC) obtained with different AIFs was performed. AUROCCs obtained with W-AIF (ranging from 0.801 to 0.843) were significantly higher than FH-AIF (ranging from 0.698 to 0.780, 0.002 ≤ P ≤ 0.045) and similar to or higher than Ind-AIF (ranging from 0.591 to 0.839, 0.014 ≤ P ≤ 0.9). Ind-AIF and FH-AIF provided similar AUROCC (0.34 ≤ P ≤ 0.81). The pairwise correlation of K(trans) values was moderate to very strong when comparing W-AIF with FH-AIF (the Spearman's correlation coefficients [SCCs] ranged from 0.55 to 0.93) and very weak to moderate when comparing W-AIF with Ind-AIF (the SCCs ranged from 0.018 to 0.59) or FH-AIF with Ind-AIF (the SCCs ranged from 0.30 to 0.51). W-AIF yielded a higher performance than FH-AIF and a similar or higher performance than Ind-AIF in distinguishing PCa from benign tissue. © 2015 Wiley Periodicals, Inc.

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…

AcEST: DK952686 [AcEST

Lifescience Database Archive (English)

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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

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

The Optimal Dispatch of a Power System Containing Virtual Power Plants under Fog and Haze Weather

Directory of Open Access Journals (Sweden)

Yajing Gao

2016-01-01

Full Text Available With the growing influence of fog and haze (F-H weather and the rapid development of distributed energy resources (DERs and smart grids, the concept of the virtual power plant (VPP employed in this study would help to solve the dispatch problem caused by multiple DERs connected to the power grid. The effects of F-H weather on photovoltaic output forecast, load forecast and power system dispatch are discussed according to real case data. The wavelet neural network (WNN model was employed to predict photovoltaic output and load, considering F-H weather, based on the idea of “similar days of F-H”. The multi-objective optimal dispatch model of a power system adopted in this paper contains several VPPs and conventional power plants, under F-H weather, and the mixed integer linear programming (MILP and the Yalmip toolbox of MATLAB were adopted to solve the dispatch model. The analysis of the results from a case study proves the validity and feasibility of the model and the algorithms.

Elevated Atherosclerosis-Related Gene Expression, Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

DEFF Research Database (Denmark)

Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon

2015-01-01

OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypoth......OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate...... in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). APPROACH AND RESULTS: We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT......LDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT. CONCLUSIONS: Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly...

TFH-derived dopamine accelerates productive synapses in germinal centres.

Science.gov (United States)

Papa, Ilenia; Saliba, David; Ponzoni, Maurilio; Bustamante, Sonia; Canete, Pablo F; Gonzalez-Figueroa, Paula; McNamara, Hayley A; Valvo, Salvatore; Grimbaldeston, Michele; Sweet, Rebecca A; Vohra, Harpreet; Cockburn, Ian A; Meyer-Hermann, Michael; Dustin, Michael L; Doglioni, Claudio; Vinuesa, Carola G

2017-07-20

Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (T FH ) cells in germinal centres. The rapid T-B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human T FH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. T FH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human T FH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T-B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T-B-cell synapse may be advantageous in the face of infection.

Tribological properties of epoxy composite coatings reinforced with functionalized C-BN and H-BN nanofillers

Science.gov (United States)

Yu, Jingjing; Zhao, Wenjie; Wu, Yinghao; Wang, Deliang; Feng, Ruotao

2018-03-01

A series of epoxy resin (EP) composite coatings reinforced with functionalized cubic boron nitride (FC-BN) and functionalized hexagonal boron nitride (FH-BN) were fabricated successfully on 316L stainless steel by hand lay-up technique. The structure properties were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The morphologies were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Moreover, UMT-3 tribometer and surface profiler were used to investigate tribological behaviors of as-prepared composite coatings under dry friction and seawater conditions respectively. The results demonstrated that the presence of FC-BN or FH-BN fillers could greatly decrease the friction coefficient (COF) and wear rate of epoxy, in addition, composite coatings possess better tribological properties under seawater condition which was attributed to the lubricating effect of seawater. Moreover, FC-BN endows the composite coatings the highest wear resistance, and FH-BN /EP composite coatings exhibited the best friction reduction performance which is attributed to the self-lubricating performance of lamella structure for FH-BN sheet.

Familial hypercholesterolemia: A review

International Nuclear Information System (INIS)

Varghese, Mithun J

2014-01-01

Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism resulting in elevated serum low-density lipoprotein (LDL) cholesterol levels leading to increased risk for premature cardiovascular diseases (CVDs). The diagnosis of this condition is based on clinical features, family history, and elevated LDL-cholesterol levels aided more recently by genetic testing. As the atherosclerotic burden is dependent on the degree and duration of exposure to raised LDL-cholesterol levels, early diagnosis and initiation of treatment is paramount. Statins are presently the mainstay in the management of these patients, although newer drugs, LDL apheresis, and other investigational therapies may play a role in certain subsets of FH, which are challenging to treat. Together these novel treatments have notably improved the prognosis of FH, especially that of the heterozygous patients. Despite these achievements, a majority of children fail to attain targeted lipid goals owing to persistent shortcomings in diagnosis, monitoring, and treatment. This review aims to highlight the screening, diagnosis, goals of therapy, and management options in patients with FH

The Role of Esophageal Hypersensitivity in Functional Heartburn.

Science.gov (United States)

Kondo, Takashi; Miwa, Hiroto

2017-08-01

Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.

Electroconvection in one-dimensional liquid crystal cells

Science.gov (United States)

Huh, Jong-Hoon

2018-04-01

We investigate the alternating current (ac) -driven electroconvection (EC) in one-dimensional cells (1DCs) under the in-plane switching mode. In 1DCs, defect-free EC can be realized. In the presence and absence of external multiplicative noise, the features of traveling waves (TWs), such as their Hopf frequency fH and velocity, are examined in comparison with those of conventional two-dimensional cells (2DCs) accompanying defects of EC rolls. In particular, we show that the defects significantly contribute to the features of the TWs. Additionally, owing to the defect-free EC in the 1DCs, the effects of the ac and noise fields on the TW are clarified. The ac field linearly increases fH, independent of the ac frequency f . The noise increases fH monotonically, but fH does not vary below a characteristic noise intensity VN*. In addition, soliton-like waves and unfamiliar oscillation of EC vortices in 1DCs are observed, in contrast to the localized EC (called worms) and the oscillation of EC rolls in 2DCs.

The limited use of the fluency heuristic: Converging evidence across different procedures.

Science.gov (United States)

Pohl, Rüdiger F; Erdfelder, Edgar; Michalkiewicz, Martha; Castela, Marta; Hilbig, Benjamin E

2016-10-01

In paired comparisons based on which of two objects has the larger criterion value, decision makers could use the subjectively experienced difference in retrieval fluency of the objects as a cue. According to the fluency heuristic (FH) theory, decision makers use fluency-as indexed by recognition speed-as the only cue for pairs of recognized objects, and infer that the object retrieved more speedily has the larger criterion value (ignoring all other cues and information). Model-based analyses, however, have previously revealed that only a small portion of such inferences are indeed based on fluency alone. In the majority of cases, other information enters the decision process. However, due to the specific experimental procedures, the estimates of FH use are potentially biased: Some procedures may have led to an overestimated and others to an underestimated, or even to actually reduced, FH use. In the present article, we discuss and test the impacts of such procedural variations by reanalyzing 21 data sets. The results show noteworthy consistency across the procedural variations revealing low FH use. We discuss potential explanations and implications of this finding.

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

Repeatability in Color Measurements of a Spectrophotometer using Different Positioning Devices.

Science.gov (United States)

Hemming, Michael; Kwon, So Ran; Qian, Fang

2015-12-01

This study aimed to evaluate the repeatability of color measurements of an intraoral spectrophotometer with the use of three different methods by two operators. A total of 60 teeth were obtained, comprising 30 human maxillary teeth [central incisors (n = 10); canines (n = 10); molars (n = 10)] and 30 artificial teeth [lateral incisors (n = 10); premolar (n = 20)]. Multiple repeated color measurements were obtained from each tooth using three measuring methods by each of the two operators. Five typodonts with alternating artificial and human teeth were made. Measurements were taken by two operators with the Vita EasyShade spectrophotometer using the custom tray (CT), custom jig (CJ) and free hand (FH) method, twice, at an interval of 2 to 7 days. Friedman test was used to detect difference among the three color measuring methods. Post hoc Wilcoxon signed-rank test with Bonferroni correction applied was used for pair-wise comparison of color measurements among the three methods. Additionally, a paired-sample t-test was used to assess a significant difference between the two duplicated measurements made on the same tooth by the same operator for each color parameter and measuring method. For operator A, mean (SD) overall color change-ΔE* (SD) perceived for FH, CT and CJ were 2.21(2.00), 2.39 (1.58) and 2.86 (1.92), respectively. There was statistically significant difference in perceived ΔE* in FH vs CJ (p = 0.0107). However, there were no significant differences between FH and CT (p = 0.2829) or between CT and CJ (p = 0.1159). For operator B mean ΔE* (SD) for FH, CT and CJ were 3.24 (3.46), 1.95 (1.19) and 2.45 (1.56), respectively. There was a significant difference between FH and CT (p = 0.0031). However, there were no statistically significant differences in ΔE* in FH vs CJ (p = 0.3696) or CT vs CJ (p = 0.0809). The repeatability of color measurements was different among the three measuring methods by operators. Overall, the CT method worked well for both

Evaluation of lipid extractability after flash hydrolysis of algae

Energy Technology Data Exchange (ETDEWEB)

Teymouri, Ali; Adams, Kameron J.; Dong, Tao; Kumar, Sandeep

2018-07-01

Microalgae is identified as a promising feedstock for producing renewable liquid transportation fuels; however, lipids extraction from microalgae for downstream processing to biofuels is one of the important challenges for algal based biorefineries. This work aims at evaluating the potential of applying flash hydrolysis (FH) as a chemical-free technique to increase the lipids extractability of algal biomass as well as its integration with the hydrothermal liquefaction (HTL) of microalgae to enhance the biocrude yields and characteristics for fuel production. To this aim, the FH process was performed on three different algal species (Scenedesmus sp., Nannochloropsis sp., and Chlorella vulgaris) at 280 degrees C and 10 s of residence time. Following FH, in addition to the nutrients rich hydrolysate, approximately, 40 wt% of solids containing almost all (>90 wt%) the lipids termed as biofuels intermediates (BI), were recovered. Kinetics study on lipids extractability from the BI and their lipid profile analyses were conducted for each algal species. The results showed that the FH process had significantly enhanced the lipids extractability. For all three algae species, lipid yields from BI were higher than that of the raw algae. Lipid yields of Chlorella vulgaris in the first 15 min were more than five times higher (52.3 +/- 0.8 vs. 10.7 +/- 0.9 wt%) than that of raw algae during n-hexane based solvent extraction. The kinetics of lipids extractability followed a zero-order reaction rate for all wet raw microalgae and the BI of Scenedesmus sp., while the BI recovered from the other two algal species were determined as a second-order reaction. Comparison of fatty acids profiles indicated the contribution of the FH process in saturating fatty acids. Subsequent to lipids extraction, a conventional hydrothermal liquefaction was performed at 350 degrees C and 1 h to compare the biocrude yields from raw versus BI of Chlorella vulgaris microalgae. The results showed that the

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.

