Hey2 functions in parallel with Hes1 and Hes5 for mammalian auditory sensory organ development

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Chin Michael T

2008-02-01

Full Text Available Abstract Background During mouse development, the precursor cells that give rise to the auditory sensory organ, the organ of Corti, are specified prior to embryonic day 14.5 (E14.5. Subsequently, the sensory domain is patterned precisely into one row of inner and three rows of outer sensory hair cells interdigitated with supporting cells. Both the restriction of the sensory domain and the patterning of the sensory mosaic of the organ of Corti involve Notch-mediated lateral inhibition and cellular rearrangement characteristic of convergent extension. This study explores the expression and function of a putative Notch target gene. Results We report that a putative Notch target gene, hairy-related basic helix-loop-helix (bHLH transcriptional factor Hey2, is expressed in the cochlear epithelium prior to terminal differentiation. Its expression is subsequently restricted to supporting cells, overlapping with the expression domains of two known Notch target genes, Hairy and enhancer of split homolog genes Hes1 and Hes5. In combination with the loss of Hes1 or Hes5, genetic inactivation of Hey2 leads to increased numbers of mis-patterned inner or outer hair cells, respectively. Surprisingly, the ectopic hair cells in Hey2 mutants are accompanied by ectopic supporting cells. Furthermore, Hey2-/-;Hes1-/- and Hey2-/-;Hes1+/- mutants show a complete penetrance of early embryonic lethality. Conclusion Our results indicate that Hey2 functions in parallel with Hes1 and Hes5 in patterning the organ of Corti, and interacts genetically with Hes1 for early embryonic development and survival. Our data implicates expansion of the progenitor pool and/or the boundaries of the developing sensory organ to account for patterning defects observed in Hey2 mutants.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

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Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Associations of Leu72Met Polymorphism of Preproghrelin with Ratios of Plasma Lipids Are Diversified by a High-Carbohydrate Diet in Healthy Chinese Adolescents.

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Su, Mi; Qiu, Li; Wang, Qian; Jiang, Zhen; Liu, Xiao Juan; Lin, Jia; Fang, Ding Zhi

2015-01-01

The association of preproghrelin Leu72Met polymorphism with plasma lipids profile was inconsistently reported and needs more studies to be confirmed. Our study was to investigate the changes of plasma lipids ratios after a high-carbohydrate (high-CHO) diet in healthy Chinese adolescents with different genotypes of this polymorphism. Fifty-three healthy university students were given a washout diet of 54.1% carbohydrate for 7 days, followed by a high-CHO diet of 70.1% carbohydrate for 6 days. The anthropometric and biological parameters were analyzed at baseline and before and after the high-CHO diet. When compared with those before the high-CHO diet, body mass index (BMI) decreased in the male and female Met72 allele carriers. Decreased low-/high-density lipoprotein cholesterol (LDL-C/HDL-C) was observed in all participants except the female subjects with the Leu72Leu genotype. TG/HDL-C and log (TG/HDL-C) were increased only in the female subjects with the Leu72Leu genotype. These results suggest that the Met72 allele of preproghrelin Leu72Met polymorphism may be associated with decreased BMI induced by the high-CHO diet in male and female adolescents, while the Leu72 allele with increased TG/HDL-C and log (TG/HDL-C) in the female adolescents only. Furthermore, the decreasing effect of the high-CHO diet on LDL/HDL-C may be eliminated in the female Leu72Leu homozygotes. © 2015 S. Karger AG, Basel.

Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism.

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Roberts, Stephanie A; Moon, Jennifer E; Dauber, Andrew; Smith, Jessica R

2017-03-01

Primary nonautoimmune hyperthyroidism is a rare cause of neonatal hyperthyroidism. This results from an activating mutation in the thyrotropin-receptor (TSHR). It can be inherited in an autosomal dominant manner or occur sporadically as a de novo mutation. Affected individuals display a wide phenotype from severe neonatal to mild subclinical hyperthyroidism. We describe a 6-month-old boy with a de novo mutation in the TSHR gene who presented with accelerated growth, enlarging head circumference, tremor and thyrotoxicosis. Genomic DNA from the patient's and parents' peripheral blood leukocytes was extracted. Exons 9 and 10 of the TSHR gene were amplified by PCR and sequenced. Sequencing exon 10 of the TSHR gene revealed a novel heterozygous missense mutation substituting cytosine to adenine at nucleotide position 1534 in the patient's peripheral blood leukocytes. This leads to a substitution of leucine to methionine at amino acid position 512. The mutation was absent in the parents. In silico modeling by PolyPhen-2 and SIFT predicted the mutation to be deleterious. The p.Leu512Met mutation (c.1534C>A) of the TSHR gene has not been previously described in germline or somatic mutations. This case presentation highlights the possibility of mild thyrotoxicosis in affected individuals and contributes to the understanding of sporadic non-autoimmune primary hyperthyroidism.

Leu72Met and Other Intronic Polymorphisms in the and Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population

OpenAIRE

Faris Elbahi Joatar; Ali Ahmed Al Qarni; Muhalab E. Ali; Abdulaziz Al Masaud; Abdirashid M. Shire; Nagalla Das; Khalid Gumaa; Hayder A. Giha

2017-01-01

Background Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associatio...

Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism

Science.gov (United States)

Roberts, Stephanie A.; Moon, Jennifer E.; Dauber, Andrew; Smith, Jessica R.

2018-01-01

Background Primary nonautoimmune hyperthyroidism is a rare cause of neonatal hyperthyroidism. This results from an activating mutation in the thyrotropin-receptor (TSHR). It can be inherited in an autosomal dominant manner or occur sporadically as a de novo mutation. Affected individuals display a wide phenotype from severe neonatal to mild subclinical hyperthyroidism. We describe a 6-month-old boy with a de novo mutation in the TSHR gene who presented with accelerated growth, enlarging head circumference, tremor and thyrotoxicosis. Methods Genomic DNA from the patient’s and parents’ peripheral blood leukocytes was extracted. Exons 9 and 10 of the TSHR gene were amplified by PCR and sequenced. Results Sequencing exon 10 of the TSHR gene revealed a novel heterozygous missense mutation substituting cytosine to adenine at nucleotide position 1534 in the patient’s peripheral blood leukocytes. This leads to a substitution of leucine to methionine at amino acid position 512. The mutation was absent in the parents. In silico modeling by PolyPhen-2 and SIFT predicted the mutation to be deleterious. Conclusions The p.Leu512Met mutation (c.l534C>A) of the TSHR gene has not been previously described in germline or somatic mutations. This case presentation highlights the possibility of mild thyrotoxicosis in affected individuals and contributes to the understanding of sporadic non-autoimmune primary hyperthyroidism. PMID:28195550

Association between the ghrelin Leu72Met polymorphism and type 2 diabetes risk: a meta-analysis.

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Liao, Ning; Xie, Zi-Kang; Huang, Jian; Xie, Zheng-Fu

2013-04-01

Data on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic. We searched for case-control studies using electronic databases (Medline and PubMed) and reference lists of studies. Odds ratios (OR) and 95% confidence intervals (CI) assuming dominant, recessive and homozygote comparison genetic models were calculated. Six case-control studies involving a total of 3417 cases and 3081 controls were included in this meta-analysis. No association was found between the ghrelin Leu72Met polymorphism and type 2 diabetes risk in the overall population in dominant, recessive and homozygote comparison models. However, in subgroup analyses stratified by ethnicity, we found that the risk for type 2 diabetes was decreased in subjects with Met72+ genotypes in Caucasians (OR=0.79, 95% CI: 0.64-0.98, P(z)=0.030). The ghrelin Leu72Met polymorphism was protective against type 2 diabetes in Caucasians. Future studies performed in larger sample size are needed to allow a more definitive conclusion. Copyright © 2012 Elsevier B.V. All rights reserved.

Simple and effective procedure for conformational search of macromolecules. Application to Met- and Leu-Enkephalin

Energy Technology Data Exchange (ETDEWEB)

Meirovitch, H.; Meirovitch, E. (Florida State Univ., Tallahassee, FL (United States)); Michel, A.G. (Institut de Recherches Serrier, Suresnes (France)); Vasquez, M. (Protein Design Lab., Mountain View, CA (United States))

1994-06-23

A simple and efficient method for searching the conformational space of macromolecules is presented. With this method an initial set of relatively low-energy structures is generated, and their energies are further minimized with a procedure that enables escaping from local energy minima. Illustrative calculations are described for Met- and Leu-enkephalin. 37 refs., 1 tab.

Leu72Met and Other Intronic Polymorphisms in the and Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population

Directory of Open Access Journals (Sweden)

Faris Elbahi Joatar

2017-09-01

Full Text Available BackgroundGhrelin (GHRL, a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs, namely the Leu72Met polymorphism (rs696217 TG, with type 2 diabetes mellitus (T2DM and insulin resistance (IR, while others have not. The controversies in these associations raise the issue of ‘which SNPs in which populations.’ The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis.MethodsBlood was collected from 208 Saudi subjects with (n=107 and without (n=101 T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT and GHSR (rs509030 GC genes. In addition, plasma GHRL levels were measured by a radioimmunoassay.ResultsNone of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region.ConclusionNeither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

A role for the transcription factor HEY1 in glioblastoma

DEFF Research Database (Denmark)

Hulleman, Esther; Quarto, Micaela; Vernell, Richard

2009-01-01

Glioblastoma multiforme (GBM), the highest-grade glioma, is the most frequent tumour of the brain with a very poor prognosis and limited therapeutic options. Although little is known about the molecular mechanisms that underlie glioblastoma formation, a number of signal transduction routes......, such as the Notch and Ras signalling pathways, seem to play an important role in the formation of GBM. In the present study, we show by in situ hybridization on primary tumour material that the transcription factor HEY1, a target of the Notch signalling pathway, is specifically upregulated in glioma...... and that expression of HEY1 in GBM correlates with tumour-grade and survival. In addition, we show by chromatin immunoprecipitations, luciferase assays and Northern blot experiments that HEY1 is a bona fide target of the E2F family of transcription factors, connecting the Ras and Notch signalling pathways. Finally...

Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population.

Science.gov (United States)

Joatar, Faris Elbahi; Al Qarni, Ali Ahmed; Ali, Muhalab E; Al Masaud, Abdulaziz; Shire, Abdirashid M; Das, Nagalla; Gumaa, Khalid; Giha, Hayder A

2017-09-01

Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of 'which SNPs in which populations.' The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis. Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay. None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region. Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR. Copyright © 2017 Korean Endocrine Society

A Sordaria macrospora mutant lacking the leu1 gene shows a developmental arrest during fruiting body formation.

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Kück, Ulrich

2005-10-01

Developmental mutants with defects in fruiting body formation are excellent resources for the identification of genetic components that control cellular differentiation processes in filamentous fungi. The mutant pro4 of the ascomycete Sordaria macrospora is characterized by a developmental arrest during the sexual life cycle. This mutant generates only pre-fruiting bodies (protoperithecia), and is unable to form ascospores. Besides being sterile, pro4 is auxotrophic for leucine. Ascospore analysis revealed that the two phenotypes are genetically linked. After isolation of the wild-type leu1 gene from S. macrospora, complementation experiments demonstrated that the gene was able to restore both prototrophy and fertility in pro4. To investigate the control of leu1 expression, other genes involved in leucine biosynthesis specifically and in the general control of amino acid biosynthesis ("cross-pathway control") have been analysed using Northern hybridization and quantitative RT-PCR. These analyses demonstrated that genes of leucine biosynthesis are transcribed at higher levels under conditions of amino acid starvation. In addition, the expression data for the cpc1 and cpc2 genes indicate that cross-pathway control is superimposed on leucine-specific regulation of fruiting body development in the leu1 mutant. This was further substantiated by growth experiments in which the wild-type strain was found to show a sterile phenotype when grown on a medium containing the amino acid analogue 5-methyl-tryptophan. Taken together, these data show that pro4 represents a novel mutant type in S. macrospora, in which amino acid starvation acts as a signal that interrupts the development of the fruiting body.

Simultaneous extraction of. beta. -endorphin and leu- and met-enkephalins from human and rat plasma

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Bhathena, S.J.; Smith, P.M.; Kennedy, B.W. (Dept. of Agriculture, Beltsville, MD (USA)); Voyles, N.R.; Recant, L. (Diabetes Research Laboratory, Washington, DC (USA))

1989-01-01

A simple, rapid and reliable procedure is described to simultaneously concentrated and purify {beta}-endorphin, leu-and met-enkephalins from small volumes of human and rat plasma before radioimmunoassay is performed. It uses C{sub 18} Sep-Pak reverse phase cartridges. The effectiveness of different protease inhibitors in preventing degradation of opiates by plasma and different solvent systems for eluting opiates is also evaluated.

The Pai-associated leuX specific tRNA5(Leu) affects type 1fimbriation in pathogenic Escherichia coli by control of FimB recombinase expression

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Ritter, A.; Gally, D.; Olsen, Peter Bjarke

1997-01-01

The uropathogenic Escherichia coli strain 536 (06:K15:H31) carries two large chromosomalpathogenicity islands (Pais). Both Pais are flanked by tRNA genes. Spontaneous deletion of Pai IIresults in truncation of the leuX tRNA5Leu gene. This tRNA is required for the expression of type 1fimbriae (Fim...

Age-related decreases in the concentration of Met- and Leu-enkephalin and neurotensin in the basal ganglia or rats

International Nuclear Information System (INIS)

Ceballos, M.L. de; Boyce, S.; Taylor, M.; Jenner, P.; Marsden, C.D.

1987-01-01

Previous studies using radioimmunoassay procedures have failed to show age-related changes in the concentration of Met-and Leu-enkephalin or neurotensin in rat basal ganglia. In contrast, using a combined high-pressure liquid chromatography (HLPC)- radioimmunoassay (RIA) technique we now report considerable decreases in the levels of these neuropeptides in areas of basal ganglia of 22 months-old compared to 3 months-old male Wistar rats. The concentration of Met-enkephalin was greatly reduced in the striatum and nucleus accumbens, but not in substantia nigra, of old compared to young animals. There was a similarly large decrease in Leu-enkephalin content in striatum of old rats with less marked decreases occurring in both the nucleus accumbens and substantia nigra. Neurotensin levels in the striatum and substantia nigra were greatly reduced in old rats, with a less marked decrease in the nucleus accumbens

Age-related decreases in the concentration of Met- and Leu-enkephalin and neurotensin in the basal ganglia or rats

Energy Technology Data Exchange (ETDEWEB)

Ceballos, M.L. de; Boyce, S; Taylor, M; Jenner, P; Marsden, C D

1987-03-20

Previous studies using radioimmunoassay procedures have failed to show age-related changes in the concentration of Met-and Leu-enkephalin or neurotensin in rat basal ganglia. In contrast, using a combined high-pressure liquid chromatography (HLPC)- radioimmunoassay (RIA) technique we now report considerable decreases in the levels of these neuropeptides in areas of basal ganglia of 22 months-old compared to 3 months-old male Wistar rats. The concentration of Met-enkephalin was greatly reduced in the striatum and nucleus accumbens, but not in substantia nigra, of old compared to young animals. There was a similarly large decrease in Leu-enkephalin content in striatum of old rats with less marked decreases occurring in both the nucleus accumbens and substantia nigra. Neurotensin levels in the striatum and substantia nigra were greatly reduced in old rats, with a less marked decrease in the nucleus accumbens.

Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits

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Bing, C; Ambye, L; Fenger, M

2005-01-01

Recently, low-frequency polymorphisms in the coding region of the ghrelin gene were suggested to be involved in the aetiology of obesity and to modulate glucose-induced insulin secretion in different ethnic study groups. The objective of the present large study was to investigate whether the Leu7...

MET overexpression, gene amplification and relevant clinicopathological features in gastric adenocarcinoma.

Science.gov (United States)

Zhang, Jing; Guo, Lei; Liu, Xiuyun; Li, Wenbin; Ying, Jianming

2017-02-07

This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected. MET overexpression (IHC 3+) was observed in 6.0% (49/816) of the cohort. MET overexpression rate was higher in patients with poor prognostic factors, such as clinical stages III/IV (p =0.012) and pathologic stages T3/T4 (p =0.027). The HER2 overexpression (IHC 3+) rate was 8.8% (72/816) and MET overexpression rate was higher in HER2 positive patients (9.7%, 7/72). A high concordance rate (94.6%) between MET overexpression and gene amplification was demonstrated. Therefore, MET overexpression could serve as a prognostic biomarker and a potential therapeutic target for gastric cancer.

Mutations Phe785Leu and Thr618Met in Na+, K+-ATPase, Associated with Familial Rapid-Onset Dystonia Parkinsonism, Interfere with Na+ Interaction by Distinct Mechanisms

DEFF Research Database (Denmark)

Schack, Vivien Rodacker; Toustrup-Jensen, Mads Schak; Vilsen, Bente

The Na+, K+-ATPase plays key roles in brain function. Recently, missense mutations in the Na+, K+-ATPase were found associated with familial rapid-onset dystonia parkinsonism (FRDP). Here, we have characterized the functional consequences of FRDP mutations Phe785Leu and Thr618Met. Both mutations...... lead to functionally altered, but active, Na+, K+-pumps that display reduced apparent affinity for cytoplasmic Na+, but the underlying mechanism differs between the mutants. In Phe785Leu, the interaction of the E1 form with Na+ is defective, and the E1-E2 equilibrium is not displaced. In Thr618Met......, the Na+ affinity is reduced because of displacement of the conformational equilibrium in favor of the K+-occluded E2(K2) form. In both mutants, K+ interaction at the external activating sites of the E2P phosphoenzyme is normal. The change of cellular Na+ homeostasis is likely a major factor contributing...

Mutations Phe785Leu and Thr618Met in Na+, K+-ATPase, Associated with Familial Rapid-Onset Dystonia Parkinsonism, Interfere with Na+ Interaction by Distinct Mechanisms

DEFF Research Database (Denmark)

Schack, Vivien Rodacker; Toustrup-Jensen, Mads Schak; Vilsen, Bente

The Na+, K+-ATPase plays key roles in brain function. Recently, missense mutations in the Na+, K+-ATPase were found associated with familial rapid-onset dystonia parkinsonism (FRDP). We have characterized the functional consequences of FRDP mutations Phe785Leu and Thr618Met. Both mutations lead...... to functionally altered, but active, Na+, K+-pumps that display reduced apparent affinity for cytoplasmic Na+, but the underlying mechanism differs between the mutants. In Phe785Leu, the interaction of the E1 form with Na+ is defective, and the E1-E2 equilibrium is not displaced. In Thr618Met, the Na+ affinity...... is reduced because of displacement of the conformational equilibrium in favor of the K+-occluded E2(K2) form. In both mutants, K+ interaction at the external activating sites of the E2P phosphoenzyme is normal. The change of cellular Na+ homeostasis is likely a major factor contributing to the development...

Hey! A Fire Ant Stung Me!

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... Videos for Educators Search English Español Hey! A Fire Ant Stung Me! KidsHealth / For Kids / Hey! A ... Me picó una roja o colorada! What's a Fire Ant? There are many different types of fire ...

Molecular cloning of Ly-1, a membrane glycoprotein of mouse T lymphocytes and a subset of B cells: molecular homology to its human counterpart Leu-1/T1 (CD5)

International Nuclear Information System (INIS)

Huang, H.J.S.; Jones, N.H.; Strominger, J.L.; Herzenberg, L.A.

1987-01-01

The authors report the isolation of cDNA clones of the mouse lymphocyte differentiation antigen Ly-1. One of these cDNA clones was confirmed to be full-length by DNA sequencing and by expression of Ly-1 by L cells transfected with this clone. Analysis of the predicted amino acid sequence indicated that the Ly-1 polypeptide is synthesized with a 23 amino acid leader and that the mature protein consists of an amino-terminal region of 347 amino acids, a transmembrane sequence of 30 residues, and a carboxyl-terminal region of 94 amino acids. The amino-terminal region appears to be divided into two subregions by a threonine- and proline-rich sequence of 23 amino acids that is highly conserved between Ly-1 and its human homologue Leu-1 (CD5) in position and amino acid composition. The first amino-terminal subregion of 111 amino acids is predicted to be arranged in a β-pleated sheet structure of six strands. The entire amino-terminal region is rich in cysteine, with all of its 22 cysteine residues conserved between Ly-1 and Leu-1. The carboxyl-terminal region has no cysteins. Ly-1 and Leu-1 are 63% identical, with a gradient of identical residues from 43% for the first amino-terminal to 58% for the second amino-terminal subregion and 90% for the carboxyl-terminal region. The predicted secondary structure of the first amino-terminal subregion and identities of certain conserved residues among most members of the immunoglobulin gene superfamily suggest that Ly-1 and Leu-1 are distant members of this family

Polymorphisms of the ghrelin/obestatin gene and ghrelin levels in Chinese children with short stature.

Science.gov (United States)

Zou, Chao Chun; Huang, Ke; Liang, Li; Zhao, Zheng Yan

2008-07-01

To investigate the role of ghrelin and polymorphisms of ghrelin/obestatin gene in children with short stature. A total of 117 GH deficient (GHD) and 81 idiopathic short stature (ISS) children were studied. The controls consisted of 125 age and gender-matched healthy children. The Arg51Gln, Leu72Met and Gln90Leu polymorphisms were genotyped using MassArray and total plasma ghrelin was measured by radioimmunoassay. In this study, the frequency of the Arg51Gln polymorphism was very low (0% in controls and 1.0% in patients). The frequency of the Gln90Leu polymorphism was 1.6% in controls and 0.5% in patients, respectively. Higher frequencies of Leu72Met (34.4% in controls and 39.9% in patients) and Met72Met genotypes (4.0% in controls and 2.0% in patients) were found. The differences in the Arg51Gln, Leu72Met or Gln90Leu genotypes and allele frequencies between patients and controls were not significant. Also, there were no significant differences in the Leu72Met genotypes and allele frequencies between GHD and ISS subgroups. There were no significant differences in clinical characteristics and biochemistry markers (including ghrelin levels) among the different genotypes of Leu72Met. However, plasma ghrelin levels in the GHD group were significantly lower than those of controls (P = 0.001). These results suggest that ghrelin may have a role in GH secretion and controlling growth. Lower ghrelin levels, but not ghrelin/obestatin polymorphism, might contribute to GHD.

Hey! A Mosquito Bit Me! (For Kids)

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... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Español Hey! A Mosquito Bit Me! KidsHealth / For Kids / Hey! A Mosquito Bit Me! Print en español ¡ ...

Genetic interaction between the ero1-1 and leu2 mutations in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

López-Mirabal, H Reynaldo; Winther, Jakob R; Kielland-Brandt, Morten C

2007-01-01

of the ero1-1 mutation were carried out in a leu2 mutant. The ero1-1 leu2 strain does not grow in standard synthetic complete medium at 30 degrees C, a defect that can be remedied by increasing the L-leucine concentration in the medium or by transforming the ero1-1 leu2 strain with the LEU2 wild-type allele...

Development of a chromosomally integrated metabolite-inducible Leu3p-alpha-IPM "off-on" gene switch.

Directory of Open Access Journals (Sweden)

Maria Poulou

2010-08-01

Full Text Available Present technology uses mostly chimeric proteins as regulators and hormones or antibiotics as signals to induce spatial and temporal gene expression.Here, we show that a chromosomally integrated yeast 'Leu3p-alpha-IotaRhoMu' system constitutes a ligand-inducible regulatory "off-on" genetic switch with an extensively dynamic action area. We find that Leu3p acts as an active transcriptional repressor in the absence and as an activator in the presence of alpha-isopropylmalate (alpha-IotaRhoMu in primary fibroblasts isolated from double transgenic mouse embryos bearing ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence of the branched amino acid biosynthetic pathway in animals, metabolically stable alpha-IPM presents an EC(50 equal to 0.8837 mM and fast "OFF-ON" kinetics (t(50ON = 43 min, t(50OFF = 2.18 h, it enters the cells via passive diffusion, while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex vivo.Our results demonstrate that the 'Leu3p-alpha-IotaRhoMu' constitutes a simpler and safer system for inducible gene expression in biomedical applications.

A three-step programmed method for the identification of causative gene mutations of maturity onset diabetes of the young (MODY).

Science.gov (United States)

Li, Qian; Cao, Xi; Qiu, Hai-Yan; Lu, Jing; Gao, Rui; Liu, Chao; Yuan, Ming-Xia; Yang, Guang-Ran; Yang, Jin-Kui

2016-08-22

To establish a three-step programmed method to find gene mutations related to maturity onset diabetes of the young (MODY). Target region capture and next-generation sequencing (NGS) were performed using customized oligonucleotide probes designed to capture suspected genes for MODY in 11 probands with clinically diagnosed MODY. The suspected associations of certain genes with MODY were then confirmed by Sanger sequencing in the probands and their family members. Finally, to validate variants of one of the genes of interest (glucokinase, GCK) as pathogenic mutations, protein function editing by the variant genes was assessed. In the target region capture and NGS phase, a total of nine variants of seven genes (GCK, WFS1, SLC19A2, SH2B1, SERPINB4, RFX6, and GATA6) were identified in eight probands. Two heterozygous GCK mutations located on the same allele (p.Leu77Arg and p.Val101Met) were identified in a MODY family. Sanger sequencing was used to confirm the variants identified by NGS to be present in probands and their diabetic family members, but not in non-diabetic family members. Finally, enzyme kinetic and thermal stability analyses revealed that the p.Leu77Arg mutation or the p.Leu77Arg mutation in combination with the p.Val101Met mutation inactivates GCK function and stability, while mutation of p.Val101Met alone does not. The p.Leu77Arg but not p.Val101Met GCK mutation is therefore considered a pathogenic mutation associated with MODY. Genetic screening coupled with gene-editing protein function testing is an effective and reliable method by which causative gene mutations of MODY can be identified. Copyright © 2016 Elsevier B.V. All rights reserved.

Performance of PARR-1 with LEU Fuel

International Nuclear Information System (INIS)

Pervez, S.; Latif, M.; Bokhari, I.H.; Bakhtyar, S.

2005-01-01

Pakistan Research Reactor (PARR-1) went critical in 1965 with HEU fuel. The reactor core was converted to LEU fuel with power upgradation from 5 MW to 10 MW in 1992. The reactor has been operated with LEU fuel for about 10,000 hours and has produced about 66,000 MWh energy up to now. Average burn up of the irradiated fuel is about 42 %. The fuel performance during the last 12 years has been excellent. Post irradiation visual inspection of the fuel has revealed no abnormality. During operation there have been no signs of releases in the pool water establishing the full integrity of this fuel. The reactor has been mainly utilized for radioisotope production, beam tube experiments including neutron diffraction studies, neutron radiography etc. Studies have been completed to operate the reactor with a mixed core (HEU + LEU) to utilize the less burned HEU fuel elements. A major project of production of fission Moly using PARR-1 is in the final stages. (author)

Formyl Met-Leu-Phe-Stimulated FPR1 Phosphorylation in Plate-Adherent Human Neutrophils: Enhanced Proteolysis but Lack of Inhibition by Platelet-Activating Factor

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Algirdas J. Jesaitis

2018-01-01

Full Text Available N-formyl-Met-Leu-Phe (fMLF is a model PAMP/DAMP driving human PMN to sites of injury/infection utilizing the GPCR, FPR1. We examined a microtiter plate format for measurement of FPR1 phosphorylation in adherent PMN at high densities and found that a new phosphosensitive FPR1 fragment, 25K-FPR1, accumulates in SDS-PAGE extracts. 25K-FPR1 is fully inhibited by diisopropylfluorophosphate PMN pretreatment but is not physiologic, as its formation failed to be significantly perturbed by ATP depletion, time and temperature of adherence, or adherence mechanism. 25K-FPR1 was minimized by extracting fMLF-exposed PMN in lithium dodecylsulfate at 4°C prior to reduction/alkylation. After exposure of adherent PMN to a 5 log range of PAF before or after fMLF, unlike in suspension PMN, no inhibition of fMLF-induced FPR1 phosphorylation was observed. However, PAF induced the release of 40% of PMN lactate dehydrogenase, implying significant cell lysis. We infer that PAF-induced inhibition of fMLF-dependent FPR1 phosphorylation observed in suspension PMN does not occur in the unlysed adherent PMN. We speculate that although the conditions of the assay may induce PAF-stimulated necrosis, the cell densities on the plates may approach levels observed in inflamed tissues and provide for an explanation of PAF’s divergent effects on FPR1 phosphorylation as well as PMN function.

High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study.

Science.gov (United States)

Laurila, M; Santaniemi, M; Kesäniemi, Y A; Ukkola, O

2014-11-01

The aim of our investigation was to find out if ghrelin concentrations or polymorphisms predict the future risk for cardiovascular diseases and cancer in a population-based cohort initiated in 1991 (491 hypertensive and 513 control subjects). Total mortality and hospital events were followed up for 19 years. Fasting total ghrelin concentrations were determined and Arg51Gln, Leu72Met and -501 A > C polymorphisms identified. Cox regression analysis was performed. The mean value in the control cohort was 674 pg/ml whereas in the hypertensive cohort it was 661 pg/ml. The associations found suggest that in the controls the highest ghrelin quartile protected from CHD (coronary heart disease). The results were significant without or with adjustments for age, sex, smoking, systolic blood pressure and LDL cholesterol, BMI, type 2 diabetes or QUICK index. C/C variant of the promoter associated with the prevention of IHD (ischemic heart disease) in the hypertensive group (pghrelin concentration was related to protection from CHD and Leu72Leu genotype to prevention of cancer in healthy adults during the 19 years follow-up. C/C promoter protects from IHD in the hypertensive subjects. Copyright © 2014 Elsevier Inc. All rights reserved.

Mutations in MC1R Gene Determine Black Coat Color Phenotype in Chinese Sheep

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Guang-Li Yang

2013-01-01

Full Text Available The melanocortin receptor 1 (MC1R plays a central role in regulation of animal coat color formation. In this study, we sequenced the complete coding region and parts of the 5′- and 3′-untranslated regions of the MC1R gene in Chinese sheep with completely white (Large-tailed Han sheep, black (Minxian Black-fur sheep, and brown coat colors (Kazakh Fat-Rumped sheep. The results showed five single nucleotide polymorphisms (SNPs: two non-synonymous mutations previously associated with coat color (c.218 T>A, p.73 Met>Lys. c.361 G>A, p.121 Asp>Asn and three synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200 Leu>Leu. c.735 C>T, p.245 Ile>Ile. Meanwhile, all mutations were detected in Minxian Black-fur sheep. However, the two nonsynonymous mutation sites were not in all studied breeds (Large-tailed Han, Small-tailed Han, Gansu Alpine Merino, and China Merino breeds, all of which are in white coat. A single haplotype AATGT (haplotype3 was uniquely associated with black coat color in Minxian Black-fur breed (P=9.72E-72, chi-square test. The first and second A alleles in this haplotype 3 represent location at 218 and 361 positions, respectively. Our results suggest that the mutations of MC1R gene are associated with black coat color phenotype in Chinese sheep.

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

International Nuclear Information System (INIS)

Ball, G.; Pond, R.; Hanan, N.; Matos, J.

1995-01-01

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

Association analysis of 94 candidate genes and schizophrenia-related endophenotypes.

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Tiffany A Greenwood

Full Text Available While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI, P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility

Leu-9 (CD 7) positivity in acute leukemias: a marker of T-cell lineage?

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Ben-Ezra, J; Winberg, C D; Wu, A; Rappaport, H

1987-01-01

Monoclonal antibody Leu-9 (CD 7) has been reported to be a sensitive and specific marker for T-cell lineage in leukemic processes, since it is positive in patients whose leukemic cells fail to express other T-cell antigens. To test whether Leu-9 is indeed specific for T-cell leukemias, we examined in detail 10 cases of acute leukemia in which reactions were positive for Leu-9 and negative for other T-cell-associated markers including T-11, Leu-1, T-3, and E-rosettes. Morphologically and cytochemically, 2 of these 10 leukemias were classified as lymphoblastic, 4 as myeloblastic, 2 as monoblastic, 1 as megakaryoblastic, and 1 as undifferentiated. The case of acute megakaryoblastic leukemia is the first reported case to be Leu-9 positive. None of the 10 were TdT positive. Of six cases (two monoblastic, one lymphoblastic, one myeloblastic, one megakaryoblastic, and one undifferentiated) in which we evaluated for DNA gene rearrangements, only one, a peroxidase-positive leukemia, showed a novel band on study of the T-cell-receptor beta-chain gene. We therefore conclude that Leu-9 is not a specific marker to T-cell lineage and that, in the absence of other supporting data, Leu-9 positivity should not be used as the sole basis of classifying an acute leukemia as being T-cell derived.

Assessment of MC1R and α-MSH gene sequences in Iranian vitiligo patients

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Eskandani M

2010-01-01

Full Text Available Background: Vitiligo is an acquired pigmentary disorder of the skin that is caused by unknown factors and is characterized by white and depigmented patches that enlarge and become more numerous with time. Genetic factors, oxidative stress, autoimmunity, and neurochemical agents, such as catecholamines might also contribute to vitiligo. Cutaneous pigmentation is determined by the amounts of eumelanin and pheomelanin synthesized by the epidermal melanocytes and interference of melanocortin-1 receptor (MC1R, a G-protein coupled receptor, its normal agonist, alpha-melanocyte stimulating hormone (α-MSH, and key enzymes, such as tyrosinase, to protect against sun-induced DNA damage. The MC1R, a 7 pass trans-membrane G-protein coupled receptor, is a key control point in melanogenesis. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to pheomelanin production, resulting in a red or yellow coat color. Aim: In this research, we aim to examine the genetic variety of MC1R and α-MSH gene in 20 Iranian vitiligo patients and 20 healthy controls. Materials and Methods: Analysis of the MC1R coding gene was performed with direct sequencing. Results: We found the following 9 MC1R coding region variants: Arg163Gl (G488A, Arg227Leu (G680A, Val 97Phe (G289T, Asp184Asn (G550A, Arg227Lys (G680A, Arg142His (G425A, Val60Leu (G178T, Val247Met (C739A, and Val174Ile (G520A. We also found 2 frameshift changes: one of them was the Insertion of C (frameshift in Pro136, stop at Trp148 and the other, Insertion of G (frameshift in Pro256, stop at Trp 333. Of all the changes, the most common was Val60Leu at 5% in patients vs 20% in controls, Val247Met at 15% in patients vs 0% in controls and Val174Ile at 15% in controls and 0% in patients. The other variants showed a frequency <5% in both patients and controls. Also in this study, we have examined the frequency of single nucleotide polymorphisms within the α-MSH genes with direct sequencing in

A novel mutation in the albumin gene (c.1A>C) resulting in analbuminemia.

Science.gov (United States)

Caridi, Gianluca; Dagnino, Monica; Lugani, Francesca; Shalev, Stavit A; Campagnoli, Monica; Galliano, Monica; Spiegel, Ronen; Minchiotti, Lorenzo

2013-01-01

Analbuminemia (OMIM # 103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene. We report here the clinical and molecular characterisation of two new cases of congenital analbuminemia diagnosed in two members of the Druze population living in a Galilean village (Northern Israel) on the basis of their low level of circulating albumin. The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis, and the mutated region was submitted to DNA sequencing. Both the analbuminemic subjects resulted homozygous for a previously unreported c.1 A>C transversion, for which we suggest the name Afula from the hospital where the two cases were investigated. This mutation causes the loss of the primary start codon ATG for Met1, which is replaced by a - then untranslated - triplet CTG for Leu. (p.Met1Leu). The use of an alternative downstream ATG codon would probably give rise to a completely aberrant polypeptide chain, leading to a misrouted intracellular transport and a premature degradation. The discovery of this new ALB mutation, probably inherited from a common ancestor, sheds light on the molecular mechanism underlying the analbuminemic trait and may serve in the development of a rapid genetic test for the identification of a-symptomatic heterozygous carriers in the Druze population in the Galilee. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

TOLL-LIKE RECEPTOR 7 GENE Gln11Leu MISSENSEMUTATION AND SUSCEPTIBILITY TO PSORIASIS

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E. S. Galimova

2017-01-01

Full Text Available Toll-like receptor (TLR are responsible for recognizing various molecular patterns associated with pathogens. Their expression have been detected in skin cells such as keratinocytes and melanocytes. Numerous experimental studies demonstrate the key role of TLRs in the pathogenesis of immune diseases, including psoriasis. The objective of this study is to analyze the associations of polymorphisms in TLR7 gene and the risk of psoriasis development. DNA samples were collected from 138 patients with psoriasis and 317 healthy controls. Genotyping of rs179003, rs179008, rs179020, rs850632, rs12013728 polymorphic loci in TLR7 gene was performed using the SNPlex™method (AB, USA. SNP in the TLR7 gene rs179008 (Gln11Leu was associated with psoriasis in entire psoriasis, late onset and sporadic subgroups (Рс = 0.0065, OR = 1.95; Рс = 0.0004, OR = 2.50; Рс = 0.0078, OR = 2.2, respectively. In conclusion, this study is the first to identify genetic variants of the TLR7 gene significantly associated with psoriasis. 

TOLL-LIKE RECEPTOR 7 GENE Gln11Leu MISSENSEMUTATION AND SUSCEPTIBILITY TO PSORIASIS

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E. S. Galimova

2017-01-01

Full Text Available Toll-like receptor (TLR are responsible for recognizing various molecular patterns associated with pathogens. Their expression have been detected in skin cells such as keratinocytes and melanocytes. Numerous experimental studies demonstrate the key role of TLRs in the pathogenesis of immune diseases, including psoriasis. The objective of this study is to analyze the associations of polymorphisms in TLR7 gene and the risk of psoriasis development. DNA samples were collected from 138 patients with psoriasis and 317 healthy controls. Genotyping of rs179003, rs179008, rs179020, rs850632, rs12013728 polymorphic loci in TLR7 gene was performed using the SNPlex™method (AB, USA. SNP in the TLR7 gene rs179008 (Gln11Leu was associated with psoriasis in entire psoriasis, late onset and sporadic subgroups (Рс = 0.0065, OR = 1.95; Рс = 0.0004, OR = 2.50; Рс = 0.0078, OR = 2.2, respectively. In conclusion, this study is the first to identify genetic variants of the TLR7 gene significantly associated with psoriasis.

Analysis of manganese superoxide dismutase (MnSOD: Ala-9Val and glutathione peroxidase (GSH-Px: Pro 197 Leu gene polymorphisms in mood disorders.

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Birgül Elbozan Cumurcu

2013-05-01

Full Text Available We investigated the etiopathogenetic role of manganese superoxide dismutase (MnSOD (Ala-9Val and glutathione peroxidase (GSH-Px (Pro 197 Leu gene polymorphisms in patients diagnosed with major depressive disorder (MDD and bipolar I disorder (BD. Eighty patients with MDD, 82 patients with BD (total 162 patients and 96 healthy controls were enrolled in this study and genotyped using a Real Time-Quantitative Polymer Chain Reaction (RT-qPCR-based method. The patients with BD and MDD and the controls had a similar distribution of the genotypes and alleles in the Ala-9Val MnSOD gene polymorphism. Comparison of the MDD group and control group regarding the Pro197 Leu GSH-Px gene polymorphism revealed similar genotype distribution but different allele distribution. The BD group and control group were similar both for genotypes and for alleles when compared regarding the Pro 197 Leu GSH-Px gene polymorphism. The combined analysis (MDD plus BD also failed to find any association between the Ala-9Val MnSOD and Pro 197 Leu GSH-Px gene polymorphism. Although small statistical power of the current study the significant difference between patients with depression and the control group for the Pro 197 Leu GSH-Px polymorphism indicates that the distribution of these alleles may have a contribution in the physiopathogenesis of depression. One of the limitation of the current study is that the sample size is too small. Understanding of the exact role of Pro 197 LeuGSH-Px polymorphism in the development of depression needs to further studies with more sample size and high statistical power.

Induction of epigenetic variation in Arabidopsis by over-expression of DNA METHYLTRANSFERASE1 (MET1.

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Samuel Brocklehurst

Full Text Available Epigenetic marks such as DNA methylation and histone modification can vary among plant accessions creating epi-alleles with different levels of expression competence. Mutations in epigenetic pathway functions are powerful tools to induce epigenetic variation. As an alternative approach, we investigated the potential of over-expressing an epigenetic function, using DNA METHYLTRANSFERASE1 (MET1 for proof-of-concept. In Arabidopsis thaliana, MET1 controls maintenance of cytosine methylation at symmetrical CG positions. At some loci, which contain dense DNA methylation in CG- and non-CG context, loss of MET1 causes joint loss of all cytosines methylation marks. We find that over-expression of both catalytically active and inactive versions of MET1 stochastically generates new epi-alleles at loci encoding transposable elements, non-coding RNAs and proteins, which results for most loci in an increase in expression. Individual transformants share some common phenotypes and genes with altered gene expression. Altered expression states can be transmitted to the next generation, which does not require the continuous presence of the MET1 transgene. Long-term stability and epigenetic features differ for individual loci. Our data show that over-expression of MET1, and potentially of other genes encoding epigenetic factors, offers an alternative strategy to identify epigenetic target genes and to create novel epi-alleles.

LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.

Science.gov (United States)

Milkereit, Ruth; Persaud, Avinash; Vanoaica, Liviu; Guetg, Adriano; Verrey, Francois; Rotin, Daniela

2015-05-22

Mammalian target of rapamycin 1 (mTORC1), a master regulator of cellular growth, is activated downstream of growth factors, energy signalling and intracellular essential amino acids (EAAs) such as Leu. mTORC1 activation occurs at the lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal EAA (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown. Here we identified the lysosomal protein LAPTM4b as a binding partner for the Leu transporter, LAT1-4F2hc (SLC7A5-SLAC3A2). We show that LAPTM4b recruits LAT1-4F2hc to lysosomes, leading to uptake of Leu into lysosomes, and is required for mTORC1 activation via V-ATPase following EAA or Leu stimulation. These results demonstrate a functional Leu transporter at the lysosome, and help explain the inside-out lysosomal activation of mTORC1 by Leu/EAA.

Stimulation of Escherichia coli F-18Col- Type-1 fimbriae synthesis by leuX

DEFF Research Database (Denmark)

Newman, Joseph V.; Burghoff, Robert L.; Pallesen, Lars

1994-01-01

Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomycin-treated mouse large intestine. E. coli F-18Col-, a derivative of E. coli F-18 which no longer makes the E. coli F-18 colicin, colonizes the large intestine as well as E. coli F-18 when fed to mice...... alone but is eliminated when fed together with E. coli F-18. Recently we randomly cloned E. coli F-18 DNA into E. coli F-18Col- and let the mouse intestine select the best colonizer. In this way, we isolated a 6.5-kb E. coli F-18 DNA sequence that simultaneously stimulated synthesis of type 1 fimbriae...... and enhanced E. coli F-18Col- colonizing ability. In the present investigation we show that the gene responsible for stimulation of type 1 fimbriae synthesis appears to be leuX, which encodes a tRNA specific for the rare leucine codon UUG. Moreover, it appears that expression of leuX may be regulated by two...

Leu452His mutation in lipoprotein lipase gene transfer associated with hypertriglyceridemia in mice in vivo.

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Kaiyue Sun

Full Text Available Mutated mouse lipoprotein lipase (LPL containing a leucine (L to histidine (H substitution at position 452 was transferred into mouse liver by hydrodynamics-based gene delivery (HD. Mutated-LPL (MLPL gene transfer significantly increased the concentrations of plasma MLPL and triglyceride (TG but significantly decreased the activity of plasma LPL. Moreover, the gene transfer caused adiposis hepatica and significantly increased TG content in mouse liver. To understand the effects of MLPL gene transfer on energy metabolism, we investigated the expression of key functional genes related to energy metabolism in the liver, epididymal fat, and leg muscles. The mRNA contents of hormone-sensitive lipase (HSL, adipose triglyceride lipase (ATGL, fatty acid-binding protein (FABP, and uncoupling protein (UCP were found to be significantly reduced. Furthermore, we investigated the mechanism by which MLPL gene transfer affected fat deposition in the liver, fat tissue, and muscle. The gene expression and protein levels of forkhead Box O3 (FOXO3, AMP-activated protein kinase (AMPK, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α were found to be remarkably decreased in the liver, fat and muscle. These results suggest that the Leu452His mutation caused LPL dysfunction and gene transfer of MLPL in vivo produced resistance to the AMPK/PGC-1α signaling pathway in mice.

A neutronic feasibility study for LEU conversion of the SAFARI-1 reactor

International Nuclear Information System (INIS)

Pond, R.B.; Hanan, N.A.; Matos, J.E.; Ball, G.

2000-01-01

A neutronic feasibility study to convert the SAFARI-1 reactor from HEU to LEU fuel was performed at Argonne National Laboratory in cooperation with NECSA. Comparisons were made of the reactor performance with the current 90% enriched HEU fuel type (UAl) and two 19.75% enriched LEU fuel types (U 3 Si 2 and U7Mo). The thermal fluxes with the LEU fuels were 3 - 9% lower than with the current HEU fuel. For the same fuel assembly design, a uranium density of approximately 4.5 g/cm 3 was required with U 3 Si 2 -Al fuel and a uranium density of about 4.6 g/cm 3 was required with U7Mo-Al fuel to match the 24.6-day cycle of the UAl-alloy fuel with 0.92 gU/cm 3 . The selection of a suitable LEU fuel and the decision to convert SAFARI-1 will be an economic matter that depends upon the fuel type, fuel assembly design, experiment performance and fuel cycle costs. (author)

Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents.

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Zhu, J F; Liang, L; Zou, C C; Fu, J F

2010-09-01

To evaluate the role of fasting plasma ghrelin levels [ln(ghrelin)] and polymorphisms of ghrelin gene in Chinese obese children. Genotyping for ghrelin polymorphism was performed in 230 obese and 100 normal weight children. Among them, plasma ghrelin levels were measured in 91 obese and 23 health subjects. (1) Bivariate correlation analysis showed the ln(ghrelin) was inversely correlated with abnormality of glucose metabolism (r = -0.240, P = 0.023). Stepwise multiple regression analysis showed that abnormality of glucose metabolism was an independent determinant of plasma ghrelin levels (P = 0.023). (2) There was no difference in frequency of Leu72Met polymorphisms between obese and control groups (36.09 vs. 41.00%). Ghrelin is associated with obesity in childhood, especially associated with the glucose homeostasis. Lower ghrelin levels might be a result of obesity, but not a cause of obesity. The Leu72Met polymorphism of ghrelin gene is not associated with obesity and metabolic syndrome in Chinese children.

Ser80Ile mutation and a concurrent Pro25Leu variant of the VHL gene in an extended Hungarian von Hippel-Lindau family

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Fazakas Ferenc

2008-04-01

Full Text Available Abstract Von Hippel-Lindau disease (VHL is a rare autosomal dominant disease characterized by development of cystic and tumorous lesions at multiple sites, including the brain, spinal cord, kidneys, adrenals, pancreas, epididymis and eyes. The clinical phenotype results from molecular abnormalities of the VHL tumor suppressor gene, mapped to human chromosome 3p25-26. The VHL gene encodes two functionally active VHL proteins due to the presence of two translational initiation sites separated by 53 codons. The majority of disease-causing mutations have been detected downstream of the second translational initiation site, but there are conflicting data as to whether few mutations located in the first 53 codons, such as the Pro25Leu could have a pathogenic role. In this paper we report a large Hungarian VHL type 2 family consisting of 32 members in whom a disease-causing AGT80AAT (Ser80Ile c.239G>A, p.Ser80Ile mutation, but not the concurrent CCT25CTT (Pro25Leu c.74C>T, p.Pro25Leu variant co-segregated with the disease. To our knowledge, the Ser80Ile mutation has not been previously described in VHL type 2 patients with high risk of pheochromocytoma and renal cell cancer. Therefore, this finding represents a novel genotype-phenotype association and VHL kindreds with Ser80Ile mutation will require careful surveillance for pheochromocytoma. We concluded that the Pro25Leu variant is a rare, neutral variant, but the presence such a rare gene variant may make genetic counseling difficult.

Progress in the neutronic core conversion (HEU-LEU) analysis of Ghana research reactor-1.

Energy Technology Data Exchange (ETDEWEB)

Anim-Sampong, S.; Maakuu, B. T.; Akaho, E. H. K.; Andam, A.; Liaw, J. J. R.; Matos, J. E.; Nuclear Engineering Division; Ghana Atomic Energy Commission; Kwame Nkrumah Univ. of Science and Technology

2006-01-01

The Ghana Research Reactor-1 (GHARR-1) is a commercial version of the Miniature Neutron Source Reactor (MNSR) and has operated at different power levels since its commissioning in March 1995. As required for all nuclear reactors, neutronic and thermal hydraulic analysis are being performed for the HEU-LEU core conversion studies of the Ghana Research Reactor-1 (GHARR-1) facility, which is a commercial version of the Miniature Neutron Source Reactor (MNSR). Stochastic Monte Carlo particle transport methods and tools (MCNP4c/MCNP5) were used to fine-tune a previously developed 3-D MCNP model of the GHARR-1 facility and perform neutronic analysis of the 90.2% HEU reference and candidate LEU (UO{sub 2}, U{sub 3}Si{sub 2}, U-9Mo) fresh cores with varying enrichments from 12.6%-19.75%. In this paper, the results of the progress made in the Monte Carlo neutronic analysis of the HEU reference and candidate LEU fuels are presented. In particular, a comparative performance assessment of the LEU with respect to neutron flux variations in the fission chamber and experimental irradiation channels are highlighted.

A Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for clade-specific flucytosine resistance in Candida dubliniensis.

LENUS (Irish Health Repository)

McManus, Brenda A

2009-11-01

The population structure of the opportunistic yeast pathogen Candida dubliniensis is composed of three main multilocus sequence typing clades (clades C1 to C3), and clade C3 predominantly consists of isolates from the Middle East that exhibit high-level resistance (MIC(50) > or = 128 microg\\/ml) to the fungicidal agent flucytosine (5FC). The close relative of C. dubliniensis, C. albicans, also exhibits clade-specific resistance to 5FC, and resistance is most commonly mediated by an Arg101Cys substitution in the FUR1 gene encoding uracil phosphoribosyltransferase. Broth microdilution assays with fluorouracil (5FU), the toxic deaminated form of 5FC, showed that both 5FC-resistant and 5FC-susceptible C. dubliniensis isolates exhibited similar 5FU MICs, suggesting that the C. dubliniensis cytosine deaminase (Fca1p) encoded by C. dubliniensis FCA1 (CdFCA1) may play a role in mediating C. dubliniensis clade-specific 5FC resistance. Amino acid sequence analysis of the CdFCA1 open reading frame (ORF) identified a homozygous Ser29Leu substitution in all 12 5FC-resistant isolates investigated which was not present in any of the 9 5FC-susceptible isolates examined. The tetracycline-inducible expression of the CdFCA1 ORF from a 5FC-susceptible C. dubliniensis isolate in two separate 5FC-resistant clade C3 isolates restored susceptibility to 5FC, demonstrating that the Ser29Leu substitution was responsible for the clade-specific 5FC resistance and that the 5FC resistance encoded by FCA1 genes with the Ser29Leu transition is recessive. Quantitative real-time PCR analysis showed no significant difference in CdFCA1 expression between 5FC-susceptible and 5FC-resistant isolates in either the presence or the absence of subinhibitory concentrations of 5FC, suggesting that the Ser29Leu substitution in the CdFCA1 ORF is the sole cause of 5FC resistance in clade C3 C. dubliniensis isolates.

Preparation, crystallization and preliminary X-ray analysis of the methionine synthase (MetE) from Streptococcus mutans

International Nuclear Information System (INIS)

Fu, Tian-Min; Zhang, Xiao-Yan; Li, Lan-Fen; Liang, Yu-He; Su, Xiao-Dong

2006-01-01

Methionine synthase (MetE) from S. mutans was expressed, purified and crystallized. Diffraction data have been collected to 2.2 Å resolution. The Streptococcus mutans metE gene encodes methionine synthase (MetE), which catalyzes the direct transfer of a methyl group from methyltetrahydrofolate to homocysteine in the last step of methionine synthesis. metE was cloned into pET28a and the gene product was expressed at high levels in the Escherichia coli strain BL21 (DE3). MetE was purified to homogeneity using Ni 2+ -chelating chromatography followed by size-exclusion chromatography. Crystals of the protein were obtained by the hanging-drop vapour-diffusion method and diffracted to 2.2 Å resolution. The crystal belongs to space group P2 1 , with unit-cell parameters a = 52.85, b = 99.48, c = 77.88 Å, β = 94.55°

The probability distribution of side-chain conformations in [Leu] and [Met]enkephalin determines the potency and selectivity to mu and delta opiate receptors

DEFF Research Database (Denmark)

Nielsen, Bjørn Gilbert; Jensen, Morten Østergaard; Bohr, Henrik

2003-01-01

The structure of enkephalin, a small neuropeptide with five amino acids, has been simulated on computers using molecular dynamics. Such simulations exhibit a few stable conformations, which also have been identified experimentally. The simulations provide the possibility to perform cluster analysis...... in the space defined by potentially pharmacophoric measures such as dihedral angles, side-chain orientation, etc. By analyzing the statistics of the resulting clusters, the probability distribution of the side-chain conformations may be determined. These probabilities allow us to predict the selectivity...... of [Leu]enkephalin and [Met]enkephalin to the known mu- and delta-type opiate receptors to which they bind as agonists. Other plausible consequences of these probability distributions are discussed in relation to the way in which they may influence the dynamics of the synapse....

Identification of auxotrophic mutants of the yeast Kluyveromyces marxianus by non-homologous end joining-mediated integrative transformation with genes from Saccharomyces cerevisiae.

Science.gov (United States)

Yarimizu, Tohru; Nonklang, Sanom; Nakamura, Junpei; Tokuda, Shuya; Nakagawa, Takaaki; Lorreungsil, Sasithorn; Sutthikhumpha, Surasit; Pukahuta, Charida; Kitagawa, Takao; Nakamura, Mikiko; Cha-Aim, Kamonchai; Limtong, Savitree; Hoshida, Hisashi; Akada, Rinji

2013-12-01

The isolation and application of auxotrophic mutants for gene manipulations, such as genetic transformation, mating selection and tetrad analysis, form the basis of yeast genetics. For the development of these genetic methods in the thermotolerant fermentative yeast Kluyveromyces marxianus, we isolated a series of auxotrophic mutants with defects in amino acid or nucleic acid metabolism. To identify the mutated genes, linear DNA fragments of nutrient biosynthetic pathway genes were amplified from Saccharomyces cerevisiae chromosomal DNA and used to directly transform the K. marxianus auxotrophic mutants by random integration into chromosomes through non-homologous end joining (NHEJ). The appearance of transformant colonies indicated that the specific S. cerevisiae gene complemented the K. marxianus mutant. Using this interspecific complementation approach with linear PCR-amplified DNA, we identified auxotrophic mutations of ADE2, ADE5,7, ADE6, HIS2, HIS3, HIS4, HIS5, HIS6, HIS7, LYS1, LYS2, LYS4, LYS9, LEU1, LEU2, MET2, MET6, MET17, TRP3, TRP4 and TRP5 without the labour-intensive requirement of plasmid construction. Mating, sporulation and tetrad analysis techniques for K. marxianus were also established. With the identified auxotrophic mutant strains and S. cerevisiae genes as selective markers, NHEJ-mediated integrative transformation with PCR-amplified DNA is an attractive system for facilitating genetic analyses in the yeast K. marxianus. Copyright © 2013 John Wiley & Sons, Ltd.

Preparation, crystallization and preliminary X-ray analysis of the methionine synthase (MetE) from Streptococcus mutans

Energy Technology Data Exchange (ETDEWEB)

Fu, Tian-Min; Zhang, Xiao-Yan; Li, Lan-Fen; Liang, Yu-He, E-mail: liangyh@pku.edu.cn; Su, Xiao-Dong [National Laboratory of Protein Engineering and Plant Genetic Engineering, Peking University, Beijing 100871 (China); Department of Biochemistry and Molecular Biology, College of Life Sciences, Peking University, Beijing 100871 (China)

2006-10-01

Methionine synthase (MetE) from S. mutans was expressed, purified and crystallized. Diffraction data have been collected to 2.2 Å resolution. The Streptococcus mutans metE gene encodes methionine synthase (MetE), which catalyzes the direct transfer of a methyl group from methyltetrahydrofolate to homocysteine in the last step of methionine synthesis. metE was cloned into pET28a and the gene product was expressed at high levels in the Escherichia coli strain BL21 (DE3). MetE was purified to homogeneity using Ni{sup 2+}-chelating chromatography followed by size-exclusion chromatography. Crystals of the protein were obtained by the hanging-drop vapour-diffusion method and diffracted to 2.2 Å resolution. The crystal belongs to space group P2{sub 1}, with unit-cell parameters a = 52.85, b = 99.48, c = 77.88 Å, β = 94.55°.

Met kerse op met -konstruksies 1 : 'n Verwysingspuntperspektief ...

African Journals Online (AJOL)

Met kerse op met-konstruksies1: 'n Verwysingspuntperspektief. Johanna Messerschmidt, Luna Bergh. Abstract. This article analyses the usage of the Afrikaans preposition met ('with'). The analysis is done within the framework of Cognitive Linguistics and more specifically within the model proposed by Langacker (1993) ...

Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study.

Science.gov (United States)

Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

2017-10-01

Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- control study included 92 SCZ patients and 92 healthy controls (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A)) were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Results: The findings revealed that the COMT Val158Met (G>A) polymorphism was not associated with the risk/protective of SCZ in all models (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793, P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667, 95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR = 2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925, P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG, OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). Conclusion: The results did not support an association between COMT Val158Met (G>A) variant and risk/protective of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase the risk of SCZ development. Further studies and different ethnicities are recommended to confirm the findings.

Paraoxonase-1 genetic polymorphisms and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides

International Nuclear Information System (INIS)

Singh, Satyender; Kumar, Vivek; Thakur, Sachin; Banerjee, Basu Dev; Rautela, Rajender Singh; Grover, Shyam Sunder; Rawat, Devendra Singh; Pasha, Syed Tazeen; Jain, Sudhir Kumar; Ichhpujani, Rattan Lal; Rai, Arvind

2011-01-01

Human paraoxonase 1 (PON1) is a lipoprotein-associated enzyme involved in the detoxification of organophosphate pesticides (OPs) by hydrolyzing the bioactive oxons. Polymorphisms of the PON1 gene are responsible for variation in the expression and catalytic activity of PON1 enzyme. In the present study, we have determined (a) the prevalence of two common PON1 polymorphisms, (b) the activity of PON1 and acetylcholinesterase enzymes, and (c) the influence of PON1 genotypes and phenotypes variation on DNA damage in workers exposed to OPs. We examined 230 subjects including 115 workers exposed to OPs and an equal number of normal healthy controls. The results revealed that PON1 activity toward paraoxon (179.19 ± 39.36 vs. 241.52 ± 42.32 nmol/min/ml in controls) and phenylacetate (112.74 ± 17.37 vs. 134.28 ± 25.49 μmol/min/ml in controls) was significantly lower in workers than in control subjects (p 192 QR (Gln/Arg) and PON1 55 LM (Leu/Met) in workers and control subjects (p > 0.05). The PON1 activity toward paraoxonase was found to be significantly higher in the R/R (Arg/Arg) genotypes than Q/R (Gln/Arg) and lowest in Q/Q (Gln/Gln) genotypes in both workers and control subjects (p 55 LM (Leu/Met), PON1 activity toward paraoxonase was observed to be higher in individuals with L/L (Leu/Leu) genotypes and lowest in individuals with M/M (Met/Met) genotypes in both groups (p < 0.001). No influence of PON1 genotypes and phenotypes was seen on the activity of acetylcholinesterase and arylesterase. The DNA damage was observed to be significantly higher in workers than in control subjects (p < 0.05). Further, the individuals who showed least paraoxonase activity i.e., those with (Q/Q [Gln/Gln] and M/M [Met/Met]) genotypes showed significantly higher DNA damage compared to other isoforms in workers exposed to OPs (p < 0.05). The results indicate that the individuals with PON1 Q/Q and M/M genotypes are more susceptible toward genotoxicity. In conclusion, the study suggests

Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans.

Science.gov (United States)

Ghisari, Mandana; Long, Manhai; Bonefeld-Jørgensen, Eva C

2013-01-01

The Indigenous Arctic population is of Asian descent, and their genetic background is different from the Caucasian populations. Relatively little is known about the specific genetic polymorphisms in genes involved in the activation and detoxification mechanisms of environmental contaminants in Inuit and its relation to health risk. The Greenlandic Inuit are highly exposed to legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), and an elucidation of gene-environment interactions in relation to health risks is needed. The aim of this study was to determine and compare the genotype and allele frequencies of the cytochrome P450 CYP1A1 Ile462Val (rs1048943), CYP1B1 Leu432Val (rs1056836) and catechol-O-methyltransferase COMT Val158Met (rs4680) in Greenlandic Inuit (n=254) and Europeans (n=262) and explore the possible relation between the genotypes and serum levels of POPs. The genotype and allele frequency distributions of the three genetic polymorphisms differed significantly between the Inuit and Europeans. For Inuit, the genotype distribution was more similar to those reported for Asian populations. We observed a significant difference in serum polychlorinated biphenyl (CB-153) and the pesticide 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) levels between Inuit and Europeans, and for Inuit also associations between the POP levels and genotypes for CYP1A1, CYP1B1 and COMT. Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies.

C-MET overexpression and amplification in gliomas.

Science.gov (United States)

Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

2015-01-01

We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

Activation of the AMPK/Sirt1 pathway by a leucine-metformin combination increases insulin sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and increases life span in Caenorhabditis elegans.

Science.gov (United States)

Banerjee, Jheelam; Bruckbauer, Antje; Zemel, Michael B

2016-11-01

We have previously shown leucine (Leu) to activate Sirt1 by lowering its K M for NAD + , thereby amplifying the effects of other sirtuin activators and improving insulin sensitivity. Metformin (Met) converges on this pathway both indirectly (via AMPK) and by direct activation of Sirt1, and we recently found Leu to synergize with Met to improve insulin sensitivity and glycemic control while achieving ~80% dose-reduction in diet-induced obese mice. Accordingly, we sought here to define the mechanism of this interaction. Muscle cells C2C12 and liver cells HepG2 were used to test the effect of Met-Leu on Sirt1 activation. Caenorhabditis elegans was used for glucose utilization and life span studies. Leu (0.5mmol/L)+Met (50-100μmol/L) synergistically activated Sirt1 (pmetformin exerted no independent effect at any concentration (0.1-0.5mmol/L). Thus, Leu and Met synergize to enable Sirt1 activation at low NAD + concentrations (typical of energy replete states). Sirt1 and AMPK activations are required for Met-Leu's full action, which result in improvements in energy metabolism and insulin sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain

DEFF Research Database (Denmark)

Lind, B; Koefoed, P; Thorsen, S

2001-01-01

the intracellular content of mutant and wild-type protein was similar. Northern blot analysis of total mRNA from transfected cells showed no reduction of the mutant protein C mRNA compared with wild-type protein C mRNA. Collectively, these results indicate that the Ser270Leu mutation in the affected family caused......Heterozygosity for a C8524T transition in the protein C gene converting Ser270(TCG) to Leu(TTG) in the protease domain was identified in a family with venous thrombosis. The mutation was associated with parallel reduction in plasma levels of protein C anticoagulant activity and protein C antigen......, which is consistent with a type 1 deficiency. Transient expression of mutant protein C cDNA in human kidney 293 cells and analysis of protein C antigen in culture media and cell lysates showed that the secretion of mutant protein compared with wild-type protein was reduced by at least 97% while...

Recurrent MET fusion genes represent a drug target in pediatric glioblastoma

DEFF Research Database (Denmark)

Sehested, Astrid Marie

2016-01-01

Pediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously unidentified gene fusions involving the MET oncogene in ∼10% of cases. These MET...

[Leu31, Pro34]neuropeptide Y

DEFF Research Database (Denmark)

Fuhlendorff, J; Gether, U; Aakerlund, L

1990-01-01

Two types of binding sites have previously been described for 36-amino acid neuropeptide Y (NPY), called Y1 and Y2 receptors. Y2 receptors can bind long C-terminal fragments of NPY-e.g., NPY-(13-36)-peptide. In contrast, Y1 receptors have until now only been characterized as NPY receptors that do...... not bind such fragments. In the present study an NPY analog is presented, [Leu31, Pro34]NPY, which in a series of human neuroblastoma cell lines and on rat PC-12 cells can displace radiolabeled NPY only from cells that express Y1 receptors and not from those expressing Y2 receptors. The radiolabeled analog......, [125I-Tyr36] monoiodo-[Leu31, Pro34]NPY, also binds specifically only to cells with Y1 receptors. The binding of this analog to Y1 receptors on human neuroblastoma cells is associated with a transient increase in cytoplasmic free calcium concentrations similar to the response observed with NPY. [Leu31...

RERTR progress in Mo-99 production from LEU

Energy Technology Data Exchange (ETDEWEB)

Vandegrift, G.F.; Conner, C.; Aase, S.; Bakel, A.; Bowers, D.; Freiberg, E.; Gelis, A.; Quigley, K.J.; Snelgrove, J.L. [Argonne National Laboratory 9700 S. Cass Avenue, Argonne, IL (United States)

2002-07-01

The ANL RERTR program is performing R and D supporting conversion of {sup 99}Mo production from HEU to LEU targets. Irradiation and processing of LEU targets were demonstrated at the Argentine Ezeiza Atomic Center. Target irradiation and disassembly were flawless, but the processing is not fully developed. In addition to preparing for, assisting in, and analyzing results of the demonstration, we performed other R and D related to LEU conversion: (1) designing a prototype production dissolver for digesting irradiated LEU foils in alkaline solutions and developing means to simplify digestion, (2) modifying ion-exchange columns used in the CNEA recovery and purification of {sup 99}Mo to deal with the lower volumes generated from LEU-foil digestion, (3) measuring the performance of new inorganic sorbents that outperform alumina for recovering Mo(VI) from nitric acid solutions containing high concentrations of uranium nitrate, and (4) developing means to facilitate the concentration and calcination of waste nitric-acid/LEU-nitrate solutions from {sup 99} Mo production. (author)

Followup calculations for the UVAR LEU conversion

International Nuclear Information System (INIS)

Rydin, R.; Hosticka, B.; Burns, T; Hubbard, T.; Mulder, R

2004-01-01

The UVAR reactor was successfully converted to LEU fuel in April 1994. Void coefficient measurements were made on the 4- by-4 fully-graphite-reflected LEU-1 core configuration, and an isothermal temperature coefficient measurement was made on the operational 4-by-5 partially-graphite-reflected LEU-2 core configuration. Both of these experiments have now been modeled in their critical configurations using the 3DBUM code. The LEU cores were also modeled using the Monte Carlo code MCNP in order to obtain a neutron/gamma source for BNCT filter design calculations. Advanced BNCT filters have been evaluated using both MCNP and the discrete ordinates code DORT. The results indicate that the UVAR would be an ideal source for the BNCT treatment of brain tumors. (author)

Followup calculations for the UVAR LEU conversion

International Nuclear Information System (INIS)

Rydin, R.A.; Hosticka, B.; Burns, T.

1995-01-01

The UVAR reactor was successfully converted to LEU fuel in April 1994. Void coefficient measurements were made on the 4-by-4 fully-graphite-reflected LEU-1 core configuration, and an isothermal temperature coefficient measurement was made on the operational 4-by-5 partially-graphite-reflected LEU-2 core configuration. Both of these experiments have now been modeled in their critical configurations using the 3DBUM code. The LEU cores were also modeled using the Monte Carlo code MCNP in order to obtain a neutron/gamma source for BNCT filter design calculations. Advanced BNCT filters have been evaluated using both MCNP and the discrete ordinates code DORT. The results indicate that the UVAR would be an ideal source for the BNCT treatment of brain tumors

Molecular Genetic Analysis of the PLP1 Gene in 38 Families with PLP1-related disorders: Identification and Functional Characterization of 11 Novel PLP1 Mutations

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Marchiani Valentina

2011-06-01

Full Text Available Abstract Background The breadth of the clinical spectrum underlying Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is due to the extensive allelic heterogeneity in the X-linked PLP1 gene encoding myelin proteolipid protein (PLP. PLP1 mutations range from gene duplications of variable size found in 60-70% of patients to intragenic lesions present in 15-20% of patients. Methods Forty-eight male patients from 38 unrelated families with a PLP1-related disorder were studied. All DNA samples were screened for PLP1 gene duplications using real-time PCR. PLP1 gene sequencing analysis was performed on patients negative for the duplication. The mutational status of all 14 potential carrier mothers of the familial PLP1 gene mutation was determined as well as 15/24 potential carrier mothers of the PLP1 duplication. Results and Conclusions PLP1 gene duplications were identified in 24 of the unrelated patients whereas a variety of intragenic PLP1 mutations were found in the remaining 14 patients. Of the 14 different intragenic lesions, 11 were novel; these included one nonsense and 7 missense mutations, a 657-bp deletion, a microdeletion and a microduplication. The functional significance of the novel PLP1 missense mutations, all occurring at evolutionarily conserved residues, was analysed by the MutPred tool whereas their potential effect on splicing was ascertained using the Skippy algorithm and a neural network. Although MutPred predicted that all 7 novel missense mutations would be likely to be deleterious, in silico analysis indicated that four of them (p.Leu146Val, p.Leu159Pro, p.Thr230Ile, p.Ala247Asp might cause exon skipping by altering exonic splicing elements. These predictions were then investigated in vitro for both p.Leu146Val and p.Thr230Ile by means of RNA or minigene studies and were subsequently confirmed in the case of p.Leu146Val. Peripheral neuropathy was noted in four patients harbouring intragenic mutations that altered RNA

Backbone and sidechain methyl Ile (δ1), Leu and Val chemical shift assignments of RDE-4 (1-243), an RNA interference initiation protein in C. elegans.

Science.gov (United States)

Chiliveri, Sai Chaitanya; Kumar, Sonu; Marelli, Udaya Kiran; Deshmukh, Mandar V

2012-10-01

The RNAi pathway of several organisms requires presence of double stranded RNA binding proteins for functioning of Dicer in gene regulation. In C. elegans, a double stranded RNA binding protein, RDE-4 (385 aa, 44 kDa) recognizes long exogenous dsRNA and initiates the RNAi pathway. We have achieved complete backbone and stereospecific methyl sidechain Ile (δ1), Leu and Val chemical shifts of first 243 amino acids of RDE-4, namely RDE-4ΔC.

TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy.

Science.gov (United States)

Rajkumar, Thangarajan; Samson, Mani; Rama, Ranganathan; Sridevi, Veluswami; Mahji, Urmila; Swaminathan, Rajaraman; Nancy, Nirmala K

2008-11-01

The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.

An alternative LEU design for the FRM-II

International Nuclear Information System (INIS)

Hanan, N.A.; Mo, S.C.; Smith, R.S.; Matos, J.E.

1996-01-01

The Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm 3 and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime (50 days) and the same neutron flux performance. LEU silicide fuel with 4.5 g/cm 3 has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. The following issues raised by TUM were addressed in Ref. 1: qualification of HEU and LEU silicide fuels, gamma heating in the heavy water reflector, radiological consequences of larger fission product and plutonium inventories in the LEU core, and cost and schedule. The conclusions of these analyses are summarized below. This paper addresses three additional safety issues that were raised by TUM in Ref. 2: stability of the involute fuel plates, a hypothetical accident involving the configuration of the reflector, and a loss of primary coolant flow transient due to an interrupted power supply. Based on the excellent results for the Alternative LEU Design that were obtained in these analyses, the RERTR Program concludes that all of the major technical issues regarding use of LEU fuel instead of HEU fuel in the FRM-II have been successfully resolved and that it is definitely feasible to use LEU fuel in the FRM-II without compromising the safety or performance of the facility

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset.

Science.gov (United States)

Dardennes, Roland M; Zizzari, Philippe; Tolle, Virginie; Foulon, Christine; Kipman, Amélie; Romo, Lucia; Iancu-Gontard, Dana; Boni, Claudette; Sinet, Pierre-Marie; Thérèse Bluet, Marie; Estour, Bruno; Mouren, Marie-Christine; Guelfi, Julien-Daniel; Rouillon, Frédéric; Gorwood, Philip; Epelbaum, Jacques

2007-02-01

Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.

Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

DEFF Research Database (Denmark)

Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y

2015-01-01

by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c......Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...... needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...

Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study

OpenAIRE

Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

2017-01-01

Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- contro...

CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism

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Georgios Daniil

2016-11-01

Four different heterozygous germline CACNA1H variants were identified. A de novo Cav3.2 p.Met1549Ile variant was found in early onset PA and multiplex developmental disorder. Cav3.2 p.Ser196Leu and p.Pro2083Leu were found in two patients with FH, and p.Val1951Glu was identified in one patient with APA. Electrophysiological analysis of mutant Cav3.2 channels revealed significant changes in the Ca2+ current properties for all mutants, suggesting a gain of function phenotype. Transfections of mutant Cav3.2 in H295R-S2 cells led to increased aldosterone production and/or expression of genes coding for steroidogenic enzymes after K+ stimulation. Identification of CACNA1H mutations associated with early onset PA, FH, and APA suggests that CACNA1H might be a susceptibility gene predisposing to PA with different phenotypic presentations, opening new perspectives for genetic diagnosis and management of patients with PA.

HEU/LEU-conversion of BER II successfully finished

International Nuclear Information System (INIS)

Haas, K.; Fischer, C.-O.; Krohn, H.

2000-01-01

The BER II (Berliner Experimental Reactor) research reactor is a swimming pool type reactor located in Berlin, Germany. The reactor operates with a thermal power of 10 MW and is primarily used to produce neutrons for neutron scattering experiments. The conversion from HEU- to LEU-fuel elements began in August, 1997. At the last RERTR Meeting 1999 in Budapest, Hungary, Hahn-Meitner-Institut (HMI) presented a 'Status Report' on the conversion of 10 HEU/LEU mixed cores. In February 2000, HMI finished the HEU/LEU-conversion. Hereby, the first pure LEU-standard-core went into operation. Our second LEU-core just ends its operation at the end of July. The third LEU-core will be built up in the beginning of August. The average burn-up rate was improved from 50 - 55% (HEU) to 60 - 65% (LEU). Therefore, only 14 elements/year are now used instead of 28/year. The following report describes our first steps in building pure LEU-cores from mixed HEU/LEU-cores, as well as our initial experience using the pure LEU-cores. (author)

Microcystis aeruginos strain [D-Leu1] Mcyst-LR producer, from Buenos Aires province, Argentina

Directory of Open Access Journals (Sweden)

Lorena Rosso

2014-04-01

Full Text Available Objective: To show the toxicological and phylogenetic characterization of a native Microcystis aeruginosa (M. aeruginosa strain (named CAAT 2005-3 isolated from a water body of Buenos Aires province, Argentine. Methods: A M. aeruginosa strain was isolated from the drainage canal of the sewage treatment in the town of Pila, Buenos Aires province, Argentina and acclimated to laboratory conditions. The amplification of cpcBA-IGS Phcocyanin (PC, intergenic spacer and flanking regions was carried out in order to build a phylogenetic tree. An exactive/orbitrap mass spectrometer equipped with an electrospray ionization source (Thermo Fisher Scientific, Bremen, Germany was used for the LC/ESI-HRMS microcystins analysis. The number of cell/mL and [D-Leu1] Mcyst-LR production obtained as a function of time was modelled using the Gompertz equation. Results: The phylogenetic analysis showed that the sequence clustered with others M. aeruginosa sequences obtained from NCBI. The first Argentinian strain of M. aeruginosa (CAAT 2005-3 growing under culture conditions maintains the typical colonial architecture of M. aeruginosa with profuse mucilage. M. aeruginosa CAAT 2005-3 expresses a toxin variant, that was identified by LC-HRMS/Orbitrapas as [D-Leu1] microcystin-LR ([M+H]+=1 037.8 m/z. Conclusions: [D-Leu1] microcystin-LR has been also detected in M. aeruginosa samples from Canada, Brazil and Argentina. This work provides the basis for technological development and production of analytical standards of toxins present in our region.

Techno-economic study on conversion of SAFARI-1 to LEU silicide fuel

International Nuclear Information System (INIS)

Ball, G.; Malherbe, F.J.

2004-01-01

This paper marks the conclusion of the techno-economic study into the conversion of SAFARI-1 reactor in South Africa to LEU silicide fuel. Several different fuel types were studied and their characteristics compared to the current HEU fuel. The technical feasibility of operating SAFARI-1 with the different fuels as well as the overall economic impact of the fuels is discussed and conclusions drawn.(author)

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

Directory of Open Access Journals (Sweden)

José Ángel Cahua-Pablo

2015-09-01

Full Text Available Metabolic syndrome (MetS is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD. Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR = 2.9; p = 0.013 in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04. Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006. In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001. In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

Pressure effect on the conformational equilibrium of [Leu]{sup 5}-enkephalin in water

Energy Technology Data Exchange (ETDEWEB)

Shimizu, A [Department of Environmental Engineering for Symbiosis, Soka University, 1-326 Tangi-cho, Hachioji, Tokyo, 192-8577 (Japan); Takekiyo, T; Yoshimura, Y [Department of Applied Chemistry, National Defence Academy, 1-10-20 Hashirimizu, Yokosuka, Kanagawa, 239-8686 (Japan); Kato, M; Taniguchi, Y, E-mail: shimizu@soka.ac.j, E-mail: take214@nda.ac.j [Department of Applied Chemistry, Ritsumeikan University, 1-1-1, Nojihigashi, Kusatsu, Shiga, 525-8577 (Japan)

2010-03-01

The conformational stability of [Leu]{sup 5}-enkephalin,Tyr-Gly-Gly-Phe-Leu, in water have been investigated under high pressure by FTIR spectroscopy. Three peaks at 1638, 1650, and 1680 cm{sup -1} were determined by second derivative FTIR spectra in the amide I' region of [Leu]{sup 5}-enkephalin. The peaks at 1637 and 1680 cm{sup -1} are assigned to the {beta}-strand and turn structures, respectively. These peaks mean that [Leu]{sup 5}-enkephalin takes a {beta}-hairpin-like structure in water. Moreover, the absorbance at 1638 cm{sup -1} increases with increasing pressure, and this change shows a sigmoidal curve. Thus, we concluded that [Leu]{sup 5}-enkephalin has the {beta}-hairpin-like and disordered structures in water. From the FTIR profile at high pressures, the {beta}-hairpin-like structure of [Leu]{sup 5}-enkephalin is stabilized by a high pressures. Our result shows that the folded structures such as {alpha}-helix and {beta}-hairpin structures of short peptide such as [Leu]{sup 5}-enkephalin are stabilized at high pressures.

The Environment Shapes the Inner Vestibule of LeuT

DEFF Research Database (Denmark)

Sohail, Azmat; Jayaraman, Kumaresan; Venkatesan, Santhoshkannan

2016-01-01

Human neurotransmitter transporters are found in the nervous system terminating synaptic signals by rapid removal of neurotransmitter molecules from the synaptic cleft. The homologous transporter LeuT, found in Aquifex aeolicus, was crystallized in different conformations. Here, we investigated t...... showed TM1A movements, consistent with the simulations, confirming a substantially different inward-open conformation in lipid bilayer from that inferred from the crystal structure....... the inward-open state of LeuT. We compared LeuT in membranes and micelles using molecular dynamics simulations and lanthanide-based resonance energy transfer (LRET). Simulations of micelle-solubilized LeuT revealed a stable and widely open inward-facing conformation. However, this conformation was unstable...... in a membrane environment. The helix dipole and the charged amino acid of the first transmembrane helix (TM1A) partitioned out of the hydrophobic membrane core. Free energy calculations showed that movement of TM1A by 0.30 nm was driven by a free energy difference of ~15 kJ/mol. Distance measurements by LRET...

Production of MO-99 from LEU targets-base-side processing

International Nuclear Information System (INIS)

Vandegrift, George F.; Koma, Yoshikazu; Cols, Hector; Conner, Cliff; Aase, Scott; Peter, Magdalin; Walker, David; Leonard, Ralph A.; Snelgrove, James L.

2000-01-01

Argonne National Laboratory (ANL) is cooperating with the Argentine Comision Nacional de Energia Atomica (CNEA) to convert their 99 Mo production process, which uses high enriched uranium (HEU), to low-enriched uranium (LEU). Progress discussed in this year's paper includes optimization of (1) the digestion of LEU foil by sodium hydroxide solution and (2) the primary recovery of molybdenum by anion exchange. Also discussed are ANL/CNEA plans for demonstrating the irradiation and digestion of LEU-foil targets and recovering 99 Mo in Argentina later this year. Our results show that, up to this point in our study, conversion of the CNEA process to LEU appears viable. (author)

Neutronic calculations of PARR-1 cores using LEU silicide fuel

International Nuclear Information System (INIS)

Arshad, M.; Bakhtyar, S.; Hayat, T.; Salahuddin, A.

1991-08-01

Detailed neutronic calculations have been carried out for different PARR-1 cores utilizing low enriched uranium (LEU) silicide fuel and operating at an upgraded power of 9 MW. The calculations include the search for critical loadings in open and stall ends of the pool, neutronic analysis of the first full equilibrium core and calculations cores. The burnup study of inventory have also been carried out. Further, the reactivity coefficients of the first full power operation core are evaluated for use in the accident analysis. 14 figs. (author)

An alternative LEU design for the FRM-II

International Nuclear Information System (INIS)

Hanan, N.A.; Mo, S.C.; Smith, R.S.; Matos, J.E.

1997-02-01

The Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm[sup 3] and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime (50 days) and the same neutron flux performance (8 x 10[sup 14] n/cm[sup 2]/s in the reflector). LEU silicide fuel with 4.5 g/cm[sup 3] has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. Computer models for the HEU and LEU designs have been exchanged between TUM and ANL and discrepancies have been resolved. The following issues are addressed: qualification of HEU and LEU silicide fuels, stability of the fuel plates, gamma heating in the heavy water reflector, a hypothetical accident involving the configuration of the reflector, a loss of primary coolant flow transient due to an interrupted power supply, the radiological consequences of larger fission product and plutonium inventories in the LEU core, and cost and schedule. Calculations were also done to address the possibility that new high density LEU fuels could be developed that would allow conversion of the TUM HEU design to LEU fuel. Based on the excellent results for the Alternative LEU Design that were obtained in these analyses, the RERTR Program concludes that all of the major technical issues regarding use of LEU fuel instead of HEU fuel in the FRM-II have been successfully resolved and that it is definitely feasible to use LEU fuel in the FRM-II without compromising the safety or performance of the facility

MET gene exon 14 deletion created using the CRISPR/Cas9 system enhances cellular growth and sensitivity to a MET inhibitor.

Science.gov (United States)

Togashi, Yosuke; Mizuuchi, Hiroshi; Tomida, Shuta; Terashima, Masato; Hayashi, Hidetoshi; Nishio, Kazuto; Mitsudomi, Tetsuya

2015-12-01

MET splice site mutations resulting in an exon 14 deletion have been reported to be present in about 3% of all lung adenocarcinomas. Patients with lung adenocarcinoma and a MET splice site mutation who have responded to MET inhibitors have been reported. The CRISPR/Cas9 system is a recently developed genome-engineering tool that can easily and rapidly cause small insertions or deletions. We created an in vitro model for MET exon 14 deletion using the CRISPR/Cas9 system and the HEK293 cell line. The phenotype, which included MET inhibitor sensitivity, was then investigated in vitro. Additionally, MET splice site mutations were analyzed in several cancers included in The Cancer Genome Atlas (TCGA) dataset. An HEK293 cell line with a MET exon 14 deletion was easily and rapidly created; this cell line had a higher MET protein expression level, enhanced MET phosphorylation, and prolonged MET activation. In addition, a direct comparison of phenotypes using this system demonstrated enhanced cellular growth, colony formation, and MET inhibitor sensitivity. In the TCGA dataset, lung adenocarcinomas had the highest incidence of MET exon 14 deletions, while other cancers rarely carried such mutations. Approximately 10% of the lung adenocarcinoma samples without any of driver gene alterations carried the MET exon 14 deletion. These findings suggested that this system may be useful for experiments requiring the creation of specific mutations, and the present experimental findings encourage the development of MET-targeted therapy against lung cancer carrying the MET exon 14 deletion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

RET/PTC1-Driven Neoplastic Transformation and Proinvasive Phenotype of Human Thyrocytes Involve Met Induction and β-Catenin Nuclear Translocation1

Science.gov (United States)

Cassinelli, Giuliana; Favini, Enrica; Degl'Innocenti, Debora; Salvi, Alessandro; De Petro, Giuseppina; Pierotti, Marco A; Zunino, Franco; Borrello, Maria Grazia; Lanzi, Cinzia

2009-01-01

Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC). We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, β-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and β-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F) devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of β-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated β-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes β-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs. PMID:19107227

Identification of cloned genes that complement the rad50-1, rad51-1, rad54-3 and rad55-3 mutations in yeast

International Nuclear Information System (INIS)

Calderon, I.L.; Contopoulou, C.R.; Mortimer, R.K.

1982-01-01

Plasmids that complement the rad50-1, rad51-1, rad54-3 and rad55-3 mutations in yeast, have been isolated. They were obtained by transforming strains, carrying the leu2-112 leu2-3 alleles and the particular rad mutation, with YEp13 plasmids containing near random yeast DNA inserts. Rad + clones were identified among the Leu + transformants. Integration by targeting into the RAD55 locus showed that the rad55-3 complementing plasmid contained the actual RAD55 gene. BamHI fragments from each of the plasmids that complement rad50-1, rad51-1 and rad54-3, all of which lacked Rad + activity, were subcloned into the integrating plasmid YIp5 and the hybrid plasmids were used to transform a Rad + Ura - strain to Ura + . By genetic mapping, the rad51 and rad54 subclones were shown to integrate at their respective loci. However, the rad50 subclones integrated at a site unlinked to the RAD50 locus. This suggests that no homology exists between this BamHI fragment and the RAD50 gene. Integration at the RAD54 locus of the rad54 subclone made the host cell Ura + but Rad - ; excision of the plasmid was shown to be x-ray inducible and to restore the Ura - Rad + phenotype. These results indicate that the BamHI fragment of the RAD54 plasmid is internal to the RAD54 gene. We can conclude also that the RAD54 gene is not essential as cells bearing a disrupted copy of this gene are able to survive. Additionally, a plasmid carrying an amber suppressor has been isolated and characterized

LEU fuel cycle analyses for the Belgian BR2 Research Reactor

International Nuclear Information System (INIS)

Deen, J.R.; Snelgrove, J.L.

1988-01-01

Equilibrium fuel cycle characteristics were calculated for reference HEU and two proposed LEU fuel cycles using an 11-group diffusion-theory neutron flux solution in hexagonal-Z geometry. The diffusion theory model was benchmarked with a detailed Monte Carlo core model. The two proposed LEU fuel designs increased the 235 U loading 20% and the fuel meat volume 51%. The first LEU design used 10 B as a burnable absorber. Either proposed LEU fuel element would provide equilibrium fuel cycle characteristics similar to those of the HEU fuel cycle. Irradiation rates of Co control followers and Ir disks in the center of the core were reduced 6 ± 1% in the LEU equilibrium core compared to reference HEU core. 11 refs., 4 figs., 5 tabs

Preliminary LEU fuel cycle analyses for the Belgian BR2 reactor

International Nuclear Information System (INIS)

Deen, J.R.; Snelgrove, J.L.

1986-01-01

Fuel cycle calculations have been performed with reference HEU fuel and LEU fuel using Cd wires or boron as burnable absorbers. The 235 U content in the LEU element has increased 20% to 480g compared to the reference HEU element. The number of fuel plates has remained unchanged while the fuel meat thickness has increased to 0.76 mm from 0.51 mm. The LEU meat density is 5.1 Mg U/m 3 . The reference fuel cycle was a 31 element core operating at 56 MW with a 19.8 day cycle length and eight fresh elements loaded per cycle. Comparable fuel cycle characteristics can be achieved using the proposed LEU fuel element with either Cd wires or boron burnable absorbers. The neutron flux for E/sub n/ > 1 eV changes very little (<5%) in LEU relative to HEU cores. Thermal flux reductions are 5 to 10% in non-fueled positions, and 20 to 30% in fuel elements

Ghrelin gene polymorphisms in rheumatoid arthritis.

Science.gov (United States)

Ozgen, Metin; Koca, Suleyman Serdar; Etem, Ebru Onalan; Yuce, Huseyin; Aydin, Suleyman; Isik, Ahmet

2011-07-01

Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA). The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis. The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group. A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Factor XIII Val34Leu is a genetic factor involved in the etiology of venous thrombosis

NARCIS (Netherlands)

Franco, R. F.; Reitsma, P. H.; Lourenço, D.; Maffei, F. H.; Morelli, V.; Tavella, M. H.; Araújo, A. G.; Piccinato, C. E.; Zago, M. A.

1999-01-01

A mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5'-untranslated region of the FXII gene (46 C->T) was identified which is

BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

Science.gov (United States)

Zhao, Mingzhe; Chen, Lu; Yang, Jiarun; Han, Dong; Fang, Deyu; Qiu, Xiaohui; Yang, Xiuxian; Qiao, Zhengxue; Ma, Jingsong; Wang, Lin; Jiang, Shixiang; Song, Xuejia; Zhou, Jiawei; Zhang, Jian; Chen, Mingqi; Qi, Dong; Yang, Yanjie; Pan, Hui

2018-02-01

Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinguishing Isomeric Peptides: The Unimolecular Reactivity and Structures of (LeuPro)M+ and (ProLeu)M+ (M = Alkali Metal).

Science.gov (United States)

Jami-Alahmadi, Yasaman; Linford, Bryan D; Fridgen, Travis D

2016-12-29

The unimolecular chemistries and structures of gas-phase (ProLeu)M + and (LeuPro)M + complexes when M = Li, Na, Rb, and Cs have been explored using a combination of SORI-CID, IRMPD spectroscopy, and computational methods. CID of both (LeuPro)M + and (ProLeu)M + showed identical fragmentation pathways and could not be differentiated. Two of the fragmentation routes of both peptides produced ions at the same nominal mass as (Pro)M + and (Leu)M + , respectively. For the litiated peptides, experiments revealed identical IRMPD spectra for each of the m/z 122 and 138 ions coming from both peptides. Comparison with computed IR spectra identified them as the (Pro)Li + and (Leu)Li + , and it is concluded that both zwitterionic and canonical forms of (Pro)Li + exist in the ion population from CID of both (ProLeu)Li + and (LeuPro)Li + . The two isomeric peptide complexes could be distinguished using IRMPD spectroscopy in both the fingerprint and the CH/NH/OH regions. The computed IR spectra for the lowest energy structures of each charge solvated complexes are consistent with the IRMPD spectra in both regions for all metal cation complexes. Through comparison between the experimental spectra, it was determined that in lithiated and sodiated ProLeu, metal cation is bound to both carbonyl oxygens and the amine nitrogen. In contrast, the larger metal cations are bound to the two carbonyls, while the amine nitrogen is hydrogen bonded to the amide hydrogen. In the lithiated and sodiated LeuPro complexes, the metal cation is bound to the amide carbonyl and the amine nitrogen while the amine nitrogen is hydrogen bonded to the carboxylic acid carbonyl. However, there is no hydrogen bond in the rubidiated and cesiated complexes; the metal cation is bound to both carbonyl oxygens and the amine nitrogen. Details of the position of the carboxylic acid C═O stretch were especially informative in the spectroscopic confirmation of the lowest energy computed structures.

Ghrelin and obestatin plasma levels and ghrelin/obestatin prepropeptide gene polymorphisms in small for gestational age infants.

Science.gov (United States)

Zhang, Shulian; Zhai, Guanpeng; Zhang, Jinping; Zhou, Jianguo; Chen, Chao

2014-12-01

To investigate plasma ghrelin and obestatin levels, and ghrelin/obestatin prepropeptide gene polymorphisms, in sequentially enrolled small for gestational age (SGA) infants. Neonates were sequentially enrolled into this study and were then subdivided into different groups, according to different study aims and availability of study materials. Consequently, plasma ghrelin and obestatin levels were measured in term SGA, term appropriate for gestational age (AGA), term large for gestational age (LGA), preterm SGA and preterm AGA neonates. Levels of both peptides were also measured in AGA infants of different gestational ages, and in term AGA neonates at different days following birth. Three ghrelin/obestatin prepropeptide gene single nucleotide polymorphisms (SNPs), Arg51Gln, Leu72Met, and Gln90Leu, were measured in neonates. The study involved a total cohort of 581 neonates. Out of 150 neonates (30 term AGA, 30 term SGA, 30 term LGA, 30 preterm AGA, and 30 preterm SGA), plasma obestatin levels were significantly higher in term SGA versus term LGA neonates (0.21 ± 0.02 ng/ml versus 0.17 ± 0.01 ng/ml, respectively). Out of a wider cohort, there were no significant differences in genotypes and allele frequencies of Arg51Gln, Leu72Met, and Gln90Leu SNPs between term SGA and AGA neonates, or between preterm SGA and AGA neonates. Ghrelin/obestatin prepropeptide polymorphisms were not found to be associated with SGA status in neonates; however, ghrelin and obestatin levels may be involved in growth and development. Further studies are required to understand the relationship between ghrelin, obestatin and prenatal development. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Cardiac abnormalities in diabetic patients with mutation in the mitochondrial tRNA Leu(UUR)Gene

International Nuclear Information System (INIS)

Ueno, Hiroshi; Shiotani, Hideyuki

1999-01-01

An A-to-G transition at position 3243 of the mitochondrial DNA is known to be a pathogenic factor for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), diabetes and cardiomyopathy. This mutation causes dysfunction of the central nervous system in MELAS. Because the heart, as well as the brain and nervous system, is highly dependent on the energy produced by mitochondrial oxidation, these tissues are more vulnerable to mitochondrial defects. Cardiac abnormalities were assessed in 10 diabetic patients associated with this mutation using echocardiography and 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, and compared with 19 diabetic patients without the mutation. Duration of diabetes, therapy, control of blood glucose and diabetic complications, such as diabetic retinopathy and nephropathy, were not different between the 2 groups. Diabetic patients with the mutation had a significantly thicker interventricular septum (16.8±3.7 vs 11.0±1.6 mm, p 0.05). In conclusion, left ventricular hypertrophy with or without abnormal wall motion and severely reduced MIBG uptake may be characteristic in diabetic patients with a mutation in the mitochondrial tRNA Leu(UUR) gene. (author)

Neutron flux measurement in the central channel (XC-1) of TRIGA 14 MW LEU core

International Nuclear Information System (INIS)

BARBOS, D.; BUSUIOC, P.; ROTH, Cs.; PAUNOIU, C.

2008-01-01

The TRIGA 14 MW reactor, operated by Institute for Nuclear Research Pitesti, Romania, is a pool type reactor, and has a rectangular shape which holds fuel bundles and is surrounded with beryllium reflectors. Each fuel bundle is composed of 25 nuclear fuel rods. The TRIGA 14 MW reactor was commissioned 28 years ago with HEU fuel rods. The conversion was gradually achieved, starting in February 1992 and completed in March 2006. The full conversion of the 14 MW TRIGA Research Reactor was completed in May 2006 and each step of the conversion was achieved by removal of HEU fuel, replaced by LEU fuel, accompanied by a large set of theoretical evaluation and physical measurements intended to confirm the performances of gradual conversion. After the core full conversion, a program of measurements and comparisons with previous results of core physics and measurements is underway, allowing data acquisition for normal operation, demonstration of safety and economics of the converted core. Neutron flux spectrum measurements in the XC in the XC-1 water 1 water-filled channel were performed using multi multi-foil activation techniques. The neutron spectra and flux are obtained by unfolding from measured reaction rates using SAND II computer code. The integral neutron flux value for LEU core is greater of 13% than for the standard HEU core. Also thermal neutron flux value for converted LEU core is smaller by 0.38% than for the standard HEU core. These differences appear because the foil activation detectors have been irradiated using a pneumatic rabbit having a diameter of 32 mm, whereas foil irradiations in standard HEU core has been performed with a pneumatic rabbit having a diameter of 14 mm, and therefore the neutron spectra in LEU core is less thermalized and the weight of fast neutron is greater

Key considerations in the conversion to LEU of a Mo-99 commercially producing reactor: SAFARI-1 of South Africa

International Nuclear Information System (INIS)

Stumpf, W.E.; Vermaak, A.P.; Ball, G.

2000-01-01

Apart from the technological demands and considerations associated with the conversion of a Mo-99 commercially producing reactor to LEU, a number of commercial challenges also need to be addressed. This is particularly the case when the reactor is primarily used as a source for the production, on an uninterrupted basis, of significant quantities of Mo-99 to satisfy long term commitments to a range of global customers. This paper highlights key business considerations which are applicable in the conversion process of firstly, reactor fuel to LEU and secondly target plates for Mo-99, also to LEU, using the SAFARI-1 reactor in South Africa as a typical example of such a commercially utilized reactor. (author)

Key considerations in the conversion to LEU of a Mo-99 commercially producing reactor: SAFARI-1 of South Africa

Energy Technology Data Exchange (ETDEWEB)

Stumpf, W E; Vermaak, A P; Ball, G [NECSA, PO Box 582, Pretoria (South Africa)

2000-10-01

Apart from the technological demands and considerations associated with the conversion of a Mo-99 commercially producing reactor to LEU, a number of commercial challenges also need to be addressed. This is particularly the case when the reactor is primarily used as a source for the production, on an uninterrupted basis, of significant quantities of Mo-99 to satisfy long term commitments to a range of global customers. This paper highlights key business considerations which are applicable in the conversion process of firstly, reactor fuel to LEU and secondly target plates for Mo-99, also to LEU, using the SAFARI-1 reactor in South Africa as a typical example of such a commercially utilized reactor. (author)

Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women

DEFF Research Database (Denmark)

Bräuner, Elvira V; Loft, Steffen; Wellejus, Anja

2014-01-01

these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk....... When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We...

Differential impact of Met receptor gene interaction with early-life stress on neuronal morphology and behavior in mice.

Science.gov (United States)

Heun-Johnson, Hanke; Levitt, Pat

2018-02-01

Early adversity in childhood increases the risk of anxiety, mood, and post-traumatic stress disorders in adulthood, and specific gene-by-environment interactions may increase risk further. A common functional variant in the promoter region of the gene encoding the human MET receptor tyrosine kinase (rs1858830 ' C' allele) reduces expression of MET and is associated with altered cortical circuit function and structural connectivity. Mice with reduced Met expression exhibit changes in anxiety-like and conditioned fear behavior, precocious synaptic maturation in the hippocampus, and reduced neuronal arbor complexity and synaptogenesis. These phenotypes also can be produced independently by early adversity in wild-type mice. The present study addresses the outcome of combining early-life stress and genetic influences that alter timing of maturation on enduring functional and structural phenotypes. Using a model of reduced Met expression ( Met +/- ) and early-life stress from postnatal day 2-9, social, anxiety-like, and contextual fear behaviors in later life were measured. Mice that experienced early-life stress exhibited impairments in social interaction, whereas alterations in anxiety-like behavior and fear learning were driven by Met haploinsufficiency, independent of rearing condition. Early-life stress or reduced Met expression decreased arbor complexity of ventral hippocampal CA1 pyramidal neurons projecting to basolateral amygdala. Paradoxically, arbor complexity in Met +/- mice was increased following early-life stress, and thus not different from arbors in wild-type mice raised in control conditions. The changes in dendritic morphology are consistent with the hypothesis that the physiological state of maturation of CA1 neurons in Met +/- mice influences their responsiveness to early-life stress. The dissociation of behavioral and structural changes suggests that there may be phenotype-specific sensitivities to early-life stress.

Conceptual designs parameters for MURR LEU U-Mo fuel conversion design demonstration experiment. Revision 1

International Nuclear Information System (INIS)

Stillman, J.; Feldman, E.; Stevens, J.

2013-01-01

The design parameters for the conceptual design of a fuel assembly containing U-10Mo fuel foils with low-enriched uranium (LEU) for the University of Missouri Research Reactor (MURR) are described. The Design Demonstration Experiment (MURR-DDE) will use a prototypic MURR-LEU element manufactured according to the parameters specified here. Also provided are calculated performance parameters for the LEU element in the MURR, and a set of goals for the MURR-DDE related to those parameters. The conversion objectives are to develop a fuel element design that will ensure safe reactor operations, as well as maintaining existing performance. The element was designed by staff members of the Global Threat Reduction Initiative (GTRI) Reactor Conversion Program at the Argonne National Laboratory (ANL) and the MURR Facility. A set of manufacturing assumptions were provided by the Fuel Development (FD) and Fuel Fabrication Capability (FFC) pillars of the GTRI Reduced Enrichment for Research and Test Reactors (RERTR) program to reliably manufacture the fuel plates. The proposed LEU fuel element has an overall design and exterior dimensions that are similar to those of the current highly-enriched uranium (HEU) fuel elements. There are 23 fuel plates in the LEU design. The overall thickness of each plate is 44 mil, except for the exterior plate that is furthest from the center flux trap (plate 23), which is 49 mil thick. The proposed LEU fuel plates have U-10Mo monolithic fuel foils with a 235U enrichment of 19.75% varying from 9 mil to 20 mil thick, and clad with Al-6061 aluminum. A thin layer of zirconium exists between the fuel foils and the aluminum as a diffusion barrier. The thinnest nominal combined zirconium and aluminum clad thickness on each side of the fuel plates is 12 mil. The LEU U-10Mo monolithic fuel is not yet qualified as driver fuel in research reactors, but is under intense development under the auspices of the GTRI FD and FFC programs.

Natural convection cooling of LEU cores for Pakistan research reactor-1

International Nuclear Information System (INIS)

Khan, L.A.; Bokhari, I.H.; Akhtar, K.M.

1991-08-01

The first high power and equilibrium LEU cores of PARR-1 have been analysed to assess the maximum operating power based on natural convection cooling, need for forced cooling to remove the decay heat and to estimate safety margins that commensurate with the predetermined power limit. Computer code NATCON and standard correlations have been used for the analysis. The parameters studied includes coolant velocity, temperature distribution in the core, heat fluxes at onset of nucleate boiling, pulsed boiling and burnup. (author)

Backbone and stereospecific (13)C methyl Ile (δ1), Leu and Val side-chain chemical shift assignments of Crc.

Science.gov (United States)

Sharma, Rakhi; Sahu, Bhubanananda; Ray, Malay K; Deshmukh, Mandar V

2015-04-01

Carbon catabolite repression (CCR) allows bacteria to selectively assimilate a preferred compound among a mixture of several potential carbon sources, thus boosting growth and economizing the cost of adaptability to variable nutrients in the environment. The RNA-binding catabolite repression control (Crc) protein acts as a global post-transcriptional regulator of CCR in Pseudomonas species. Crc triggers repression by inhibiting the expression of genes involved in transport and catabolism of non-preferred substrates, thus indirectly favoring assimilation of preferred one. We report here a nearly complete backbone and stereospecific (13)C methyl side-chain chemical shift assignments of Ile (δ1), Leu and Val of Crc (~ 31 kDa) from Pseudomonas syringae Lz4W.

Genomics of a Metamorphic Timing QTL: met1 Maps to a Unique Genomic Position and Regulates Morph and Species-Specific Patterns of Brain Transcription

Science.gov (United States)

Page, Robert B.; Boley, Meredith A.; Kump, David K.; Voss, Stephen R.

2013-01-01

Very little is known about genetic factors that regulate life history transitions during ontogeny. Closely related tiger salamanders (Ambystoma species complex) show extreme variation in metamorphic timing, with some species foregoing metamorphosis altogether, an adaptive trait called paedomorphosis. Previous studies identified a major effect quantitative trait locus (met1) for metamorphic timing and expression of paedomorphosis in hybrid crosses between the biphasic Eastern tiger salamander (Ambystoma tigrinum tigrinum) and the paedomorphic Mexican axolotl (Ambystoma mexicanum). We used existing hybrid mapping panels and a newly created hybrid cross to map the met1 genomic region and determine the effect of met1 on larval growth, metamorphic timing, and gene expression in the brain. We show that met1 maps to the position of a urodele-specific chromosome rearrangement on linkage group 2 that uniquely brought functionally associated genes into linkage. Furthermore, we found that more than 200 genes were differentially expressed during larval development as a function of met1 genotype. This list of differentially expressed genes is enriched for proteins that function in the mitochondria, providing evidence of a link between met1, thyroid hormone signaling, and mitochondrial energetics associated with metamorphosis. Finally, we found that met1 significantly affected metamorphic timing in hybrids, but not early larval growth rate. Collectively, our results show that met1 regulates species and morph-specific patterns of brain transcription and life history variation. PMID:23946331

COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

Directory of Open Access Journals (Sweden)

ramin saravani

2017-10-01

Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

LEU fuel powder technology at Babcock and Wilcox (USA)

International Nuclear Information System (INIS)

Bogacik, K.E.

1984-01-01

This paper traces BandW involvement in HEU fuel manufacturing to the current work directed at LEU reactor technology. Past work at BandW in areas such as alloying, fuel handling and core manufacturing has been of significant benefit to the current LEU fuel processing requirements. Recent investigations and process developments for production of LEU aluminide and silicide fuels are discussed. Techniques for alloying by vacuum are melting, followed by comminution methods after alloying, are presented for both the LEU aluminide and silicide fuel powders. Powder processing discussions include compacting techniques used by BandW for these alloys. This overview of BandW's LEU i nvolvement provides details of specific modifications and process developments in powdered fuels. Product attributes such as powder chemistry, size, and other physical properties of each LEU fuel are presented. (author)

Characterization and sequencing of the active site of 1-aminocyclopropane-1-carboxylate synthase

International Nuclear Information System (INIS)

Yip, Wing-Kin; Dong, Jian-Guo; Yang, S.F.; Kenny, J.W.; Thompson, G.A.

1990-01-01

The pyridoxal phosphate (PLP)-dependent 1-aminocyclopropane-1-carboxylic acid (ACC) synthase the key enzyme in ethylene biosynthesis, is inactivated by its substrate S-adenosylmethionine (AdoMet). Apple ACC synthase was purified with an immunoaffinity gel, and its active site was probed with NaB 3 H 4 or Ado[ 14 C]Met. Peptide sequencing of both 3 H- and 14 C-labeled peptides revealed a common dodecapeptide of Ser-Leu-Ser-Xaa-Asp-Leu-Gly-Leu-Pro-Gly-Phe-Arg, where Xaa was the modified, radioactive residue in each case. Acid hydrolysis of the 3 H-labeled enzyme released radioactive N-pyridoxyllysine, indicating that the active-site peptide contained lysine at position 4. Mass spectrometry of the 14 C-labeled peptide indicated a protonated molecular ion at m/z 1390.6, from which the mass of Xaa was calculated to be 229, a number that is equivalent to the mass of a lysine residue alkylated by the 2-aminobutyrate portion of AdoMet, as we previously proposed. These results indicate that the same active-site lysine binds the PLP and convalently links to the 2-aminobutyrate portion of AdoMet during inactivation. The active site of tomato ACC synthase was probed in the same manner with Ado [ 14 C]Met. Sequencing of the tomato active-site peptide revealed two highly conserved dodecapeptides; the minor peptide possessed a sequence identical to that of the apple enzyme, whereas the major peptide differed from the minor peptide in that methionine replaced leucine at position 6

The conversion of NRU from HEU to LEU fuel

International Nuclear Information System (INIS)

Sears, D.F.; Atfield, M.D.; Kennedy, I.C.

1990-01-01

The program at Chalk River Nuclear Laboratories (CRNL) to develop and test low-enriched uranium fuel (LEU, 3 Si, USiAl, USi Al and U 3 Si 2 (U-3.96 wt% Si; U-3.5 wt% Si-1.5 wt% AL; U-3.2 wt%; Si-3 wt% Al; U-7.3 wt% Si, respectively). Fuel elements were fabricated with uranium loadings suitable for NRU, 3.15 gU/cm 3 , and for NRX, 4.5 gU/cm 3 , and were irradiated under normal fuel-operating conditions. Eight experimental irradiations involving 100 mini-elements and 84 full-length elements (7X12-element rods) were completed to qualify the LEU fuel and the fabrication technology. Post irradiation examinations confirmed that the performance of the LEU fuel, and that of a medium enrichment uranium (MEU, 45% U-235) alloy fuel tested as a back-up, was comparable to the HEU fuel. The uranium silicide dispersion fuel swelling was approximately linear up to burnups exceeding NRU's design terminal burnup (80 at%). NRU was partially converted to LEU fuel when the first 31 prototype fuel rods manufactured with industrial scale production equipment were installed in the reactor. The rods were loaded in NRU at a fuelling rate of about two rods per week over the period 1988 September to December. This partial LEU core (one third of a full NRU core) has allowed the reactor engineers and physicists to evaluate the bulk effects of the LEU conversion on NRU operations. As expected, the irradiation is proceeding without incident

Met1-linked Ubiquitination in Immune Signalling

DEFF Research Database (Denmark)

Fiil, Berthe Katrine; Gyrd-Hansen, Mads

2014-01-01

Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...

Preliminary Thermohydraulic Analysis of a New Moderated Reactor Utilizing an LEU-Fuel for Space Nuclear Thermal Propulsion

International Nuclear Information System (INIS)

Nam, Seung Hyun; Choi, Jae Young; Venneria, Paolo F.; Jeong, Yong Hoon; Chang, Soon Heung

2015-01-01

analyses of neutronics and thermo-hydraulics were carried out with the assumption of an expander cycle in steady-state. The result demonstrates that the feasible design space for the reactor design potentially involves the P/D range of 1.66 - 1.76, the power range of 200 - 250 MW th and the FWT range of 0.50 - 1.25 mm to meet the major design parameters and criteria. Accordingly, the referential rocket performance are estimated to be in the range of 11.94 - 14.84 MPa in maximum system pressure, the thrust range of 41.0 - 53.6 kN, the T/W eng range of 3.39 - 4.44 and the I sp range of 855.4 - 904.4 according to the major parameters. The performance of the KANUTER-LEU is comparable with that of the existing HEU-NTR engines in spite of the heavy LEU fuel loading according to the mission performance comparison

Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro)

DEFF Research Database (Denmark)

Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda

2012-01-01

Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third...... and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome...

Progress in chemical processing of LEU targets for 99Mo production - 1997

International Nuclear Information System (INIS)

Vandegrift, G.F.; Conner, C.; Sedlet, J.; Wygmans, D.G.; Wu, D.; Iskander, F.; Landsberger, S.

1997-01-01

Presented here are recent experimental results of our continuing development activities associated with converting current processes for producing fission-product 99 Mo from targets using high-enriched uranium (HEU) to low-enriched uranium (LEU). Studies were focused in four areas: (1) measuring the chemical behavior of iodine, rhodium, and silver in the LEU-modified Cintichem process, (2) performing experiments and calculations to assess the suitability of zinc fission barriers for LEU metal foil targets, (3) developing an actinide separations method for measuring alpha contamination of the purified 99 Mo product, and (4) developing a cooperation with Sandia National Laboratories and Los Alamos National Laboratory that will lead to approval by the U.S. Federal Drug Administration for production of 99 Mo from LEU targets. Experimental results continue to show the technical feasibility of converting current HEU processes to LEU. (author)

Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia coli chromosome

International Nuclear Information System (INIS)

Takase, I.; Ishino, F.; Wachi, M.; Kamata, H.; Doi, M.; Asoh, S.; Matsuzawa, H.; Ohta, T.; Matsuhashi, M.

1987-01-01

The coding of two rare lipoproteins by two genes, rlpA and rlpB, located in the leuS-dacA region (15 min) on the Escherichia coli chromosome was demonstrated by expression of subcloned genes in a maxicell system. The formation of these two proteins was inhibited by globomycin, which is an inhibitor of the signal peptidase for the known lipoproteins of E. coli. In each case, this inhibition was accompanied by formation of a new protein, which showed a slightly lower mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which we suppose to be a prolipoprotein with an N-terminal signal peptide sequence similar to those of the bacterial major lipoproteins and lysis proteins of some bacteriocins. The incorporation of 3 H-labeled palmitate and glycerol into the two lipoproteins was also observed. Sequencing of DNA showed that the two lipoprotein genes contained sequences that could code for signal peptide sequences of 17 amino acids (rlpA lipoprotein) and 18 amino acids (rlpB lipoprotein). The deduced sequences of the mature peptides consisted of 345 amino acids (M/sub r/ 35,615, rlpA lipoprotein) and 175 amino acids (M/sub r/ 19,445, rlpB lipoprotein), with an N-terminal cysteine to which thioglyceride and N-fatty acyl residues may be attached. These two lioproteins may be important in duplication of the cells

Highly efficient residue-selective labeling with isotope-labeled Ile, Leu, and Val using a new auxotrophic E. coli strain

International Nuclear Information System (INIS)

Miyanoiri, Yohei; Ishida, Yojiro; Takeda, Mitsuhiro; Terauchi, Tsutomu; Inouye, Masayori; Kainosho, Masatsune

2016-01-01

We recently developed a practical protocol for preparing proteins bearing stereo-selectively 13 C-methyl labeled leucines and valines, instead of the commonly used 13 C-methyl labeled precursors for these amino acids, by E. coli cellular expression. Using this protocol, proteins with any combinations of isotope-labeled or unlabeled Leu and Val residues were prepared, including some that could not be prepared by the precursor methods. However, there is still room for improvement in the labeling efficiencies for Val residues, using the methods with labeled precursors or Val itself. This is due to the fact that the biosynthesis of Val could not be sufficiently suppressed, even by the addition of large amounts of Val or its precursors. In this study, we completely solved this problem by using a mutant strain derived from E. coli BL21(DE3), in which the metabolic pathways depending on two enzymes, dihydroxy acid dehydratase and β-isopropylmalate dehydrogenase, are completely aborted by deleting the ilvD and leuB genes, which respectively encode these enzymes. The ΔilvD E. coli mutant terminates the conversion from α,β-dihydroxyisovalerate to α-ketoisovalerate, and the conversion from α,β-dihydroxy-α-methylvalerate to α-keto-β-methylvalerate, which produce the preceding precursors for Val and Ile, respectively. By the further deletion of the leuB gene, the conversion from Val to Leu was also fully terminated. Taking advantage of the double-deletion mutant, ΔilvDΔleuB E. coli BL21(DE3), an efficient and residue-selective labeling method with various isotope-labeled Ile, Leu, and Val residues was established.

Highly efficient residue-selective labeling with isotope-labeled Ile, Leu, and Val using a new auxotrophic E. coli strain

Energy Technology Data Exchange (ETDEWEB)

Miyanoiri, Yohei [Nagoya University, Structural Biology Research Center, Graduate School of Science (Japan); Ishida, Yojiro [Rutgers University-Robert Wood Johnson Medical School, Center for Advanced Biotechnology and Medicine (United States); Takeda, Mitsuhiro [Nagoya University, Structural Biology Research Center, Graduate School of Science (Japan); Terauchi, Tsutomu [Tokyo Metropolitan University, Graduate School of Science and Engineering (Japan); Inouye, Masayori [Rutgers University-Robert Wood Johnson Medical School, Center for Advanced Biotechnology and Medicine (United States); Kainosho, Masatsune, E-mail: kainosho@tmu.ac.jp [Nagoya University, Structural Biology Research Center, Graduate School of Science (Japan)

2016-06-15

We recently developed a practical protocol for preparing proteins bearing stereo-selectively {sup 13}C-methyl labeled leucines and valines, instead of the commonly used {sup 13}C-methyl labeled precursors for these amino acids, by E. coli cellular expression. Using this protocol, proteins with any combinations of isotope-labeled or unlabeled Leu and Val residues were prepared, including some that could not be prepared by the precursor methods. However, there is still room for improvement in the labeling efficiencies for Val residues, using the methods with labeled precursors or Val itself. This is due to the fact that the biosynthesis of Val could not be sufficiently suppressed, even by the addition of large amounts of Val or its precursors. In this study, we completely solved this problem by using a mutant strain derived from E. coli BL21(DE3), in which the metabolic pathways depending on two enzymes, dihydroxy acid dehydratase and β-isopropylmalate dehydrogenase, are completely aborted by deleting the ilvD and leuB genes, which respectively encode these enzymes. The ΔilvD E. coli mutant terminates the conversion from α,β-dihydroxyisovalerate to α-ketoisovalerate, and the conversion from α,β-dihydroxy-α-methylvalerate to α-keto-β-methylvalerate, which produce the preceding precursors for Val and Ile, respectively. By the further deletion of the leuB gene, the conversion from Val to Leu was also fully terminated. Taking advantage of the double-deletion mutant, ΔilvDΔleuB E. coli BL21(DE3), an efficient and residue-selective labeling method with various isotope-labeled Ile, Leu, and Val residues was established.

A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice

Directory of Open Access Journals (Sweden)

Antje Bruckbauer

2016-01-01

Full Text Available Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.

Status of HEU-LEU conversion of FRJ-2

International Nuclear Information System (INIS)

Damm, G.; Nabbi, R.

2002-01-01

The operator of the German FRJ-2 research reactor, 'Research Center Juelich', has participated from the beginning in the RERTR programme and made comprehensive contributions to the test and use of LEU fuel for HEU-LEU-conversion measures. The originally planned time scale for the conversion of FRJ-2 was significantly delayed because of a change of the manufacturer of the LEU fuel elements and a 4 years shutdown of the reactor for refurbishment purposes. In the meantime the new LEU fuel elements are qualified and tested in the reactor. In the moment calculations for the safety report are made and it is planned to apply for the license of FRJ-2 operation with LEU fuel at the beginning of 2003. In order to get most reliable results a sophisticated computational method based on a MCNP model coupled with the depletion code BURN was developed for reactor physical calculations, core conversion studies and fuel element performance analysis and applied to the mixed and LEU core. The licensing schedule and results of latest calculations for the conversion study will be presented. The simulations shows that the thermal flux in the LEU core is about 19% resulting in a lower burnup rate. But in the reflector area around the core and in the center of the cold n source the neutron flux reduction remains limited to 6%. Due to a harder neutron spectrum in the LEU core the kinetic and safety related parameters are slightly reduced. Using the ORIGEN code it could be shown that the increase of the total fission products inventory amounts to about 6% compared to a HEU core. As a consequence of the high amount of U-238, the amount of U-235 in the LEU core has to be about 27% higher than in the HEU core but the U-235 burnup is approx. 5% lower due to the contribution of fissile plutonium. (author)

Reprocessing of LEU silicide fuel at Dounreay

International Nuclear Information System (INIS)

Cartwright, P.

1996-01-01

UKAEA have recently reprocessed two LEU silicide fuel elements in their MTR fuel reprocessing plant at Dounreay. The reprocessing was undertaken to demonstrate UKAEA's commitment to the world-wide research reactor communities future needs. Reprocessing of LEU silicide fuel is seen as a waste treatment process, resulting in the production of a liquid feed suitable for conditioning in a stable form of disposal. The uranium product from the reprocessing can be used as a blending feed with the HEU to produce LEU for use in the MTR cycle. (author)

HEU benchmark calculations and LEU preliminary calculations for IRR-1

International Nuclear Information System (INIS)

Caner, M.; Shapira, M.; Bettan, M.; Nagler, A.; Gilat, J.

2004-01-01

We performed neutronics calculations for the Soreq Research Reactor, IRR-1. The calculations were done for the purpose of upgrading and benchmarking our codes and methods. The codes used were mainly WIMS-D/4 for cell calculations and the three dimensional diffusion code CITATION for full core calculations. The experimental flux was obtained by gold wire activation methods and compared with our calculated flux profile. The IRR-1 is loaded with highly enriched uranium fuel assemblies, of the plate type. In the framework of preparation for conversion to low enrichment fuel, additional calculations were done assuming the presence of LEU fresh fuel. In these preliminary calculations we investigated the effect on the criticality and flux distributions of the increase of U-238 loading, and the corresponding uranium density.(author)

Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis.