Lipoprotein-associated phospholipase A2 mass and activity in children with heterozygous familial hypercholesterolemia and unaffected siblings: effect of pravastatin.

Science.gov (United States)

Ryu, Sung Kee; Hutten, Barbara A; Vissers, Maud N; Wiegman, Albert; Kastelein, John J P; Tsimikas, Sotirios

2011-01-01

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent risk factor of cardiovascular disease and a target of treatment. Lp-PLA(2) levels in children have not been previously reported. The effect of statin therapy on Lp-PLA(2) mass and activity in children with familial hypercholesterolemia (FH) is also not known. Lp-PLA(2) mass and activity levels were measured at baseline and after 2 years in 178 children with FH randomized to pravastatin or placebo and in 78 unaffected and untreated siblings. At the end of the randomized period, all FH children were then placed on pravastatin for an additional 2 years, and Lp-PLA(2) mass and activity levels were correlated with changes in carotid intima-media thickness during 4 years of follow-up. Baseline levels of Lp-PLA(2) mass and activity were significantly greater in children with FH compared with unaffected siblings (mass: 240.3 ± 41.6 vs 222.1 ± 36.5 ng/mL, P = .002; activity: 205.7 ± 41.6 vs 124.3±23.0 nmol/min/mL, P vs 231.5 ± 34.8 ng/mL, P = .001) and activity (178.8 ± 37.3 vs 206.2 ± 33.5 nmol/min/mL, P children with heterozygous FH compared with unaffected siblings and are significantly reduced by pravastatin therapy. Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.

White Matter Brain Lesions in Midlife Familial Hypercholesterolemic Patients at 3-Tesla Magnetic Resonance Imaging

Energy Technology Data Exchange (ETDEWEB)

Schmitz, S.A.; O' Regan, D.P.; Fitzpatrick, J.; Neuwirth, C.; Potter, E.; Tosi, I.; Hajnal, J.V.; Naoumova, R.P. (Imaging Sciences Dept. and Clinical Research Facility, MRC Clinical Sciences Centre, London (GB))

2008-03-15

Background: Patients with hypercholesterolemia of 60 years and older have an increased risk for white matter brain lesions and dementia. Purpose: To investigate whether patients with familial hypercholesterolemia (FH) develop white matter lesions at 3-Tesla (T) MRI as early as in midlife. Material and Methods: Non-diabetic, non-smoking, and non-hypertensive heterozygous FH patients on treatment with maximally tolerated dose of a statin for more than 5 years (n = 14) and matched controls (n = 22) aged 25 to 60 years of age were studied. Imaging was performed at 3T with a fluid-attenuated T2-weighted MR pulse sequence and a T1-weighted spin-echo pulse sequence following 10 ml of i.v. gadopentetate dimeglumine. Images were evaluated by two independent readers. Fasting blood samples were taken. Student's t test was employed at P<0.05. Results: Three volunteers and one FH patient had white matter lesions (P<0.53). No other evidence of past ischemic stroke was observed. Mean total serum cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the FH group (6.0+-1.1 vs. 5.1+-0.9 mmol/l, P<0.02 and 4.1+-0.9 vs. 3.1+-0.8 mmol/l, P<0.004, respectively). Conclusion: Heterozygous FH patients on statin treatment in the age range of 25 to 60 years are not at increased risk of white matter lesions at 3T MRI

White Matter Brain Lesions in Midlife Familial Hypercholesterolemic Patients at 3-Tesla Magnetic Resonance Imaging

International Nuclear Information System (INIS)

Schmitz, S.A.; O'Regan, D.P.; Fitzpatrick, J.; Neuwirth, C.; Potter, E.; Tos i, I.; Hajnal, J.V.; Naoumova, R.P.

2008-01-01

Background: Patients with hypercholesterolemia of 60 years and older have an increased risk for white matter brain lesions and dementia. Purpose: To investigate whether patients with familial hypercholesterolemia (FH) develop white matter lesions at 3-Tesla (T) MRI as early as in midlife. Material and Methods: Non-diabetic, non-smoking, and non-hypertensive heterozygous FH patients on treatment with maximally tolerated dose of a statin for more than 5 years (n = 14) and matched controls (n = 22) aged 25 to 60 years of age were studied. Imaging was performed at 3T with a fluid-attenuated T2-weighted MR pulse sequence and a T1-weighted spin-echo pulse sequence following 10 ml of i.v. gadopentetate dimeglumine. Images were evaluated by two independent readers. Fasting blood samples were taken. Student's t test was employed at P<0.05. Results: Three volunteers and one FH patient had white matter lesions (P<0.53). No other evidence of past ischemic stroke was observed. Mean total serum cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the FH group (6.0±1.1 vs. 5.1±0.9 mmol/l, P<0.02 and 4.1±0.9 vs. 3.1±0.8 mmol/l, P<0.004, respectively). Conclusion: Heterozygous FH patients on statin treatment in the age range of 25 to 60 years are not at increased risk of white matter lesions at 3T MRI

The influence of young age and positive family history on local recurrence after three treatment strategies for ductal carcinoma in situ

International Nuclear Information System (INIS)

Szelei-Stevens, Kathleen A.; Kuske, Robert R.; Bolton, John S.; Bowen, John C.; Fuhrman, George M.; Fineberg, Barbara B.

1997-01-01

Purpose: Three recent studies have investigated the influence of a positive family history (+FH) of breast cancer on the prognosis of DCIS patients treated by conservative surgery and radiation therapy (CS+RT), with two studies showing a higher risk of locoregional relapse (LRR) in these patients (pts) and another showing no significant difference. Since three treatment strategies have been used for DCIS at our institution, we evaluated the influence of +FH and young age on outcome by treatment method. Materials and Methods: Between 1/1/82 and 12/31/92, one hundred and twenty-eight pts were treated for DCIS by mastectomy (Mast) (n=50, 39%), local excision alone (Loc Exc) (n=43, 34%), and CS+RT (n=35, 27%). No pts were lost to follow-up. Median follow-up (FUP) is 6.0 years. Median age was 59 years (range 28 to 86). Thirty-nine pts had a +FH of breast cancer, 26 in a first-degree relative (mother or sister), and 26 in a second-degree relative (grandmother, aunt, or cousin). Thirteen pts had a +FH in both first and second-degree relatives. Final margins of resection were positive in three pts, negative in 97, and unknown in 28. Thirty-four pts had comedo histologic subtype. Results: Six women developed a recurrence in the treated breast, and all of these were initially treated by Loc Exc. There were no recurrences in the Mast or CS+RT groups. The five year overall actuarial LRR rate was 95.2%. The 5- and 10-year overall survival (OS) rates were 95.4% and 85.7% respectively. The cause-specific survival (CSS) was 99.2% and 97.3% at 5 and 10 years. Pts with a +FH had a 10.3% LRR, versus a 2.3% LRR for pts with a negative FH (p 0.05). Four of 44 pts (9.1%) 50 years of age or younger recurred, compared to 2 of 84 pts (2.4%) over the age of 50 (p = 0.10). Fifteen pts in this study had both a +FH and were 50 years of age or younger. Among these women, the recurrence rate was 20%. Women in this group treated by Loc Exc had a LRR of 38% (3 of 8). Other factors such as

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

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.

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

Silk-fibrin/hyaluronic acid composite gels for nucleus pulposus tissue regeneration.

Science.gov (United States)

Park, Sang-Hyug; Cho, Hongsik; Gil, Eun Seok; Mandal, Biman B; Min, Byoung-Hyun; Kaplan, David L

2011-12-01

Scaffold designs are critical for in vitro culture of tissue-engineered cartilage in three-dimensional environments to enhance cellular differentiation for tissue engineering and regenerative medicine. In the present study we demonstrated silk and fibrin/hyaluronic acid (HA) composite gels as scaffolds for nucleus pulposus (NP) cartilage formation, providing both biochemical support for NP outcomes as well as fostering the retention of size of the scaffold during culture due to the combined features of the two proteins. Passage two (P2) human chondrocytes cultured in 10% serum were encapsulated within silk-fibrin/HA gels. Five study groups with fibrin/HA gel culture (F/H) along with varying silk concentrations (2% silk gel only, fibrin/HA gel culture with 1% silk [F/H+1S], 1.5% silk [F/H+1.5S], and 2% silk [F/H+2S]) were cultured in serum-free chondrogenic defined media (CDM) for 4 weeks. Histological examination with alcian blue showed a defined chondrogenic area at 1 week in all groups that widened homogenously until 4 weeks. In particular, chondrogenic differentiation observed in the F/H+1.5S had no reduction in size throughout the culture period. The results of biochemical and molecular biological evaluations supported observations made during histological examination. Mechanical strength measurements showed that the silk mixed gels provided stronger mechanical properties for NP tissue than fibrin/HA composite gels in CDM. This effect could potentially be useful in the study of in vitro NP tissue engineering as well as for clinical implications for NP tissue regeneration.

Longitudinal investigation of the relationship between family history of psychosis and affective disorders and Child Behavior Checklist ratings in clinical high-risk adolescents.

Science.gov (United States)

Simeonova, Diana I; Lee, Frances J; Walker, Elaine F

2015-08-01

This is the first study to investigate whether positive family history (FH) of psychosis and affective disorders moderates the relationship between child diagnostic status and parent-reported social and behavioral problems on the Child Behavior Checklist (CBCL) in clinical high-risk adolescents. This longitudinal investigation assessed 122 participants (mean age=14.25±1.8years) from three groups (at-risk, other personality disorders, non-psychiatric controls) at baseline and one year follow-up. As predicted, there was a main effect of FH for a number of CBCL scales indicating higher scores for adolescents with positive FH. The findings also demonstrate a significant Diagnostic Status×Family History interaction for several behavioral scales providing support for FH as a concurrent and longitudinal moderator of the relationship between diagnostic status and CBCL scales. The moderating effect is present for areas of functioning associated with depression, anxiety, social adjustment, thought problems, attention problems, and aggressive behavior. The findings also indicate that both positive and negative symptoms are related to the genetic vulnerability for developing psychosis in clinical high-risk individuals, particularly those symptoms reflective of emotional, attentional, and interpersonal functioning. The present findings are novel and have significant clinical and research implications. This investigation provides a platform for future studies to clarify further the role of FH in clinical high-risk individuals and contributes to integration of this knowledge in the development of early intervention and prevention approaches in at-risk populations for the emergence of severe mental illness. Copyright © 2015 Elsevier B.V. All rights reserved.

Parent-child genetic testing for familial hypercholesterolaemia in an Australian context.

Science.gov (United States)

Pang, Jing; Martin, Andrew C; Bates, Timothy R; Hooper, Amanda J; Bell, Damon A; Burnett, John R; Norman, Richard; Watts, Gerald F

2018-04-06

The aim of this study was to evaluate the clinical outcome of parent-child testing for familial hypercholesterolaemia (FH) employing genetic testing and the likely additional cost of treating each child. Parent-child testing for gene variants causative of FH was carried out according to Australian guidelines. The number of new cases detected, the low-density lipoprotein (LDL)-cholesterol that best predicted a mutation and the proportional reduction in LDL-cholesterol following statin treatment was evaluated. Treatment costs were calculated as the cost per mmol/L reduction in LDL-cholesterol. A total of 126 adult patients, known to have a pathogenic mutation causative of FH, and their children were studied. From 244 children identified, 148 (60.7%) were genetically screened; 84 children were identified as mutative positive (M+) and 64 as mutative negative. Six of the M+ children were already on statin treatment; 40 were subsequently treated with low-dose statins, with LDL-cholesterol falling significantly by 38% (P < 0.001). The estimated cost per mmol/L reduction of LDL-cholesterol of a child receiving statins from ages 10 to 18 years is AU$1361, which can potentially be cost-effective. An LDL-cholesterol threshold of 3.5 mmol/L had a sensitivity of 92.8% and specificity of 96.6% for the detection of a mutation. Genetic testing of children of affected parents with FH is an effective means of detecting new cases of FH. Cascade testing can enable early statin therapy with significant reductions in LDL-cholesterol concentration. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

Energy Technology Data Exchange (ETDEWEB)

Schmitz, Stephan A.; O' Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V. [Hammersmith Hospital Campus, Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London (United Kingdom); Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P. [MRC Clinical Sciences Centre, Clinical Research Facility, London (United Kingdom); Hammersmith Hospital, Lipid Clinic, London (United Kingdom)

2007-11-15

Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 {+-} 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 {+-} 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 {+-} 4.2 vs. 4.5 {+-} 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

International Nuclear Information System (INIS)

Schmitz, Stephan A.; O'Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V.; Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P.

2007-01-01

Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 ± 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 ± 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 ± 4.2 vs. 4.5 ± 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

Plasticity of cardiovascular function in snapping turtle embryos (Chelydra serpentina): chronic hypoxia alters autonomic regulation and gene expression.

Science.gov (United States)

Eme, John; Rhen, Turk; Tate, Kevin B; Gruchalla, Kathryn; Kohl, Zachary F; Slay, Christopher E; Crossley, Dane A

2013-06-01

Reptile embryos tolerate large decreases in the concentration of ambient oxygen. However, we do not fully understand the mechanisms that underlie embryonic cardiovascular short- or long-term responses to hypoxia in most species. We therefore measured cardiac growth and function in snapping turtle embryos incubated under normoxic (N21; 21% O₂) or chronic hypoxic conditions (H10; 10% O₂). We determined heart rate (fH) and mean arterial pressure (Pm) in acute normoxic (21% O₂) and acute hypoxic (10% O₂) conditions, as well as embryonic responses to cholinergic, adrenergic, and ganglionic pharmacological blockade. Compared with N21 embryos, chronic H10 embryos had smaller bodies and relatively larger hearts and were hypotensive, tachycardic, and following autonomic neural blockade showed reduced intrinsic fH at 90% of incubation. Unlike other reptile embryos, cholinergic and ganglionic receptor blockade both increased fH. β-Adrenergic receptor blockade with propranolol decreased fH, and α-adrenergic blockade with phentolamine decreased Pm. We also measured cardiac mRNA expression. Cholinergic tone was reduced in H10 embryos, but cholinergic receptor (Chrm2) mRNA levels were unchanged. However, expression of adrenergic receptor mRNA (Adrb1, Adra1a, Adra2c) and growth factor mRNA (Igf1, Igf2, Igf2r, Pdgfb) was lowered in H10 embryos. Hypoxia altered the balance between cholinergic receptors, α-adrenoreceptor and β-adrenoreceptor function, which was reflected in altered intrinsic fH and adrenergic receptor mRNA levels. This is the first study to link gene expression with morphological and cardioregulatory plasticity in a developing reptile embryo.

Temperature-dependent sex determination modulates cardiovascular maturation in embryonic snapping turtles Chelydra serpentina.

Science.gov (United States)

Alvine, Travis; Rhen, Turk; Crossley, Dane A

2013-03-01

We investigated sex differences in cardiovascular maturation in embryos of the snapping turtle Chelydra serpentina, a species with temperature-dependent sex determination. One group of eggs was incubated at 26.5°C to produce males. Another group of eggs was incubated at 26.5°C until embryos reached stage 17; eggs were then shifted to 31°C for 6 days to produce females, and returned to 26.5°C for the rest of embryogenesis. Thus, males and females were at the same temperature when autonomic tone was determined and for most of development. Cholinergic blockade increased resting blood pressure (P(m)) and heart rate (f(H)) in both sexes at 75% and 90% of incubation. However, the magnitude of the f(H) response was enhanced in males compared with females at 90% of incubation. β-adrenergic blockade increased P(m) at 75% of incubation in both sexes but had no effect at 90% of incubation. β-adrenergic blockade reduced f(H) at both time points but produced a stronger response at 90% versus 75% of incubation. We found that α-adrenergic blockade decreased P(m) in both sexes at 75% and 90% of incubation and decreased f(H) at 75% of incubation in both sexes. At 90% of incubation, f(H) decreased in females but not males. Although these data clearly demonstrate sexual dimorphism in the autonomic regulation of cardiovascular physiology in embryos, further studies are needed to test whether differences are caused by endocrine signals from gonads or by a hormone-independent temperature effect.

Anxiety, depression, and health-related quality of life in heterozygous familial hypercholesterolemia: A systematic review and meta-analysis.

Science.gov (United States)

Akioyamen, Leo E; Genest, Jacques; Shan, Shubham D; Inibhunu, Happy; Chu, Anna; Tu, Jack V

2018-06-01

Heterozygous familial hypercholesterolemia (FH) is a common genetic disease predisposing affected individuals to a high risk of cardiovascular disease. Yet, considerable uncertainty exists regarding its impact on psychosocial wellbeing. We performed a systematic review and meta-analysis of the association between FH and symptoms of anxiety and depression, and health-related quality of life (HRQL). We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO, and PubMed for peer-reviewed literature published in English between January 1, 1990 and January 1, 2018. Quantitative and qualitative studies were eligible if they included patients with confirmed FH and evaluated its association with symptoms of anxiety or depression, or HRQL. We performed a narrative synthesis of studies, including thematic analysis of qualitative studies, and where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals. We found 10 eligible studies measuring HRQL, depression and anxiety. Random-effects meta-analysis of 4 (n = 4293) and 5 studies (n = 5098), respectively, showed that patients with FH had slightly lower symptoms of anxiety (SMD: -0.29 [95% CI: -0.53, -0.04]) and mental HRQL (SMD: -0.10 [95% -0.20, -0.00]) relative to general population controls. No significant differences existed in depressive symptoms (SMD: 0.04 [95% CI: -0.12, 0.19]) or physical HRQL scores (SMD: 0.02 [95% CI: -0.09, 0.12]). Our systematic review suggests that patients with FH may report small but measurable differences in anxiety symptoms and mental HRQL. Copyright © 2018 Elsevier Inc. All rights reserved.

Three-dimensional Frankfort horizontal plane for 3D cephalometry: a comparative assessment of conventional versus novel landmarks and horizontal planes.