Directory of Open Access Journals (Sweden)

Marco Cassano

2008-09-01

Full Text Available Hepatocyte Growth Factor (HGF is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation.Magic-Factor 1 (Met-Activating Genetically Improved Chimeric Factor-1 or Magic-F1 is an HGF-derived, engineered protein that contains two Met-binding domains repeated in tandem. It has a reduced affinity for Met and, in contrast to HGF it elicits activation of the AKT but not the ERK signaling pathway. As a result, Magic-F1 is not mitogenic but conserves the ability to promote cell survival. Here we show that Magic-F1 protects myogenic precursors against apoptosis, thus increasing their fusion ability and enhancing muscular differentiation. Electrotransfer of Magic-F1 gene into adult mice promoted muscular hypertrophy and decreased myocyte apoptosis. Magic-F1 transgenic mice displayed constitutive muscular hypertrophy, improved running performance and accelerated muscle regeneration following injury. Crossing of Magic-F1 transgenic mice with alpha-sarcoglycan knock-out mice -a mouse model of muscular dystrophy- or adenovirus-mediated Magic-F1 gene delivery resulted in amelioration of the dystrophic phenotype as measured by both anatomical/histological analysis and functional tests.Because of these features Magic-F1 represents a novel molecular tool to counteract muscle wasting in major

Synthesis and preliminary evaluation of 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) in HSV1-tk gene transduced hepatoma cell

Energy Technology Data Exchange (ETDEWEB)

Moon, Byung Seok; Lee, Tae Sup [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Myoung Keun [Yonsei University, Wonju (Korea, Republic of)] (and others)

2006-08-15

The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl) guanine ([{sup 18}F]FHBG) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with K[{sup 18}F]/K2.2.2. in acetonitrile using N2-monomethoxytrityl-9-[4-(tosly)-3-monomethoxytritylmethylbutl] guanine as a precursor, followed by deprotection with 1 N HCI. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of [{sup 18}F]FHBG were performed, and was analyzed correlation between [{sup 18}F]FHBG uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor beating Balb/c-nude mouse model. [{sup 18}F]FHBG was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiochemical yield was about 20-25% (corrected for decay), radiochemical purity was > 95% and specific activity was around > 55.5 GBq/ {mu} mol. Specific accumulation of [{sup 18}F]FHBG was observed in HSV1-tk gene transduced MCA-tk cells but not MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked [{sup 18}F]FHBG was retained inside of cells. The uptake of [{sup 18}F]FHBG was showed a highly significant linear correlation (R{sup 2} = 0.995) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. [{sup 18}F]FHBG appears

Neutronic analysis for conversion of the Ghana Research Reactor-1 facility using Monte Carlo methods and UO{sub 2} LEU fuel

Energy Technology Data Exchange (ETDEWEB)

Anim-Sampong, S.; Akaho, E.H.K.; Maakuu, B.T.; Gbadago, J.K. [Ghana Research Reactor-1 Centre, Dept. of Nuclear Engineering and Materials Science, National Nuclear Research Institute, Ghana Atomic Energy Commission, Legon, Accra (Ghana); Andam, A. [Kwame Nkrumah Univ. of Science and Technology, Dept. of Physics (Ghana); Liaw, J.J.R.; Matos, J.E. [Argonne National Lab., RERTR Programme, Div. of Nuclear Engineering (United States)

2007-07-01

Monte Carlo particle transport methods and software (MCNP) have been applied to the modelling, simulation and neutronic analysis for the conversion of the HEU-fuelled (high enrichment uranium) core of the Ghana Research Reactor-1 (GHARR-1) facility. The results show that the MCNP model of the GHARR-1 facility, which is a commercial version of the Miniature Neutron Source Reactor (MNSR) is good as the simulated neutronic and other reactor physics parameters agree with very well with experimental and zero power results. Three UO{sub 2} LEU (low enrichment uranium) fuels with different enrichments (12.6% and 19.75%), core configurations, core loadings were utilized in the conversion studies. The nuclear criticality and kinetic parameters obtained from the Monte Carlo simulation and neutronic analysis using three UO{sub 2} LEU fuels are in close agreement with results obtained for the reference 90.2% U-Al HEU core. The neutron flux variation in the core, fission chamber and irradiation channels for the LEU UO{sub 2} fuels show the same trend as the HEU core as presented in the paper. The Monte Carlo model confirms a reduction (8% max) in the peak neutron fluxes simulated in the irradiation channels which are utilized for experimental and commercial activities. However, the reductions or 'losses' in the flux levels neither affects the criticality safety, reactor operations and safety nor utilization of the reactor. Employing careful core loading optimization techniques and fuel loadings and enrichment, it is possible to eliminate the apparent reductions or 'losses' in the neutron fluxes as suggested in this paper. Concerning neutronics, it can be concluded that all the 3 LEU fuels qualify as LEU candidates for core conversion of the GHARR-1 facility.

Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT.

Science.gov (United States)

Merkle, Patrick S; Gotfryd, Kamil; Cuendet, Michel A; Leth-Espensen, Katrine Z; Gether, Ulrik; Loland, Claus J; Rand, Kasper D

2018-05-01

LeuT, a prokaryotic member of the neurotransmitter:sodium symporter (NSS) family, is an established structural model for mammalian NSS counterparts. We investigate the substrate translocation mechanism of LeuT by measuring the solution-phase structural dynamics of the transporter in distinct functional states by hydrogen/deuterium exchange mass spectrometry (HDX-MS). Our HDX-MS data pinpoint LeuT segments involved in substrate transport and reveal for the first time a comprehensive and detailed view of the dynamics associated with transition of the transporter between outward- and inward-facing configurations in a Na + - and K + -dependent manner. The results suggest that partial unwinding of transmembrane helices 1/5/6/7 drives LeuT from a substrate-bound, outward-facing occluded conformation toward an inward-facing open state. These hitherto unknown, large-scale conformational changes in functionally important transmembrane segments, observed for LeuT in detergent-solubilized form and when embedded in a native-like phospholipid bilayer, could be of physiological relevance for the translocation process.

Development of production of {sup 99}Mo from LEU target

Energy Technology Data Exchange (ETDEWEB)

Adang, H G; Mutalib, A; Lubis, H [Radioisotope Production Centre, National Atomic Energy Agency, Kawasan Puspiptek, Serpong (Indonesia); and others

1998-10-01

{sup 99}TC, the most popular radioisotope in nuclear medicine, is daughter of {sup 99}Mo. {sup 99}Mo is produced in research reactor by irradiating of high enriched uranium (HEU). However, in recent year, strict regulation that has been implemented by USA DOE and NPT has led to the difficulty in getting HEU. Therefore, BATAN has tried to develop the production of {sup 99}Mo by using low enriched uranium (LEU). The research involves the use of LEU in the production of {sup 99}Mo. This research was started in 1994 by joint-research between BATAN and Argonne National Laboratory USA. This program is divided into three research groups. The first group emphasizes its research on fabrication of LEU foil that is going to be irradiated. The second group studies the irradiation`s aspects and physical characteristic of irradiated LEU foils. The third group studies the radiochemical separation process of fission product {sup 99}Mo from solution of irradiated LEU foils. There are five steps that are carried out in studying of radiochemical separation of {sup 99}Mo from irradiated LEU. First is designing a dissolver that is going to be used in dissolving of LEU foil and testing its reliability. Second is dissolving LEU in the new design dissolver. Third is evaluation the modified of Cintichem`s radiochemical separation process of {sup 99}Mo from LEU. Forth is modifying the Cintichem`s radiochemical separation process of {sup 99}Mo from the solution of irradiated LEU. And fifth is using the modified of Cintichem`s radiochemical separation process for separation {sup 99}Mo from solution of irradiated LEU. The first through the forth steps of experiments were already carried out and will be reported in this workshop, whereas the fifth step of experiment is going to be conducted in February 1998. (author)

Dissection of combinatorial control by the Met4 transcriptional complex.

Science.gov (United States)

Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

2010-02-01

Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

[D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, small molecule synthetic peptide leptin mimetics, improve glycemic control in diet-induced obese (DIO) mice.

Science.gov (United States)

Wang, Anke; Anderson, Brian M; Novakovic, Zachary M; Grasso, Patricia

2018-03-01

We have previously shown that following oral delivery in dodecyl maltoside (DDM), [D-Leu-4]-OB3 and its myristic acid conjugate, MA-[D-Leu-4]-OB3, improved energy balance and glucose homeostasis in genetically obese/diabetic mouse models. More recently, we have provided immunohistochemical evidence indicating that these synthetic peptide leptin mimetics cross the blood-brain barrier and concentrate in the area of the arcuate nucleus of the hypothalamus in normal C57BL/6J and Swiss Webster mice, in genetically obese ob/ob mice, and in diet-induced obese (DIO) mice. In the present study, we describe the effects of oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on glycemic control in diet-induced (DIO) mice, a non-genetic rodent model of obesity and its associated insulin resistance, which more closely recapitulates common obesity and diabetes in humans. Male C57BL/6J and DIO mice, 17, 20, and 28 weeks of age, were maintained on a low-fat or high-fat diet and given vehicle (DDM) alone or [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in DDM by oral gavage for 12 or 14 days. Body weight gain, food and water intake, fasting blood glucose, oral glucose tolerance, and serum insulin levels were measured. Our data indicate that (1) [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 restore glucose tolerance in male DIO mice maintained on a high-fat diet to levels comparable to those of non-obese C57BL/6J wild-type mice of the same age and sex maintained on a low-fat diet; and (2) the influence of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on glycemic control appears to be independent of their effects on energy balance. These results suggest that [D-Leu-4]-OB3 and/or MA-[D-Leu-4]-OB3 may have application to the management of the majority of cases of common obesity in humans, a state characterized at least in part, by leptin resistance resulting from a defect in leptin transport across the blood-brain barrier. They further suggest that these small molecule synthetic peptide leptin mimetics, through their

Preliminary Thermohydraulic Analysis of a New Moderated Reactor Utilizing an LEU-Fuel for Space Nuclear Thermal Propulsion

Energy Technology Data Exchange (ETDEWEB)

Nam, Seung Hyun; Choi, Jae Young; Venneria, Paolo F.; Jeong, Yong Hoon; Chang, Soon Heung [KAIST, Daejeon (Korea, Republic of)

2015-10-15

preliminary design analyses of neutronics and thermo-hydraulics were carried out with the assumption of an expander cycle in steady-state. The result demonstrates that the feasible design space for the reactor design potentially involves the P/D range of 1.66 - 1.76, the power range of 200 - 250 MW{sub th} and the FWT range of 0.50 - 1.25 mm to meet the major design parameters and criteria. Accordingly, the referential rocket performance are estimated to be in the range of 11.94 - 14.84 MPa in maximum system pressure, the thrust range of 41.0 - 53.6 kN, the T/W{sub eng} range of 3.39 - 4.44 and the I{sub sp} range of 855.4 - 904.4 according to the major parameters. The performance of the KANUTER-LEU is comparable with that of the existing HEU-NTR engines in spite of the heavy LEU fuel loading according to the mission performance comparison.

[Expression of Jagged1 mRNA in human epithelial ovarian carcinoma tissues and effect of RNA interference of Jagged1 on growth of xenograft in nude mice].

Science.gov (United States)

Liu, G Y; Gao, Z H; Li, L; Song, T T; Sheng, X G

2016-06-25

To investigate the expression of Jagged1 in human epithelial ovarian carcinoma tissues and the effect of Jagged1 on growth of xenograft in nude mice. (1) Forty-eight cases of ovarian cancer and 30 cases of patients with benign epithelial ovarian tumor in the Henan Province Xinxiang Central Hospital during Feb. 2011 to Mar. 2014 were enrolled in this study. The mRNA expression of Jagged1, Notch1 and the downstream target genes Hes1, Hey1 were analyzed by using realtime PCR method. (2) The ovarian cancer xenograft models in nude mice were constructed by injecting SKOV3 cells in axillary subcutaneouswere. The nude mice were randomly divided into Jagged1 interference group, blank plasmid group and control group. Each group had 10 mice. They were transfected with pcDNA3.1(+)-siRNA-Jagged1, blank plasmid pDC3.1 and phosphate buffer, respectively. The tumor volumes and tumor masses were measured 14 days after transfection and the inhibition rate was calculated. The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues after transfection in each group was detected by using realtime PCR technique and the relative protein expression of Jagged1, Notch1, Hes1 and Hey1 in xenograft tissues was detected by utilizing western blot method. (1) The relative mRNA expression of Jagged1, Notch1, Hes1 and Hey1 in ovarian cancer tissues were higher than benign ovarian tumor tissues, the differences were statistically significant (Ptissues of nude micein Jagged1 interference group were lower than that in the other two groups, the differences were statistically significant (Ptissues of nude mice among the three groups (P>0.05). Jagged1 is highly expressed in epithelial ovarian carcinoma. Jagged1 gene interference in xenograft tumor can inhibit ovarian cancer cell growth and improve tumor suppressor rate, which probably play roles by inhibiting Notch1 signaling pathway.

Study of expression of genes cIAP and cMET, in liver tissue with and without neoplasia of Rattus norvegicus

International Nuclear Information System (INIS)

Coto Valverde, Daniel Esteban

2010-01-01

The expression levels of cIAP genes and cMET were determined in liver tissues with and without neoplasm of the organism Rattus norvegicus, for prevention, diagnosis and treatment of hepatocellular carcinoma. The technique of reaction Polymerase Chain in real time (qPCR), is used to obtain the expression, of both genes cIAP and cMET, and this has decreased in neoplastic samples compared to samples not affected. The expression of these genes has been analyzed in samples with neoplastic formations, but treated with an anti-tumor agent. The expression has presented an increase of the cMET gene, unlike the cIAP gene, which has decreased its expression. Perform statistical analysis has been impossible because the number of samples used has been reduced. The results obtained differ with those expected theoretically. (author) [es

Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students.

Science.gov (United States)

Hinney, Anke; Hoch, Anne; Geller, Frank; Schäfer, Helmut; Siegfried, Wolfgang; Goldschmidt, Hanspeter; Remschmidt, Helmut; Hebebrand, Johannes

2002-06-01

Ghrelin induces obesity via central and peripheral mechanisms. Administration of ghrelin leads to increased food intake and decreased fat utilisation in rodents. Ghrelin levels are decreased in obese individuals. Recently, a polymorphism (Arg-51-Gln) within the ghrelin gene (GHRL) was described to be associated with obesity. We screened the GHRL coding region in 215 extremely obese German Children and adolescents (study group 1) and 93 normal weight students (study group 2) by single strand conformation polymorphism analysis (SSCP). We found the two previously described single nucleotide polymorphisms (SNP: Arg-51-Gln and Leu-72-Met) in similar frequencies in study groups 1 and 2 (allele frequencies were: 0.019 and 0.016 for the 51-Gln allele and 0.091 and 0.086 for the 72-Met allele, respectively). Hence, we could not confirm the previous finding. Additionally, two novel variants were identified within the coding region: (1) We detected one healthy normal weight individual with a frameshift mutation (2bp deletion at codon 34). This frameshift mutation affects the coding region of the mature ghrelin. Hence, it is highly likely that the normal weight student is haplo-insufficient for ghrelin. (2) An A to T transversion leads to an amino acid exchange from Gln to Leu at amino acid position 90. The frequency of the 90-Leu allele was significantly higher in the extremely obese children and adolescents (0.063) than in the normal weight students (0.016; nominal p = 0.011). Additionally, we genotyped 134 underweight students and 44 normal weight adults for this SNP. Genotype frequencies were similar in extremely obese children and adolescents, underweight students and normal weight adults (p > 0.8). In conclusion, we identified four sequence variants in the coding region of the ghrelin gene in individuals belonging to different weight extremes. A frameshift mutation was detected in a normal weight individual. None of the variants seem to influence weight regulation.

N-AC-l-Leu-PEI-mediated miR-34a delivery improves osteogenic differentiation under orthodontic force.

Science.gov (United States)

Yu, Wenwen; Zheng, Yi; Yang, Zhujun; Fei, Hongbo; Wang, Yang; Hou, Xu; Sun, Xinhua; Shen, Yuqin

2017-12-15

Rare therapeutic genes or agents are reported to control orthodontic bone remodeling. MicroRNAs have recently been associated with bone metabolism. Here, we report the in vitro and in vivo effects of miR-34a on osteogenic differentiation under orthodontic force using an N -acetyl-L-leucine-modified polyethylenimine ( N -Ac-l-Leu-PEI) carrier. N -Ac-l-Leu-PEI exhibited low cytotoxicity and high miR-34a transfection efficiency in rat bone mineral stem cells and local alveolar bone tissue. After transfection, miR-34a enhanced the osteogenic differentiation of Runx2 and ColI , Runx2 and ColI protein levels, and early osteogenesis function under orthodontic strain in vitro . MiR-34a also enhanced alveolar bone remodeling under orthodontic force in vivo , as evidenced by elevated gene and protein expression, upregulated indices of alveolar bone anabolism, and diminished tooth movement. We determined that the mechanism miR-34a in osteogenesis under orthodontic force may be associated with GSK-3β. These results suggested that miR-34a delivered by N -Ac-l-Leu-PEI could be a potential therapeutic target for orthodontic treatment.

Comparison of the FRM-II HEU design with an alternative LEU design. Attachment

International Nuclear Information System (INIS)

Hanan, N.A.; Mo, S.C.; Smith, R.S.; Matos, J.E.

2004-01-01

After presentation of the foregoing paper by Dr. Nelson Hanan of Argonne National Laboratory (ANL) proposing an alternative LEU core with one fuel ring and a power level of 33 MW, a presentation was made by Dr. Klaus Boning of the Technical University of Munich comparing the FRM-II HEU design with an LEU design by Tlm that had two fuel rings and a power level of 40 MW. Dr. Boning raised the following issues concerning the use of LEU fuel in FRM-H reactor designs: (1) qualification of HEU and LEU silicide fuels, (2) gamma heating in the heavy water reflector, (3) the radiological consequences of hypothetical accidents, and (4) cost and schedule. These issues are addressed in this Attachment. In his presentation, Dr. Hanan mentioned that ANL was also investigating other LEU designs. This work led to a second alternative LEU design that has the same neutron flux performance (8 x 10 14 n/cm 2 /s peak neutron flux in the reflector) and the same fuel lifetime (50 full power days) as the HEU design, but uses LEU silicide fuel with a uranium density of only 4.5 g/cm 3 . This design was achieved by using a fuel plate that has a fuel meat thickness of 0.76 mm, a cladding thickness of 0.38 mm, and a water channel gap of 2.2 mm. A comparison is shown of the main characteristics of this second alternative LEU design with those of the FRM-II HEU design. The ANL core again has one fuel ring with the same dimensions. With this LEU design, a two stage process is no longer necessary because LEU silicide fuel with a uranium density of 4.5 g/cm 3 is fully qualified, licensable, and available now for use in a high flux reactor such as the FRM-II

Infantile presentation of the mtDNA A3243G tRNA(Leu (UUR)) mutation.

NARCIS (Netherlands)

Okhuijsen-Kroes, E.J.; Trijbels, J.M.F.; Sengers, R.C.A.; Mariman, E.C.M.; Heuvel, L.P.W.J. van den; Wendel, U.A.H.; Koch, G.; Smeitink, J.A.M.

2001-01-01

Mitochondrial DNA (mtDNA) disorders are clinically very heterogeneous, ranging from single organ involvement to severe multisystem disease. One of the most frequently observed mtDNA mutations is the A-to-G transition at position 3243 of the tRNA(Leu (UUR)) gene. This mutation is often related to

RET/PTC1-Driven Neoplastic Transformation and Proinvasive Phenotype of Human Thyrocytes Involve Met Induction and β-Catenin Nuclear Translocation

Directory of Open Access Journals (Sweden)

Giuliana Cassinelli

2009-01-01

Full Text Available Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC. We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, β-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and β-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of β-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated β-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes β-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs.

Progress in chemical treatment of LEU targets by the modified Cintichem process

International Nuclear Information System (INIS)

Wu, D.; Landsberger, S.; Vandegrift, G.F.

1996-01-01

Presented here are recent experimental results on tests of a modified Cintichem process for producing 99 Mo from low enriched uranium (LEU). Studies were focused in three areas: (1) testing the effects on 99 Mo recovery and purity of dissolving LEU foil in nitric acid alone, rather than in the sulfuric/nitric acid mixture currently used, (2) measuring decontamination factors for radionuclide impurities in each purification step, and (3) testing the effects on processing of adding barrier materials to the LEU metal-foil target. The experimental results show that switching from dissolving the target in the sulfuric/nitric mixture to using nitric acid alone should cause no significant difference in 99 Mo product yield or purity. Further, the results show that overall decontamination factors for gamma emitters in the LEU-target processing are high enough to meet the purity requirements for the 99 Mo product. The results also show that the selected barrier materials, Cu, Fe, and Ni, do not interfere with 99 Mo recovery and can be removed during chemical processing of the LEU target

Peptide (Lys-Leu) and amino acids (Lys and Leu) supplementations improve physiological activity and fermentation performance of brewer's yeast during very high-gravity (VHG) wort fermentation.

Science.gov (United States)

Yang, Huirong; Zong, Xuyan; Cui, Chun; Mu, Lixia; Zhao, Haifeng

2017-12-22

Lys and Leu were generally considered as the key amino acids for brewer's yeast during beer brewing. In the present study, peptide Lys-Leu and a free amino acid (FAA) mixture of Lys and Leu (Lys + Leu) were supplemented in 24 °P wort to examine their effects on physiological activity and fermentation performance of brewer's yeast during very high-gravity (VHG) wort fermentation. Results showed that although both peptide Lys-Leu and their FAA mixture supplementations could increase the growth and viability, intracellular trehalose and glycerol content, wort fermentability, and ethanol content for brewer's yeast during VHG wort fermentation, and peptide was better than their FAA mixture at promoting growth and fermentation for brewer's yeast when the same dose was kept. Moreover, peptide Lys-Leu supplementation significantly increased the assimilation of Asp, but decreased the assimilation of Gly, Ala, Val, (Cys)2, Ile, Leu, Tyr, Phe, Lys, Arg, and Pro. However, the FAA mixture supplementation only promoted the assimilation of Lys and Leu, while reduced the absorption of total amino acids to a greater extent. Thus, the peptide Lys-Leu was more effective than their FAA mixture on the improvement of physiological activity, fermentation performance, and nitrogen metabolism of brewer's yeast during VHG wort fermentation. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

A neutronic feasibility study for LEU conversion of the High Flux Beam Reactor (HFBR)

International Nuclear Information System (INIS)

Pond, R.B.; Hanan, N.A.; Matos, J.E.

1997-01-01

A neutronic feasibility study for converting the High Flux Beam Reactor at Brookhaven National Laboratory from HEU to LEU fuel was performed at Argonne National Laboratory. The purpose of this study is to determine what LEU fuel density would be needed to provide fuel lifetime and neutron flux performance similar to the current HEU fuel. The results indicate that it is not possible to convert the HFBR to LEU fuel with the current reactor core configuration. To use LEU fuel, either the core needs to be reconfigured to increase the neutron thermalization or a new LEU reactor design needs to be considered. This paper presents results of reactor calculations for a reference 28-assembly HEU-fuel core configuration and for an alternative 18-assembly LEU-fuel core configuration with increased neutron thermalization. Neutronic studies show that similar in-core and ex-core neutron fluxes, and fuel cycle length can be achieved using high-density LEU fuel with about 6.1 gU/cm 3 in an altered reactor core configuration. However, hydraulic and safety analyses of the altered HFBR core configuration needs to be performed in order to establish the feasibility of this concept. (author)

Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene

DEFF Research Database (Denmark)

hart, Leen M; Hansen, Torben; Rietveld, Ingrid

2005-01-01

Previously, we have shown that a mutation in the mitochondrial DNA-encoded tRNA(Leu(UUR)) gene is associated with type 2 diabetes. One of the consequences of this mutation is a reduced aminoacylation of tRNA(Leu(UUR)). In this study, we have examined whether variants in the leucyl tRNA synthetase...... gene (LARS2), involved in aminoacylation of tRNA(Leu(UUR)), associate with type 2 diabetes. Direct sequencing of LARS2 cDNA from 25 type 2 diabetic subjects revealed eight single nucleotide polymorphisms. Two of the variants were examined in 7,836 subjects from four independent populations...... in the Netherlands and Denmark. A -109 g/a variant was not associated with type 2 diabetes. Allele frequencies for the other variant, H324Q, were 3.5% in type 2 diabetic and 2.7% in control subjects, respectively. The common odds ratio across all four studies was 1.40 (95% CI 1.12-1.76), P = 0.004. There were...

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

OpenAIRE

Saliba,Louise F.; Reis,Rodrigo S.; Brownson,Ross C.; Hino,Adriano A.; Tureck,Luciane V.; Valko,Cheryl; Souza,Ricardo L.R. de; Furtado-Alle,Lupe

2014-01-01

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (...

Agonist properties of a stable hexapeptide analog of neurotensin, N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1).

Science.gov (United States)

Akunne, H C; Demattos, S B; Whetzel, S Z; Wustrow, D J; Davis, D M; Wise, L D; Cody, W L; Pugsley, T A; Heffner, T G

1995-04-18

The major signal transduction pathway for neurotensin (NT) receptors is the G-protein-dependent stimulation of phospholipase C, leading to the mobilization of intracellular free Ca2+ ([Ca2+]i) and the stimulation of cyclic GMP. We investigated the functional actions of an analog of NT(8-13), N alpha MeArg-Lys-Pro-Trp-tLeu-Leu (NT1), and other NT related analogs by quantitative measurement of the cytosolic free Ca2+ concentration in HT-29 (human colonic adenocarcinoma) cells using the Ca(2+)-sensitive dye fura-2/AM and by effects on cyclic GMP levels in rat cerebellar slices. The NT receptor binding affinities for these analogs to HT-29 cell membranes and newborn (10-day-old) mouse brain membranes were also investigated. Data obtained from HT-29 cell and mouse brain membrane preparations showed saturable single high-affinity sites and binding densities (Bmax) of 130.2 and 87.5 fmol/mg protein, respectively. The respective KD values were 0.47 and 0.39 nM, and the Hill coefficients were 0.99 and 0.92. The low-affinity levocabastine-sensitive site was not present (K1 > 10,000) in either membrane preparation. Although the correlation of binding between HT-29 cell membranes and mouse brain membranes was quite significant (r = 0.92), some of the reference agents had lower binding affinities in the HT-29 cell membranes. The metabolically stable compound NT1 plus other NT analogs and related peptides [NT, NT(8-13), xenopsin, neuromedin N, NT(9-13), kinetensin and (D-Trp11)-NT] increased intracellular Ca2+ levels in HT-29 cells, indicating NT receptor agonist properties. The effect of NT1 in mobilizing [Ca2+]i blocked by SR 48692, a non-peptide NT antagonist. Receptor binding affinities of NT analogs to HT-29 cell membranes were positively correlated with potencies for mobilizing intracellular calcium in the same cells. In addition, NT1 increased cyclic GMP levels in rat cerebellar slices, confirming the latter findings of its NT agonist action. These results substantiate

Synthesis of high specific active tritiated Leu-enkephalin in the leucine residue

Energy Technology Data Exchange (ETDEWEB)

Baba, S.; Hasegawa, H.; Shinohara, Y. (Tokyo Coll. of Pharmacy (Japan))

1989-12-01

Leu-enkephalin labelled with tritium in the Leu residue has been prepared. Synthesis of the precursor peptide, (4,5-dehydroLeu{sup 5}-)Leu-enkephalin, was carried out by solid phase synthesis using Fmoc amino acid derivatives. The peptide was tritiated catalytically yielding {sup 3}H-Leu-enkephalin with a specific radioactivity of 4.39 TBq/mmol. The distribution of tritium label was investigated by reversed-phase high performance liquid chromatography with a synchronized accumulating radioisotope detector following acidic and enzymatic hydrolysis, which confirmed that the tritium label was entirely located at the Leu residue. (author).

Induction of CD4 suppressor T cells with anti-Leu-8 antibody

International Nuclear Information System (INIS)

Kanof, M.E.; Strober, W.; James, S.P.

1987-01-01

To characterize the conditions under which CD4 T cells suppress polyclonal immunoglobulin synthesis, we investigated the capacity of CD4 T cells that coexpress the surface antigen recognized by the monoclonal antibody anti-Leu-8 to mediate suppression. In an in vitro system devoid of CD8 T cells, CD4, Leu-8+ T cells suppressed pokeweed mitogen-induced immunoglobulin synthesis. Similarly, suppressor function was induced in unfractionated CD4 T cell populations after incubation with anti-Leu-8 antibody under cross-linking conditions. This induction of suppressor function by anti-Leu-8 antibody was not due to expansion of the CD4, Leu-8+ T cell population because CD4 T cells did not proliferate in response to anti-Leu-8 antibody. However, CD4, Leu-8+ T cell-mediated suppression was radiosensitive. Finally, CD4, Leu-8+ T cells do not inhibit immunoglobulin synthesis when T cell lymphokines were used in place of helper CD4 T cells (CD4, Leu-8- T cells), suggesting that CD4 T cell-mediated suppression occurs at the T cell level. We conclude that CD4 T cells can be induced to suppress immunoglobulin synthesis by modulation of the membrane antigen recognized by anti-Leu-8 antibody

Development of Fission Mo-99 Process for LEU Dispersion Target

Energy Technology Data Exchange (ETDEWEB)

Lee, Seung Kon; Lee, Su Seung; Hong, Soon Bog; Jang, Kyung Duk; Park, Ul Jae; Lee, Jun Sig [KAERI, Daejeon (Korea, Republic of)

2016-05-15

KAERI (Korea Atomic Energy Research Institute) is developing LEU-based fission {sup 99}Mo production process which is connected to the new research reactor (Kijang New Research Reactor, KJRR), which is being constructed in Gijang, Busan, Korea. Historically, the most fission {sup 99}Mo producers have been used highly enriched uranium (HEU) targets so far. However, to reduce the use of HEU in private sector for non-proliferation, {sup 99}Mo producers are forced to convert their HEU-based process to use low enriched uranium (LEU) targets. Economic impact of a target conversion from HEU to LEU is significant. Overall cost for the production of the fission {sup 99}Mo increases significantly with the conversion of fission {sup 99}Mo targets from HEU to LEU. It is not only because the yield of LEU is only 50% of HEU, but also because radioactive waste production increases 200%. On the basis, worldwide efforts on the development of {sup 99}Mo production process that is optimized for the LEU target become an important issue. In this study, fission {sup 99}Mo process with non-irradiated LEU targets was presented except separation and purification steps. Pre- and post-irradiation tests of the fission {sup 99}Mo target will be done in 4th quarter of 2016.

The whole-core LEU silicide fuel demonstration in the JMTR

Energy Technology Data Exchange (ETDEWEB)

Aso, Tomokazu; Akashi, Kazutomo; Nagao, Yoshiharu [Japan Atomic Energy Research Institute, Ibaraki-ken (Japan)] [and others

1997-08-01

The JMTR was fully converted to LEU silicide (U{sub 3}Si{sub 2}) fuel with cadmium wires as burnable absorber in January, 1994. The reduced enrichment program for the JMTR was initiated in 1979, and the conversion to MEU (enrichment ; 45%) aluminide fuel was carried out in 1986 as the first step of the program. The final goal of the program was terminated by the present LEU conversion. This paper describes the results of core physics measurement through the conversion phase from MEU fuel core to LEU fuel core. Measured excess reactivities of the LEU fuel cores are mostly in good agreement with predicted values. Reactivity effect and burnup of cadmium wires, therefore, were proved to be well predicted. Control rod worth in the LEU fuel core is mostly less than that in the MEU fuel core. Shutdown margin was verified to be within the safety limit. There is no significant difference in temperature coefficient of reactivity between the MEU and LEU fuel cores. These results verified that the JMTR was successfully and safely converted to LEU fuel. Extension of the operating cycle period was achieved and reduction of spend fuel elements is expected by using the fuel with high uranium density.

Development of Fission Mo-99 Process for LEU Dispersion Target

International Nuclear Information System (INIS)

Lee, Seung Kon; Lee, Su Seung; Hong, Soon Bog; Jang, Kyung Duk; Park, Ul Jae; Lee, Jun Sig

2016-01-01

KAERI (Korea Atomic Energy Research Institute) is developing LEU-based fission 99 Mo production process which is connected to the new research reactor (Kijang New Research Reactor, KJRR), which is being constructed in Gijang, Busan, Korea. Historically, the most fission 99 Mo producers have been used highly enriched uranium (HEU) targets so far. However, to reduce the use of HEU in private sector for non-proliferation, 99 Mo producers are forced to convert their HEU-based process to use low enriched uranium (LEU) targets. Economic impact of a target conversion from HEU to LEU is significant. Overall cost for the production of the fission 99 Mo increases significantly with the conversion of fission 99 Mo targets from HEU to LEU. It is not only because the yield of LEU is only 50% of HEU, but also because radioactive waste production increases 200%. On the basis, worldwide efforts on the development of 99 Mo production process that is optimized for the LEU target become an important issue. In this study, fission 99 Mo process with non-irradiated LEU targets was presented except separation and purification steps. Pre- and post-irradiation tests of the fission 99 Mo target will be done in 4th quarter of 2016

Val158Met polymorphism in the COMT gene is associated with hypersomnia and mental health-related quality of life in a Colombian sample.

Science.gov (United States)

Jiménez, Karen M; Pereira-Morales, Angela J; Forero, Diego A

2017-03-22

The identification of genes that are risk factors for major depressive disorder remains a main task for global psychiatric research. The Catechol-O-methyltransferase (COMT) gene has been an important candidate risk factor for several psychiatric disorders. Previous studies have shown that a functional polymorphism (Val158Met) in this gene has an effect on several brain circuits and endophenotypes of psychiatric relevance. The aim of this study was to explore the association of a functional polymorphism in the COMT gene with psychological distress, sleep problems and health-related quality of life. Two hundred seventy young Colombian subjects (mean age: 21.3 years; range: 18-57 years) completed the Patient Health Questionnaire-9, the Perceived Stress Scale, the Oviedo Sleep Questionnaire and the 12-Item Short-Form Health Survey and were genotyped for the Val158Met polymorphism (rs4680) in the COMT gene. A linear regression analysis, adjusting for potential confounding factors, was carried out. Subjects that were Met carriers (Val/Met and Met/Met genotypes) showed higher scores for hypersomnia (p=0.001) and lower scores for mental health-related quality of life (p=0.007), these associations remained significant after correcting for multiple testing. These findings support the hypothesis of a broad effect of the Val158Met polymorphism in the COMT gene on several dimensions of behavior and neuropsychiatric symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

The global threat reduction initiative and conversion of isotope production to LEU targets

International Nuclear Information System (INIS)

Kuperman, A. J.

2005-01-01

The U.S. Global Threat Reduction Initiative (GTRI) has given a decisive impetus to the RERTR program's longstanding goal of converting worldwide production of medical radioisotopes from reliance on bomb-grade, highly enriched uranium (HEU) to low-enriched uranium (LEU) unsuitable for weapons. Although the four major; isotope producers continue to resist calls for conversion, they face mounting pressure from a variety of fronts including: (1) GTRI; (2) a related, multilateral U.S. initiative to forge agreement on conversion among the states that are home to the major producers; (3) an IAEA effort to provide technical assistance that will facilitate large-scale production of medical isotopes using LEU by producers who seek to do so; (4) planned production in the United States of substantial quantities of medical isotopes using LEU; and (5) pending U.S. legislation that would prohibit the export of HEU for production of isotopes as soon as alternative, LEU-produced isotopes are available. Accordingly, it now appears inevitable that worldwide isotope production will be converted from reliance on HEU to LEU. The only remaining question is which producers will be the first to reliably deliver sizeable quantities of LEU-produced isotopes and thereby capture global market share from the others. (author)

Association Between Genetic Polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT Genes and Radiosensitivity in Breast Cancer Patients

International Nuclear Information System (INIS)

Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

2011-01-01

Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be

31 CFR 540.308 - Low Enriched Uranium (LEU).

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Low Enriched Uranium (LEU). 540.308... OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY HIGHLY ENRICHED URANIUM (HEU) AGREEMENT ASSETS CONTROL REGULATIONS General Definitions § 540.308 Low Enriched Uranium (LEU). The term low enriched...

Preliminary Results of Ancillary Safety Analyses Supporting TREAT LEU Conversion Activities

Energy Technology Data Exchange (ETDEWEB)

Brunett, A. J. [Argonne National Lab. (ANL), Argonne, IL (United States); Fei, T. [Argonne National Lab. (ANL), Argonne, IL (United States); Strons, P. S. [Argonne National Lab. (ANL), Argonne, IL (United States); Papadias, D. D. [Argonne National Lab. (ANL), Argonne, IL (United States); Hoffman, E. A. [Argonne National Lab. (ANL), Argonne, IL (United States); Kontogeorgakos, D. C. [Argonne National Lab. (ANL), Argonne, IL (United States); Connaway, H. M. [Argonne National Lab. (ANL), Argonne, IL (United States); Wright, A. E. [Argonne National Lab. (ANL), Argonne, IL (United States)

2015-10-01

The Transient Reactor Test Facility (TREAT), located at Idaho National Laboratory (INL), is a test facility designed to evaluate the performance of reactor fuels and materials under transient accident conditions. The facility, an air-cooled, graphite-moderated reactor designed to utilize fuel containing high-enriched uranium (HEU), has been in non-operational standby status since 1994. Currently, in support of the missions of the Department of Energy (DOE) National Nuclear Security Administration (NNSA) Material Management and Minimization (M3) Reactor Conversion Program, a new core design is being developed for TREAT that will utilize low-enriched uranium (LEU). The primary objective of this conversion effort is to design an LEU core that is capable of meeting the performance characteristics of the existing HEU core. Minimal, if any, changes are anticipated for the supporting systems (e.g. reactor trip system, filtration/cooling system, etc.); therefore, the LEU core must also be able to function with the existing supporting systems, and must also satisfy acceptable safety limits. In support of the LEU conversion effort, a range of ancillary safety analyses are required to evaluate the LEU core operation relative to that of the existing facility. These analyses cover neutronics, shielding, and thermal hydraulic topics that have been identified as having the potential to have reduced safety margins due to conversion to LEU fuel, or are required to support the required safety analyses documentation. The majority of these ancillary tasks have been identified in [1] and [2]. The purpose of this report is to document the ancillary safety analyses that have been performed at Argonne National Laboratory during the early stages of the LEU design effort, and to describe ongoing and anticipated analyses. For all analyses presented in this report, methodologies are utilized that are consistent with, or improved from, those used in analyses for the HEU Final Safety Analysis

The University of Missouri Research Reactor HEU to LEU conversion project status

Energy Technology Data Exchange (ETDEWEB)

McKibben, James C; Kutikkad, Kiratadas; Foyto, Leslie P; Peters, Nickie J; Solbrekken, Gary L; Kennedy, John [University of Missouri Research Reactor, Missouri (United States); Stillman, John A; Feldman, Earl E; Tzanos, Constantine P; Stevens, John G [Argonne National Laboratory, Argonne, Illinois (United States)

2012-03-15

The University of Missouri Research Reactor (MURR) is one of five U.S. high performance research and test reactors that are actively collaborating with the U.S. Department of Energy (DOE) to find a suitable low-enriched uranium (LEU) fuel replacement for the currently required highly-enriched uranium (HEU) fuel. A conversion feasibility study based on U-10Mo monolithic LEU fuel was completed in 2009. It was concluded that the proposed LEU fuel assembly design, in conjunction with an increase in power level from 10 to 12 MWth, will (1) maintain safety margins during operation, (2) allow operating fuel cycle lengths to be maintained for efficient and effective use of the facility, and (3) preserve an acceptable level and spectrum of key neutron fluxes to meet the scientific mission of the facility. The MURR and Argonne National Laboratory (ANL) team is continuing to work toward realization of the conversion. The 'Preliminary Safety Analysis Report Methodologies and Scenarios for LEU Conversion of MURR' was completed in June 2011. This report documents design parameter values critical to the Fuel Development (FD), Fuel Fabrication Capability (FFC) and Hydromechanical Fuel Test Facility (HMFTF) projects. The report also provides a preliminary evaluation of safety analysis techniques and data that will be needed to complete the fuel conversion Safety Analysis Report (SAR), especially those related to the U-10Mo monolithic LEU fuel. Specific studies are underway to validate the proposed path to an LEU fuel conversion. Coupled fluid-structure simulations and experiments are being conducted to understand the hydrodynamic plate deformation risk for 0.965 mm (38 mil) thick fuel plates. Methodologies that were recently developed to answer the U.S. Nuclear Regulatory Commission (NRC) Request for Additional Information (RAI) regarding the MURR 2006 relicensing submittal will be used in the LEU conversion effort. Transition LEU fuel elements that will have a minimal impact on

Ross operation in children and young adults: the Alder Hey case series

Directory of Open Access Journals (Sweden)

Pozzi Marco

2004-04-01

Full Text Available Abstract Background The ideal prosthesis for aortic valve replacement in children and young adults has not been found yet. In recent years there has been a renewed interest in the replacement of aortic valve with the pulmonary autograft owing to its advantages of lack of anticoagulation, potential for growth and excellent haemodynamic performance. The purpose of this study was to review our institutional experience at Alder Hey hospital with the Ross procedure in children and young adults. Methods From November 1996 to September 2003, 38 patients (mean age, 13.1 ± 5.7 years underwent the Ross procedure for various aortic valve diseases using the root replacement technique. Clinical and echocardiographic follow-up was performed early (within 30 days, 3 to 6 months, and yearly after surgery. Medical records of all patients were reviewed retrospectively. Results There was 1 perioperative death. The patients were followed-up for a median interval of 36 months and up to 7 years. One patient died 3 years after surgery secondary to ventricular arrhythmia with overall mortality of 5.3%. Actuarial survival at 7 years was 94 ± 2.5% and there was 100% freedom from reoperation for autograft valve dysfunction or any other cause. Balloon dilatation was required in 2 patients for pulmonary homograft stenosis. The haemodynamics at the latest follow-up were also similar to those at the time of discharge after surgery. There was no progression in the degree of aortic regurgitation for 11 patients with trivial and 3 with mild regurgitation. Conclusion Our experience demonstrates that Ross operation is an attractive option for aortic valve replacement in children and young adults. Not only can the operation be accomplished with a low operative risk but the valve function stays normal over a long period of time with minimal alteration in lifestyle and no need for repeated operations to replace the valve as a result of somatic growth of the children.