Science.gov (United States)

Pittayapat, Pisha; Jacobs, Reinhilde; Bornstein, Michael M; Odri, Guillaume A; Lambrichts, Ivo; Willems, Guy; Politis, Constantinus; Olszewski, Raphael

2018-05-25

To assess the reproducibility of landmarks in three dimensions that determine the Frankfort horizontal plane (FH) as well as two new landmarks, and to evaluate the angular differences of newly introduced planes to the FH. Three-dimensional (3D) surface models were created from CBCT scans of 26 dry human skulls. Porion (Po), orbitale (Or), internal acoustic foramen (IAF), and zygomatico-maxillary suture (ZyMS) were indicated in the software by three observers twice with a 4-week interval. Angles between two FHs (FH 1: Or-R, Or-L, mid-Po; FH 2: Po-R, Po-L, mid-Or) and between FHs and new planes (Plane 1-6) were measured. Coordinates were exported to a spreadsheet. A statistical analysis was performed to define the landmark reproducibility and 3D angles. Intra- and inter-observer landmark reproducibility showed mean difference more than 1 mm for x-coordinates of all landmarks except IAF. IAF showed significantly better reproducibility than other landmarks (P Plane 3, connecting Or-R, Or-L and mid-IAF, and Plane 4, connecting Po-R, Po-L and mid-ZyMS, both showed an angular difference of less than 1 degree when compared to FHs. This study revealed poor reproducibility of the traditional FH landmarks on the x-axis and good reproducibility of a new landmark tested to replace Po, the IAF. Yet, Or showed superior results compared to ZyMS. The potential of using new horizontal planes was demonstrated. Future studies should focus on identification of a valid alternative for Or and ZyMS and on clinical implementation of the findings.

Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations.

Science.gov (United States)

Setia, Nitika; Saxena, Renu; Arora, Anjali; Verma, Ishwar C

2016-12-01

Homozygous familial hypercholesterolemia (FH) is a rare but serious, inherited disorder of lipid metabolism characterized by very high total and LDL cholesterol levels from birth. It presents as cutaneous and tendon xanthomas since childhood, with or without cardiac involvement. FH is commonly caused by mutations in three genes, i.e. LDL receptor (LDLR), apolipoprotein B (ApoB) and PCSK9. We aimed to determine the spectrum of mutations in cases of homozygous FH in Asian Indians and evaluate if there was any similarity to the mutations observed in Caucasians. Sixteen homozygous FH subjects from eleven families were analyzed for mutations by Sanger sequencing. Large rearrangements in LDLR gene were evaluated by multiplex ligation probe dependent amplification (MLPA) technique. Ten mutations were observed in LDLR gene, of which four mutations were novel. No mutation was detected in ApoB gene and common PCSK9 mutation (p.D374Y). Fourteen cases had homozygous mutations; one had compound heterozygous mutation, while no mutation was detected in one clinically homozygous case. We report an interesting "Triple hit" case with features of homozygous FH. The spectrum of mutations in the Asian Indian population is quite heterogeneous. Of the mutations identified, 40% were novel. No mutation was observed in exons 3, 9 and 14 of LDLR gene, which are considered to be hot spots in studies done on Asian Indians in South Africa. Early detection followed by aggressive therapy, and cascade screening of extended families has been initiated to reduce the morbidity and mortality in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

AcEST: DK949619 [AcEST

Lifescience Database Archive (English)

Full Text Available =Mi... 75 3e-12 tr|Q4R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy ... 75 3e-12 tr|B7FH62|B7FH6...tr|Q4R1A7|Q4R1A7_PEDDU Plastocyanin OS=Pediastrum duplex GN=Pcy PE=4 SV=1 Length

Critical windows in embryonic development: Shifting incubation temperatures alter heart rate and oxygen consumption of Lake Whitefish (Coregonus clupeaformis) embryos and hatchlings.

Science.gov (United States)

Eme, J; Mueller, C A; Manzon, R G; Somers, C M; Boreham, D R; Wilson, J Y

2015-01-01

Critical windows are periods of developmental susceptibility when the phenotype of an embryonic, juvenile or adult animal may be vulnerable to environmental fluctuations. Temperature has pervasive effects on poikilotherm physiology, and embryos are especially vulnerable to temperature shifts. To identify critical windows, we incubated whitefish embryos at control temperatures of 2°C, 5°C, or 8°C, and shifted treatments among temperatures at the end of gastrulation or organogenesis. Heart rate (fH) and oxygen consumption ( [Formula: see text] ) were measured across embryonic development, and [Formula: see text] was measured in 1-day old hatchlings. Thermal shifts, up or down, from initial incubation temperatures caused persistent changes in fH and [Formula: see text] compared to control embryos measured at the same temperature (2°C, 5°C, or 8°C). Most prominently, when embryos were measured at organogenesis, shifting incubation temperature after gastrulation significantly lowered [Formula: see text] or fH. Incubation at 2°C or 5°C through gastrulation significantly lowered [Formula: see text] (42% decrease) and fH (20% decrease) at 8°C, incubation at 2°C significantly lowered [Formula: see text] (40% decrease) and fH (30% decrease) at 5°C, and incubation at 5°C and 8°C significantly lowered [Formula: see text] at 2°C (27% decrease). Through the latter half of development, [Formula: see text] and fH in embryos were not different from control values for thermally shifted treatments. However, in hatchlings measured at 2°C, [Formula: see text] was higher in groups incubated at 5°C or 8°C through organogenesis, compared to 2°C controls (43 or 65% increase, respectively). Collectively, these data suggest that embryonic development through organogenesis represents a critical window of embryonic and hatchling phenotypic plasticity. This study presents an experimental design that identified thermally sensitive periods for fish embryos. Crown Copyright �

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents

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Natália Portela

Full Text Available Abstract Background: A family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise. Objective: To test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise. Methods: The study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years and 14 without (FH-; 27 ± 5 years a family history of hypertension. Blood pressure, heart rate (DIXTAL®, forearm blood flow (Hokanson®, and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®. Results: At rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96, heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18, forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16, and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21, respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86, heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86, and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25, respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03. Conclusion: Normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.

Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins.

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Victoria Martínez-Sernández

Full Text Available MF6p/FhHDM-1 is a small cationic heme-binding protein which is recognized by the monoclonal antibody (mAb MF6, and abundantly present in parenchymal cells and secreted antigens of Fasciola hepatica. Orthologs of this protein (MF6p/HDMs also exist in other causal agents of important foodborne trematodiasis, such as Clonorchis sinensis, Opisthorchis viverrini and Paragonimus westermani. Considering that MF6p/FhHDM-1 is relevant for heme homeostasis in Fasciola and was reported to have immunomodulatory properties, this protein is expected to be a useful target for vaccination. Thus, in this study we mapped the epitope recognized by mAb MF6 and evaluated its antigenicity in sheep. The sequence of the MF6p/FhHDM-1 ortholog from F. gigantica (MF6p/FgHDM-1 was also reported. By means of ELISA inhibitions with overlapping synthetic peptides, we determined that the epitope recognized by mAb MF6 is located within the C-terminal moiety of MF6p/FhHDM-1, which is the most conserved region of MF6p/HDMs. By immunoblotting analysis of parasite extracts and ELISA inhibitions with synthetic peptides we also determined that mAb MF6 reacted with the same intensity with F. hepatica and F. gigantica, and in decreasing order of intensity with C. sinensis, O.viverrini and P. westermani orthologs. On the contrary, mAb MF6 showed no reactivity against Dicrocoelium dendriticum and Schistosoma mansoni. The study of the recognition of peptides covering different regions of MF6p/FhHDM-1 by sera from immunized sheep revealed that the C-terminal moiety is the most antigenic, thus being of potential interest for vaccination. We also demonstrated that the production of antibodies to MF6p/FhHDM-1 in sheep infected by F. hepatica occurs relatively early and follows the same pattern as those produced against L-cathepsins.

IDENTIFICATION OF PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA IN THE RUSSIAN POPULATION USING THE EXAMPLE OF MOSCOW CITY AND MOSCOW REGION

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I. V. Sergienko

2018-01-01

Full Text Available Aim. To estimate the prevalence of familial hypercholesterolemia (FH in a sample of Moscow city and Moscow region patients with hypercholesterolemia (HCh based on lipid spectrum and instrumental methods.Material and methods. The study included two samples of patients (age >18 years, with total cholesterol (TCh level ≥7.5 mmol/l and/or low-density lipoprotein (LDL cholesterol level ≥4.9 mmol/l. First sample (n=60 was included to determine secondary hyperlipidemia frequency in newly diagnosed HCh, with measurement of thyroid hormone, glucose and glycated hemoglobin (HbA1c levels. Patients of the second sample (n=432 from Russian registry of FH (RuFH were studied by drug therapy assessment, lipid profile measurements, calculation of FH probability according to Dutch and British criteria, carotids duplex scanning (CDS, cardiac perfusion single-photon emission computed tomography (SPECT/CT using rest/stress protocol.Results. The incidence of secondary dyslipidemia due to diabetes or hypothyroidism in patients with severe HCh was 18.3%. Monotherapy with atorvastatin (34.2% or rosuvastatin (31.8%, combined therapy with statins and other lipid-lowering drugs (24.4% prevails in the structure of lipidlowering therapy in patients with severe HCh. The frequency of "definite" FH according to Dutch criteria in HCh patients was 15.3%, "probable" – 18.1%. Patients with definite FH diagnosis showed higher level of TCh (p<0.001, LDL cholesterol (p<0.001, proprotein convertase subtilisin/kexin type 9 (p<0.001, lower high-density lipoprotein (HDL; p=0.02, and triglycerides (p<0.001. At that HDL cholesterol levels differed only in patients treated with lipid-lowering drugs. Patients with lipid-lowering therapy had significantly higher values of total stenosis percent, the number of plaques, intima-media complex thickness (p<0.001. Patients with lipid-lowering therapy with a definite and probable FH diagnosis had significantly worse values of CDS parameters

[The characteristics of esophagogastric junction contractile index in patients with gastroesophageal reflux disease or functional heartburn].

Science.gov (United States)

Wang, K; Duan, L P; Ge, Y; Xia, Z W; Xu, Z J

2016-04-01

To study the role of esophagogastric junction contractile index (EGJ-CI) in evaluating the function of anti-reflux barrier, and in differentiating patients with gastroesophageal reflux disease (GERD) from those with functional heartburn (FH). A total of 115 patients presenting heartburn were enrolled in the study from January 2012 to June 2015.All subjects had completed Gerd-Q questionnaire and undergone gastroscopy, 24-hour pH-impedance monitoring and esophageal high-resolution manometry. GERD patients were divided into as reflux esophagitis, acid-nonerosive reflux disease (NERD) and weakly acid-NERD groups. Patients with normal esophageal mucosa, normal acid exposure and negative proton pump inhibitor test were enrolled in FH group. EGJ-CI (mmHg·cm) as well as EGJ rest pressure and 4s integrated relaxation pressure (IRP 4s) were measured. Among the 115 patients, 18 were reflux esophagitis [(49.0±18.9) years, M∶F=10∶8], 25 were acid-NERD [(48.7±14.4) years, M∶F=13∶12], 37 were weakly acid-NERD [(52.0±14.8) years, M∶F=15∶22] and 35 were FH [(53.6±14.8), M∶F=8∶27]. No differences of Gerd-Q scores were noticed between the four groups. (1)Negative correlations were demonstrated between EGJ-CI and esophageal acid exposure time (r=-0.283, P=0.002), EGJ-CI and acid reflux events (r=-0.233, P=0.012), EGJ-CI and weakly acid reflux events (r=-0.213, P=0.022), EGJ-CI and non-acid reflux events (r=-0.200, P=0.032). (2)The value of EGJ-CI was significantly higher in FH patients than in the three subgroups of GERD(all P<0.01). EGJ rest pressure of FH group was higher than that of acid-NERD (P<0.01). IRP 4s in acid-NERD group was lower than that of FH and weakly acid-NERD (P<0.05). (3)The area under curve (AUC) of EGJ-CI was higher than that of EGJ-CIT, EGJ rest pressure or IRP 4s(0.686 vs 0.678, 0.641 and 0.578). The cut-off value of EGJ-CI to differentiate GERD from FH was 9.74 mmHg·cm with sensitivity 82.86% and specificity 51.52%. The EGJ-CI values are

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.

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

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

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

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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.

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.

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.

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, ...

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

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....

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...

A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia.

Science.gov (United States)

Langslet, Gisle; Breazna, Andrei; Drogari, Euridiki

2016-01-01

The efficacy and safety of atorvastatin in children/adolescents aged 10-17 years with heterozygous familial hypercholesterolemia (HeFH) have been demonstrated in trials of up to 1 year in duration. However, the efficacy/safety of >1 year use of atorvastatin in children/adolescents with HeFH, including children from 6 years of age, has not been assessed. To characterize the efficacy and safety of atorvastatin over 3 years and to assess the impact on growth and development in children aged 6-15 years with HeFH. A total of 272 subjects aged 6-15 years with HeFH and low-density lipoprotein cholesterol (LDL-C) ≥4.0 mmol/L (154 mg/dL) were enrolled in a 3-year study (NCT00827606). Subjects were initiated on atorvastatin (5 mg or 10 mg) with doses increased to up to 80 mg based on LDL-C levels. Mean percentage reductions from baseline in LDL-C at 36 months/early termination were 43.8% for subjects at Tanner stage (TS) 1 and 39.9% for TS ≥2. There was no evidence of variations in the lipid-lowering efficacy of atorvastatin between the TS groups analyzed (1 vs ≥2) or in subjects aged Atorvastatin had a favorable safety and tolerability profile, and only 6 (2.2%) subjects discontinued because of adverse events. Atorvastatin over 3 years was efficacious, had no impact on growth/maturation, and was well tolerated in children and adolescents with HeFH aged 6-15 years. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Impaired Fasting Glucose in Omani Adults with no Family History of Type 2 Diabetes

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Sawsan Al-Sinani

2014-05-01

Full Text Available Objectives: The aim of this study was to estimate the prevalence of impaired fasting glucose (IFG among Omani adults with no family history (FH of diabetes and to investigate the factors behind the risk of developing type 2 diabetes (T2D, while excluding a FH of diabetes. Methods: A total of 1,182 Omani adults, aged ≥40 years, visited the Family Medicine & Community Health Clinic at Sultan Qaboos University Hospital, Oman, on days other than the Diabetes Clinic days, from July 2010 to July 2011. The subjects were interviewed and asked if they had T2D or a FH of T2D. Results: Only 191 (16% reported no personal history of T2D or FH of the disease. Of these, anthropometric and biochemical data was complete in 159 subjects. Of these a total of 42 (26% had IFG according to the American Diabetes Association criteria. Body mass index, fasting insulin, haemoglobin A1C and blood pressure (BP, were significantly higher among individuals with IFG (P <0.01, P <0.05, P <0.01 and P <0.01, respectively. In addition, fasting insulin, BP and serum lipid profile were correlated with obesity indices (P <0.05. Obesity indices were strongly associated with the risk of IFG among Omanis, with waist circumference being the strongest predictor. Conclusion: Despite claiming no FH of diabetes, a large number of Omani adults in this study had a high risk of developing diabetes. This is possibly due to environmental factors and endogamy. The high prevalence of obesity combined with genetically susceptible individuals is a warning that diabetes could be a future epidemic in Oman.

Automated method to compute Evans index for diagnosis of idiopathic normal pressure hydrocephalus on brain CT images

Science.gov (United States)

Takahashi, Noriyuki; Kinoshita, Toshibumi; Ohmura, Tomomi; Matsuyama, Eri; Toyoshima, Hideto

2017-03-01

The early diagnosis of idiopathic normal pressure hydrocephalus (iNPH) considered as a treatable dementia is important. The iNPH causes enlargement of lateral ventricles (LVs). The degree of the enlargement of the LVs on CT or MR images is evaluated by using a diagnostic imaging criterion, Evans index. Evans index is defined as the ratio of the maximal width of frontal horns (FH) of the LVs to the maximal width of the inner skull (IS). Evans index is the most commonly used parameter for the evaluation of ventricular enlargement. However, manual measurement of Evans index is a time-consuming process. In this study, we present an automated method to compute Evans index on brain CT images. The algorithm of the method consisted of five major steps: standardization of CT data to an atlas, extraction of FH and IS regions, the search for the outmost points of bilateral FH regions, determination of the maximal widths of both the FH and the IS, and calculation of Evans index. The standardization to the atlas was performed by using linear affine transformation and non-linear wrapping techniques. The FH regions were segmented by using a three dimensional region growing technique. This scheme was applied to CT scans from 44 subjects, including 13 iNPH patients. The average difference in Evans index between the proposed method and manual measurement was 0.01 (1.6%), and the correlation coefficient of these data for the Evans index was 0.98. Therefore, this computerized method may have the potential to accurately compute Evans index for the diagnosis of iNPH on CT images.

Relative volume measured with magnetic resonance imaging is an articular collapse predictor in hematological pediatric patients with femoral head osteonecrosis.

Science.gov (United States)

Ippolito, Davide; Masetto, Alessandro; Talei Franzesi, Cammillo; Bonaffini, Pietro A; Casiraghi, Alessandra; Sironi, Sandro

2016-08-28

To assess the potential value of femoral head (FH) volume measurements to predict joint collapse, as compared to articular surface involvement, in post-treatment osteonecrosis (ON) in pediatric patients affected by lymphoproliferative diseases. Considering 114 young patients with lymphoproliferative diseases undergone a lower-limbs magnetic resonance imaging (MRI) examination between November 2006 and August 2012 for a suspected post-treatment ON, we finally considered a total of 13 cases (7 males, mean age 15.2 ± 4.8 years), which developed a FH ON lesions (n = 23). The MRI protocol included coronal short tau inversion recovery and T1-weighted sequences, from the hips to the ankles. During the follow-up (elapsed time: 9.2 ± 2 mo), 13/23 FH articular surface (FHS) developed articular deformity. The first MRI studies with diagnosis of ON were retrospectively analyzed, measuring FH volume (FHV), FHS, ON volume (ONV) and the articular surface involved by ON (ONS). The relative involvement of FHS, in terms of volume [relative volume (RV): ONV/FHV] and articular surface [relative surface (RS): ONS/FHS], was then calculated. By using receiver operating characteristic curve analysis (threshold of 23% of volume involvement), RV predicted articular deformity in 13/13 FHS [sensitivity 100%, specificity 90%, accuracy 95%, positive predictive value (PPV) 93%, negative predictive value (NPV) 100%]. Considering a threshold of 50% of articular involvement, RS predicted articular deformity in 10/13 femoral heads (sensitivity 77%, specificity 100%, accuracy 87%, PPV 100%, NPV 77%). RV might be a more reliable parameter than RS in predicting FH deformity and could represent a potential complementary diagnostic tool in the follow-up of femoral heads ON lesions.

The role of the vagus nerve in the generation of cardiorespiratory interactions in a neotropical fish, the pacu, Piaractus mesopotamicus.

Science.gov (United States)

Leite, Cleo Alcantara Costa; Taylor, E W; Guerra, C D R; Florindo, L H; Belão, T; Rantin, F T

2009-08-01

The role of the vagus nerve in determining heart rate (f(H)) and cardiorespiratory interactions was investigated in a neotropical fish, Piaractus mesopotamicus. During progressive hypoxia f(H) initially increased, establishing a 1:1 ratio with ventilation rate (f(R)). Subsequently there was a hypoxic bradycardia. Injection of atropine abolished a normoxic inhibitory tonus on the heart and the f(H) adjustments during progressive hypoxia, confirming that they are imposed by efferent parasympathetic inputs via the vagus nerve. Efferent activity recorded from the cardiac vagus in lightly anesthetized normoxic fish included occasional bursts of activity related to spontaneous changes in ventilation amplitude, which increased the cardiac interval. Restricting the flow of aerated water irrigating the gills resulted in increased respiratory effort and bursts of respiration-related activity in the cardiac vagus that seemed to cause f(H) to couple with f(R). Cell bodies of cardiac vagal pre-ganglionic neurons were located in two distinct groups within the dorsal vagal motor column having an overlapping distribution with respiratory motor-neurons. A small proportion of cardiac vagal pre-ganglionic neurons (2%) was in scattered positions in the ventrolateral medulla. This division of cardiac vagal pre-ganglionic neurons into distinct motor groups may relate to their functional roles in determining cardiorespiratory interactions.

Growth trajectory and pubertal tempo from birth till final height in a girl with Wolf-Hirschhorn syndrome.