[In vitro release of [5Met]- and [5Leu]-enkephalins from the rat brain crude synaptosomal (P2) fraction: Ca2+-dependency of K+-stimulation and effects of various drugs].

Science.gov (United States)

Koida, M; Takahashi, M; Takenaga, K

1983-01-01

The rat brain P2 fraction was suspended in Krebs Ringer bicarbonate buffer containing 20 microM bacitracin and incubated at 37 degrees C for 10 min under an atmosphere of 95% O2-5% CO2. Incubation was terminated by centrifugation at 4 degrees C and 10,000 X g for 10 min. The supernatant was designated as the S1 fraction, and from the pellet, the S2 to S4 fractions were collected by repeated suspension, incubation, and centrifugation. The radioimmunoassays of each S fraction revealed the spontaneous release of [5Met]- and [5Leu]-enkephalins at the ratio of 2 to 1. The peptide contents gradually decreased from S1 to S4, but the release tended to become constant in S3 and S4. Thus, the effects of some ions and drugs on the release were compared at the stage of obtaining the S3 fraction. The release of both peptides were significantly stimulated in 50 mM KCl buffer, and the stimulatory effect appears to be dependent on Ca2+ concentration. Veratrine and A23187 were also effective stimulants of the release. On the other hand, neither spontaneous nor K+-stimulated release of enkephalins was affected by morphine (1 microM), naloxone (1 microM), kyotorphin (1 or 10 microM), and Li+ (50 mM). Similar results were obtained with the release of 3H-noradrenaline taken up in vitro by the P2 fraction. The usability of the P2 fraction as an in vitro model for the study of stimulus-coupled release of enkephalins was discussed with some limitations found herein.

In Praise of a Model but Not Its Conclusions: Commentary on Cooper, Catmur, and Heyes (2012)

Science.gov (United States)

Bertenthal, Bennett I.; Scheutz, Matthias

2013-01-01

Cooper et al. (this issue) develop an interactive activation model of spatial and imitative compatibilities that simulates the key results from Catmur and Heyes (2011) and thus conclude that both compatibilities are mediated by the same processes since their single model can predict all the results. Although the model is impressive, the…

Radiological consequence analysis with HEU and LEU fuels

Energy Technology Data Exchange (ETDEWEB)

Woodruff, W.L.; Warinner, D.K.; Matos, J.E.

1984-01-01

A model for estimating the radiological consequences from a hypothetical accident in HEU and LEU fueled research and test reactors is presented. Simple hand calculations based on fission product yield table inventories and non-site specific dispersion data may be adequate in many cases. However, more detailed inventories and site specific data on meteorological conditions and release rates and heights can result in substantial reductions in the dose estimates. LEU fuel gives essentially the same doses as HEU fuel. The plutonium buildup in the LEU fuel does not significantly increase the radiological consequences. The dose to the thyroid is the limiting dose. 10 references, 3 figures, 7 tables.

Radiological consequence analysis with HEU and LEU fuels

International Nuclear Information System (INIS)

Woodruff, W.L.; Warinner, D.K.; Matos, J.E.

1984-01-01

A model for estimating the radiological consequences from a hypothetical accident in HEU and LEU fueled research and test reactors is presented. Simple hand calculations based on fission product yield table inventories and non-site specific dispersion data may be adequate in many cases. However, more detailed inventories and site specific data on meteorological conditions and release rates and heights can result in substantial reductions in the dose estimates. LEU fuel gives essentially the same doses as HEU fuel. The plutonium buildup in the LEU fuel does not significantly increase the radiological consequences. The dose to the thyroid is the limiting dose. 10 references, 3 figures, 7 tables

Polymorphisms in phase I and phase II genes and breast cancer risk and relations to persistent organic pollutant exposure

DEFF Research Database (Denmark)

Ghisari, Mandana; Eiberg, Hans; Long, Manhai

2014-01-01

BACKGROUND: We have previously reported that chemicals belonging to the persistent organic pollutants (POPs) such as perfluorinated compounds (PFAS) and polychlorinated biphenyls (PCBs) are risk factors in Breast Cancer (BC) development in Greenlandic Inuit women. The present case-control study...... on BC risk in Greenlandic Inuit women. METHODS: The study population consisted of 31 BC cases and 115 matched controls, with information on serum levels of POPs. Genotyping was conducted for CYP1A1 (Ile462Val; rs1048943), CYP1B1 (Leu432Val; rs1056836), COMT (Val158Met; rs4680), CYP17A1 (A1> A2; rs743572...... aimed to investigate the main effect of polymorphisms in genes involved in xenobiotic metabolism and estrogen biosynthesis, CYP1A1, CYP1B1, COMT and CYP17, CYP19 and the BRCA1 founder mutation in relation to BC risk and to explore possible interactions between the gene polymorphisms and serum POP levels...

Physiological studies in aerobic batch cultivations of Saccharomyces cerevisiae strains harboring the MEL1 gene

DEFF Research Database (Denmark)

Østergaard, Simon; Roca, Christophe Francois Aime; Ronnow, B.

2000-01-01

Physiological studies of Saccharomyces cerevisiae strains harboring the MEL1 gene were carried out in aerobic batch cultivations on glucose-galactose mixtures and on the disaccharide melibiose, which is hydrolyzed by the enzyme melibiase (Mel1, EC 3.2.1.22) into a glucose and a galactose moiety...... rates were 2.5-3.3-fold higher on glucose than on galactose for all the strains examined, and hence, ethanol production was pronounced on glucose due to respiro-fermentative metabolism. The T256 strain and the T200 strain having the MEL1 gene inserted in the HXK2 locus and the LEU2 locus, respectively...

Neutronic and thermo-hydraulic design of LEU core for Japan Research Reactor 4

International Nuclear Information System (INIS)

Arigane, Kenji; Watanabe, Shukichi; Tsuruta, Harumichi

1988-04-01

As a part of the Reduced Enrichment Research and Test Reactor (RERTR) program in JAERI, the enrichment reduction for Japan Research Reactor 4 (JRR-4) is in progress. A fuel element using a 19.75 % enriched UAlx-Al dispersion type with a uranium density of 2.2 g/cm 3 was designed as the LEU fuel and the neutronic and thermo-hydraulic performances of the LEU core were compared with those of the current HEU core. The results of the neutronic design are as follows: (1) the excess reactivity of the LEU core becomes about 1 % Δk/k less, (2) the thermal neutron flux in the fuel region decreases about 25 % on the average, (3) the thermal neutron fluxes in the irradiation pipes are almost the same and (4) the core burnup lifetime becomes about 20 % longer. The thermo-hydraulic design also shows that: (1) the fuel plate surface temperature decreases about 10 deg C due to the increase of the number of fuel plates and (2) the temperature margin with respect to the ONB temperature increases. Therefore, it is confirmed that the same utilization performance as the HEU core is attainable with the LEU core. (author)

242-A Campaign 94-1 post run document

International Nuclear Information System (INIS)

Guthrie, M.D.

1994-01-01

The purpose of this post-run document is to summarize the results of 242-A Evaporator Campaign 94-1 as required. Campaign 94-1 represents the first Evaporator operation since 1989, following completion of the B-534 upgrades and Liquid Effluent Retention Facility (LERF) construction. The purpose of Campaign 94-1 was to concentrate dilute waste from TK-102-AW, TK-106-AW, and TK-103-AP. From an available 2.87 million gallon feedstock of dilute waste contained in 102-AW, 106-AW and 103-AP, an overall Waste Volume Reduction (WVR) of 2.39 million gallons (83% WVRF) was achieved. At the completion of the campaign, approximately 477,000 gallons of dilute double-shell slurry feed (DDSSF) was produced with a SpG. of 1.25--1.30. Total process condensate discharged to LERF was 3.09 million gallons, achieving a condensate/WVR ratio of 1.29. Throughput for Campaign 94-1 was 5.27 million gallons. Total steam condensate and cooling water discharge to B-pond was 4.7 and 216 million gallons respectively. The evaporator operated approximately 43 days of the 60 day campaign for a total operating efficiency of 73%. Campaign 94-1 was completed without any discharge limit, Operating Specification Document, or Operational Safety Requirement violations. Major problems encountered during the run included the following: (1) high CA1 deentrainment pad dP's caused by foaming, (2) condensate pump P-C100 failure, and (3) ion exchange column dP's and efficiency

Analysis of the TREAT LEU Conceptual Design

Energy Technology Data Exchange (ETDEWEB)

Connaway, H. M. [Argonne National Lab. (ANL), Argonne, IL (United States); Kontogeorgakos, D. C. [Argonne National Lab. (ANL), Argonne, IL (United States); Papadias, D. D. [Argonne National Lab. (ANL), Argonne, IL (United States); Brunett, A. J. [Argonne National Lab. (ANL), Argonne, IL (United States); Mo, K. [Argonne National Lab. (ANL), Argonne, IL (United States); Strons, P. S. [Argonne National Lab. (ANL), Argonne, IL (United States); Fei, T. [Argonne National Lab. (ANL), Argonne, IL (United States); Wright, A. E. [Argonne National Lab. (ANL), Argonne, IL (United States)

2016-03-01

Analyses were performed to evaluate the performance of the low enriched uranium (LEU) conceptual design fuel for the conversion of the Transient Reactor Test Facility (TREAT) from its current highly enriched uranium (HEU) fuel. TREAT is an experimental nuclear reactor designed to produce high neutron flux transients for the testing of reactor fuels and other materials. TREAT is currently in non-operational standby, but is being restarted under the U.S. Department of Energy’s Resumption of Transient Testing Program. The conversion of TREAT is being pursued in keeping with the mission of the Department of Energy National Nuclear Security Administration’s Material Management and Minimization (M3) Reactor Conversion Program. The focus of this study was to demonstrate that the converted LEU core is capable of maintaining the performance of the existing HEU core, while continuing to operate safely. Neutronic and thermal hydraulic simulations have been performed to evaluate the performance of the LEU conceptual-design core under both steady-state and transient conditions, for both normal operation and reactivity insertion accident scenarios. In addition, ancillary safety analyses which were performed for previous LEU design concepts have been reviewed and updated as-needed, in order to evaluate if the converted LEU core will function safely with all existing facility systems. Simulations were also performed to evaluate the detailed behavior of the UO₂-graphite fuel, to support future fuel manufacturing decisions regarding particle size specifications. The results of these analyses will be used in conjunction with work being performed at Idaho National Laboratory and Los Alamos National Laboratory, in order to develop the Conceptual Design Report project deliverable.

The ORR Whole-Core LEU Fuel Demonstration

International Nuclear Information System (INIS)

Bretscher, M.M.; Snelgrove, J.L.

1990-01-01

The ORR Whole-Core LEU Fuel Demonstration, conducted as part of the US Reduced Enrichment Research and Test Reactor Program, has been successfully completed. Using commercially-fabricated U 3 Si 2 -Al 20%-enriched fuel elements (4.8 g U/cc) and fuel followers (3.5 g U/cc), the 30-MW Oak Ridge Research Reactor was safely converted from an all-HEU core, through a series of HEU/LEU mixed transition cores, to an all-LEU core. There were no fuel element failures and average discharge burnups were measured to be as high as 50% for the standard elements and 75% for the fuel followers. Experimental results for burnup-dependent critical configurations, cycle-averaged fuel element powers, and fuel-element-averaged 235 U burnups validated predictions based on three-dimensional depletion calculations. Calculated values for plutonium production and isotopic mass ratios as functions of 235 U burnup support the corresponding measured quantities. In general, calculations for reaction rate distributions, control rod worths, prompt neutron decay constants, and isothermal temperature coefficients were found to agree with corresponding measured values. Experimentally determined critical configurations for fresh HEU and LEU cores radially reflected with water and with beryllium are well-predicted by both Monte Carlo and diffusion calculations. 17 refs

Oral delivery of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics: Immunofluorescent localization in the mouse hypothalamus.

Science.gov (United States)

Anderson, Brian M; Jacobson, Lauren; Novakovic, Zachary M; Grasso, Patricia

2017-06-01

This study describes the localization of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3, synthetic peptide leptin mimetics, in the hypothalamus of Swiss Webster and C57BL/6J wild-type mice, leptin-deficient ob/ob mice, and leptin-resistant diet-induced obese (DIO) mice. The mice were given [D-Leu-4]-OB3 or MA-[D-Leu-4]-OB3 in 0.3% dodecyl maltoside by oral gavage. Once peak serum concentrations were reached, the mice received a lethal dose of pentobarbital and were subjected to intracardiac perfusion fixation. The brains were excised, post-fixed in paraformaldehyde, and cryo-protected in sucrose. Free-floating frozen coronal sections were cut at 25-µm and processed for imaging by immunofluorescence microscopy. In all four strains of mice, dense staining was concentrated in the area of the median eminence, at the base and/or along the inner wall of the third ventricle, and in the brain parenchyma at the level of the arcuate nucleus. These results indicate that [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 cross the blood-brain barrier and concentrate in an area of the hypothalamus known to regulate energy balance and glucose homeostasis. Most noteworthy is the localization of [D-Leu-4]-OB3 immunoreactivity within the hypothalamus of DIO mice via a conduit that is closed to leptin in this rodent model, and in most cases of human obesity. Together with our previous studies describing the effects of [D-Leu-4]-OB3 and MA-[D-Leu-4]-OB3 on energy balance, glucose regulation, and signal transduction pathway activation, these findings are consistent with a central mechanism of action for these synthetic peptide leptin mimetics, and suggest their potential usefulness in the management of leptin-resistant obesity and type 2 diabetes in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Cardiac abnormalities in diabetic patients with mutation in the mitochondrial tRNA {sup Leu(UUR)}Gene

Energy Technology Data Exchange (ETDEWEB)

Ueno, Hiroshi [Hyogo Medical Center for Adults, Akashi (Japan); Shiotani, Hideyuki

1999-11-01

An A-to-G transition at position 3243 of the mitochondrial DNA is known to be a pathogenic factor for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), diabetes and cardiomyopathy. This mutation causes dysfunction of the central nervous system in MELAS. Because the heart, as well as the brain and nervous system, is highly dependent on the energy produced by mitochondrial oxidation, these tissues are more vulnerable to mitochondrial defects. Cardiac abnormalities were assessed in 10 diabetic patients associated with this mutation using echocardiography and {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, and compared with 19 diabetic patients without the mutation. Duration of diabetes, therapy, control of blood glucose and diabetic complications, such as diabetic retinopathy and nephropathy, were not different between the 2 groups. Diabetic patients with the mutation had a significantly thicker interventricular septum (16.8{+-}3.7 vs 11.0{+-}1.6 mm, p<0.001) than those without the mutation. Fractional shortening was lower in diabetic patients with the mutation than those without it (30.7{+-}7.0 vs 42.5{+-}6.6, p<0.001). MIBG uptake on the delayed MIBG image was significantly lower in diabetic patients with the mutation than in those without the mutation (mean value of the heart to mediastinum ratio: 1.6{+-}0.2 vs 2.0{+-}0.4, p>0.05). In conclusion, left ventricular hypertrophy with or without abnormal wall motion and severely reduced MIBG uptake may be characteristic in diabetic patients with a mutation in the mitochondrial tRNA {sup Leu(UUR)} gene. (author)

The Emergence of Quinolone Resistant Shigella sonnei, Pondicherry, India.

Directory of Open Access Journals (Sweden)

Ankita Das

Full Text Available Ciprofloxacin resistant Shigella sonnei across the globe have been increasing alarmingly. In order to understand the emergence of S.sonnei with respect to ciprofloxacin resistance in our patient population, the following study was carried out. Of the 184 Shigella sp. Isolated from 2012 to 2015, 34 S.sonnei which were confirmed by standard methods and subjected to antimicrobial susceptibility testing were selected. The minimum inhibitory concentrations (MICs of 16/34 quinolone resistant isolates tested ranged from 4micrograms/ml to 16micrograms/ml for ciprofloxacin, from 16 micrograms/ml to 64 micrograms/ml for ofloxacin and from 16micrograms/ml to 64micrograms/ml for levofloxacin. Sequence determination of the quinolone resistance determining regions of gyrA, gyrB, parC, and parE genes showed mutations in GyrA at Gln69/Trp, Phe71/Ser, Ser72/Pro, Met75/Leu, Ser90/Cys, Met94/Leu, His106/Pro, Asn161/His, Thr163/Ala and in ParC at Ala64/Asp. Among the plasmid-mediated quinolone resistance (PMQRs targets investigated,qnrB was the most (93.7% prevalent followed by qnrC (18.7%. None hadqnrA, qnrS and qepA. Two (0.1% of the isolates harboured theaac(6'-lb gene. Drug accumulation assay detected the presence of efflux pump activity in 9/15 (60% among ciprofloxacin resistant isolates. All isolates harboured the ipaH gene followed by ial (17.6%, sen (11.7%, set1A&set1B (5.8% genes. None had stx1 element. PCR for Enterobacterial repetitive intergenic consensus (ERIC sequences resulted in 4 unique clusters, of which Type III was the most (44% dominant but there was no correlation between the ERIC types and the antibiotic resistance pattern or the virulence profile. A documented increase in S.sonnei harbouring the qnrgenes and some unusual genes like set1Aand indicate an ongoing process of horizontal gene transfer. The accumulation of novel mutations in GyrA and ParC in the presence of efflux pump and PMQR genes contributed to the raised MIC to quinolones

Whole-core LEU fuel demonstration in the ORR

International Nuclear Information System (INIS)

Snelgrove, J.L.; Bretscher, M.M.; Cornella, R.J.; Hobbs, R.W.

1985-01-01

A whole-core demonstration of LEU fuel in the ORR is expected to begin during November 1985. Fuel elements will contain U 3 Si 2 at 4.8 Mg U/m 3 and shim rod fuel followers will contain U 3 Si 2 at 3.5 Mg U/m 3 . Fuel fabrication is underway at B and W, CERCA, and NUKEM, with shipments scheduled to commence in October. The primary objectives of the demonstration are to provide data for validation of LEU and mixed-core fuel cycle calculations and to provide a large-scale demonstration of the acceptable performance of production-line U 3 Si 2 fuel elements. It is planned to approach the full LEU core through a series of mixed cores. Measurements to be made include flux distribution, reactivity swing, control rod worths, cycle length, fuel discharge burnup, gamma heating rates, β/sub eff/l, and isothermal temperature coefficient. Measurements will also be made on fresh LEU and fresh HEU critical configurations. Preliminary safety approval has been received and the final safety assessment is being reviewed

Standardization of specifications and inspection procedures for LEU plate-type research reactor fuels

International Nuclear Information System (INIS)

1988-06-01

With the transition to high density uranium LEU fuel, fabrication costs of research reactor fuel elements have a tendency to increase because of two reasons. First, the amount of the powder of the uranium compound required increases by more than a factor of five. Second, fabrication requirements are in many cases nearer the fabrication limits. Therefore, it is important that measures be undertaken to eliminate or reduce unnecessary requirements in the specification or inspection procedures of research reactor fuel elements utilizing LEU. An additional stimulus for standardizing specifications and inspection procedures at this time is provided by the fact that most LEU conversions will occur within a short time span, and that nearly all of them will require preparation of new specifications and inspection procedures. In this sense, the LEU conversions offer an opportunity for improving the rationality and efficiency of the fuel fabrication and inspection processes. This report focuses on the standardization of specifications and inspection processes of high uranium density LEU fuels for research reactors. However, in many cases the results can also be extended directly to other research reactor fuels. 15 refs, 1 fig., 3 tabs

Preliminary design study for a carbide LEU-nuclear thermal rocket

International Nuclear Information System (INIS)

Venneri, P.F.; Kim, Y.

2014-01-01

Nuclear space propulsion is a requirement for the successful exploration of the solar system. It offers the possibility of having both a high specific impulse and a relatively high thrust, allowing rapid transit times with a minimum usage of fuel. This paper proposes a nuclear thermal rocket design based on heritage NERVA rockets that makes use of Low Enriched Uranium (LEU) fuel. The Carbide LEU Nuclear Thermal Rocket (C-LEU-NTR) is designed to fulfill the rocket requirements as set forth in the NASA 2009 Mars Mission Design Reference Architecture 5.0, that is provide 25,000 lbf of thrust, operate at full power condition for at least two hours, and have a specific impulse close to 900 s. The neutronics analysis was done using MCNP5 with the ENDF/B-VII.1 neutron library. The thermal hydraulic calculations and size optimization were completed with a finite difference code being developed at the Center for Space Nuclear Research. (authors)

Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T], A Second and Third Case Described in Two Unrelated Dutch Families

NARCIS (Netherlands)

Pondman, Kirsten M.; Brinkman, Jacoline W.; van der Straaten, Hanneke M.; Stroobants, An K.; Harteveld, Cornelis L.

2018-01-01

We report two families, members of which are carriers of a hemoglobin (Hb) variant previously described as Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T; p.Pro115Leu]. In the first family of Dutch origin, the proband, a 32-year-old male and his 65-year-old father, were both carriers of Hb

Lack of association between urotensin-II (UTS2 gene polymorphisms (Thr21Met and Ser89Asn and migraine

Directory of Open Access Journals (Sweden)

Betül Ozan

2017-08-01

Full Text Available Migraine is a common neurovascular brain disorder with heterogeneous clinical presentation, including recurrent headache attacks. The pathophysiology of migraine is complex, and a number of genomic regions have been associated with the development of migraine. In this study, we analyzed the allele and genotype frequencies of the urotensin-II gene (UTS2 polymorphisms, Thr21Met and Ser89Asn, among Turkish patients with migraine. A total of 146 patients with migraine (14 with aura [MA group] and 132 without aura [MO group] were genotyped for Thr21Met and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. No significant differences were observed in allele and genotype frequencies for Thr21Met and Ser89Asn polymorphisms between the patients with migraine and control group. Similarly, we did not observe significant differences in allele and genotype frequencies between MA and MO and control group. Moreover, the haplotype analysis showed no association between UTS2 gene haplotypes (MN, MS, TN, and TS and migraine. In summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk factors for migraine in our sample of Turkish migraine patients.

Data Compilation for AGR-1 Baseline Coated Particle Composite LEU01-46T

International Nuclear Information System (INIS)

Hunn, John D.; Lowden, Richard Andrew

2006-01-01

This document is a compilation of characterization data for the AGR-1 baseline coated particle composite LEU01-46T, a composite of four batches of TRISO-coated 350 (micro)m 19.7% low enrichment uranium oxide/uranium carbide kernels (LEUCO). The AGR-1 TRISO-coated particles consist of a spherical kernel coated with a ∼ 50% dense carbon buffer layer (100 (micro)m nominal thickness) followed by a dense inner pyrocarbonlayer (40 (micro)m nominal thickness) followed by a SiC layer (35 (micro)m nominal thickness) followed by another dense outer pyrocarbon layer (40 (micro)m nominal thickness). The coated particles, were produced by ORNL for the Advanced Gas Reactor Fuel Development and Qualification (AGR) program to be put into compacts for insertion in the first irradiation test capsule, AGR-1. The kernels were obtained from BWXT and identified as composite (G73D-20-69302). The BWXT kernel lot G73D-20-69302 was riffled into sublots for characterization and coating by ORNL and identified as LEU01-?? (where ?? is a series of integers beginning with 01). Additional particle batches were coated with only buffer or buffer plus inner pyrocarbon (IPyC) layers using similar process conditions as used for the full TRISO batches comprising the LEU01-46T composite. These batches were fabricated in order to qualify that the process conditions used for buffer and IPyC would produce acceptable densities, as described in sections 8 and 9. These qualifying batches used 350 (micro)m natural uranium oxide/uranium carbide kernels (NUCO). The kernels were obtained from BWXT and identified as composite G73B-NU-69300. The use of NUCO surrogate kernels is not expected to significantly effect the densities of the buffer and IPyC coatings. Confirmatory batches using LEUCO kernels from G73D-20-69302 were coated and characterized to verify this assumption. The AGR-1 Fuel Product Specification and Characterization Guidance (INL EDF-4380, Rev. 6) provides the requirements necessary for acceptance

Nascent peptide-mediated translation elongation arrest coupled with mRNA degradation in the CGS1 gene of Arabidopsis

Science.gov (United States)

Onouchi, Hitoshi; Nagami, Yoko; Haraguchi, Yuhi; Nakamoto, Mari; Nishimura, Yoshiko; Sakurai, Ryoko; Nagao, Nobuhiro; Kawasaki, Daisuke; Kadokura, Yoshitomo; Naito, Satoshi

2005-01-01

Expression of the Arabidopsis CGS1 gene that codes for cystathionine γ-synthase is feedback regulated at the step of mRNA stability in response to S-adenosyl-L-methionine (AdoMet). A short stretch of amino acid sequence, called the MTO1 region, encoded by the first exon of CGS1 itself is involved in this regulation. Here, we demonstrate, using a cell-free system, that AdoMet induces temporal translation elongation arrest at the Ser-94 codon located immediately downstream of the MTO1 region, by analyzing a translation intermediate and performing primer extension inhibition (toeprint) analysis. This translation arrest precedes the formation of a degradation intermediate of CGS1 mRNA, which has its 5′ end points near the 5′ edge of the stalled ribosome. The position of ribosome stalling also suggests that the MTO1 region in nascent peptide resides in the ribosomal exit tunnel when translation elongation is temporarily arrested. In addition to the MTO1 region amino acid sequence, downstream Trp-93 is also important for the AdoMet-induced translation arrest. This is the first example of nascent peptide-mediated translation elongation arrest coupled with mRNA degradation in eukaryotes. Furthermore, our data suggest that the ribosome stalls at the step of translocation rather than at the step of peptidyl transfer. PMID:16027170

Preliminary investigations for technology assessment of 99Mo production from LEU [low enriched uranium] targets

International Nuclear Information System (INIS)

Vandegrift, G.F.; Chaiko, D.J.; Heinrich, R.R.; Kucera, E.T.; Jensen, K.J.; Poa, D.S.; Varma, R.; Vissers, D.R.

1986-11-01

This paper presents the results of preliminary studies on the effects of substituting low enriched uranium (LEU) for highly enriched uranium (HEU) in targets for the production of fission product 99 Mo. Issues that were addressed are: (1) purity and yield of the 99 Mo//sup 99m/Tc product, (2) fabrication of LEU targets and related concerns, and (3) radioactive waste. Laboratory experimentation was part of the efforts for issues (1) and (2); thus far, radioactive waste disposal has only been addressed in a paper study. Although the reported results are still preliminary, there is reason to be optimistic about the feasibility of utilizing LEU targets for 99 Mo production. 37 refs., 1 fig., 5 tabs

Nota sobre un modelo de J. D. Hey para una empresa bajo incertidumbre en el precio que no busca necesariamente maximizar el beneficio

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Alberto A. Álvarez López

2000-01-01

Full Text Available En el trabajo de Holthausen (1979 se estudia el comportamiento de una empresa competitiva bajo incertidumbre en el precio que tiene la opci´on de operar en un mercado de futuros. En el art´ıculo de Hey (1981b, el autor extiende este modelo al considerar una empresa que, en vez de buscar maximizar el beneficio (como la empresa original, busca maximizar el rendimiento neto por trabajador (labor-managed firm. En el presente trabajo estudiamos ciertos aspectos relacionados con la empresa del modelo de Hey no tratados por el autor, ni tampoco tratados en el contexto del trabajo original de Holthausen.

Supply of low enriched (LEU) and highly enriched uranium (HEU) for research reactors

International Nuclear Information System (INIS)

Mueller, H.

1997-01-01

Enriched uranium for research reactors in the form of LEU /= low enriched uranium at 19.75% U-235) and HEU (= highly enriched uranium at 90 to 93% U-235) was and is - due to its high U-235 enrichment - a political fuel other than enriched uranium for power reactors. The sufficient availability of LEU and HEU is a vital question for research reactors, especially in Europe, in order to perform their peaceful research reactor programs. In the past the USA were in the Western hemisphere sole supplier of LEU and HEU. Today the USA have de facto stopped the supply of LEU and HEU, for HEU mainly due to political reasons. This paper deals, among others, with the present availability of LEU and HEU for European research reactors and touches the following topics: - historical US supplies, - influence of the RERTR-program, - characteristics of LEU and HEU, - military HEU enters the civil market, -what is the supply situation for LEU and HEU today? - outlook for safe supplies of LEU and HEU. (author)

GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer

DEFF Research Database (Denmark)

Hansen, Rikke Dalgaard; Krath, Britta N.; Frederiksen, Kirsten

2009-01-01

polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective “Diet, Cancer and Health” study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled...... and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993–1997. GPX1 Pro198Leu, hOGG1 Ser326Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among......198Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence....

A radiological consequence analysis with HEU and LEU fuels

International Nuclear Information System (INIS)

Woodruff, W.L.; Warinner, D.K.; Matos, J.E.

1985-01-01

A model for estimating the radiological consequences from a hypothetical accident in HEU and LEU fueled research and test reactors is presented. Simple hand calculations based on fission product yield table inventories and nonsite specific dispersion data may be adequate in many cases. However, more detailed inventories and site specific data on meteorological conditions and release rates and heights can result in substantial reductions in the dose estimates. LEU fuel gives essentially the same doses as HEU fuel. The plutonium buildup in the LEU fuel does not significantly increase the radiological consequences. The dose to the thyroid is the limiting dose. (author)

Fluxes at experiment facilities in HEU and LEU designs for the FRM-II

International Nuclear Information System (INIS)

Hanan, N. A.

1998-01-01

An Alternative LEU Design for the FRM-II proposed by the RERTR Program at Argonne National Laboratory (ANL) has a compact core consisting of a single fuel element that uses LEU silicide fuel with a uranium density of 4.5 g/cm 3 and has a power level of 32 MW. Both the HEU design by the Technical University of Munich (TUM) and the alternative LEU design by ANL have the same fuel lifetime(50 days) and the same neutron flux performance (8 x 10 14 n/cm 2 -s in the reflector). LEU silicide fuel with 4.5 g/cm 3 has been thoroughly tested and is fully-qualified, licensable, and available now for use in a high flux reactor such as the FRM-II. Several issues that were raised by TUM have been addressed in Refs. 1-3. The conclusions of these analyses are summarized below. This paper addresses four additional issues that have been raised in several forums, including Ref 4: heat generation in the cold neutron source (CNS), the gamma and fast neutron fluxes which are components of the reactor noise in neutron scattering experiments in the experiment hall of the reactor, a fuel cycle length difference, and the reactivity worth of the beam tubes and other experiment facilities. The results show that: (a) for the same thermal neutron flux, the neutron and gamma heating in the CNS is smaller in the LEU design than in the HEU design, and cold neutron fluxes as good or better than those of the HEU design can be obtained with the LEU design; (b) the gamma and fast neutron components of the reactor noise in the experiment hall are about the same in both designs; (c) the fuel cycle length is 50 days for both designs; and (d) the absolute value of the reactivity worth of the beam tubes and other experiment facilities is smaller in the LEU design, allowing its fuel cycle length to be increased to 53 or 54 days. Based on the excellent results for the Alternative LEU Design that were obtained in all analyses, the RERTR Program reiterates its conclusion that there are no major technical

IRS1, TCF7L2, ADRB1, PPARG, and HHEX Polymorphisms Associated with Atherogenic Risk in Mexican Population

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B. I. Estrada-Velasco

2013-01-01

Full Text Available Objective. We aimed to explore the association between polymorphisms of IRS1 (rs1801278, TCF7L2 (rs7903146 and rs12255372, ADRB1 (rs1801253, PPARG (rs1801282, and HHEX (rs5015480 genes with atherogenic risk (AI = Total cholesterol/HDL in MetS, T2D, and healthy populations from the Mexican Social Security Institute. Methodology and Results. Four hundred thirty-five MetS, 517 T2D, and 547 healthy individuals were selected. The association between the SNPs and the atherogenic index was evaluated by multiple linear regression and multinomial logistic regression models. The ADRB1 gene showed a statistically significant association with high-risk atherogenic index, OR=2.94 (IC 95% 1.64–5.24; P<0.0001 for the Arg/Gly variant, under the dominant model an OR=2.96 (IC 95% 1.67–5.25; P<0.0001, and under the Log additive model an OR=2.52 (IC 95% 1.54–4.15; P<0.0001. Conclusions. The Arg389Gly polymorphism of the ADRB1 gene may be a worthy biological marker to predict the risk of developing cardiovascular diseases given a high-risk atherogenic index.

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese.

Science.gov (United States)

Xu, Ling-Ling; Xiang, Hong-Ding; Qiu, Chang-Chun; Xu, Qun

2008-06-01

To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects. Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

Analysis of the Ford Nuclear Reactor LEU core

Energy Technology Data Exchange (ETDEWEB)

Rathkopf, J A; Drumm, C R; Martin, W R; Lee, J C [Department of Nuclear Engineering, University of Michigan, Ann Arbor, MI (United States)

1983-09-01

This paper has summarized the current status of the effort to analyze the FNR HEU/LEU cores and to compare the calculated results with measurements. In general, calculated predictions of experimental results are quite good, especially for global parameters such as reactivity, as seen in the single HEU/LEU element substitution experiment and the LEU full core critical loading. Shim rod worths are predicted well for two of the rods but too high for a third rod possibly due to inaccurate thermal flux distribution calculation. The calculated thermal flux maps show excellent agreement with experiment throughout the FNR core. In the heavy water tank, however, experimental values for the thermal flux obtained by different methods are inconsistent among themselves as well as with the calculated finding. Work is under.way to use our computational tools to correct the discrepancies between the various measurement techniques and to improve the computational results for flux distribution and the rod worth experiment. Although uncertainties exist in our analysis, as evidenced by the discrepancies mentioned above, we consider our present calculational package to be a useful, reasonably accurate, and efficient system for performing analyses of MTR LEU/HEU core configurations.

The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review.

Science.gov (United States)

Ghalandari, Hamid; Hosseini-Esfahani, Firoozeh; Mirmiran, Parvin

2015-07-01

Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it. The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review. The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships. In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association.

Comparison of the FRM-II HEU design with an alternative LEU design

International Nuclear Information System (INIS)

Mo, S.C.; Hanan, N.A.; Matos, J.E.

2004-01-01

The FRM-II reactor design of the Technical University of Munich has a compact core that utilizes fuel plates containing highly-enriched uranium (HEU, 93%). This paper presents an alternative core design utilizing low-enriched uranium (LEU, 3 that provides nearly the same neutron flux for experiments as the HEU design, but has a less favourable fuel cycle economy. If an LEU fuel with a uranium density of 6.0 - 6.5 g/cm 3 . were developed, the alternative design would provide the same neutron flux and use the same number of cores per year as the HEU design. The results of this study show that there are attractive possibilities for using LEU fuel instead of HEU fuel in the FRM-II. Further optimization of the LEU design and near-term availability of LEU fuel with a uranium density greater than 4.8 g/cm 3 would enhance the performance of the LEU core. The REKIR Program is ready to exchange information with the Technical University of Munich to resolve any differences that may exist and to identify design modifications that would optimize reactor performance utilizing LEU fuel. (author)

Making of fission 99Mo from LEU silicide(s): A radiochemists' view

International Nuclear Information System (INIS)

Kolar, Z.I.; Wolterbeek, H.Th.

2005-01-01

The present-day industrial scale production of 99 Mo is fission based and involves thermal-neutron irradiation in research reactors of highly enriched uranium (HEU, > 20 % 235 U) containing targets, followed by radiochemical processing of the irradiated targets resulting in the final product: a 99 Mo containing chemical compound of molybdenum. In 1978 a program (RERTR) was started to develop a substitute for HEU reactor fuel i.e. a low enriched uranium (LEU, 235 U) one. In the wake of that program studies were undertaken to convert HEU into LEU based 99 Mo production. Both new targets and radiochemical treatments leading to 99 Mo compounds were proposed. One of these targets is based on LEU silicide, U 3 Si 2 . Present paper aims at comparing LEU U 3 Si 2 and LEU U 3 Si with another LEU target i.e. target material and arriving at some preferences pertaining to 99 Mo production. (author)

HEU to LEU conversion and blending facility: Metal blending alternative to produce LEU oxide for disposal

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-09-01

US DOE is examining options for disposing of surplus weapons-usable fissile materials and storage of all weapons-usable fissile materials. The nuclear material is converted to a form more proliferation- resistant than the original form. Blending HEU (highly enriched uranium) with less-enriched uranium to form LEU has been proposed as a disposition option. Five technologies are being assessed for blending HEU. This document provides data to be used in environmental impact analysis for the HEU-LEU disposition option that uses metal blending with an oxide waste product. It is divided into: mission and assumptions, conversion and blending facility descriptions, process descriptions and requirements, resource needs, employment needs, waste and emissions from plant, hazards discussion, and intersite transportation.

HEU to LEU conversion and blending facility: Metal blending alternative to produce LEU oxide for disposal

International Nuclear Information System (INIS)

1995-09-01

US DOE is examining options for disposing of surplus weapons-usable fissile materials and storage of all weapons-usable fissile materials. The nuclear material is converted to a form more proliferation- resistant than the original form. Blending HEU (highly enriched uranium) with less-enriched uranium to form LEU has been proposed as a disposition option. Five technologies are being assessed for blending HEU. This document provides data to be used in environmental impact analysis for the HEU-LEU disposition option that uses metal blending with an oxide waste product. It is divided into: mission and assumptions, conversion and blending facility descriptions, process descriptions and requirements, resource needs, employment needs, waste and emissions from plant, hazards discussion, and intersite transportation

ANL progress in developing an LEU target and process for Mo-99 production: Cooperation with CNEA

International Nuclear Information System (INIS)

Gelis, A.V.; Vandegrift, G.F.; Aase, S.B.; Bakel, A.J.; Falkenberg, J.R.; Regalbuto, M.C.; Quigley, K.J.

2003-01-01

The primary mission of the Reduced Enrichment in Research and Test Reactors (RERTR) Program is to facilitate the conversion of research and test-reactor fuel and targets from high-enriched uranium (HEU) to low-enriched uranium (LEU). One of the current goals at Argonne National Laboratory (ANL) is to assist the Argentine Comision Nacional de Energia Atomica (CNEA) in developing an LEU foil target and a process for 99 Mo production. Specifically addressed in this paper is ANL R and D related to this conversion: (1) designing a prototype production vessel for digesting irradiated LEU foils in alkaline solutions and (2) developing a new digestion method to address all issues related to HEU to LEU conversion. (author)

The whole-core LEU fuel demonstration in the ORR

International Nuclear Information System (INIS)

Snelgrove, J.L.; Bretscher, M.M.; Cornella, R.J.; Hobbs, R.W.

1985-01-01

A whole-core demonstration of LEU fuel in the ORR is expected to begin during November 1985. Fuel elements will contain U 3 Si 2 at 4.8 Mg U/m 3 and shim rod fuel followers will contain U 3 Si 2 at 3.5 Mg U/m 3 . Fuel fabrication is underway at B and W, CERCA, and NUKEM, with shipments scheduled to commence in October. The primary objectives of the demonstration are to provide data for validation of LEU and mixed-core fuel cycle calculations and to provide a large-scale demonstration of the acceptable performance of production-line U 3 Si 2 fuel elements. It is planned to approach the full LEU core through a series of mixed cores. Measurements to be made include flux distribution, reactivity swing, control rod worth, cycle length, fuel discharge burn-up, gamma heating rate, β eff /l, and isothermal temperature coefficient. Measurements will also be made on fresh LEU and fresh HEU critical configurations. Preliminary safety approval has been received and the final safety assessment is being reviewed. Key issues being addressed in the safety assessment are fuel performance, radiological consequences, margin to burnout and transient behavior. The LEU core is comparable in all safety aspects to the HEU core and the transition core is only marginally worse owing to higher power seeking factors. (author)

Neutronic calculations in core conversion of the IAN-R1 research reactor from MTR HEU to TRIGA LEU fuel

International Nuclear Information System (INIS)

Sarta Fuentes, Jose A.; Castiblanco, L.A.

2003-01-01

With cooperation of the International Atomic Energy Agency (IAEA), neutronic calculations were carried out for conversion of the Ian-R1 Reactor from MTR-HEU fuel to TRIGA-LEU fuel. In order to establish a staff for neutronic calculation at the Instituto de Cancan's Nucleares y Energia s Alternatives (INEA) a program was established. This program included training, acquisition of hardware, software and calculation for the core with MTR-HEU fuel , enriched nominally to 93% and calculation for several arrangements with the TRIGA-LEU fuel, enriched to 19.7%. The results were verified and compared with several groups of calculation at the Instituto Nacional de Investigaciones Nucleares (ININ) in Mexico, and General Atomics (GA) in United States. As a result of this program, several technical reports have been wrote. (author)

Operating experience, measurements, and analysis of the LEU whole core demonstration at the FNR

International Nuclear Information System (INIS)

Weha, D.K.; Drumm, C.R.; King, J.S.; Martin, W.R.; Lee, J.C.

1984-01-01

The 2-MW Ford Nuclear Reactor at the University of Michigan is serving as the demonstration reactor for the MTR-type low enrichment (LEU) fuel for the Reduced Enrichment for Research and Test Reactor program. Operational experience gained through six months of LEU core operation and seven months of mixed HEU-LEU core operation is presented. Subcadmium flux measurements performed with rhodium self-powered neutron detectors and iron wire activations are compared with calculations. Measured reactivity parameters are compared for HEU and LEU cores. Finally, the benchmark calculations for several HEU, LEU, and mixed HEU-LEU FNR cores and the International Atomic Energy Agency (IAEA) benchmark problem are presented. (author)

The manufacture of LEU fuel elements at Dounreay

Energy Technology Data Exchange (ETDEWEB)

Gibson, J.

1997-08-01

Two LEU test elements are being manufactured at Dounreay for test irradiation in the HFR at Petten, The Netherlands. This paper describes the installation of equipment and the development of the fabrication and inspection techniques necessary for the manufacture of LEU fuel plates. The author`s experience in overcoming the technical problems of stray fuel particles, dog-boning, uranium homogeneity and the measurement of uranium distribution is also described.

Total synthesis of fully tritiated Leu-enkephalin by enzymatic coupling

Energy Technology Data Exchange (ETDEWEB)

Hellio, F.; Lecocq, G.; Morgat, J.L.; Gueguen, P. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service de Biochimie)

1990-09-01

This paper describes the total enzymatic synthesis of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) in which all residues were labelled with tritium. Carboxypeptidase Y from Saccharomyces cerevisiae was the coupling enzyme. ({sup 3}H)-Tyr-NH{sub 2}, ({sup 3}H)-Gly-Oet, ({sup 3}H)-Phe-NH{sub 2} and ({sup 3}H)-Leu-NH{sub 2} were prepared with specific radioactivities ranging between 20 and 60 Ci/mmol (740 to 2220 GBq/mmol). Using a microscale procedure, we obtained a fully tritiated hormone having a specific radioactivity equal to 139 Ci/mmol (5143 GBq/mmol), in agreement with the summation of the specific radioactivities of constituting residue. The radioactive hormone had antigenic properties identical to those of native Leu-enkephalin. It also bound to rat brain opiate receptors like the parental hormone. (author).

Associations of MYF5 gene polymorphisms with meat quality traits in different domestic pig (Sus scrofa populations

Directory of Open Access Journals (Sweden)

Min Liu

2007-03-01

Full Text Available The MYF5 gene is first inducibly expressed in muscle cell during embryonic muscle development and plays an important role in regulating the differentiation of skeletal muscle precursors. In this study we used PCR-RFLP to investigate two pig (Sus scrofa populations (n = 302 for two MYF5 gene polymorphisms, a previously unreported novel Met-Leu shift single nucleotide polymorphism (SNP MYF5/Hsp92II located on exon 1 and the previously identified intron 1 MYF5/HinfI SNP. Haplotype and association analysis showed that haplotypes of the two SNPs were significantly associated with drip loss rate (DLR, p < 0.05, water holding capacity (WHC, p < 0.05, biceps femoris meat color value (MCV2, p < 0.05, biceps femoris marbling score (MM2, p < 0.01, longissimus dorsi intramuscular fat percentage (IMF, p < 0.01 and longissimus dorsi Water moisture content (WM, p < 0.01 in the population 2. However, further studies are needed to confirm these preliminary results.

Targeting MET Amplification as a New Oncogenic Driver

International Nuclear Information System (INIS)

Kawakami, Hisato; Okamoto, Isamu; Okamoto, Wataru; Tanizaki, Junko; Nakagawa, Kazuhiko; Nishio, Kazuto

2014-01-01

Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy

Targeting MET Amplification as a New Oncogenic Driver

Energy Technology Data Exchange (ETDEWEB)

Kawakami, Hisato [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okamoto, Isamu, E-mail: okamotoi@kokyu.med.kyushu-u.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582 (Japan); Okamoto, Wataru [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Transrlational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 (Japan); Tanizaki, Junko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, HIM223, 450 Brookline Avenue, Boston, MA 02215 (United States); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan)

2014-07-22

Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

Mutations at the S1 sites of methionine aminopeptidases from Escherichia coli and Homo sapiens reveal the residues critical for substrate specificity.

Science.gov (United States)

Li, Jing-Ya; Cui, Yong-Mei; Chen, Ling-Ling; Gu, Min; Li, Jia; Nan, Fa-Jun; Ye, Qi-Zhuang

2004-05-14

Methionine aminopeptidase (MetAP) catalyzes the removal of methionine from newly synthesized polypeptides. MetAP carries out this cleavage with high precision, and Met is the only natural amino acid residue at the N terminus that is accepted, although type I and type II MetAPs use two different sets of residues to form the hydrophobic S1 site. Characteristics of the S1 binding pocket in type I MetAP were investigated by systematic mutation of each of the seven S1 residues in Escherichia coli MetAP type I (EcMetAP1) and human MetAP type I (HsMetAP1). We found that Tyr-65 and Trp-221 in EcMetAP1, as well as the corresponding residues Phe-197 and Trp-352 in HsMetAP1, were essential for the hydrolysis of a thiopeptolide substrate, Met-S-Gly-Phe. Mutation of Phe-191 to Ala in HsMetAP1 caused inactivity in contrast to the full activity of EcMetAP1(Y62A), which may suggest a subtle difference between the two type I enzymes. The more striking finding is that mutation of Cys-70 in EcMetAP1 or Cys-202 in HsMetAP1 opens up the S1 pocket. The thiopeptolides Leu-S-Gly-Phe and Phe-S-Gly-Phe, with previously unacceptable Leu or Phe as the N-terminal residue, became efficient substrates of EcMetAP1(C70A) and HsMetAP1(C202A). The relaxed specificity shown in these S1 site mutants for the N-terminal residues was confirmed by hydrolysis of peptide substrates and inhibition by reaction products. The structural features at the enzyme active site will be useful information for designing specific MetAP inhibitors for therapeutic applications.

Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility.

Science.gov (United States)

Geber, A; Hitchcock, C A; Swartz, J E; Pullen, F S; Marsden, K E; Kwon-Chung, K J; Bennett, J E

1995-01-01

We have cloned and sequenced the structural genes encoding the delta 5,6 sterol desaturase (ERG3 gene) and the 14 alpha-methyl sterol demethylase (ERG11 gene) from Candida glabrata L5 (leu2). Single and double mutants of these genes were created by gene deletion. The phenotypes of these mutants, including sterol profiles, aerobic viabilities, antifungal susceptibilities, and generation times, were studied. Strain L5D (erg3 delta::LEU2) accumulated mainly ergosta-7,22-dien-3 beta-ol, was aerobically viable, and remained susceptible to antifungal agents but had a slower generation time than its parent strain. L5LUD (LEU2 erg11 delta::URA3) strains required medium supplemented with ergosterol and an anaerobic environment for growth. A spontaneous aerobically viable mutant, L5LUD40R (LEU erg11 delta::URA3), obtained from L5LUD (LEU2 erg11 delta::URA3), was found to accumulate lanosterol and obtusifoliol, was resistant to azole antifungal agents, demonstrated some increase in resistance to amphotericin B, and exhibited a 1.86-fold increase in generation time in comparison with L5 (leu2). The double-deletion mutant L5DUD61 (erg3 delta::LEU2 erg11 delta::URA3) was aerobically viable, produced mainly 14 alpha-methyl fecosterol, and had the same antifungal susceptibility pattern as L5LUD40R (LEU2 erg11 delta::URA3), and its generation time was threefold greater than that of L5 (leu2). Northern (RNA) analysis revealed that the single-deletion mutants had a marked increase in message for the undeleted ERG3 and ERG11 genes. These results indicate that differences in antifungal susceptibilities and the restoration of aerobic viability exist between the C. glabrata ergosterol mutants created in this study and those sterol mutants with similar genetic lesions previously reported for Saccharomyces cerevisiae. PMID:8593007

OTULIN antagonizes LUBAC signaling by specifically hydrolyzing met1-linked polyubiquitin

DEFF Research Database (Denmark)

Keusekotten, K.; Elliott, P.R.; Kulathu, Y.

2013-01-01

The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has...... not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate...

ANL progress in developing a target and process for converting CNEA Mo-99 production to LEU

International Nuclear Information System (INIS)

Vandegrift, G.F.; Gelis, A.; Aase, S.; Bakel, A.; Freiberg, E.; Conner, C.

2002-01-01

The primary mission of the Reduced Enrichment in Research and Test Reactors (RERTR) Program is to facilitate the conversion of research and test reactor fuel and targets from high-enriched uranium (HEU) to low-enriched uranium (LEU). One of the current goals at Argonne National Laboratory (ANL) is to convert 99 Mo production at Argentine Commission Nacional de Energia Atomica (CNEA) from HEU to LEU targets. Specifically addressed in this paper is ANL R and D related to this conversion: (1) designing a prototype production vessel for digesting irradiated LEU foils in alkaline solutions, (2) developing means to improve digestion efficiency, and (3) modifying ion-exchange processes used in the CNEA recovery and purification of 99 Mo to deal with the lower volumes generated from LEU-foil digestion. (author)

HEU to LEU conversion and blending facility: UNH blending alternative to produce LEU oxide for disposal

International Nuclear Information System (INIS)

1995-09-01

The United States Department of Energy (DOE) is examining options for the disposition of surplus weapons-usable fissile materials and storage of all weapons-usable fissile materials. Disposition is a process of use or disposal of material that results in the material being converted to a form that is substantially and inherently more proliferation-resistant than is the original form. Examining options for increasing the proliferation resistance of highly enriched uranium (HEU) is part of this effort. This report provides data to be used in the environmental impact analysis for the uranyl nitrate hexahydrate blending option to produce oxide for disposal. This the Conversion and Blending Facility (CBF) alternative will have two missions (1) convert HEU materials into HEU uranyl nitrate (UNH) and (2) blend the HEU uranyl nitrate with depleted and natural assay uranyl nitrate to produce an oxide that can be stored until an acceptable disposal approach is available. The primary emphasis of this blending operation will be to destroy the weapons capability of large, surplus stockpiles of HEU. The blended LEU product can only be made weapons capable again by the uranium enrichment process. The blended LEU will be produced as a waste suitable for storage or disposal

HEU to LEU conversion and blending facility: UNH blending alternative to produce LEU oxide for disposal

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-09-01

The United States Department of Energy (DOE) is examining options for the disposition of surplus weapons-usable fissile materials and storage of all weapons-usable fissile materials. Disposition is a process of use or disposal of material that results in the material being converted to a form that is substantially and inherently more proliferation-resistant than is the original form. Examining options for increasing the proliferation resistance of highly enriched uranium (HEU) is part of this effort. This report provides data to be used in the environmental impact analysis for the uranyl nitrate hexahydrate blending option to produce oxide for disposal. This the Conversion and Blending Facility (CBF) alternative will have two missions (1) convert HEU materials into HEU uranyl nitrate (UNH) and (2) blend the HEU uranyl nitrate with depleted and natural assay uranyl nitrate to produce an oxide that can be stored until an acceptable disposal approach is available. The primary emphasis of this blending operation will be to destroy the weapons capability of large, surplus stockpiles of HEU. The blended LEU product can only be made weapons capable again by the uranium enrichment process. The blended LEU will be produced as a waste suitable for storage or disposal.

Milk protein responses to balanced amino acid and removal of Leucine and Arginine supplied from jugular-infused amino acid mixture in lactating dairy cows.

Science.gov (United States)

Tian, W; Wang, H R; Wu, T Y; Ding, L Y; Zhao, R; Khas, E; Wang, C F; Zhang, F Q; Mi, F Y; Wang, L; Ning, L T

2017-10-01

This study was undertaken to evaluate the milk protein response when cows were supplied a balanced AA profile and to determine whether a deficiency of Leucine (Leu) or Arginine (Arg) had a negative effect on milk protein. Eight mid-lactation Holstein cows were randomly assigned to 5-day continuous jugular infusions of saline (CTL), EAA mixture prepared on the profile of casein and supplied (in % of lysine (Lys)) 100% of Lys, 33.3% of methionine (Met), 110.2% of Leu, 43.6% of Arg, 50.8% of threonine (Thr), 81.6% of valine (Val), 69.7% of isoleucine (Ile), 61.4% of phenylalanine (Phe) and 34.2% of histidine (His) (Casein, 160 g/d), EAA mixture excluding Leu (-Leu, 163 g/d) or EAA mixture excluding Arg (-Arg, 158 g/d) in a duplicated 4 × 4 Latin square design with four infusion periods separated by 7-day interval period. The basal diet supplied 1.6 Mcal NE L and 94.4 g MP per 1 kg DM to meet requirements for lactation. The Casein treatment provided a balanced supply (in % of MP) of 10.3% Leu and 5.3% Arg, whereas in the two subsequent -Leu and -Arg treatments, the concentration of Leu and Arg was reduced to 8.4 and 4.6% respectively. Dry matter intake (15.4 kg/day) was not affected by treatments. The Casein treatment increased milk yield (14.9%, p < 0.001), milk protein yield (120 g, p < 0.001) and milk protein efficiency (0.03, p = 0.099) than CTL treatment. However, the -Leu treatment decreased the responses of above-measured parameters by 6.25%, 70 g, 0.05 (p < 0.06) (compared with Casein). These effects of Leu were related to decreased Leu concentration and improved concentration of Ile and Val in plasma. The -Arg treatment decreased the plasma Arg concentration than the Casein treatment, whereby resulted in the decrease of milk yield (5.7%, p = 0.073), milk protein yield (60 g, p = 0.011) and milk protein efficiency (0.04, p = 0.037). In conclusion, supply of EAA profile of casein can increase the lactation production in dairy cows, and 8

The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma

International Nuclear Information System (INIS)

Revet, Ingrid; Huizenga, Gerda; Chan, Alvin; Koster, Jan; Volckmann, Richard; Sluis, Peter van; Ora, Ingrid; Versteeg, Rogier; Geerts, Dirk

2008-01-01

Neuroblastoma is an embryonal tumour of the peripheral sympathetic nervous system (SNS). One of the master regulator genes for peripheral SNS differentiation, the homeobox transcription factor PHOX2B, is mutated in familiar and sporadic neuroblastomas. Here we report that inducible expression of PHOX2B in the neuroblastoma cell line SJNB-8 down-regulates MSX1, a homeobox gene important for embryonic neural crest development. Inducible expression of MSX1 in SJNB-8 caused inhibition of both cell proliferation and colony formation in soft agar. Affymetrix micro-array and Northern blot analysis demonstrated that MSX1 strongly up-regulated the Delta-Notch pathway genes DLK1, NOTCH3, and HEY1. In addition, the proneural gene NEUROD1 was down-regulated. Western blot analysis showed that MSX1 induction caused cleavage of the NOTCH3 protein to its activated form, further confirming activation of the Delta-Notch pathway. These experiments describe for the first time regulation of the Delta-Notch pathway by MSX1, and connect these genes to the PHOX2B oncogene, indicative of a role in neuroblastoma biology. Affymetrix micro-array analysis of a neuroblastic tumour series consisting of neuroblastomas and the more benign ganglioneuromas showed that MSX1, NOTCH3 and HEY1 are more highly expressed in ganglioneuromas. This suggests a block in differentiation of these tumours at distinct developmental stages or lineages

Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.

Science.gov (United States)

Tavera-Tapia, A; Pérez-Cabornero, L; Macías, J A; Ceballos, M I; Roncador, G; de la Hoya, M; Barroso, A; Felipe-Ponce, V; Serrano-Blanch, R; Hinojo, C; Miramar-Gallart, M D; Urioste, M; Caldés, T; Santillan-Garzón, S; Benitez, J; Osorio, A

2017-02-01

There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX). A case-control association study was performed to establish its prevalence in Spanish population, in a series of 1477 BRCAX families and 589 controls further screened, and NGS panels were used for ATM mutational screening in a cohort of 392 HBOC Spanish BRCAX families and 350 patients affected with diseases not related to breast cancer. Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited. ATM mutation prevalence in Spanish population highlights the importance of considering ATM pathogenic variants linked to breast cancer susceptibility.

GLUTATHIONE PEROXIDASE-1 PRO200LEU POLYMORPHISM (RS1050450) IS ASSOCIATED WITH MORBID OBESITY INDEPENDENTLY OF THE PRESENCE OF PREDIABETES OR DIABETES IN WOMEN FROM CENTRAL MEXICO.

Science.gov (United States)

Hernández Guerrero, César; Hernández Chávez, Paulina; Martínez Castro, Noemí; Parra Carriedo, Alicia; García Del Rio, Sandra; Pérez Lizaur, Ana

2015-10-01

obesity affects more than a third of Mexican population. Oxidative stress participates actively in the etiology of this phenomenon. Glutathione peroxidase-1 (GPX-1) plays a protective role against oxidative stress. The SNP Pro200Leu (rs10504050) has been reported to affect the activity of the enzyme. to determine the frequency of rs10504050 polymorphism in women with obesity and normal weight control, asses the concentration of peripheral TBARS and evaluate the consumption of pro and antioxidants. 104 women with obesity and 70 healthy controls (CG) were included in the study. Anthropometric, biochemical, clinical and dietary features were evaluated. GPx-1 rs10504050 was determined by PCR/RFLP method. TBARS was assayed spectrophotometrically in plasma. The subjects were stratified and compared by obesity grades and by subgroups of prediabetes and diabetes condition. Statistical analysis included ANOVA of Kruskal Wallis, Xi squared and Pearson correlation. for rs10504050 polymorphism there were differences (Xi2 = 6; p = 0.01) between frequency (0.61) of obese carriers (Pro/Leu plus Leu/Leu) and CG carriers (0.42), and between (Xi2 = 8; p = 0.004) morbid (IMC > 40) obesity (0.74) and CG carriers. The obese group (OB) showed a prevalence of 66% of prediabetes plus diabetes. There were no differences in frequencies of rs10504050 in OB with pre or diabetes versus CG, or versus obese participants without diabetes. TBARS concentration was greater in all the degrees of OB versus CG. GPx-1 Pro200Leu polymorphism was associated with obesity especially with morbid obesity, but not with obese participants with prediabetes or diabetes. Oxidative stress is present in all grades of obesity significantly. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Fuel cycle cost study with HEU and LEU fuels

International Nuclear Information System (INIS)

Matos, J.E.; Freese, K.E.

1984-01-01

Fuel cycle costs are compared for a range of 235 U loadings with HEU and LEU fuels using the IAEA generic 10 MW reactor as an example. If LEU silicide fuels are successfully demonstrated and licensed, the results indicate that total fuel cycle costs can be about the same or lower than those with the HEU fuels that are currently used in most research reactors

Four inducible promoters for controlled gene expression in the oleaginous yeast Rhodotorula toruloides

Directory of Open Access Journals (Sweden)

Alexander Michael Bedford Johns

2016-10-01

Full Text Available Rhodotorula (Rhodosporidium toruloides is an oleaginous yeast with great biotechnological potential, capable of accumulating lipid up to 70 % of its dry biomass, and of carotenoid biosynthesis. However, few molecular genetic tools are available for manipulation of this basidiomycete yeast and its high genomic GC content can make routine cloning difficult. We have developed plasmid vectors for transformation of R. toruloides which include elements for Saccharomyces cerevisiae in-yeast assembly; this method is robust to the assembly of GC-rich DNA and of large plasmids. Using such vectors we screened for controllable promoters, and identified inducible promoters from the genes NAR1, ICL1, CTR3 and MET16. These four promoters have independent induction/repression conditions and exhibit different levels and rates of induction in R. toruloides, making them appropriate for controllable transgene expression in different experimental situations. Nested deletions were used to identify regulatory regions in the four promoters, and to delimit the minimal inducible promoters, which are as small as 200 bp for the NAR1 promoter. The NAR1 promoter shows very tight regulation under repressed conditions as determined both by an EGFP reporter gene and by conditional rescue of a leu2 mutant. These new tools facilitate molecular genetic manipulation and controllable gene expression in R. toruloides.

Progress on LEU very high density fuel and target development in Argentina

International Nuclear Information System (INIS)

Balart, S.; Cabot, P.; Calzetta, O.; Duran, A.; Garces, J.; Hermida, J.D.; Manzini, A.; Pasqualini, E.; Taboada, H.

2006-01-01

Since last RRFM meeting, CNEA has continued on new LEU fuel and target development activities. Main goals are the plan to convert our RA-6 reactor from HEU to a new LEU core, to get a comprehensive understanding of U-Mo/Al compounds phase formation in dispersed and monolithic fuels, to develop possible solutions to VHD dispersed and monolithic fuels technical problems, to optimize techniques to recover U from silicide scrap samples as cold test for radiowaste separation for final conditioning of silicide spent fuels. and to improve the diffusion of LEU target and radiochemical technology for radioisotope production. Future plans include: - Completion of the RA-6 reactor conversion to LEU; - Improvement on fuel development and production facilities to implement new technologies, including NDT techniques to assess bonding quality; - Irradiation of miniplates and full scale fuel assembly at RA-3 and plans to perform irradiation on higher power and temperature regime reactors; - Optimization of LEU target and radiochemical techniques for radioisotope production. (author)

A study for association and interaction analysis to metabolic syndrome and the ESR1 gene on cardiovascular autonomic neuropathy in a Chinese Han population.

Science.gov (United States)

Zeng, Fangfang; Zhou, Linuo; Tang, Zihui

2016-01-01

The aim of this study was to investigate the association and interaction of metabolic syndrome (MetS) and estrogen receptor alpha 1 (ESR1) gene polymorphisms on cardiovascular autonomic neuropathy (CAN). A large-scale, population-based study was conducted to analyze the interaction of MetS and ESR1 gene polymorphisms to CAN, including a total of 1977 Chinese subjects. The most common studied single nucleotide polymorphism of ESR1 gene-rs9340799, was genotyped. Multiple logistic regression (MLR) was performed to evaluate the interaction effect of environmental variables and gene polymorphisms. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). After controlling potential confounders, MLR showed that significant association between MetS and CAN (p interaction was estimated by using RETI = 0.396 (95 % CI 0.262 to 0.598), AP = 0.216 (95 % CI -0.784 to 1.216) and S = 1.906 (95 % CI 0.905 to 4.015). The present findings suggest that MetS is significantly associated with CAN and provide evidence for the hypothesis that MetS and ESR1 gene polymorphism (rs9340799) have interactive effects on CAN. ClinicalTrials gov Identifier NCT02461342.

Relationships between the functional PPARalpha Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people

DEFF Research Database (Denmark)

Sparsø, Thomas; Hussain, Meena S; Andersen, Gitte

2007-01-01

Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor capable of regulating the expression of genes involved in peroxisomal and mitochondrial beta-oxidation pathways. The common Leu162Val polymorphism in the gene encoding PPARalpha has inconsistently shown association...

Analysis of PGC-1α variants Gly482Ser and Thr612Met concerning their PPARγ2-coactivation function

International Nuclear Information System (INIS)

Nitz, Inke; Ewert, Agnes; Klapper, Maja; Doering, Frank

2007-01-01

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a cofactor involved in adaptive thermogenesis, fatty acid oxidation, and gluconeogenesis. Dysfunctions of this protein are likely to contribute to the development of obesity and the metabolic syndrome. This is in part but not definitely confirmed by results of population studies. The aim of this study was to investigate if common genetic variants rs8192678 (Gly482Ser) and rs3736265 (Thr612Met) in the PGC-1α gene lead to a functional consequence in cofactor activity using peroxisome proliferator-activated receptor-γ 2 (PPARγ2) as interacting transcription factor. Reporter gene assays in HepG2 cells with wildtype and mutant proteins of both PGC1α and PPARγ2 (Pro12Ala, rs1801282) using the acyl-CoA-binding protein (ACBP) promoter showed no difference in coactivator activity. This is First study implicating that the Gly482Ser and Thr612Met polymorphisms in PGC-1α and Pro12Ala polymorphism in PPARγ2 do not affect the functional integrity of these proteins

Interaction between Obesity and the NFKB1 - 94ins/delATTG Promoter Polymorphism in Relation to Incident Acute Coronary Syndrome

DEFF Research Database (Denmark)

Stegger, Jakob Gerhard; Schmidt, Erik Berg; Berentzen, Tina Landsvig

2013-01-01

The NF-κB transcription factor family regulates several genes encoding pro-inflammatory and anti-inflammatory proteins in adipose tissues and in atherosclerotic plaques. The deletion variant allele of the NFKB1 - 94ins/delATTG promoter polymorphism leads to lower transcript levels of the p50...... subunit, and the variant allele has been associated with the risk of several inflammatory diseases as well as coronary heart disease where inflammation is important in the pathogenesis. The objective of this study was to explore the potential interaction between the NFKB1-94ins/delATTG promoter...

Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder Polimorfismo do gene do fator neurotrófico derivado do cérebro val66met e função executiva em pacientes com transtorno bipolar

Directory of Open Access Journals (Sweden)

Juliana Fernandes Tramontina

2009-06-01

Full Text Available OBJECTIVE: In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF and the performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian patients with bipolar disorder. METHOD: Sixty-four patients with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. RESULTS: The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF genotype frequency and other Wisconsin Card Sorting Test domains. CONCLUSION: Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gene polymorphism.OBJETIVO: O presente estudo tem por objetivo investigar a associação entre o polimorfismo val66met do gene do fator neurotrófico derivado do cérebro (BDNF e o desempenho cognitivo no Teste Wisconsin de Classificação de Cartas em uma amostra de pacientes bipolares brasileiros caucasianos. MÉTODO: Sessenta e quatro pacientes com transtorno bipolar foram avaliados em relação a sua cognição por meio do Teste Wisconsin de Classificação de Cartas que foi comparada com a freqüência alélica e genotípica do polimorfismo val66met do gene do fator neurotrófico derivado do cérebro. RESULTADOS: O percentual de erros não-perseverativos foi significativamente maior nos indivíduos com genótipo val/val. Não foi encontrada diferença significativa entre a freqüência genotípica do polimorfismo do BDNF e os outros domínios do Teste Wisconsin de Classificação de Cartas. CONCLUSÃO: O estudo do polimorfismo val66met em relação ao desempenho executivo em pacientes bipolares caucasianos de uma

Neutronic performance of a 14 MW TRIGA reactor: LEU vs HEU fuel

International Nuclear Information System (INIS)

Bretscher, M.M.; Snelgrove, J.L.; Cornella, R.J.

1983-01-01

A primary objective of the US Reduced Enrichment Research and Test Reactor (RERTR) Program is to develop means for replacing, wherever possible, currently used highly-enriched uranium (HEU) fuel ( 235 U enrichment > 90%) with low-enriched uranium (LEU) fuel ( 235 U enrichment < 20%) without significantly degrading the performance of research and test reactors. The General Atomic Company has developed a low-enriched but high uranium content Er-U-ZrH/sub 1.6/ fuel to enable the conversion of TRIGA reactors (and others) from HEU to LEU. One possible application is to the water-moderated 14 MW TRIGA Steady State Reactor (SSR) at the Romanian Institute for Nuclear Power Reactors. The work reported here was undertaken for the purpose of comparing the neutronic performance of the SSR for HEU fuel with that for LEU fuel. In order to make these relative comparisons as valid as possible, identical methods and models were used for the neutronic calculations

DNA Repair Mechanism Gene, XRCC1A (Arg194Trp) but not XRCC3 (Thr241Met) Polymorphism Increased the Risk of Breast Cancer in Premenopausal Females: A Case–Control Study in Northeastern Region of India

Science.gov (United States)

Ahmed, Jishan; Narain, Kanwar; Mukherjee, Kaustab; Majumdar, Gautam; Chenkual, Saia; Zonunmawia, Jason C.

2017-01-01

X-ray repair cross complementary group gene is one of the most studied candidate gene involved in different types of cancers. Studies have shown that X-ray repair cross complementary genes are significantly associated with increased risk of breast cancer in females. Moreover, studies have revealed that X-ray repair cross complementary gene polymorphism significantly varies between and within different ethnic groups globally. The present case–control study was aimed to investigate the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast cancer in females from northeastern region of India. The present case–control study includes histopathologically confirmed and newly diagnosed 464 cases with breast cancer and 534 apparently healthy neighborhood community controls. Information on sociodemographic factors and putative risk factors were collected from each study participant by conducting face-to-face interviews. Genotyping of X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross complementary 3 (Thr241Met) was carried out by polymerase chain reaction-restriction fragment length polymorphism. For statistical analysis, both univariate and multivariate logistic regression analyses were performed. We also performed stratified analysis to find out the association of X-ray repair cross complementary genes with the risk of breast cancer stratified based on menstrual status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray repair cross complementary 1A (Arg194Trp) gene significantly increased the risk of breast cancer (adjusted odds ratio = 1.44, 95% confidence interval = 1.06-1.97, P India which may be beneficial for prognostic purposes. PMID:29332455

LEU fuel fabrication program for the RECH-1 reactor. Status report

International Nuclear Information System (INIS)

Chavez, J.C.; Barrera, M.; Jimenez, O.; Lisboa, J.; Marin, J.

2000-01-01

In 1995 a 50 LEU U 3 Si 2 fuel elements fabrication program for the RECH-1 research reactor was established at the Comision Chilena de Energia Nuclear, CCHEN. After a fabrication process qualification stage, in 1998, four elements were early delivered to the reactor in order to start an irradiation qualification stage. The irradiation has reached an estimated 10% burn-up and no fabrication problems have been detected up to this burn-up level. During 1999 and up to the first quarter of 2000, 19 fuel elements were produced and 7 fuel elements are expected for the end of 2000. This report presents an updated summary of the main results obtained in this fuel fabrication program. A summary of other activities generated by this program, such as in core follow-up of the four leader fuel elements, ISO 9001 implementation for the fabrication process and a fabrication and qualification optimization planning, is also presented here. (author)

Establishing a LEU MTR fuel manufacturing facility in South Africa

International Nuclear Information System (INIS)

Jamie, R.W.; Kocher, A.

2010-01-01

The South African MTR Fuel Manufacturing Facility was established in the 1970's to supply SAFARI-1 with Fuel Elements and Control Rods. South African capability was developed in parallel with the uranium enrichment program to meet the needs of the Reactor. Further to the July 2005 decision by the South African Governmnent to convert both SAFARI-1 and the Fuel Plant to LEU, the SAFARI-1 phase has been successfully completed and Necsa has commenced with the conversion of the MTR Fuel Manufacturing Facility. In order to establish, validate and qualify the facility, Necsa has entered into a co-operation and technology transfer agreement with AREVA CERCA, the French manufacturer of Research Reactor fuel elements. Past experiences, conversion challenges and the status of the MTR Fuel Facility Project are discussed. On-going co-operation with AREVA CERCA to implement the local manufacture of LEU fuel is explained and elaborated on. (author)

[RIT1: a novel gene associated with Noonan syndrome].

Science.gov (United States)

Arroyo-Carrera, I; Solo de Zaldivar-Tristancho, M; Martin-Fernandez, R; Vera-Torres, M; Gonzalez de Buitrago-Amigo, J F; Botet-Rodriguez, J

2016-10-16

Noonan syndrome is the most frequent of the congenital group of malformation syndromes caused by germline mutations that encode components of the RAS/MAPK pathway, termed RASopathies, one of the most frequent congenital genetic disorders in the clinical practice. Recently RIT1 mutations have been reported in patients with Noonan syndrome. A 7 years-old girl with a clinical diagnosis of Noonan syndrome, and with a hypertrophic cardiomyopathy included in her clinical manifestations, where a de novo heterozygous, probably pathogenic, novel mutation in RIT1, c.295T>C (p.Phe99Leu), has been identified. RIT1 shares homology with other RAS proteins and the expression of mutant alleles demonstrates a gain-of-function effect supporting a causative role in Noonan syndrome pathogenesis. Data suggest that the frequency of RIT1 mutations can be estimated as 3-5% in Noonan syndrome patients. These cases compared with Noonan patients harboring mutations in other genes are characterized by high frequency of prenatal abnormalities and hypertrophic cardiomyopathy, and lower frequencies of short stature and pectus abnormalities. We emphasize the importance of the novel identified genes in order to be included in the diagnostic panels.

Purification and partial characterization of Phaseolus vulgaris seed aminopeptidase

Directory of Open Access Journals (Sweden)

Abdala A.P.

1999-01-01

Full Text Available The aminopeptidase activity of Phaseolus vulgaris seeds was measured using L-Leu-p-nitroanilide and the L-aminoacyl-ß-naphthylamides of Leu, Ala, Arg and Met. A single peak of aminopeptidase activity on Leu-ß-naphthylamide was eluted at 750 µS after gradient elution chromatography on DEAE-cellulose of the supernatant of a crude seed extract. The effluent containing enzyme activity was applied to a Superdex 200 column and only one peak of aminopeptidase activity was obtained. SDS-polyacrylamide gel electrophoresis (10% presented only one protein band with molecular mass of 31 kDa under reducing and nonreducing conditions. The aminopeptidase has an optimum pH of 7.0 for activity on all substrates tested and the highest Vmax/KM ratio for L-Leu-ß-naphthylamide. The enzyme activity was increased 40% by 0.15 M NaCl, inhibited 94% by 2.0 mM Zn2+, inhibited 91% by sodium p-hydroxymercuribenzoate and inhibited 45% by 0.7 mM o-phenanthroline and 30 µM EDTA. Mercaptoethanol (3.3 mM, dithioerythritol (1.7 mM, Ala, Arg, Leu and Met (70 µM, p-nitroaniline (0.25 mM and ß-naphthylamine (0.53 mM had no effect on enzyme activity when assayed with 0.56 mM of substrate. Bestatin (20 µM inhibited 18% the enzyme activity. The aminopeptidase activity in the seeds decayed 50% after two months when stored at 4oC and room temperature. The enzyme is leucyl aminopeptidase metal- and thiol group-dependent.

Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project.

Science.gov (United States)

Bubendorf, Lukas; Dafni, Urania; Schöbel, Martin; Finn, Stephen P; Tischler, Verena; Sejda, Aleksandra; Marchetti, Antonio; Thunnissen, Erik; Verbeken, Eric K; Warth, Arne; Sansano, Irene; Cheney, Richard; Speel, Ernst Jan M; Nonaka, Daisuke; Monkhorst, Kim; Hager, Henrik; Martorell, Miguel; Savic, Spasenija; Kerr, Keith M; Tan, Qiang; Tsourti, Zoi; Geiger, Thomas R; Kammler, Roswitha; Schulze, Katja; Das-Gupta, Ashis; Shames, David; Peters, Solange; Stahel, Rolf A

2017-09-01

In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome. Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio≥2 (with average MET GCN≥4), high MET GCN as CGN≥5 and MET IHC+ as ≥2+ intensity in ≥50% of tumor cells. A total of 182 MET IHC+ and EGFR/KRAS WT tumors were analyzed for METex14 skipping mutation. MET IHC+ was found in 23.8% of 2432 patients, significantly associated with female gender, small tumor size, and adenocarcinoma histology. We observed a high inter-laboratory variability in IHC and SISH analysis. MET amplification prevailed in 4.6% and MET GCN≥5 in 4.1% of 1572 patients. MET amplification and MET GCN≥5 were not significantly associated with any tumor characteristics or stage. Both were significantly associated with IHC MET positivity (poverexpression, SISH MET amplification or high MET GCN was found with OS, RFS or TTR. MET overexpression is found in 23.8% of surgically resected NSCLC. MET amplification prevails in 4.6% and is associated with MET overexpression. Both have no influence on prognosis. The large inter-laboratory variability in IHC highlights the challenge of MET IHC analysis in routine practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis.

Science.gov (United States)

Bozkaya, Giray; Korhan, Peyda; Cokaklı, Murat; Erdal, Esra; Sağol, Ozgül; Karademir, Sedat; Korch, Christopher; Atabey, Neşe

2012-09-11

Hepatocyte growth factor (HGF) induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC). MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s) is in hepatocarcinogenesis. MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

Cooperative interaction of MUC1 with the HGF/c-Met pathway during hepatocarcinogenesis

Directory of Open Access Journals (Sweden)

Bozkaya Giray

2012-09-01

Full Text Available Abstract Background Hepatocyte growth factor (HGF induced c-Met activation is known as the main stimulus for hepatocyte proliferation and is essential for liver development and regeneration. Activation of HGF/c-Met signaling has been correlated with aggressive phenotype and poor prognosis in hepatocellular carcinoma (HCC. MUC1 is a transmembrane mucin, whose over-expression is reported in most cancers. Many of the oncogenic effects of MUC1 are believed to occur through the interaction of MUC1 with signaling molecules. To clarify the role of MUC1 in HGF/c-Met signaling, we determined whether MUC1 and c-Met interact cooperatively and what their role(s is in hepatocarcinogenesis. Results MUC1 and c-Met over-expression levels were determined in highly motile and invasive, mesenchymal-like HCC cell lines, and in serial sections of cirrhotic and HCC tissues, and these levels were compared to those in normal liver tissues. Co-expression of both c-Met and MUC1 was found to be associated with the differentiation status of HCC. We further demonstrated an interaction between c-Met and MUC1 in HCC cells. HGF-induced c-Met phosphorylation decreased this interaction, and down-regulated MUC1 expression. Inhibition of c-Met activation restored HGF-mediated MUC1 down-regulation, and decreased the migratory and invasive abilities of HCC cells via inhibition of β-catenin activation and c-Myc expression. In contrast, siRNA silencing of MUC1 increased HGF-induced c-Met activation and HGF-induced cell motility and invasion. Conclusions These findings indicate that the crosstalk between MUC1 and c-Met in HCC could provide an advantage for invasion to HCC cells through the β-catenin/c-Myc pathway. Thus, MUC1 and c-Met could serve as potential therapeutic targets in HCC.

YibK is the 2'-O-methyltransferase TrmL that modifies the wobble nucleotide in Escherichia coli tRNA(Leu) isoacceptors

DEFF Research Database (Denmark)

Benítez-Páez, Alfonso; Villarroya, Magda; Douthwaite, Stephen Roger

2010-01-01

to uncover candidate E. coli genes for the missing enzyme(s). Transfer RNAs from null mutants for candidate genes were analyzed by mass spectrometry and revealed that inactivation of yibK leads to loss of 2'-O-methylation at position 34 in both tRNA(Leu)(CmAA) and tRNA(Leu)(cmnm5UmAA). Loss of Yib...... of the wobble nucleotide; YibK recognition of this target requires a pyridine at position 34 and N⁶-(isopentenyl)-2-methylthioadenosine at position 37. YibK is one of the last remaining E. coli tRNA modification enzymes to be identified and is now renamed TrmL.......Transfer RNAs are the most densely modified nucleic acid molecules in living cells. In Escherichia coli, more than 30 nucleoside modifications have been characterized, ranging from methylations and pseudouridylations to more complex additions that require multiple enzymatic steps. Most...

Future U.S. supply of Mo-99 production through fission based LEU/LEU technology

International Nuclear Information System (INIS)

James Welsh; Bigles, C.I.; Alejandro Valderrabano

2015-01-01

Coqui RadioPharmaceuticals Corp. (Coqui) has the goal of establishing a medical isotope production facility for securing a continuous domestic supply of the radioisotope molybdenum-99 for U.S. citizens. Coqui will use an LEU/LEU proven and implemented open pool, light-water, 10 MW, reactor design. The facility is being designed with twin reactors for reliability an on-site hot lab chemical processing and a waste conditioning area and a possible generator producing radio-chemistry lab. Coqui identified a 25 acre site adjacent to an existing industrial park in northern central Florida. This land was gifted and transferred to Coqui by the University of Florida Foundation. We are in the process of developing licensing documents related to the facility. The construction permit application for submission to the U.S. Nuclear Regulatory Commission is currently being prepared. Submission is scheduled for mid to late 2015. Community reaction to the proposed development has been positive. We expect to create 220 permanent jobs and we have an anticipated to be operational by 2020. (author)

Future U.S. supply of Mo-99 production through fission based LEU/LEU technology.