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Siew, Jia Xuan; Yap, Fabian

2018-01-01

Growth anomaly is a prominent feature in Wolf-Hirschhorn syndrome (WHS), a rare congenital disorder caused by variable deletion of chromosome 4p. While growth charts have been developed for WHS patients 0-4 years of age and growth data available for Japanese WHS patients 0-17 years, information on pubertal growth and final height among WHS children remain lacking. Growth hormone (GH) therapy has been reported in two GH-sufficient children with WHS, allowing for pre-puberty catch up growth; however, pubertal growth and final height information was also unavailable. We describe the complete growth journey of a GH-sufficient girl with WHS from birth until final height (FH), in relation to her mid parental height (MPH) and target range (TR). Her growth trajectory and pubertal changes during childhood, when she was treated with growth hormone (GH) from 3 years 8 months old till 6 months post-menarche at age 11 years was fully detailed. Pubertal growth characteristics and FH information in WHS is lacking.While pre-pubertal growth may be improved by GH, GH therapy may not translate to improvement in FH in WHS patients.Longitudinal growth, puberty and FH data of more WHS patients may improve the understanding of growth in its various phases (infancy/childhood/puberty).

Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia

Directory of Open Access Journals (Sweden)

Alastair G Kerr

2016-01-01

Full Text Available Familial hypercholesterolemia (FH is a life-threatening genetic disorder characterized by elevated levels of plasma low-density lipoprotein cholesterol (LDL-cholesterol. Current attempts at gene therapy for FH have been limited by the use of strong heterologous promoters which lack genomic DNA elements essential for regulated expression. Here, we have combined a minigene vector expressing the human LDLR cDNA from a 10 kb native human LDLR locus genomic DNA promoter element, with an efficient miRNA targeting 3-hydroxy-3-methylgutaryl-coenzyme A reductase (Hmgcr, to further enhance LDLR expression. We show that the combined vector suppresses endogenous Hmgcr transcripts in vivo, leading to an increase in LDLR transgene expression. In a diet-induced Ldlr-/- mouse model of FH, we show that administration of the combined vector reduces atherogenic plasma lipids by ≃32%. Finally, we demonstrate that our episomal nonviral vectors are able to reduce atherosclerosis by ≃40% after 12 weeks in vivo. Taken together, the vector system we describe exploits the normal cellular regulation of the LDLR to provide prolonged expression of LDLR through targeted knockdown of Hmgcr. This novel gene therapy system could act alone, or in synergy with current therapies that modulate intracellular cholesterol, such as statins, greatly enhancing its therapeutic application for FH.

Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.

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Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

2016-08-12

Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb*

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Li, Xueqin; Liu, Peng; Gan, Shuzhen; Zhang, Chunmao; Zheng, Yuling; Jiang, Yongqiang; Yuan, Yuan

2016-01-01

Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood. PMID:27342778

Mutational analysis and genotype-phenotype relation in familial hypercholesterolemia: The SAFEHEART registry.

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Bourbon, Mafalda; Alves, Ana Catarina; Alonso, Rodrigo; Mata, Nelva; Aguiar, Pedro; Padró, Teresa; Mata, Pedro

2017-07-01

Familial hypercholesterolemia (FH) is an autosomal dominant disease of cholesterol metabolism that confers an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Therefore, early identification and treatment of these patients can improve prognosis and reduce the burden of cardiovascular mortality. The aim of this work was to perform the mutational analysis of the SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) registry. The study recruited 2938 individuals with genetic diagnosis of FH belonging to 775 families. Statistical analysis was performed using SPSS v23. A total of 194 variants have been detected in this study, 24 of them were never described before. About 88% of the patients have a pathogenic or likely pathogenic variant. Patients with null variants have a more severe phenotype than patients with defective variants, presenting with significantly higher levels of atherogenic particles (total cholesterol, LDL-cholesterol and apolipoprotein B). This study shows the molecular characteristics of the FH patients included in the SAFEHEART registry and the relationship with the phenotypic expression. The majority of the genetic variants are considered to be pathogenic or likely pathogenic, which confers a high level of confidence to the entry and follow-up data analysis performed with this registry concerning FH patients' prognosis, treatment and survival. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropsychological Performance and Family History in Children at Age 7 who Develop Adult Schizophrenia or Bipolar Psychosis in the New England Family Studies

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Seidman, Larry J.; Cherkerzian, Sara; Goldstein, Jill M.; Agnew-Blais, Jessica; Tsuang, Ming T.; Buka, Stephen L.

2013-01-01

Objective Persons developing schizophrenia (SCZ) manifest various premorbid neuropsychological deficits, studied most often by measures of IQ. Far less is known about premorbid neuropsychological functioning in individuals who later develop bipolar psychoses (BP). We evaluated the specificity and impact of family history (FH) of psychosis on premorbid neuropsychological functioning. Methods We conducted a nested case-control study investigating the associations of neuropsychological data systematically collected at age 7 years for 99 adults with psychotic diagnoses (including 45 SCZ and 35 BP) and 101 controls, drawn from the New England cohort of the Collaborative Perinatal Project. A mixed model approach evaluated Full Scale IQ, four neuropsychological factors derived from principal components analysis, and the profile of 10 intelligence and achievement tests, controlling for maternal education, race, and intrafamilial correlation. We used a deviant responder approach (neuropsychologically impaired. Presence of psychosis in first-degree relatives (FH+) significantly increased the severity of childhood impairment for SCZ but not for BP. Conclusions Premorbid neuropsychological deficits are found in a substantial proportion of children who later develop SCZ, especially in the SCZ FH+ subgroup, but less so in BP, suggesting especially impaired neurodevelopment underlying cognition in pre-SCZ children. Future work should assess genetic and environmental factors that explain this FH effect. PMID:22575089

Prenatal diagnosis of homozygous familial hypercholesterolaemia

International Nuclear Information System (INIS)

Brown, M.S.; Kovanen, P.T.; Goldstein, J.L.; Eeckels, R.; Vandenberghe, K.; Van Den Berghe, H.; Fryns, J.P.; Cassiman, J.J.

1978-01-01

Cultured amniotic-fluid cells from a fetus at risk for homozygous familial hypercholesterolaemia (F.H.) almost completely lacked cell-surface receptors for plasma low-density lipoprotein (L.D.L.), as evidenced by direct measurement of binding, uptake, and degradation of 125 I-L.D.L. Functional consequences of L.D.L. binding to the receptor - i.e., suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and stimulation of cholesterol esterification - were proportionately reduced when compared with results in cultured amniotic cells from two control fetuses. On the basis of these findings, homozygous F.H. was diagnosed and the pregnancy was terminated at the 20th week. The diagnosis of homozygous F.H. was confirmed by a serum-cholesterol of the aborted fetus of 279 mg/dl, a value 9 times the mean of four control fetuses of similar gestational age. More than 80% of the serum-cholesterol of the affected fetus was contained within L.D.L. Prenatal diagnosis of homozygous F.H. now seems practical; moreover, the finding of a raised serum-L.D.L. in the affected fetus indicates that the L.D.L. receptor is normally functional as early as the 20th week of fetal life. (author)

Phytochemical composition, antioxidant and anti-bacterial activity of Syzygium calophyllifolium Walp. fruit.

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Sathyanarayanan, Saikumar; Chandran, Rahul; Thankarajan, Sajeesh; Abrahamse, Heidi; Thangaraj, Parimelazhagan

2018-01-01

Syzygium calophyllifolium fruits are among the important wild edibles used by the tribes of Western Ghats. However, this underutilized fruit remained unnoticed for its medicinal properties. Hence, the present study was undertaken to evaluate the antioxidant activity by DPPH · , ABTS ·+ , FRAP assays and antibacterial efficacy by well diffusion method. GC-MS and HPLC profiles of crude extract and column chromatographic fractions were also determined. The methanolic extract of fruit (MFE) showed high total phenolics, tannins and flavonoids. The faction H (FH) displayed significant antioxidant property in DPPH · (IC 50 2.1 µg/ml), ABTS ·+ (19483.29 μM Trolox equivalents/g extract) and FRAP (65.5 mM Fe(II)/mg extract) assays over MFE. Moreover, FH also exhibited good antibacterial activity against Escherichia coli (32.0 mm), Salmonella typhi (27.0 mm), Staphylococcus aureus (27.3 mm) at 100 mg/ml concentration. GC-MS revealed 12 major compounds in MFE, HPLC analysis of MFE and FH depicted the presence of rutin and ellagic acid. This study suggested that FH could have high concentration of bioactive compounds like rutin and ellagic acid or its analogues compared to MFE which may be responsible for its strong antioxidant and antibacterial activity.

Type 2 diabetes family histories, body composition and fasting glucose levels: a cross-section analysis in healthy sedentary male and female.

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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.

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

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

Distinct expression/function of potassium and chloride channels contributes to the diverse volume regulation in cortical astrocytes of GFAP/EGFP mice

Czech Academy of Sciences Publication Activity Database

Benešová, Jana; Rusňáková, Vendula; Honsa, Pavel; Pivoňková, Helena; Džamba, Dávid; Kubista, Mikael; Anděrová, Miroslava

2012-01-01

Roč. 7, č. 1 (2012), e29725 E-ISSN 1932-6203 R&D Projects: GA ČR GAP303/10/1338 Grant - others:GA ČR(CZ) GD309/08/H079 Institutional research plan: CEZ:AV0Z50390703; CEZ:AV0Z50520701 Institutional support: RVO:86652036 ; RVO:68378041 Keywords : cell volume regulation * GFAP/EGFP * ischemia Subject RIV: FH - Neurology; FH - Neurology (BTO-N) Impact factor: 3.730, year: 2012

SIKVAV-modified highly superporous PHEMA scaffolds with oriented pores for spinal cord injury repair

Czech Academy of Sciences Publication Activity Database

Kubinová, Šárka; Horák, Daniel; Hejčl, Aleš; Plichta, Zdeněk; Kotek, Jiří; Proks, Vladimír; Forostyak, Serhiy; Syková, Eva

2015-01-01

Roč. 9, č. 11 (2015), s. 1298-1309 ISSN 1932-6254 R&D Projects: GA ČR GAP304/11/0731; GA ČR(CZ) GPP304/11/P633; GA ČR GAP108/10/1560; GA ČR GAP304/11/0653 Institutional support: RVO:68378041 ; RVO:61389013 Keywords : hydrogel * oriented pores * spinal cord repair Subject RIV: FH - Neurology; FH - Neurology (UMCH-V) Impact factor: 4.710, year: 2015

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

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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...

Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score

Directory of Open Access Journals (Sweden)

Weigl K

2018-01-01

Full Text Available Korbinian Weigl,1,2 Jenny Chang-Claude,3,4 Phillip Knebel,5 Li Hsu,6 Michael Hoffmeister,1 Hermann Brenner1,2,7 1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ, Heidelberg, 2German Cancer Consortium (DKTK, German Cancer Research Center (DKFZ, Heidelberg, 3Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ, Heidelberg, 4University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, 5Department for General, Visceral and Transplantation Surgery, University Heidelberg, Heidelberg, Germany; 6Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 7Division of Preventive Oncology, German Cancer Research Center (DKFZ and National Center for Tumor Diseases (NCT, Heidelberg, Germany Background and aim: Family history (FH and genetic risk scores (GRSs are increasingly used for risk stratification for colorectal cancer (CRC screening. However, they were mostly considered alternatively rather than jointly. The aim of this study was to assess the potential of individual and joint risk stratification for CRC by FH and GRS.Patients and methods: A GRS was built based on the number of risk alleles in 53 previously identified single-nucleotide polymorphisms among 2,363 patients with a first diagnosis of CRC and 2,198 controls in DACHS [colorectal cancer: chances for prevention through screening], a population-based case-control study in Germany. Associations between GRS and FH with CRC risk were quantified by multiple logistic regression.Results: A total of 316 cases (13.4% and 214 controls (9.7% had a first-degree relative (FDR with CRC (adjusted odds ratio [aOR] 1.86, 95% CI 1.52–2.29. A GRS in the highest decile was associated with a 3.0-fold increased risk of CRC (aOR 3.00, 95% CI 2.24–4.02 compared with the lowest decile. This association was tentatively more pronounced in older age groups. FH and GRS were essentially unrelated, and their

A surface structural model for ferrihydrite I: Sites related to primary charge, molar mass, and mass density

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Hiemstra, Tjisse; Van Riemsdijk, Willem H.

2009-08-01

A multisite surface complexation (MUSIC) model for ferrihydrite (Fh) has been developed. The surface structure and composition of Fh nanoparticles are described in relation to ion binding and surface charge development. The site densities of the various reactive surface groups, the molar mass, the mass density, the specific surface area, and the particle size are quantified. As derived theoretically, molecular mass and mass density of nanoparticles will depend on the types of surface groups and the corresponding site densities and will vary with particle size and surface area because of a relatively large contribution of the surface groups in comparison to the mineral core of nanoparticles. The nano-sized (˜2.6 nm) particles of freshly prepared 2-line Fh as a whole have an increased molar mass of M ˜ 101 ± 2 g/mol Fe, a reduced mass density of ˜3.5 ± 0.1 g/cm 3, both relatively to the mineral core. The specific surface area is ˜650 m 2/g. Six-line Fh (5-6 nm) has a molar mass of M ˜ 94 ± 2 g/mol, a mass density of ˜3.9 ± 0.1 g/cm 3, and a surface area of ˜280 ± 30 m 2/g. Data analysis shows that the mineral core of Fh has an average chemical composition very close to FeOOH with M ˜ 89 g/mol. The mineral core has a mass density around ˜4.15 ± 0.1 g/cm 3, which is between that of feroxyhyte, goethite, and lepidocrocite. These results can be used to constrain structural models for Fh. Singly-coordinated surface groups dominate the surface of ferrihydrite (˜6.0 ± 0.5 nm -2). These groups can be present in two structural configurations. In pairs, the groups either form the edge of a single Fe-octahedron (˜2.5 nm -2) or are present at a single corner (˜3.5 nm -2) of two adjacent Fe octahedra. These configurations can form bidentate surface complexes by edge- and double-corner sharing, respectively, and may therefore respond differently to the binding of ions such as uranyl, carbonate, arsenite, phosphate, and others. The relatively low PZC of

Impact of breast cancer family history on tumor detection and tumor size in women newly-diagnosed with invasive breast cancer.

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Schwab, Fabienne Dominique; Bürki, Nicole; Huang, Dorothy Jane; Heinzelmann-Schwarz, Viola; Schmid, Seraina Margaretha; Vetter, Marcus; Schötzau, Andreas; Güth, Uwe

2014-03-01

This study evaluated the impact of family history (FH) on tumor detection, the patient's age and tumor size at diagnosis in breast cancer (BC). Furthermore, we investigated whether the impact of FH on these features was dependent on degree of relationship, number of relatives with a BC history, or the age of the affected relative at the time that her BC was diagnosed. Out of the entire cohort (n = 1,037), 244 patients (23.5%) had a positive FH; 159 (15.3%) had first-degree relatives affected with BC and 85 patients (8.2%) had second-degree affected relatives. Compared to women who had no BC-affected relatives, the tumors of women who had positive FH were more often found by radiological breast examination (RBE: 31.7%/27.2%, p = 0.008), and they were smaller (general tumor size: 21.8 mm/26.4 mm, p = 0.003; size of tumors found by breast self-examination (BSE): 26.1 mm/30.6 mm, p = 0.041). However, this positive effect of increased use of BC screening and smaller tumor sizes was only observed in patients whose first-degree relatives were affected (comparison with second-degree affected relatives: RBE: 43.8%/24.7%; odds ratio 2.38, p = 0.007; general tumor size: 19.3 mm/26.3 mm; mean difference (MD) -6.9, p = 0.025; tumor size found by BSE: 22.5 mm/31.0 mm; MD -8.5, p = 0.044). When more second-degree relatives or older relatives were diagnosed with BC, the tumors of these patients were similarly often detected by RBE (relationship: 24.7%/27.2%, p = 0.641; age: 33.7 %/27.2 %, p = 0.177) and had similar tumor sizes (general size: 26.3 mm/26.4 mm, p = 0.960; BSE: 31.0 mm/30.6 mm, p = 0.902) as those of women without a FH. Women with a positive FH generally use mammography screening more often and perceive changes in the breast earlier than women without such history. The increased awareness of BC risk decreases if the relationship is more distant.

Clinical evaluation of the scoring of optical findings with technetium-99m-N-pyridoxyl-5-methyl-tryptophan (PMT) hepatobiliary scintigraphy for fulminant hepatitis

International Nuclear Information System (INIS)

Uchiyama, Katsuhiro; Kuniyasu, Yoshio; Niio, Yasuo

1998-01-01

Fulminant hepatitis is one of the most life-threatening diseases for which adequate medical therapy does not exist. Then, we evaluated the usefulness of technetium-99m-N-pyridoxyl-5-methyl-tryptophan (PMT) hepatobiliary scintigraphy to estimate the diagnosis and prognosis of fulminant hepatitis. In total 60 patients, 23 with fulminant hepatitis (FH), 25 with severe acute hepatitis (SAH) and 12 with acute hepatitis (AH), computer data acquisition by gamma-camera system started just after the injection of 185 MBq 99m Tc-PMT. The optical finding score which included cardiac blood pool remaining time (0-3), distribution of radioactivity in the liver (0-3), extrahepatic bile duct (EHBD) and intestine appearance time (0-3) were studied. The cardiac blood pool remaining time score was 2.8±0.5 in FH, 2.2±0.8 in SAH, 0.9±1.1 in AH. The intrahepatic distribution score was 2.1±0.8 in FH, 0.3±0.6 in SAH, 0.1±0.3 in AH. The EHBD and intestine appearance time score was 1.9±1.1 in FH, 1.5±1.2 in SAH, 0.3±0.6 in AH. The total score was 6.7±1.4 in FH, 4.0±1.6 in SAH, 1.3±1.3 in AH. There were significantly statistical differences among three groups. While, the cardiac blood pool remaining time score was 3.0±0 in 14 hospital death patients (HD), 1.9±1.0 in 46 alive patients (AL). The intrahepatic distribution score was 2.2±0.8 in HD, 0.5±0.9 in AL. The EHBD and intestine appearance time score was 2.1±1.2 in HD, 1.2±1.1 in AL. The total score was 7.3±1.3 in HD, 3.6±2.2 in AL. There were significantly statistical differences in these groups. The optimal finding score of 99m Tc-PMT hepatobiliary scintigraphy was useful in establishing the diagnosis and prognosis of FH. (author)

Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats.

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Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Piryaei, Abbas; Ghasemi, Asghar

2018-05-01

What is the central question of this study? Does fetal hypothyroidism in rats alter uterine contractions and structure in the adult offspring? What is the main finding and its importance? Our study indicated that maternal hypothyroidism during pregnancy increased gestational length and decreased litter size. In addition, maternal hypothyroidism caused delayed puberty onset, irregular uterine contractions and histological changes in the uterus in the female offspring. This model might contribute to a better understanding of the cellular and molecular mechanisms involved in uterine contractions in fetal hypothyroidism, studies which are not possible in humans, and might help to establish therapeutic methods for these disorders observed in uterine contractions. Thyroid hormones play an essential role in fetal growth. Hypothyroidism impairs reproductive function in both humans and animals. The aim of this study was to assess the effects of fetal hypothyroidism on uterine smooth muscle contraction and structure in the adult offspring. The control group of female Wistar rats consumed tap water, whereas the hypothyroid group received water containing 0.025% of 6-propyl-2-thiouracial throughout gestation from mating until delivery. Isometric contractility and histological changes in uterine tissue were evaluated in the adult female offspring. We tested the effects of carbachol (10 -10 -10 -3  m) and oxytocin (10 -13 -10 -8  m) on uterine smooth muscle contraction in the fetal hypothyroid (FH) and control groups. Compared with control uteri, carbachol induced contractions with lower amplitude in the FH group (area under the curve: 1820.0 ± 250.0 versus 1370.0 ± 125.0 a.u., control versus FH group, respectively, P muscle layer and the cross-sectional area of the uterus were also significantly lower in the FH group. Gestational length was longer and litter size smaller in FH rats compared with control animals; FH offspring also had delayed puberty. In conclusion

Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing epitopes consisting of sialyl or sialyl-fucosyl type 1 chain.