Science.gov (United States)

Welsh, James; Bigles, Carmen I; Valderrabano, Alejandro

Coquí RadioPharmaceuticals Corp. (Coquí) has the goal of establishing a medical isotope production facility for securing a continuous domestic supply of the radioisotope molybdenum-99 for U.S. citizens. Coquí will use an LEU/LEU proven and implemented open pool, light-water, 10 MW, reactor design. The facility is being designed with twin reactors for reliability an on-site hot lab chemical processing and a waste conditioning area and a possible generator producing radio-chemistry lab. Coquí identified a 25 acre site adjacent to an existing industrial park in northern central Florida. This land was gifted and transferred to Coquí by the University of Florida Foundation. We are in the process of developing licensing documents related to the facility. The construction permit application for submission to the U.S. Nuclear Regulatory Commission is currently being prepared. Submission is scheduled for mid to late 2015. Community reaction to the proposed development has been positive. We expect to create 220 permanent jobs and we have an anticipated to be operational by 2020.

Fabrication, fabrication control and in-core follow up of 4 LEU leader fuel elements based on U3Si2 in RECH-1

International Nuclear Information System (INIS)

Chavez, J.C.; Barrera, M.; Olivares, L.; Lisboa, J.

1999-01-01

The RECH-1 MTR reactor has been converted from HEU to MEU (45% enrichment) and the decision to a LEU (20% enrichment) conversion was taken some years ago. This LEU conversion decision involved a local fuel development and fabrication based on U 3 Si 2 -Al dispersion fuel, and a fabrication qualification stage that resulted in four fuel elements fully complying with established fabrication standards for this type of fuel. This report-presents relevant points of these four leaders fuel elements fabrication, in particular a fuel plate core homogeneity control development. A summary of the intended in core follow-up studies for the leaders fuel elements is also presented here. (author)

Study of five novel non-synonymous polymorphisms in human brain-expressed genes in a Colombian sample.

Science.gov (United States)

Ojeda, Diego A; Forero, Diego A

2014-10-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) in brain-expressed genes represent interesting candidates for genetic research in neuropsychiatric disorders. To study novel nsSNPs in brain-expressed genes in a sample of Colombian subjects. We applied an approach based on in silico mining of available genomic data to identify and select novel nsSNPs in brain-expressed genes. We developed novel genotyping assays, based in allele-specific PCR methods, for these nsSNPs and genotyped them in 171 Colombian subjects. Five common nsSNPs (rs6855837; p.Leu395Ile, rs2305160; p.Thr394Ala, rs10503929; p.Met289Thr, rs2270641; p.Thr4Pro and rs3822659; p.Ser735Ala) were studied, located in the CLOCK, NPAS2, NRG1, SLC18A1 and WWC1 genes. We reported allele and genotype frequencies in a sample of South American healthy subjects. There is previous experimental evidence, arising from genome-wide expression and association studies, for the involvement of these genes in several neuropsychiatric disorders and endophenotypes, such as schizophrenia, mood disorders or memory performance. Frequencies for these nsSNPSs in the Colombian samples varied in comparison to different HapMap populations. Future study of these nsSNPs in brain-expressed genes, a synaptogenomics approach, will be important for a better understanding of neuropsychiatric diseases and endophenotypes in different populations.

Genotypes do not confer risk for delinquency but rather alter susceptibility to positive and negative environmental factors: gene-environmentinteractions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR [corrected].

Science.gov (United States)

Nilsson, Kent W; Comasco, Erika; Hodgins, Sheilagh; Oreland, Lars; Åslund, Cecilia

2014-12-10

Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene-linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency. In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1 337 high-school students, aged 17-18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses. Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × family conflicts and for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL [girls] and L [boys] vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met × 5-HTTLPR S × MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship. Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency. © The Author 2015. Published by Oxford University

Genotypes Do Not Confer Risk For Delinquency ut Rather Alter Susceptibility to Positive and Negative Environmental Factors: Gene-Environment Interactions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR

Science.gov (United States)

Comasco, Erika; Hodgins, Sheilagh; Oreland, Lars; Åslund, Cecilia

2015-01-01

Background: Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene-linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency. Methods: In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1 337 high-school students, aged 17–18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses. Results: Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × family conflicts and for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL [girls] and L [boys] vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met × 5-HTTLPR S × MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship. Conclusions: Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency. PMID

Identification of a novel amino acid racemase from a hyperthermophilic archaeon Pyrococcus horikoshii OT-3 induced by D-amino acids.

Science.gov (United States)

Kawakami, Ryushi; Ohmori, Taketo; Sakuraba, Haruhiko; Ohshima, Toshihisa

2015-08-01

To date, there have been few reports analyzing the amino acid requirement for growth of hyperthermophilic archaea. We here found that the hyperthermophilic archaeon Pyrococcus horikoshii OT-3 requires Thr, Leu, Val, Phe, Tyr, Trp, His and Arg in the medium for growth, and shows slow growth in medium lacking Met or Ile. This largely corresponds to the presence, or absence, of genes related to amino acid biosynthesis in its genome, though there are exceptions. The amino acid requirements were dramatically lost by addition of D-isomers of Met, Leu, Val, allo-Ile, Phe, Tyr, Trp and Arg. Tracer analysis using (14)C-labeled D-Trp showed that D-Trp in the medium was used as a protein component in the cells, suggesting the presence of D-amino acid metabolic enzymes. Pyridoxal 5'-phosphate (PLP)-dependent racemase activity toward Met, Leu and Phe was detected in crude extract of P. horikoshii and was enhanced in cells grown in the medium supplemented with D-amino acids, especially D-allo-Ile. The gene encoding the racemase was narrowed down to one open reading frame on the basis of enzyme purification from P. horikoshii cells, and the recombinant enzyme exhibited PLP-dependent racemase activity toward several amino acids, including Met, Leu and Phe, but not Pro, Asp or Glu. This is the first report showing the presence in a hyperthermophilic archaeon of a PLP-dependent amino acid racemase with broad substrate specificity that is likely responsible for utilization of D-amino acids for growth.

Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.

Science.gov (United States)

Plummer, J T; Evgrafov, O V; Bergman, M Y; Friez, M; Haiman, C A; Levitt, P; Aldinger, K A

2013-10-22

Single nucleotide variants (SNV) in the gene encoding the MET receptor tyrosine kinase have been associated with an increased risk for autism spectrum disorders (ASD). The MET promoter SNV rs1858830 C 'low activity' allele is enriched in ASD, associated with reduced protein expression, and impacts functional and structural circuit connectivity in humans. To gain insight into the transcriptional regulation of MET on ASD-risk etiology, we examined an interaction between the methyl CpG-binding protein 2 (MeCP2) and the MET 5' promoter region. Mutations in MeCP2 cause Rett syndrome (RTT), a predominantly female neurodevelopmental disorder sharing some ASD clinical symptoms. MeCP2 binds to a region of the MET promoter containing the ASD-risk SNV, and displays rs1858830 genotype-specific binding in human neural progenitor cells derived from the olfactory neuroepithelium. MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2. In the postmortem temporal cortex, a region normally enriched in MET, gene expression is reduced dramatically in females with RTT, although not due to enrichment of the rs1858830 C 'low activity' allele. We newly identified a sex-based reduction in MET expression, with male ASD cases, but not female ASD cases compared with sex-matched controls. The experimental data reveal a prominent allele-specific regulation of MET transcription by MeCP2. The mechanisms underlying the pronounced reduction of MET in ASD and RTT temporal cortex are distinct and likely related to factors unique to each disorder, including a noted sex bias.

Ectopic Expression of Homeobox Gene NKX2-1 in Diffuse Large B-Cell Lymphoma Is Mediated by Aberrant Chromatin Modifications

Science.gov (United States)

Nagel, Stefan; Ehrentraut, Stefan; Tomasch, Jürgen; Quentmeier, Hilmar; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A. F.

2013-01-01

Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies. PMID:23637834

Status of LEU conversion program at CRNL

International Nuclear Information System (INIS)

Kennedy, I.C.

1991-01-01

After briefly reviewing the salient features of the NRU Reactor at Chalk River Nuclear Laboratories (CRNL), the progress of our LEU fuel development and testing program is described. The results (to date) of full-size prototype fuel-rod irradiations are reviewed, and the status of the new fuel-fabrication facility on the site is updated. Although development work is proceeding on U 3 Si 2 dispersions, all indications so far are that CRNL's U 3 Si fuel is fully acceptable for reactor operation. Fuel rods from the new fabrication shop will be installed in NRU in 1990, and the complete core conversion of NRU to LEU driver fuel is expected by 1991. (orig.)

Progress in safety evaluation for the JMTR core conversion to LEU fuel

International Nuclear Information System (INIS)

Sakurai, F.; Komori, Y.; Saito, J.; Komukai, B.; Ando, H.; Nakata, H.; Sakakura, A.; Niiho, S.; Saito, M.; Futamura, Y.

1991-01-01

The JMTR (50 MWt) has been in steady operation with MEU fuel since July 1986. The effort is still continued to convert the core from MEU to LEU fuel. The LEU silicide fuel element at 4.8 gU/cm 3 with Cd wires as burnable absorbers has been selected in order to achieve upgraded fuel cycle performance of extended cycle length and reduced control rod movement operation. The neutronic calculation methods (diffusion theory model) developed for the LEU core with Cd wires was benchmarked with a detailed Monte Carlo model and verified experimentally using the critical facility, JMTRC. Hydraulic tests of the LEU silicide fuel element with Cd wires were completed with satisfactory results, and measurements of release/born (R/B) ratios of FPs of silicide fuel at high temperature are in progress. (orig.)

DNFSB Recommendation 94-1 Hanford Site Integrated Stabilization Management Plan. Volume 1

Energy Technology Data Exchange (ETDEWEB)

Gerber, E.W.

1995-10-01

The US Department of Energy (DOE) has developed an Integrated Program Plan (IPP) to address concerns identified in Defense Nuclear Facilities Safety Board Recommendation 94-1. The IPP describes the actions that DOE plans to implement at its various sites to convert excess fissile materials to forms or conditions suitable for safe interim storage. The baseline IPP was issued as DOE`s Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1 Implementation Plan (IP), which was transmitted to the DNFSB on February 28, 1995. The IPP is being further developed to include complex-wide requirements for research and development and a long-range facility requirements section. The planned additions to the baseline IPP are being developed based on a systems engineering approach that integrates facilities and capabilities at the various DOE sites and focuses on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 and to provide a basis for formulating planned additions to the IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the baseline DNFSB Recommendation 94-1 IPP. The SISMPs will be periodically updated to reflect improved integration between DOE sites as identified during the IPP systems engineering evaluations.

DNFSB Recommendation 94-1 Hanford Site Integrated Stabilization Management Plan. Volume 1

International Nuclear Information System (INIS)

Gerber, E.W.

1995-10-01

The US Department of Energy (DOE) has developed an Integrated Program Plan (IPP) to address concerns identified in Defense Nuclear Facilities Safety Board Recommendation 94-1. The IPP describes the actions that DOE plans to implement at its various sites to convert excess fissile materials to forms or conditions suitable for safe interim storage. The baseline IPP was issued as DOE's Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1 Implementation Plan (IP), which was transmitted to the DNFSB on February 28, 1995. The IPP is being further developed to include complex-wide requirements for research and development and a long-range facility requirements section. The planned additions to the baseline IPP are being developed based on a systems engineering approach that integrates facilities and capabilities at the various DOE sites and focuses on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 and to provide a basis for formulating planned additions to the IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the baseline DNFSB Recommendation 94-1 IPP. The SISMPs will be periodically updated to reflect improved integration between DOE sites as identified during the IPP systems engineering evaluations

Functional alterations due to amino acid changes and evolutionary comparative analysis of ARPKD and ADPKD genes

Directory of Open Access Journals (Sweden)

Burhan M. Edrees

2016-12-01

Full Text Available A targeted customized sequencing of genes implicated in autosomal recessive polycystic kidney disease (ARPKD phenotype was performed to identify candidate variants using the Ion torrent PGM next-generation sequencing. The results identified four potential pathogenic variants in PKHD1 gene [c.4870C>T, p.(Arg1624Trp, c.5725C>T, p.(Arg1909Trp, c.1736C>T, p.(Thr579Met and c.10628T>G, p.(Leu3543Trp] among 12 out of 18 samples. However, one variant c.4870C>T, p.(Arg1624Trp was common among eight patients. Some patient samples also showed few variants in autosomal dominant polycystic kidney disease (ADPKD disease causing genes PKD1 and PKD2 such as c.12433G>A, p.(Val4145Ile and c.1445T>G, p.(Phe482Cys, respectively. All causative variants were validated by capillary sequencing and confirmed the presence of a novel homozygous variant c.10628T>G, p.(Leu3543Trp in a male proband. We have recently published the results of these studies (Edrees et al., 2016. Here we report for the first time the effect of the common mutation p.(Arg1624Trp found in eight samples on the protein structure and function due to the specific amino acid changes of PKHD1 protein using molecular dynamics simulations. The computational approaches provide tool predict the phenotypic effect of variant on the structure and function of the altered protein. The structural analysis with the common mutation p.(Arg1624Trp in the native and mutant modeled protein were also studied for solvent accessibility, secondary structure and stabilizing residues to find out the stability of the protein between wild type and mutant forms. Furthermore, comparative genomics and evolutionary analyses of variants observed in PKHD1, PKD1, and PKD2 genes were also performed in some mammalian species including human to understand the complexity of genomes among closely related mammalian species. Taken together, the results revealed that the evolutionary comparative analyses and characterization of PKHD1, PKD1

Measurements of the HEU and LEU in-core spectra at the Ford Nuclear Reactor

Energy Technology Data Exchange (ETDEWEB)

Wehe, D K [Oak Ridge National Laboratory, Oak Ridge, TN (United States); King, J S; Lee, J C; Martin, W R [Department of Nuclear Engineering, University of Michigan, Ann Arbor, MI (United States)

1985-07-01

The Ford Nuclear Reactor (FNR) at the University of Michigan has been serving as the test site for a low-enriched uranium (LEU) fuel whole-core demonstration. As part of the experimental program, the differential neutron spectrum has been measured in a high-enriched uranium (HEU) core and an LEU core. The HEU and LEU spectra were determined by unfolding the measured activities of foils that were irradiated in the reactor. When the HEU and LEU spectra are compared from meV to 10 MeV, significant differences between the two spectra are apparent below 10 eV. These are probably caused by the additional {sup 238}U resonance absorption in the LEU fuel. No measurable difference occurs in the shape of the spectra above MeV. (author)

Mo-99 production on a LEU solution reactor

International Nuclear Information System (INIS)

Brown, R.W.; Thome, L.A.; Khvostionov, V.Y.

2005-01-01

A pilot homogenous reactor utilizing LEU has been developed by the Kurchatov Institute in Moscow along with their commercial partner TCI Medical. This solution reactor operates at levels up to 50 kilowatts and has successfully produced high quality Mo-99 and Sr-89. Radiochemical extraction of medical radionuclides from the reactor solution is performed by passing the solution across a series of inorganic sorbents. This reactor has commercial potential for medical radionuclide production using LEU UO 2 SO 4 fuel. Additional development work is needed to optimize multiple 50 kilowatt cores while at the same time, optimizing production efficiency and capital expenditure. (author)

DNFSB Recommendation 94-1 Hanford site integrated stabilization management plan, volumes 1 and 2

International Nuclear Information System (INIS)

Gerber, E.W.

1996-01-01

This document comprises the Hanford Site Integrated Stabilization Management Plan (SISMP). This document describes the DOE's plans at the Hanford Site to address concerns identified in Defense Nuclear Facilites Safety Board (DNFSB) Recommendation 94-1. This document also identifies plans for other spent nuclear fuel (SNF) inventories at the Hanford Site which are not within the scope of DNFSB Recommendation 94-1 for reference purposes because of their interrelationship with plans for SNF within the scope of DNFSB Recommendation 94-1. The SISMP was also developed to assist DOE in initial formulation of the Research and Development Plan and the Integrated Facilities Plan

Influence of IL1B, IL6 and IL10 gene variants and plasma fatty acid interaction on metabolic syndrome risk in a cross-sectional population-based study.

Science.gov (United States)

Maintinguer Norde, Marina; Oki, Erica; Ferreira Carioca, Antonio Augusto; Teixeira Damasceno, Nágila Raquel; Fisberg, Regina Mara; Lobo Marchioni, Dirce Maria; Rogero, Marcelo Macedo

2018-04-01

Metabolic syndrome (MetS) is a cluster of interrelated risk factors for type 2 diabetes mellitus, and cardiovascular disease, with underlying inflammatory pathophysiology. Genetic variations and diet are well-known risk factor for MetS, but the interaction between these two factors is less explored. The aim of the study was to evaluate the influence of interaction between SNP of inflammatory genes (encoding interleukin (IL)-6, IL-1β and IL-10) and plasma fatty acids on the odds of MetS, in a population-based cross-sectional study. Among participants of the Health Survey - São Paulo, 301 adults (19-59 y) from whom a blood sample was collected were included. Individuals with and without MetS were compared according to their plasma inflammatory biomarkers, fatty acid profile, and genotype frequency of the IL1B (rs16944, rs1143623, rs1143627, rs1143634 and rs1143643), IL6 (rs1800795, rs1800796 and rs1800797) and IL10 (rs1554286, rs1800871, rs1800872, rs1800890 and rs3024490) genes SNP. The influence of gene-fatty acids interaction on MetS risk was investigated. IL6 gene SNP rs1800795 G allele was associated with higher odds for MetS (OR = 1.88; p = 0.017). Gene-fatty acid interaction was found between the IL1B gene SNP rs116944 and stearic acid (p inter = 0.043), and between rs1143634 and EPA (p inter = 0.017). For the IL10 gene SNP rs1800896, an interaction was found for arachidonic acid (p inter = 0.007) and estimated D5D activity (p inter = 0.019). The IL6 gene SNP rs1800795 G allele is associated with increased odds for MetS. Plasma fatty acid profile interacts with the IL1B and IL10 gene variants to modulate the odds for MetS. This and other interactions of risk factors can account for the unexplained heritability of MetS, and their elucidation can lead to new strategies for genome-customized prevention of MetS. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

A fuel cycle cost study with HEU and LEU fuels

International Nuclear Information System (INIS)

Matos, J.E.; Freese, K.E.

1985-01-01

Fuel cycle costs are compared for a range of 235 U loadings with HEU and LEU fuels using the IAEA generic 10 MW reactor as an example. If LEU silicide fuels are successfully demonstrated and licensed, the results indicate that total fuel cycle costs can be about the same or lower than those with the HEU fuels that are currently used in most research reactors. (author)

A fuel cycle cost study with HEU and LEU fuels

Energy Technology Data Exchange (ETDEWEB)

Matos, J E; Freese, K E [Argonne National Laboratory, Argonne, IL (United States)

1985-07-01

Fuel cycle costs are compared for a range of {sup 235}U loadings with HEU and LEU fuels using the IAEA generic 10 MW reactor as an example. If LEU silicide fuels are successfully demonstrated and licensed, the results indicate that total fuel cycle costs can be about the same or lower than those with the HEU fuels that are currently used in most research reactors. (author)

Continuing investigations for technology assessment of 99Mo production from LEU [low enriched uranium] targets

International Nuclear Information System (INIS)

Vandegrift, G.F.; Kwok, J.D.; Marshall, S.L.; Vissers, D.R.; Matos, J.E.

1987-01-01

Currently much of the world's supply of 99m Tc for medical purposes is produced from 99 Mo derived from the fissioning of high enriched uranium (HEU). This paper presents the results of our continuing studies on the effects of substituting low enriched uranium (LEU) for HEU in targets for the production of fission product 99 Mo. Improvements in the electrodeposition of thin films of uranium metal continue to increase the appeal for the substitution of LEU metal for HEU oxide films in cylindrical targets. The process is effective for targets fabricated from stainless steel or zircaloy. Included is a cost estimate for setting up the necessary equipment to electrodeposit uranium metal on cylindrical targets. Further investigations on the effect of LEU substitution on processing of these targets are also reported. Substitution of uranium silicides for the uranium-aluminium alloy or uranium aluminide dispersed fuel used in current target designs will allow the substitution of LEU for HEU in these targets with equivalent 99 Mo-yield per target and no change in target geometries. However, this substitution will require modifications in current processing steps due to 1) the insolubility of uranium silicides in alkaline solutions and 2) the presence of significant quantities of silicate in solution. Results to date suggest that substitution of LEU for HEU can be achieved. (Author)

Reclamation and reuse of LEU silicide fuel from manufacturing scrap

International Nuclear Information System (INIS)

Gale, G.R.; Pace, B.W.; Evans, R.S.

2004-01-01

In order to provide an understanding of the organization which is the sole supplier of United States plate type research and test reactor fuel and LEU core conversions, a brief description of the structure and history is presented. Babcock and Wilcox (B and W) is a part of McDermott International, Inc. which is a large diversified corporation employing over 20,000 people primarily in engineering and construction for the off-shore oil and power generation industries throughout the world. B and W provides many energy related products requiring precision machining and high quality systems. This is accomplished by using state-of-the-art equipment, technology and highly skilled people. The RTRFE group within B and W has the ability to produce various complexly shaped fuel elements with a wide variety of fuels and enrichments. B and W RTRFE has fabricated over 200,000 plates since 1981 and gained the diversified experience necessary to satisfy many customer requirements. This accomplishment was possible with the support of McDermott International and all of its resources. B and W has always had a commitment to high quality and integrity. This is apparent by the success and longevity (125 years) of the company. A lower cost to convert cores to LEU provides direct support to RERTR and demonstrates Babcock and Wilcox's commitment to the program. As a supporter of RERTR reactor conversion from HEU to LEU, B and W has contributed a significant amount of R and D money to improve the silicide fuel process which ultimately lowers the LEU core costs. In the most recent R and D project, B and W is constructing a LEU silicide reclamation facility to re-use the unirradiated fuel scrap generated from the production process. Remanufacturing use of this fuel completes the fuel cycle and provides a contribution to LEU cores by reducing scrap inventory and handling costs, lowering initial purchase of fuel due to increasing the process yields, and lowering the replacement costs. This

Biblio-MetReS for user-friendly mining of genes and biological processes in scientific documents.

Science.gov (United States)

Usie, Anabel; Karathia, Hiren; Teixidó, Ivan; Alves, Rui; Solsona, Francesc

2014-01-01

One way to initiate the reconstruction of molecular circuits is by using automated text-mining techniques. Developing more efficient methods for such reconstruction is a topic of active research, and those methods are typically included by bioinformaticians in pipelines used to mine and curate large literature datasets. Nevertheless, experimental biologists have a limited number of available user-friendly tools that use text-mining for network reconstruction and require no programming skills to use. One of these tools is Biblio-MetReS. Originally, this tool permitted an on-the-fly analysis of documents contained in a number of web-based literature databases to identify co-occurrence of proteins/genes. This approach ensured results that were always up-to-date with the latest live version of the databases. However, this 'up-to-dateness' came at the cost of large execution times. Here we report an evolution of the application Biblio-MetReS that permits constructing co-occurrence networks for genes, GO processes, Pathways, or any combination of the three types of entities and graphically represent those entities. We show that the performance of Biblio-MetReS in identifying gene co-occurrence is as least as good as that of other comparable applications (STRING and iHOP). In addition, we also show that the identification of GO processes is on par to that reported in the latest BioCreAtIvE challenge. Finally, we also report the implementation of a new strategy that combines on-the-fly analysis of new documents with preprocessed information from documents that were encountered in previous analyses. This combination simultaneously decreases program run time and maintains 'up-to-dateness' of the results. http://metres.udl.cat/index.php/downloads, metres.cmb@gmail.com.

Biblio-MetReS for user-friendly mining of genes and biological processes in scientific documents

Directory of Open Access Journals (Sweden)

Anabel Usie

2014-02-01

Full Text Available One way to initiate the reconstruction of molecular circuits is by using automated text-mining techniques. Developing more efficient methods for such reconstruction is a topic of active research, and those methods are typically included by bioinformaticians in pipelines used to mine and curate large literature datasets. Nevertheless, experimental biologists have a limited number of available user-friendly tools that use text-mining for network reconstruction and require no programming skills to use. One of these tools is Biblio-MetReS. Originally, this tool permitted an on-the-fly analysis of documents contained in a number of web-based literature databases to identify co-occurrence of proteins/genes. This approach ensured results that were always up-to-date with the latest live version of the databases. However, this ‘up-to-dateness’ came at the cost of large execution times. Here we report an evolution of the application Biblio-MetReS that permits constructing co-occurrence networks for genes, GO processes, Pathways, or any combination of the three types of entities and graphically represent those entities. We show that the performance of Biblio-MetReS in identifying gene co-occurrence is as least as good as that of other comparable applications (STRING and iHOP. In addition, we also show that the identification of GO processes is on par to that reported in the latest BioCreAtIvE challenge. Finally, we also report the implementation of a new strategy that combines on-the-fly analysis of new documents with preprocessed information from documents that were encountered in previous analyses. This combination simultaneously decreases program run time and maintains ‘up-to-dateness’ of the results. Availability: http://metres.udl.cat/index.php/downloads, Contact: metres.cmb@gmail.com.

Evidence that the mitochondrial leucyl tRNA synthetase (LARS2) gene represents a novel type 2 diabetes susceptibility gene

NARCIS (Netherlands)

L.M. 't Hart (Leen); H.A.P. Pols (Huib); T. Hansen (Torben); I. Rietveld (Ingrid); J.M. Dekker (Jacqueline); J.A. Maassen (Johannes); M.G.A.A.M. Nijpels (Giel); G.M.C. Janssen (George); P.P. Arp (Pascal); R.J. Heine (Robert); A.G. Uitterlinden (André); T. Jorgensen (Torben); C.M. van Duijn (Cornelia); K. Borch-Johnsen; O. Pedersen (Oluf)

2005-01-01

textabstractPreviously, we have shown that a mutation in the mitochondrial DNA-encoded tRNA(Leu(UUR)) gene is associated with type 2 diabetes. One of the consequences of this mutation is a reduced aminoacylation of tRNA(Leu(UUR)). In this study, we have examined whether variants in the leucyl tRNA

Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

International Nuclear Information System (INIS)

Conde, João; Silva, Susana N; Azevedo, Ana P; Teixeira, Valdemar; Pina, Julieta Esperança; Rueff, José; Gaspar, Jorge F

2009-01-01

MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH). Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer. It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results

Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

Directory of Open Access Journals (Sweden)

Pina Julieta

2009-09-01

Full Text Available Abstract Background MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Results Using unconditional logistic regression we found that MLH3 (L844P, G>A polymorphism GA (Leu/Pro and AA (Pro/Pro genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95 (p = 0.03 and OR = 0.62 (0.41-0.94 (p = 0.03, respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83, p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49, p = 0.01], GG/AA [OR = 2.11 (1.12-3,98, p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15, p = 0.02] all associated with an increased risk for breast cancer. Conclusion It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.

Studies of genetic variability of the hepatocyte nuclear factor-1α gene in an Indian maturity-onset diabetes of the young family.

Science.gov (United States)

Yang, Jing; Jiang, Feng; Guo, Hui; Soniya, Thadimacca; Yan, Chun-Xia; Tian, Zhu-Fang; Shi, Bing-Yin

2016-01-01

Maturity-onset diabetes of the young (MODY), one of the specific types of diabetes mellitus, is a monogenetic disorder characterized by an autosomal dominant (AD) inheritance and β-cell dysfunction. To study an Indian family with clinical diagnosis of MODY and detect the genetic mutations in the aspect of molecular mechanism, seven blood samples were obtained from the diabetic patients of this pedigree and genomic DNA was extracted from peripheral leukocytes. The exon1, exon2 and exon4 of hepatocyte nuclear factor-1α (HNF-1α) gene were amplified by polymerase chain reaction. Then the products were sequenced and compared with standard sequences on gene bank. As a result, two mutations were detected in exon1. That was CTC → CTG (Leu → Leu) in codon17 and ATC → CTC (Ile → Leu) in codon27. I27L was speculated to have a close relationship with the glycometabolism and the pathogenesis of diabetes mellitus together with the putative novel mutation existed in this Indian pedigree. Meanwhile, one mutation of GGG → GGC (Gly → Gly) in codon288 of exon4 was detected in the proband. No mutations were found in exon2 but a G → T base substitution in the intron4 region among all seven samples was detected. It may have some potential effects on the onset of diabetes in this family, but we do not have any evidence right now. Although it requires further investigation on the function of mutations found in the intron region, our research may provide some clue for this issue and it deserves more attention.

Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster

DEFF Research Database (Denmark)

Eriksen, Kathrine Krageskov; Hauser, Frank; Schiøtt, Morten

2000-01-01

After screening the Berkeley Drosophila Genome Project database with sequences from a recently characterized Leu-rich repeats-containing G protein-coupled receptor (LGR) fromDrosophila (DLGR-1), we identified a second gene for a different LGR (DLGR-2) and cloned its cDNA. DLGR-2 is 1360 amino aci...... knock-out mutants, where the DLGR-2 gene is interrupted by a P element insertion, die around the time of hatching. This finding, together with the expression data, strongly suggests that DLGR-2 is exclusively involved in development....

Integrating multi-omics analyses of Nonomuraea dietziae to reveal the role of soybean oil in [(4'-OH)MeLeu]4-CsA overproduction.

Science.gov (United States)

Liu, Huanhuan; Huang, Di; Jin, Lina; Wang, Cheng; Liang, Shaoxiong; Wen, Jianping

2017-07-14

Nonomuraea dietziae is a promising microorganism to mediate the region-specific monooxygenation reaction of cyclosporine A (CsA). The main product [(4'-OH)MeLeu] 4 -CsA possesses high anti-HIV/HCV and hair growth-stimulating activities while avoiding the immunosuppressive effect of CsA. However, the low conversion efficiency restricts the clinical application. In this study, the production of [(4'-OH)MeLeu] 4 -CsA was greatly improved by 55.6% from 182.8 to 284.4 mg/L when supplementing soybean oil into the production medium, which represented the highest production of [(4'-OH)MeLeu] 4 -CsA so far. To investigate the effect of soybean oil on CsA conversion, some other plant oils (corn oil and peanut oil) and the major hydrolysates of soybean oil were fed into the production medium, respectively. The results demonstrated that the plant oils, rather than the hydrolysates, could significantly improve the [(4'-OH)MeLeu] 4 -CsA production, suggesting that soybean oil might not play its role in the lipid metabolic pathway. To further unveil the mechanism of [(4'-OH)MeLeu] 4 -CsA overproduction under the soybean oil condition, a proteomic analysis based on the two-dimensional gel electrophoresis coupled with MALDI TOF/TOF mass spectrometry was implemented. The results showed that central carbon metabolism, genetic information processing and energy metabolism were significantly up-regulated under the soybean oil condition. Moreover, the gas chromatography-mass spectrometry-based metabolomic analysis indicated that soybean oil had a great effect on amino acid metabolism and tricarboxylic acid cycle. In addition, the transcription levels of cytochrome P450 hydroxylase (CYP) genes for CsA conversion were determined by RT-qPCR and the results showed that most of the CYP genes were up-regulated under the soybean oil condition. These findings indicate that soybean oil could strengthen the primary metabolism and the CYP system to enhance the mycelium growth and the

On the genetics of loss aversion: An interaction effect of BDNF Val66Met and DRD2/ANKK1 Taq1a.

Science.gov (United States)

Voigt, Gesine; Montag, Christian; Markett, Sebastian; Reuter, Martin

2015-12-01

Loss aversion is the tendency to overweight losses compared with gains in decision situations. Several studies have investigated the neurobiological background of this phenomenon and it was found that activation in the mesolimbic-mesocortical dopamine system during a gambling decision correlates with loss aversion. In a behavioral experiment with N = 143 subjects, the present study investigates the influence of 2 functional single-nucleotide polymorphisms on the BDNF gene (BDNF Val66Met polymorphism) and ANKK1 gene (DRD2 Taq1a/ANKK1 polymorphism), that are known to affect the dopamine system, on loss aversion. Additionally, associations of alexithymia, a personality construct describing the disability to consciously experience emotions in the self, with loss aversion and with the mentioned polymorphisms were assessed using the TAS-20 questionnaire, to replicate associations that have been reported before. Results revealed a significant interaction effect of the 2 polymorphisms on loss aversion. Carriers of the genetic constellation 66Met+/A1+ had the lowest loss aversion scores, compared with all other allelic groups. According to the literature this allelic configuration is characterized by a relatively low D2/3 receptor binding in the striatum and an impaired activity-dependent secretion of BDNF. This is the first study showing that loss aversion is related to naturally occurring differences in dopamine function. (c) 2015 APA, all rights reserved).

Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta-analysis and new data

NARCIS (Netherlands)

Brandys, Marek K.; Slof-Op't Landt, Margarita C. T.; van Elburg, Annemarie A.; Ophoff, Roel; Verduijn, Willem; Meulenbelt, Ingrid; Middeldorp, Christel M.; Boomsma, Dorret I.; van Furth, Eric F.; Slagboom, Eline; Kas, Martien J. H.; Adan, Roger A. H.

2012-01-01

Objectives This study aimed to test the association between the Val158Met polymorphism (rs4680) of the catechol-O-methyl transferase gene and anorexia nervosa (AN). Methods First, an association study on two cohorts (306 cases and 1009 controls from Utrecht, and 174 cases and 466 controls from

2010 national progress report on R and D on LEU fuel and target technology in Argentina

International Nuclear Information System (INIS)

Balart, S.; Blaumann, H.; Cristini, P.; Gonzalez, A.G.; Gonzalez, R.; Hermida, J.D.; Lopez, M.; Mirandou, M.; Taboada, H.

2010-01-01

Since last RRFM meeting, CNEA has deployed several related tasks. The RA-6 MTR type reactor, converted its core from HEU to a new LEU silicide one is scaling up the power, according to a protocol requested by the national regulatory body, ARN. CNEA is deploying an intense R and D activity to fabricate both dispersed U-Mo (Al-Si matrix and Al cladding) and monolithic (Zry-4 cladding) miniplates to develop possible solutions to VHD dispersed and monolithic fuels technical problems. Some monolithic 58% enrichment U8%Mo and U10%Mo are being delivered to INL-DoE to be irradiated in ATR reactor core. A conscientious study on compound interphase formation in both cases is being carried out. CNEA, a worldwide leader on LEU technology for fission radioisotope production is providing Brazil with these radiopharmaceutical products and Egypt and Australia with the technology through INVAP SE. CNEA is also committed to improve the diffusion of LEU target and radiochemical technology for radioisotope production and target and process optimization. Future plans include: 1) Fabrication of a LEU dispersed U-Mo fuel prototype following the recommendations of the IAEA's Good Practices document, to be irradiated in a high flux reactor in the frame of the ARG/4/092 IAEA's Technical Cooperation project. 2) Development of LEU very high density monolithic and dispersed U-Mo fuel plates with Zry-4 or Al cladding as a part of the RERTR program. 3) Optimization of LEU target and radiochemical techniques for radioisotope production. (author)

DNFSB recommendation 94-1 Hanford site integrated stabilization management plan

Energy Technology Data Exchange (ETDEWEB)

McCormack, R.L.

1997-05-07

In May 1994, the Defense Nuclear Facilities Safety Board (DNFSB) issued DNFSB Recommendation 94-1 (Conway 1994), which identified concerns related to US Department of Energy (DOE) management of legacy fissile materials remaining from past defense production activities. The DNFSB expressed concern about the existing storage conditions for these materials and the slow pace at which the conditions were being remediated. The DNFSB also expressed its belief that additional delays in stabilizing these fissile materials would be accompanied by further deterioration of safety and unnecessary increased risks to workers and the public. In February 1995, DOE issued the DNFSB Recommendation 94-1 Implementation Plan (O`Leary 1995) to address the concerns identified in DNFSB Recommendation 94-1. The Implementation Plan (IP) identifies several DOE commitments to achieve safe interim storage for the legacy fissile materials, and constitutes DOE`s baseline DNFSB Recommendation 94-1 Integrated Program Plan (IPP). The IPP describes the actions DOE plans to implement within the DOE complex to convert its excess fissile materials to forms or conditions suitable for safe interim storage. The IPP was subsequently supplemented with an Integrated Facilities Plan and a Research and Development Plan, which further develop complex-wide research and development and long-range facility requirements and plans. The additions to the baseline IPP were developed based on a systems engineering approach that integrated facilities and capabilities at the various DOE sites and focused on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the DNFSB Recommendation 94-1 IP. The SISMPs also supported

DNFSB recommendation 94-1 Hanford site integrated stabilization management plan

International Nuclear Information System (INIS)

McCormack, R.L.

1997-01-01

In May 1994, the Defense Nuclear Facilities Safety Board (DNFSB) issued DNFSB Recommendation 94-1 (Conway 1994), which identified concerns related to US Department of Energy (DOE) management of legacy fissile materials remaining from past defense production activities. The DNFSB expressed concern about the existing storage conditions for these materials and the slow pace at which the conditions were being remediated. The DNFSB also expressed its belief that additional delays in stabilizing these fissile materials would be accompanied by further deterioration of safety and unnecessary increased risks to workers and the public. In February 1995, DOE issued the DNFSB Recommendation 94-1 Implementation Plan (O'Leary 1995) to address the concerns identified in DNFSB Recommendation 94-1. The Implementation Plan (IP) identifies several DOE commitments to achieve safe interim storage for the legacy fissile materials, and constitutes DOE's baseline DNFSB Recommendation 94-1 Integrated Program Plan (IPP). The IPP describes the actions DOE plans to implement within the DOE complex to convert its excess fissile materials to forms or conditions suitable for safe interim storage. The IPP was subsequently supplemented with an Integrated Facilities Plan and a Research and Development Plan, which further develop complex-wide research and development and long-range facility requirements and plans. The additions to the baseline IPP were developed based on a systems engineering approach that integrated facilities and capabilities at the various DOE sites and focused on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the DNFSB Recommendation 94-1 IP. The SISMPs also supported

HEU to LEU fuel conversion. Final report

International Nuclear Information System (INIS)

Mulder, R.U.

1994-10-01

The Nuclear Regulatory Commission issued a ruling, effective March 27, 1986, that all U.S. non-power reactors convert from HEU fuel to LEU fuel. A Reduced Enrichment for Research and Test Reactors Program was conducted by the Department of Energy at Argonne National Laboratory to coordinate the development of the high density LEU fuel and assist in the development of Safety Analysis Reports for the smaller non-power reactors. Several meetings were held at Argonne in 1987 with the non-power reactor community to discuss the conversion and to set up a conversion schedule for university reactors. EG ampersand G at Idaho was assigned the coordination of the fuel element redesigns. The fuel elements were manufactured by the Babcock ampersand Wilcox Company in Lynchburg, Virginia. The University of Virginia was awarded a grant by the DOE Idaho Operations Office in 1988 to perform safety analysis studies for the LEU conversion for its 2 MW UVAR and 100 Watt CAVALIER reactors. The University subsequently decided to shut down the CAVALIER reactor. A preliminary SAR on the UVAR, along with Technical Specification changes, was submitted to the NRC in November, 1990. An updated SAR was approved by the NRC in January, 1991. In September, 1992, representatives from the fuel manufacturer (B ampersand W) and the fuel designer (EG ampersand G, Idaho) came to the UVAR facility to observe trial fittings of new 22 plate LEU mock fuel elements. B ampersand W fabricated two non-fuel bearing elements, a regular 22 plate element and a control rod element. The elements were checked against the drawings and test fitted in the UVAR grid plate. The dimensions were acceptable and the elements fit in the grid plate with no problems. The staff made several suggestions for minor construction changes to the end pieces on the elements, which were incorporated into the final design of the actual fuel elements. Selected papers are indexed separately for inclusion in the Energy Science and Technology

HEU to LEU fuel conversion. Final report

Energy Technology Data Exchange (ETDEWEB)

Mulder, R.U.