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Kannagi, R; Kitahara, A; Itai, S; Zenita, K; Shigeta, K; Tachikawa, T; Noda, A; Hirano, H; Abe, M; Shin, S

1988-07-01

The levels of carbohydrate antigens having epitopes consisting of type 1 chain (R----Gal beta 1----GlcNAc beta 1----3Gal beta 1----R) in the sera of patients with various malignant and nonmalignant disorders have been investigated with the use of three monoclonal antibodies, N-19-9, FH-7, and FH-9. Serum levels of 2----3 sialylated Lea antigen and 2----6 sialylated Lea antigen, defined respectively by antibodies N-19-9 and FH-7, were found to be frequently high in patients with cancer of the digestive system, particularly pancreatic cancer. High levels of 2----3,2----6 disialylated Lc4 antigen, defined by antibody FH-9, were less frequent in cancer patients when compared with the other two antigens. In patients with nonmalignant disorders, especially renal and autoimmune diseases, serum levels of the two type 1 chain antigens defined by FH-7 and FH-9 were more frequently high than that defined by N-19-9. Molecular weights and other general biochemical characteristics of serum mucin carrying the type 1 chain determinants were not significantly different in cancer patients as compared with patients with nonmalignant disorders. However, the degree of glycosylation of the antigen, as assessed by its solubility in perchloric acid, showed significant differences; i.e., the mucin antigen carrying 2----6 sialylated Lea determinant in the sera of patients with nonmalignant disorders had the highest carbohydrate/protein ratio, followed by the mucin carrying the same determinant in the sera of cancer patients. Mucin antigen carrying 2----3 sialylated Lea antigen or 2----3, 2----6 disialylated Lc4 antigen in cancer patients had the lowest carbohydrate/protein ratio among the four groups tested. Thus, the carbohydrate/protein ratio in the type 1 chain mucin antigens in sera of normal subjects is higher than that in sera of cancer patients (P less than 0.05). This finding is in contrast to previous findings on the mucin antigens carrying the type 2 chain determinant (R. Kannagi

Evaluation of eating habits and lifestyle in patients with obesity before and after bariatric surgery: a single Italian center experience.

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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.

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.

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.

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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.

The feasibility and acceptability of esophageal-directed hypnotherapy for functional heartburn

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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

Pathophysiology of functional heartburn based on Rome III criteria in Japanese patients.

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Tamura, Yasuhiro; Funaki, Yasushi; Izawa, Shinya; Iida, Akihito; Yamaguchi, Yoshiharu; Adachi, Kazunori; Ogasawara, Naotaka; Sasaki, Makoto; Kaneko, Hiroshi; Kasugai, Kunio

2015-04-28

To investigate the pathophysiology of functional heartburn (FH) in Japanese patients. A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria. Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences. Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.

Substrate Specificity of Cysteine Proteases Beyond the S2 Pocket: Mutagenesis and Molecular Dynamics Investigation of Fasciola hepatica Cathepsins L

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Ileana Corvo

2018-04-01

Full Text Available Cysteine proteases are widespread in all life kingdoms, being central to diverse physiological processes based on a broad range of substrate specificity. Paralogous Fasciola hepatica cathepsin L proteases are essential to parasite invasion, tissue migration and reproduction. In spite of similarities in their overall sequence and structure, these enzymes often exhibit different substrate specificity. These preferences are principally determined by the amino acid composition of the active site's S2 subsite (pocket of the enzyme that interacts with the substrate P2 residue (Schetcher and Berger nomenclature. Although secreted FhCL1 accommodates aliphatic residues in the S2 pocket, FhCL2 is also efficient in cleaving proline in that position. To understand these differences, we engineered the FhCL1 S2 subsite at three amino acid positions to render it identical to that present in FhCL2. The substitutions did not produce the expected increment in proline accommodation in P2. Rather, they decreased the enzyme's catalytic efficiency toward synthetic peptides. Nonetheless, a change in the P3 specificity was associated with the mutation of Leu67 to Tyr, a hinge residue between the S2 and S3 subsites that contributes to the accommodation of Gly in S3. Molecular dynamic simulations highlighted changes in the spatial distribution and secondary structure of the S2 and S3 pockets of the mutant FhCL1 enzymes. The reduced affinity and catalytic efficiency of the mutant enzymes may be due to a narrowing of the active site cleft that hinders the accommodation of substrates. Because the variations in the enzymatic activity measured could not be exclusively allocated to those residues lining the active site, other more external positions might modulate enzyme conformation, and, therefore, catalytic activity.

Chicken feather hydrolysate as an inexpensive complex nitrogen source for PHA production by Cupriavidus necator on waste frying oils.

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Benesova, P; Kucera, D; Marova, I; Obruca, S

2017-08-01

The chicken feather hydrolysate (FH) has been tested as a potential complex nitrogen source for the production of polyhydroxyalkanoates by Cupriavidus necator H16 when waste frying oil was used as a carbon source. The addition of FH into the mineral salt media with decreased inorganic nitrogen source concentration improved the yields of biomass and polyhydrohyalkanoates. The highest yields were achieved when 10 vol.% of FH prepared by microwave-assisted alkaline hydrolysis of 60 g l -1 feather was added. In this case, the poly(3-hydroxybutyrate) (PHB) yields were improved by more than about 50% as compared with control cultivation. A positive impact of FH was also observed for accumulation of copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) when sodium propionate was used as a precursor. The copolymer has superior processing and mechanical properties in comparison with PHB homopolymer. The application of FH eliminated the inhibitory effect of propionate and resulted in altered content of 3-hydroxyvalerate (3HV) in copolymer. Therefore, the hydrolysed feather can serve as an excellent complex source of nitrogen for the polyhydroxyalkanoates (PHA) production. Moreover, by the combination of two inexpensive types of waste, such as waste frying oil and feather hydrolysate, it is possible to produce PHA with substantially improved efficiency and sustainability. Millions of tons of feathers, important waste product of poultry-processing industry, are disposed off annually without any further benefits. Thus, there is an inevitable need for new technologies that enable ecologically and economically sensible processing of this waste. Herein, we report that alkali-hydrolysed feathers can be used as a complex nitrogen source considerably improving polyhydroxyalkanoates production on waste frying oil employing Cupriavidus necator. © 2017 The Society for Applied Microbiology.

Influence of the hypothalamic-pituitary-adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism.

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Tirabassi, G; Chelli, F M; Ciommi, M; Lenzi, A; Balercia, G

2016-01-01

Functional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic-pituitary-adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). Fourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. FH may determine a worsening of the metabolic profile in DM-associated hypogonadism. Copyright © 2015 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

Reaching Low-Income Mothers to Improve Family Fruit and Vegetable Intake: Food Hero Social Marketing Campaign—Research Steps, Development and Testing

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Tobey, Lauren N.; Koenig, Harold F.; Brown, Nicole A.; Manore, Melinda M.

2016-01-01

The objective of this study was to create/test a social marketing campaign to increase fruit/vegetable (FV) intake within Oregon Supplemental Nutrition Assistance Program (SNAP) eligible families. Focus groups (n = 2) and pre/post campaign phone surveys (n = 2082) were conducted in intervention counties (IC) and one control county. Participants were female (86%–100%) with 1–2 children at home. Mean FV intake/without juice was 3.1 servings/day; >50% preferred the Internet for delivery of healthy eating information. Participants reported time/financial burdens, low household FV variety and desirability of frozen/canned FV, and acceptance of positive messages. A Food Hero (FH) campaign was created/delivered daily August–October 2009 to mothers through multiple channels (e.g., grocery stores, online, educators). Results showed that the IC had better FH name recall (12%) and interpretation of intended messages (60%) vs. control (3%, 23%, respectively). Compared to controls, the IC were less likely to report healthy food preparation as time consuming or a FV rich diet expensive, and it was easier to get their family to eat fruit. Results did not vary based on county/household characteristics. The FH campaign increased FH awareness and positive FV beliefs. A longer campaign with FV assessments will increase understanding of the target audience, and allow for campaign refinement. PMID:27649233

Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells.

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García, Víctor; Lara-Chica, Maribel; Cantarero, Irene; Sterner, Olov; Calzado, Marco A; Muñoz, Eduardo

2016-01-26

Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer.

Age-Based Differences in the Genetic Determinants of Glycemic Control: A Case of FOXO3 Variations.

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Liang Sun

Full Text Available Glucose homeostasis is a trait of healthy ageing and is crucial to the elderly, but less consideration has been given to the age composition in most studies involving genetics and hyperglycemia.Seven variants in FOXO3 were genotyped in three cohorts (n = 2037; LLI, MI_S and MI_N; mean age: 92.5 ± 3.6, 45.9 ± 8.2 and 46.8 ± 10.3, respectively to compare the contribution of FOXO3 to fasting hyperglycemia (FH between long-lived individuals (LLI, aged over 90 years and middle-aged subjects (aged from 35-65 years.A different genetic predisposition of FOXO3 alleles to FH was observed between LLI and both of two middle-aged cohorts. In the LLI cohort, the longevity beneficial alleles of three variants with the haplotype "AGGC" in block 1 were significantly protective to FH, fasting glucose, hemoglobin A1C and HOMA-IR. Notably, combining multifactor dimensionality reduction and logistic regression, we identified a significant 3-factor interaction model (rs2802288, rs2802292 and moderate physical activity associated with lower FH risk. However, not all of the findings were replicated in the two middle-aged cohorts.Our data provides a novel insight into the inconsistent genetic determinants between middle-aged and LLI subjects. FOXO3 might act as a shared genetic predisposition to hyperglycemia and lifespan.

Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum.

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Castiblanco-Valencia, Mónica M; Fraga, Tatiana R; Breda, Leandro C D; Vasconcellos, Sílvio A; Figueira, Cláudio P; Picardeau, Mathieu; Wunder, Elsio; Ko, Albert I; Barbosa, Angela S; Isaac, Lourdes

2016-05-01