1994-10-01

The Nuclear Regulatory Commission issued a ruling, effective March 27, 1986, that all U.S. non-power reactors convert from HEU fuel to LEU fuel. A Reduced Enrichment for Research and Test Reactors Program was conducted by the Department of Energy at Argonne National Laboratory to coordinate the development of the high density LEU fuel and assist in the development of Safety Analysis Reports for the smaller non-power reactors. Several meetings were held at Argonne in 1987 with the non-power reactor community to discuss the conversion and to set up a conversion schedule for university reactors. EG&G at Idaho was assigned the coordination of the fuel element redesigns. The fuel elements were manufactured by the Babcock & Wilcox Company in Lynchburg, Virginia. The University of Virginia was awarded a grant by the DOE Idaho Operations Office in 1988 to perform safety analysis studies for the LEU conversion for its 2 MW UVAR and 100 Watt CAVALIER reactors. The University subsequently decided to shut down the CAVALIER reactor. A preliminary SAR on the UVAR, along with Technical Specification changes, was submitted to the NRC in November, 1990. An updated SAR was approved by the NRC in January, 1991. In September, 1992, representatives from the fuel manufacturer (B&W) and the fuel designer (EG&G, Idaho) came to the UVAR facility to observe trial fittings of new 22 plate LEU mock fuel elements. B&W fabricated two non-fuel bearing elements, a regular 22 plate element and a control rod element. The elements were checked against the drawings and test fitted in the UVAR grid plate. The dimensions were acceptable and the elements fit in the grid plate with no problems. The staff made several suggestions for minor construction changes to the end pieces on the elements, which were incorporated into the final design of the actual fuel elements. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

Irradiation experiment conceptual design parameters for MURR LEU U-Mo fuel conversion

International Nuclear Information System (INIS)

Stillman, J.; Feldman, E.; Stevens, J.; Wilson, E.

2013-03-01

This report contains the results of reactor design and performance calculations for conversion of the University of Missouri Research Reactor (MURR) from the use of highly-enriched uranium (HEU) fuel to the use of low-enriched uranium (LEU) fuel. The analyses were performed by staff members of the Global Threat Reduction Initiative (GTRI) Reactor Conversion Program at the Argonne National Laboratory (ANL) and the MURR Facility. The core conversion to LEU is being performed with financial support from the U. S. government. In the framework of its non-proliferation policies, the international community presently aims to minimize the amount of nuclear material available that could be used for nuclear weapons. In this geopolitical context most research and test reactors, both domestic and international, have started a program of conversion to the use of LEU fuel. A new type of LEU fuel based on an alloy of uranium and molybdenum (U-Mo) is expected to allow the conversion of U.S. domestic high performance reactors like MURR. This report presents the nominal steady-state irradiation conditions of a key set of plates containing peak irradiation parameters found in MURR cores fueled with the LEU monolithic U-Mo alloy fuel with 10 wt% Mo.

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

Directory of Open Access Journals (Sweden)

Borda Sandra

2009-09-01

Full Text Available Abstract Background The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT gene (polymorphism Val158 Met as a risk factor for Alzheimer's disease (AD and mild cognitive impairment of amnesic type (MCI, and its synergistic effect with the apolipoprotein E gene (APOE. A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU (Spain determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR and polymerase chain reaction (PCR, and restriction fragment length polymorphism (RFLPs, respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG showed a synergistic effect with APOE ε4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p In MCI patients such as synergistic effect was only found between AG and APOE ε4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02 and was greater in men (OR = 5.88 95%CI 1.69-20.42, p Conclusion COMT (Val158 Met polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE ε4 allele that proves greater in women with AD.

COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study

Directory of Open Access Journals (Sweden)

Hayashi K

2014-06-01

Full Text Available Kenji Hayashi,1 Reiji Yoshimura,1 Shingo Kakeda,2 Taro Kishi,3 Osamu Abe,4 Wakako Umene-Nakano,1 Asuka Katsuki,1 Hikaru Hori,1 Atsuko Ikenouchi-Sugita,1 Keita Watanabe,2 Satoru Ide,2 Issei Ueda,2 Junji Moriya,2 Nakao Iwata,3 Yukunori Korogi,2 Marek Kubicki,5 Jun Nakamura1 1Department of Psychiatry, 2Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Psychiatry, Fujita Health University, Toyoake, Japan; 4Department of Radiology, Nihon University School of Medicine, Tokyo, Japan; 5Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Abstract: We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF gene, and white matter changes in patients with major depressive disorder (MDD and healthy subjects using diffusion tensor imaging (DTI. We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years. Using DTI analysis with a tract-based spatial statistics (TBSS approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects. In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05. No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association

Syntheses of deuterated leu-enkephalins and their use as internal standards for the quantification of leu-enkephalin by fast atom bombardment mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Benfenati, E. (Istituto di Ricerche Farmacologiche Mario Negri, Bergamo (Italy) Istituto di Ricerche Farmacologiche Mario Negri, Milan (Italy)); Icardi, G.; Chen, S. (Istituto di Ricerche Farmacologiche Mario Negri, Bergamo (Italy)); Fanelli, R. (Istituto di Ricerche Farmacologiche Mario Negri, Milan (Italy))

1990-04-01

We have developed a synthetic method for the preparation of di- and pentadeuterated leu-enkephalin (LE), Tyr-Gly-Gly-Phe-Leu, by proton-deuterium exchange using CF[sub 3]COOO[sup 2]H. Four to six deuterium atoms are introduced using a reaction temperature of 120[sup o]C and if 5% of [sup 2]H[sub 2]O is added the di-deuterated LE is obtained. These deuterated compounds are used as internal standards to plot calibration curves of LE using fast atom bombardment mass spectrometry. (author).

Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study

DEFF Research Database (Denmark)

Ravn-Haren, Gitte; Olsen, A.; Tjonneland, A.

2006-01-01

Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case...

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.

Science.gov (United States)

Bao, Zhao-Shi; Chen, Hui-Min; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; Hu, Hui-Min; Wang, Zheng; Li, Ming-Yang; Yao, Kun; Qiu, Xiao-Guang; Kang, Chun-Sheng; You, Yong-Ping; Fan, Xiao-Long; Song, Wei Sonya; Li, Rui-Qiang; Su, Xiao-Dong; Chen, Clark C; Jiang, Tao

2014-11-01

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs. © 2014 Bao et al.; Published by Cold Spring Harbor Laboratory Press.

A neutronic feasibility study for LEU conversion of the Brookhaven Medical Research Reactor (BMRR).

Energy Technology Data Exchange (ETDEWEB)

Hanan, N. A.

1998-01-14

A neutronic feasibility study for converting the Brookhaven Medical Research Reactor from HEU to LEU fuel was performed at Argonne National Laboratory in cooperation with Brookhaven National Laboratory. Two possible LEU cores were identified that would provide nearly the same neutron flux and spectrum as the present HEU core at irradiation facilities that are used for Boron Neutron Capture Therapy and for animal research. One core has 17 and the other has 18 LEU MTR-type fuel assemblies with uranium densities of 2.5g U/cm{sup 3} or less in the fuel meat. This LEU fuel is fully-qualified for routine use. Thermal hydraulics and safety analyses need to be performed to complete the feasibility study.

Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis

DEFF Research Database (Denmark)

Tommiska, Johanna; Känsäkoski, Johanna; Skibsbye, Lasse

2017-01-01

unrelated families harbor either of two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), in KCNQ1, a gene previously implicated in the long QT interval syndrome. Kcnq1 is expressed in hypothalamic GHRH neurons and pituitary somatotropes. Co-expressing KCNQ1 with the KCNE2 β...

Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

Science.gov (United States)

Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Cokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

2014-01-01

c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

Directory of Open Access Journals (Sweden)

Peyda Korhan

Full Text Available c-Met, the receptor for Hepatocyte Growth Factor (HGF, overexpressed and deregulated in Hepatocellular Carcinoma (HCC. Caveolin 1 (CAV1, a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

Thermal-hydraulic analysis of research reactor core with different LEU fuel types using RELAP5

Energy Technology Data Exchange (ETDEWEB)

El-Sahlamy, Neama M. [Nuclear and Radiological Regulatory Authority, Cairo (Egypt)

2017-11-15

In the current work, comparisons between the core performances when using different LEU fuels are done. The fuels tested are UA1{sub X}-A1, U{sub 3}O{sub 8}-Al, and U{sub 3}Si{sub 2}-Al fuels with 19.7 % enrichment. Calculations are done using RELAP5 code to evaluate the thermal-hydraulic performance of the IAEA benchmark 10 MW reactor. First, a reassessment of the slow reactivity insertion transient with UA1{sub X}-A1 LEU fuel to compare the results with those reported in the IAEA TECDOC [1]. Then, comparisons between the thermal-hydraulic core performances when using the three LEU fuels are done. The assessment is performed at initial power of 1.0 W. The reactor power is calculated using the RELAP5 point kinetic model. The reactivity feedback, from changes in water density and fuel temperature, is considered for all cases. From the results it is noticed that U{sub 3}Si{sub 2}-Al fuel gives the best fuel performance since it has the minimum value of peak fuel temperature and the minimum peak clad surface temperature, as operating parameters. Also, it gives the maximum value of the Critical Heat Flux Ratio and the lowest tendency to flow instability occurrence.

Thermal hydraulic analysis of the JMTR improved LEU-core

Energy Technology Data Exchange (ETDEWEB)

Tabata, Toshio; Nagao, Yoshiharu; Komukai, Bunsaku; Naka, Michihiro; Fujiki, Kazuo [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Takeda, Takashi [Radioactive Waste Management and Nuclear Facility Decommissioning Technology Center, Tokai, Ibaraki (Japan)

2003-01-01

After the investigation of the new core arrangement for the JMTR reactor in order to enhance the fuel burn-up and consequently extend the operation period, the ''improved LEU core'' that utilized 2 additional fuel elements instead of formerly installed reflector elements, was adopted. This report describes the results of the thermal-hydraulic analysis of the improved LEU core as a part of safety analysis for the licensing. The analysis covers steady state, abnormal operational transients and accidents, which were described in the annexes of the licensing documents as design bases events. Calculation conditions for the computer codes were conservatively determined based on the neutronic analysis results and others. The results of the analysis, that revealed the safety criteria were satisfied on the fuel temperature, DNBR and primary coolant temperature, were used in the licensing. The operation license of the JMTR with the improved LEU core was granted in March 2001, and the reactor operation with new core started in November 2001 as 142nd operation cycle. (author)

Development of LEU targets for 99Mo production and their chemical processing status 1989

International Nuclear Information System (INIS)

Vandegrift, G.F.; Kwok, J.D.; Chamberlain, D.B.; Hoh, J.C.; Streets, E.W.; Vogler, S.; Thresh, H.R.; Domagala, R.F.; Wiencek, T.C.; Matos, J.E.

1991-01-01

Most of the world's supply of Tc-99m for medical purposes is currently produced from Mo-99 derived from the fissioning of high enriched uranium (HEU). Substitution of low enriched uranium (LEU) silicide fuel for the HEU alloy and aluminide fuels used in current target designs will allow equivalent Mo-99 yields with no change in target geometries. Substitution of uranium metal will also allow the substitution of LEU for HEU. Efforts performed in 1989 focused on (1) fabrication of a uranium metal target by Hot Isostatic Pressing uranium metal foil to zirconium, (2) experimental investigation of the dissolution step for U 3 Si 2 targets, allowing us to present a conceptual design for the dissolution process and equipment, and (3) investigation of the procedures used to reclaim irradiated uranium from Mo-production targets, allowing us to further analyze the waste and by-product problems associated with the substitution of LEU for HEU. (orig.)

Gene expression changes in blood RNA after swimming in a chlorinated pool.

Science.gov (United States)

Salas, Lucas A; Font-Ribera, Laia; Bustamante, Mariona; Sumoy, Lauro; Grimalt, Joan O; Bonnin, Sarah; Aguilar, Maria; Mattlin, Heidi; Hummel, Manuela; Ferrer, Anna; Kogevinas, Manolis; Villanueva, Cristina M

2017-08-01

Exposure to disinfection by-products (DBP) such as trihalomethanes (THM) in swimming pools has been linked to adverse health effects in humans, but their biological mechanisms are unclear. We evaluated short-term changes in blood gene expression of adult recreational swimmers after swimming in a chlorinated pool. Volunteers swam 40min in an indoor chlorinated pool. Blood samples were drawn and four THM (chloroform, bromodichloromethane, dibromochloromethane and bromoform) were measured in exhaled breath before and after swimming. Intensity of physical activity was measured as metabolic equivalents (METs). Gene expression in whole blood mRNA was evaluated using IlluminaHumanHT-12v3 Expression-BeadChip. Linear mixed models were used to evaluate the relationship between gene expression changes and THM exposure. Thirty-seven before-after pairs were analyzed. The median increase from baseline to after swimming were: 0.7 to 2.3 for MET, and 1.4 to 7.1μg/m 3 for exhaled total THM (sum of the four THM). Exhaled THM increased on average 0.94μg/m 3 per 1 MET. While 1643 probes were differentially expressed post-exposure. Of them, 189 were also associated with exhaled levels of individual/total THM or MET after False Discovery Rate. The observed associations with the exhaled THM were low to moderate (Log-fold change range: -0.17 to 0.15). In conclusion, we identified short-term gene expression changes associated with swimming in a pool that were minor in magnitude and their biological meaning was unspecific. The high collinearity between exhaled THM levels and intensity of physical activity precluded mutually adjusted models with both covariates. These exploratory results should be validated in future studies. Copyright © 2017. Published by Elsevier B.V.

Neutronic design of a LEU [low enriched uranium] core for the Ohio State University research reactor

International Nuclear Information System (INIS)

Seshadri, M.D.; Aybar, H.S.; Aldemir, T.

1987-01-01

The 10 kw HEU fuelled Ohio State University Reactor (OSURR) will be upgraded to operate at 500 kW with standardized 125 g 235 U LEU U 3 Si 2 fuel plates. An earlier scoping study based on two-dimensional diffusion calculations has identified the potential LEU core configurations for the conversion/upgrade of OSURR using the standardized plates in a 16-plate (+ 2 dummy plates) standard and 10-scoping study is improved for a more precise determination of the excess reactivities and safety rod worths for these potential configurations. Comparison of the results obtained by the improved model to experimental results and to the results of full-core Monte Carlo simulations shows excellent agreement. The results also indicate that the conversion/upgrade of OSURR can be realized with three possible LEU core configurations while maintaining a cold, clean shutdown margin of 1.57-1.91 % Δ k/k, depending on the configuration used. (Author)

A leukocyte antigen, Leu-13, is involved in induction of resistance of human cells to x-ray cell killing by interferon-α

International Nuclear Information System (INIS)

Kita, Kazuko; Zhai, Ling; Sugaya, Shigeru; Suzuki, Nobuo

2003-01-01

We previously reported on human interferon (HuIFN)-induced resistance of human cells to X-ray and UV cell killing. In this study, we searched for the genes whose expression is responsible for the resistance, using a PCR-based mRNA differential display method and Northern blotting analysis. RSa cells were used for this analysis, because they show increased resistance to X-ray- and UV-caused cell killing by HuIFN-α treatment prior to irradiation. Messenger RNA expression levels for Leu-13, a leukocyte antigen, were markedly up-regulated in RSa cells after HuIFN-α treatment. Furthermore, pretreatment of RSa cells with antisense oligonucleotides for Leu-13 mRNA resulted in the suppression of the HuIFN-α-induced resistance of the cells to X-ray cell killing, but did not modulate HuIFN-α-induced resistance to UV cell killing. These results suggest that Leu-13 is involved in HuIFN-α-induced resistance of human cells to X-ray cell killing, but not to UV cell killing. (author)

The Val66Met polymorphism of the BDNF gene in anorexia nervosa: New data and a meta-analysis

NARCIS (Netherlands)

Brandys, Marek K.; Kas, Martien J. H.; van Elburg, Annemarie A.; Ophoff, Roel; Slof-Op't Landt, Margarita C. T.; Middeldorp, Christel M.; Boomsma, Dorret I.; van Furth, Eric F.; Slagboom, P. Eline; Adan, Roger A. H.

2013-01-01

Objectives. The Val66Met polymorphism (rs6265) of the BDNF gene is a non-synonymous polymorphism, previously associated with anorexia nervosa (AN). Methods. We genotyped rs6265 in 235 patients with AN and 643 controls. Furthermore, we performed a systematic review of all case-control and

XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population.

Science.gov (United States)

Catana, Andreea; Pop, Monica; Marginean, Dragos Horea; Blaga, Ioana Cristina; Porojan, Mihai Dumitru; Popp, Radu Anghel; Pop, Ioan Victor

2016-01-01

Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross-complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group.

Continuing investigations for technology assessment of 99Mo production from LEU [low enriched Uranium] targets

International Nuclear Information System (INIS)

Vandergrift, G.F.; Kwok, J.D.; Marshall, S.L.; Vissers, D.R.; Matos, J.E.

1987-01-01

Currently much of the world's supply of /sup 99m/Tc for medical purposes is produced from 99 Mo derived from the fissioning of high enriched uranium (HEU). The need for /sup 99m/Tc is continuing to grow, especially in developing countries, where needs and national priorities call for internal production of 99 Mo. This paper presents the results of our continuing studies on the effects of substituting low enriched Uranium (LEU) for HEU in targets for the production of fission product 99 Mo. Improvements in the electrodeposition of thin films of uranium metal are reported. These improvements continue to increase the appeal for the substitution of LEU metal for HEU oxide films in cylindrical targets. The process is effective for targets fabricated from stainless steel or hastaloy. A cost estimate for setting up the necessary equipment to electrodeposit uranium metal on cylindrical targets is reported. Further investigations on the effect of LEU substitution on processing of these targets are also reported. Substitution of uranium silicides for the uranium-aluminum alloy or uranium aluminide dispersed fuel used in other current target designs will allow the substitution of LEU for HEU in these targets with equivalent 99 Mo-yield per target and no change in target geometries. However, this substitution will require modifications in current processing steps due to (1) the insolubility of uranium silicides in alkaline solutions and (2) the presence of significant quantities of silicate in solution. Results to date suggest that both concerns can be handled and that substitution of LEU for HEU can be achieved

Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.

Science.gov (United States)

Judson, Matthew C; Bergman, Mica Y; Campbell, Daniel B; Eagleson, Kathie L; Levitt, Pat

2009-04-10

The establishment of appropriate neural circuitry depends on the coordination of multiple developmental events across space and time. These events include proliferation, migration, differentiation, and survival-all of which can be mediated by hepatocyte growth factor (HGF) signaling through the Met receptor tyrosine kinase. We previously found a functional promoter variant of the MET gene to be associated with autism spectrum disorder, suggesting that forebrain circuits governing social and emotional function may be especially vulnerable to developmental disruptions in HGF/Met signaling. However, little is known about the spatiotemporal distribution of Met expression in the forebrain during the development of such circuits. To advance our understanding of the neurodevelopmental influences of Met activation, we employed complementary Western blotting, in situ hybridization, and immunohistochemistry to comprehensively map Met transcript and protein expression throughout perinatal and postnatal development of the mouse forebrain. Our studies reveal complex and dynamic spatiotemporal patterns of expression during this period. Spatially, Met transcript is localized primarily to specific populations of projection neurons within the neocortex and in structures of the limbic system, including the amygdala, hippocampus, and septum. Met protein appears to be principally located in axon tracts. Temporally, peak expression of transcript and protein occurs during the second postnatal week. This period is characterized by extensive neurite outgrowth and synaptogenesis, supporting a role for the receptor in these processes. Collectively, these data suggest that Met signaling may be necessary for the appropriate wiring of forebrain circuits, with particular relevance to the social and emotional dimensions of behavior. (c) 2009 Wiley-Liss, Inc.

Verification of maximum radial power peaking factor due to insertion of FPM-LEU target in the core of RSG-GAS reactor

Energy Technology Data Exchange (ETDEWEB)

Setyawan, Daddy, E-mail: d.setyawan@bapeten.go.id [Center for Assessment of Regulatory System and Technology for Nuclear Installations and Materials, Indonesian Nuclear Energy Regulatory Agency (BAPETEN), Jl. Gajah Mada No. 8 Jakarta 10120 (Indonesia); Rohman, Budi [Licensing Directorate for Nuclear Installations and Materials, Indonesian Nuclear Energy Regulatory Agency (BAPETEN), Jl. Gajah Mada No. 8 Jakarta 10120 (Indonesia)

2014-09-30

Verification of Maximum Radial Power Peaking Factor due to insertion of FPM-LEU target in the core of RSG-GAS Reactor. Radial Power Peaking Factor in RSG-GAS Reactor is a very important parameter for the safety of RSG-GAS reactor during operation. Data of radial power peaking factor due to the insertion of Fission Product Molybdenum with Low Enriched Uranium (FPM-LEU) was reported by PRSG to BAPETEN through the Safety Analysis Report RSG-GAS for FPM-LEU target irradiation. In order to support the evaluation of the Safety Analysis Report incorporated in the submission, the assessment unit of BAPETEN is carrying out independent assessment in order to verify safety related parameters in the SAR including neutronic aspect. The work includes verification to the maximum radial power peaking factor change due to the insertion of FPM-LEU target in RSG-GAS Reactor by computational method using MCNP5and ORIGEN2. From the results of calculations, the new maximum value of the radial power peaking factor due to the insertion of FPM-LEU target is 1.27. The results of calculations in this study showed a smaller value than 1.4 the limit allowed in the SAR.

Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking.

Science.gov (United States)

Suchankova, Petra; Nilsson, Staffan; von der Pahlen, Bettina; Santtila, Pekka; Sandnabba, Kenneth; Johansson, Ada; Jern, Patrick; Engel, Jörgen A; Jerlhag, Elisabet

2016-03-01

The multifaceted gut-brain peptide ghrelin and its receptor (GHSR-1a) are implicated in mechanisms regulating not only the energy balance but also the reward circuitry. In our pre-clinical models, we have shown that ghrelin increases whereas GHSR-1a antagonists decrease alcohol consumption and the motivation to consume alcohol in rodents. Moreover, ghrelin signaling is required for the rewarding properties of addictive drugs including alcohol and nicotine in rodents. Given the hereditary component underlying addictive behaviors and disorders, we sought to investigate whether single nucleotide polymorphisms (SNPs) located in the pre-proghrelin gene (GHRL) and GHSR-1a gene (GHSR) are associated with alcohol use, measured by the alcohol use disorders identification test (AUDIT) and smoking. Two SNPs located in GHRL, rs4684677 (Gln90Leu) and rs696217 (Leu72Met), and one in GHSR, rs2948694, were genotyped in a subset (n = 4161) of a Finnish population-based cohort, the Genetics of Sexuality and Aggression project. The effect of these SNPs on AUDIT scores and smoking was investigated using linear and logistic regressions, respectively. We found that the minor allele of the rs2948694 SNP was nominally associated with higher AUDIT scores (P = 0.0204, recessive model) and smoking (P = 0.0002, dominant model). Furthermore, post hoc analyses showed that this risk allele was also associated with increased likelihood of having high level of alcohol problems as determined by AUDIT scores ≥ 16 (P = 0.0043, recessive model). These convergent findings lend further support for the hypothesized involvement of ghrelin signaling in addictive disorders. © 2015 Society for the Study of Addiction.

LEU fuel fabrication in Argentina

International Nuclear Information System (INIS)

Giorsetti, D.R.; Gomez, J.O.; Marajofsky, A.; Kohut, C.

1985-01-01

As an Institution, aiming to meet with its own needs, CNEA has been intensively developing reduced enriched fuel to use in its own research and test reactors. Development of the fabrication technology as well as the design, installation and operation of the manufacturing plant, have been carried out with its own funds. Irradiation and post-irradiation of test miniplates have been taking place within the framework of the RERTR program. During the last years, CNEA has developed three LEU fuel types. In the previous RERTR meetings, we presented the technological results obtained with these fuel types. This paper focuses on CNEA LEU fuel element manufacturing status and the trained personnel we can offer in design and manufacture fuel capability. CNEA has its own fuel manufacturing technology; the necessary facilities to start the fuel fabrication; qualified technicians and professionals for: fuel design and behaviour analysis; fuel manufacturing and QA; international recognition of its fuel development and manufacturing capability through its ORR miniplate irradiation; its own natural uranium and the future possibility to enrich up to 20% U 235 ; the probability to offer a competitive fuel manufacturing cost in the international market; the disposition to cooperate with all countries that wish to take part and aim to reach an self-sufficiency in their own fuel supply needs

Glucokinase gene mutations: structural and genotype-phenotype analyses in MODY children from South Italy.

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Nadia Tinto

Full Text Available BACKGROUND: Maturity onset diabetes of the young type 2 (or GCK MODY is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK. METHODOLOGY/PRINCIPAL FINDINGS: We screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%; 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: approximately 59% than in the large (4/12: 33% domain or in the connection (1/12: 8% region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD OGTT = 7.8 mMol/L (1.8] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04. CONCLUSIONS: The prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation.

Association between NFKB1 −94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis

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Xiao Yang

2014-01-01

Full Text Available Nuclear factor-κB is associated with the pathogenesis of numerous malignancies, and the functional polymorphism −94ins/del ATTG (rs28362491 in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the −94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs with their 95% confidence intervals (95% CIs to assess the association. We found that the NFKB1 promoter −94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11–1.93; dominant model, OR = 1.26, 95% CI = 1.03–1.53; recessive model, OR = 1.26, 95% CI = 1.05–1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05–1.35. Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect.

Opposing regulation of PROX1 by interleukin-3 receptor and NOTCH directs differential host cell fate reprogramming by Kaposi sarcoma herpes virus.

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Jaehyuk Yoo

Full Text Available Lymphatic endothelial cells (LECs are differentiated from blood vascular endothelial cells (BECs during embryogenesis and this physiological cell fate specification is controlled by PROX1, the master regulator for lymphatic development. When Kaposi sarcoma herpes virus (KSHV infects host cells, it activates the otherwise silenced embryonic endothelial differentiation program and reprograms their cell fates. Interestingly, previous studies demonstrated that KSHV drives BECs to acquire a partial lymphatic phenotype by upregulating PROX1 (forward reprogramming, but stimulates LECs to regain some BEC-signature genes by downregulating PROX1 (reverse reprogramming. Despite the significance of this KSHV-induced bidirectional cell fate reprogramming in KS pathogenesis, its underlying molecular mechanism remains undefined. Here, we report that IL3 receptor alpha (IL3Rα and NOTCH play integral roles in the host cell type-specific regulation of PROX1 by KSHV. In BECs, KSHV upregulates IL3Rα and phosphorylates STAT5, which binds and activates the PROX1 promoter. In LECs, however, PROX1 was rather downregulated by KSHV-induced NOTCH signal via HEY1, which binds and represses the PROX1 promoter. Moreover, PROX1 was found to be required to maintain HEY1 expression in LECs, establishing a reciprocal regulation between PROX1 and HEY1. Upon co-activation of IL3Rα and NOTCH, PROX1 was upregulated in BECs, but downregulated in LECs. Together, our study provides the molecular mechanism underlying the cell type-specific endothelial fate reprogramming by KSHV.

Greek research reactor performance characteristics after addition of beryllium reflector and LEU fuel

International Nuclear Information System (INIS)

Deen, J.R.; Snelgrove, J.L.; Papastergiou, C.

1992-01-01

The GRR-1 is a 5-MW pool-type, light-water-moderated and-cooled reactor fueled with MTR-type fuel elements. Recently received Be reflector blocks will soon be added to the core to add additional reactivity until fresh LEU fuel arrives. REBUS-3 xy fuel cycle analyses, using burnup dependent cross sections, were performed to assist in fuel management decisions for the water- and Be-reflected HEU nonequilibrium cores. Cross sections generated by EPRI-CELL have been benchmarked to identical VIM Monte Carlo models. The size of the Be-reflected LEU core has been reduced to 30 elements compared to 35 for the HEU water-reflected core, and an equilibrium cycle calculation has been performed

Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

Energy Technology Data Exchange (ETDEWEB)

Pejcha, Robert; Ludwig, Martha L. (Michigan)

2010-03-08

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two ({beta}{alpha}){sub 8} barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys){sub 3}Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E {center_dot} Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

International Nuclear Information System (INIS)

Pejcha, Robert; Ludwig, Martha L.

2005-01-01

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (βα) 8 barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys) 3 Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E · Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

Cobalamin-independent methionine synthase (MetE: a face-to-face double barrel that evolved by gene duplication.

Directory of Open Access Journals (Sweden)

Robert Pejchal

2005-02-01

Full Text Available Cobalamin-independent methionine synthase (MetE catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH, both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (betaalpha(8 barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys(3Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E.Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

Elevated Serum Brain-Derived Neurotrophic Factor (BDNF) but not BDNF Gene Val66Met Polymorphism Is Associated with Autism Spectrum Disorders.

Science.gov (United States)

Meng, Wei-Dong; Sun, Shao-Jun; Yang, Jie; Chu, Rui-Xue; Tu, Wenjun; Liu, Qiang

2017-03-01

The aim of our study was to illuminate the potential role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder (ASD). We measured the circulating levels of BDNF in serum and BDNF gene (Val66Met) polymorphisms, in which two indicators were then compared between ASD and normal controls. A total of 82 drug-naïve ASD children and 82 age- and gender-matched normal controls were enrolled in the study. Their serum BDNF levels were detected by the ELISA. BDNF Val66Met polymorphism genotyping was conducted as according to the laboratory's standard protocol in laboratory. The ASD severity assessment was mainly determined by the score of the Childhood Autism Rating Scale (CARS). ELISA assay showed that the mean serum BDNF level of children with ASD was significantly (P BDNF levels and CARS scores (P BDNF genotyping results showed that there was no difference between the ASD cases and the control. Among the children with ASD, the mean serum BDNF level of Met/Met group was lower than other groups. According to the ROC curve generated from our clinical data, the optimal cutoff value of serum BDNF levels, an indicator for diagnosis of ASD, was projected to be 12.50 ng/ml. Thus, it yielded a corresponding sensitivity of 81.7 % and the specificity of 66.9 %. Accordingly, area value under the curve was 0.836 (95 % CI, 0.774-0.897); the positive predictive value (PPV) and the negative predictive value (NPV) were 70.1 and 79.1 %, respectively. These results suggested that rather than Val66Met polymorphism, BDNF was more possible to impact the pathogenesis of ASD.

Solubilization and reconstitution of the formylmethionylleucylphenylalanine receptor coupled to guanine nucleotide regulatory protein

International Nuclear Information System (INIS)

Williamson, K.; Dickey, B.F.; Pyun, H.Y.; Navarro, J.

1988-01-01

The authors describe the solubilization, resolution, and reconstitution of the formylmethionylleucylphenylalanine (fMet-Leu-Phe) receptor and guanine nucleotide regulatory proteins (G-proteins). The receptor was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Guanine nucleotides decreased the number of high-affinity binding sites and accelerated the rate of dissociation of the receptor-ligand complex, suggesting that the solubilized receptor remained coupled to endogenous G-proteins. The solubilized receptor was resolved from endogenous G-proteins by fractionation on a wheat germ agglutinin (WGA)-Sepharose 4B column. High-affinity [ 3 H]fMet-Leu-Phe binding to the WGA-purified receptor was diminished and exhibited reduced guanine nucleotide sensitivity. High-affinity [ 3 H]fMET-Leu-Phe binding and guanine nucleotide sensitivity were reconstituted upon the addition of purified brain G-proteins. Similar results were obtained when the receptor was reconstituted with brain G-proteins into phospholipid vesicles by gel filtration chromatography. In addition, they also demonstrated fMET-Leu-Phe-dependent GTP hydrolysis in the reconstituted vesicles. The results of this work indicate that coupling of the fMet-Leu-Phe receptor to G-proteins converts the receptor to a high-affinity binding state and that agonist produces activation of G-proteins. The resolution and functional reconstitution of this receptor should provide an important step toward the elucidation of the molecular mechanism of the fMet-Leu-Phe transduction system in neutrophils

Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

International Nuclear Information System (INIS)

Tao, W.

1988-01-01

Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release [ 3 H]arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. [ 3 H]arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The [ 3 H]arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates [ 3 H] arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils

Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity.

Science.gov (United States)

Leskelä, Piia; Ukkola, Olavi; Vartiainen, Johanna; Rönnemaa, Tapani; Kaprio, Jaakko; Bouchard, Claude; Kesäniemi, Y Antero

2009-02-01

Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.

Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells.

Science.gov (United States)

Chen, Hai-ying; Ren, Xiao-yan; Wang, Wei-hua; Zhang, Ying-xin; Chen, Shuang-feng; Zhang, Bin; Wang, Le-xin

2014-07-01

Exposure of Tca-8113 cells to proteasome inhibitor carbobenzoxy-Leu-Leu-leucinal (MG-132) causing apoptosis is associated with endoplasmic reticulum (ER) stress. X-box-binding protein-1 (XBP1) is an important regulator of a subset of genes active during ER stress, which is related to cell survival and is required for tumor growth. The present study is to evaluate the effect of MG-132 on ROS production, XBP1 gene expression, tumor necrosis factor receptor-associated factor 2 (TRAF2), ASK1 and c-jun protein expression in tongue squamous cell carcinoma cell line Tca-8113 cells. ROS production was measured by reactive oxygen species assay. X-box binding protein-1 (XBP1) mRNA was analyzed by real-time-PCR, TRAF2, ASK1 and c-jun protein were investigated by western blot and immunocytochemistry respectively. The result indicated that ROS production, TRAF2, ASK1 and c-jun were elevated in MG-132 treated cells. Giving ROS scavenger N-acetyl-L-cysteine (NAC) largely prevented the effects of MG-132. Furthermore, treating with MG-132 lead to decreased XBP1 mRNA expression but could not completely block the expression of XBP1. Taken together, these findings provide the evidence that MG-132 induced ER stress lead to Tca-8113 cells apoptosis through ROS generation and TRAF2-ASK1-JNK signal pathway activation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

SMOPY, a new NDA tool for safeguards of LEU and MOX spent fuel

International Nuclear Information System (INIS)

Lebrun, A.; Merelli, M.; Szabo, J.-L.; Huver, M.; Arenas-Carrasco, J.

2001-01-01

Upon IAEA request, the French support program to IAEA Safeguards has developed a new device for control of the irradiated LEU and MOX fuels. The Safeguards Mox Python (SMOPY) is the achievement of a 4 years R and D program supported by CEA and COGEMA in partnership with Eurisys Mesures. The SMOPY system is based on the combination of 2 NDA techniques (passive neutron and room temperature gamma spectrometry) and on line interpretation tools (automatic gamma spectrum interpretation, depletion code EVO). Through the measurement managing software, all this contributes to the fully automatic measurement, interpretation and characterization of any kind of spent fuel. The device is transportable (50 kg, 60 cm) and is composed of four parts: 1. the measurement head with one high efficiency fission chamber and a micro room temperature gamma spectrometric probe; 2. the carrier which carries the measurement head. The carrier bottom fits the racks for accurate positioning and its top fits operator's fuel moving tool; 3. the portable electronic cabinet which includes both neutron and gamma electronic cards; 4. the portable PC which gets inspectors data, controls the measurement, get measured values, interprets them and immediately provides the inspector with worthwhile info for appropriate on the field decisions. Main features of SMOPY are: Discrimination of MOX versus LEU irradiated fuels in any case (conservative case is one cycle MOX versus three cycles LEU after short cooling time); Full characterization of irradiated LEU (burnup, cooling time, Pu amounts ...); Partial Defect Test on LEU fuels. A first version of SMOPY has been tested in industrial condition during summer 2000. This tests shown a need of shielding improvement around the gamma detector. A new version has been build a will be qualified during a new field test and then the system will be ready for routine operation in IAEA and commercial delivery. After giving details about the system itself, this paper

Innovative nuclear thermal rocket concept utilizing LEU fuel for space application

International Nuclear Information System (INIS)

Nam, Seung Hyun; Venneri, Paolo; Choi, Jae Young; Jeong, Yong Hoon; Chang, Soon Heung

2015-01-01

Space is one of the best places for humanity to turn to keep learning and exploiting. A Nuclear Thermal Rocket (NTR) is a viable and more efficient option for human space exploration than the existing Chemical Rockets (CRs) which are highly inefficient for long-term manned missions such as to Mars and its satellites. NERVA derived NTR engines have been studied for the human missions as a mainstream in the United States of America (USA). Actually, the NERVA technology has already been developed and successfully tested since 1950s. The state-of-the-art technology is based on a Hydrogen gas (H_2) cooled high temperature reactor with solid core utilizing High-Enriched Uranium (HEU) fuel to reduce heavy metal mass and to use fast or epithermal neutron spectrums enabling simple core designs. However, even though the NTR designs utilizing HEU is the best option in terms of rocket performance, they inevitably provoke nuclear proliferation obstacles on all Research and Development (R and D) activities by civilians and non-nuclear weapon states, and its eventual commercialization. To surmount the security issue to use HEU fuel for a NTR, a concept of the innovative NTR engine, Korea Advanced NUclear Thermal Engine Rocket utilizing Low-Enriched Uranium fuel (KANUTER-LEU) is presented in this paper. The design goal of KANUTER-LEU is to make use of a LEU fuel for its compact reactor, but does not sacrifice the rocket performance relative to the traditional NTRs utilizing HEU. KANUTER-LEU mainly consists of a fission reactor utilizing H_2 propellant, a propulsion system and an optional Electricity Generation System as a bimodal engine. To implement LEU fuel for the reactor, the innovative engine adopts W-UO_2 CERMET fuel to drastically increase uranium density and thermal neutron spectrum to improve neutron economy in the core. The moderator and structural material selections also consider neutronic and thermo-physical characteristics to reduce non-fission neutron loss and

Effects of the rad52 gene on recombination in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Prakash, S.; Prakash, L.; Burke, W.; Montelone, B.A.

1980-01-01

Effects of the rad 52 mutation in Saccharomyces cerevisiae on meiotic, γ-ray-induced, uv-induced and spontaneous mitotic recombination were studied. The rad52/rad52 diploids undergo premeiotic DNA synthesis; sporulation occurs but inviable spores are produced. Both intra and intergenic recombination during meiosis were examined in cells transferred from sporulation medium to vegetative medium at different time intervals. No intragenic recombination was observed at the his1-1/his1-315 and trp-5-2/trp5-48 heteroalleles. Gene-centromere recombination also was not observed in rad/52/rad52 diploids. No γ-ray- or uv-induced intragenic mitotic recombination is seen in rad52/rad52 diploids. The rate of spontaneous mitotic recombination is lowered five-fold at the his1-1/his1-315 and leu1-c/leu1-12 heteroalleles. Spontaneous reversion rates of both his1-1 and his1-315 were elevated 10 to 20 fold in rad52/rad52 diploids. The RAD52 gene function is required for spontaneous mitotic recombination, uv- and γ-ray-induced mitotic recombination and mitotic recombination

Analysis of Manganese Superoxide Dismutase and Glutathione Peroxidase 1 Gene Polymorphisms in Vitiligo.

Science.gov (United States)

Seçkin, Havva Yıldız; Kalkan, Göknur; Bütün, İlknur; Akbaş, Ali; Baş, Yalçın; Karakuş, Nevin; Benli, İsmail

2016-08-01

Vitiligo is a hereditary/acquired progressive pigmentation disorder characterized by discoloration of skin as a result of melanocyte dysfunction. Recent studies have proposed that oxidant/antioxidant status plays an important role in vitiligo pathogenesis because of the toxic effects on melanocytes. In this study, we aimed to investigate possible associations of MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms with vitiligo with in Turkish population. The study group consists of 57 patients with vitiligo and 69 healthy controls. Genotyping is performed to identify MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms. The method used for genotyping was based on the PCR amplification and detection of polymorphisms by hybridization probes labeled with fluorescent dyes. Both the genotype and allele frequencies of MnSOD Ala-9Val (p = 0.817 and p = 0.553, respectively) and GPx1 Pro198Leu polymorphisms (p = 0.422 and p = 0.673, respectively) were not significantly different between vitiligo patients and the control group. Although no significant difference was found, this is the first report investigating the possible associations between the MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms in Turkish population. Further studies with large populations will be able to clarify the association better.

Diploid yeast cells yield homozygous spontaneous mutations

Science.gov (United States)

Esposito, M. S.; Bruschi, C. V.; Brushi, C. V. (Principal Investigator)

1993-01-01

A leucine-requiring hybrid of Saccharomyces cerevisiae, homoallelic at the LEU1 locus (leu1-12/leu1-12) and heterozygous for three chromosome-VII genetic markers distal to the LEU1 locus, was employed to inquire: (1) whether spontaneous gene mutation and mitotic segregation of heterozygous markers occur in positive nonrandom association and (2) whether homozygous LEU1/LEU1 mutant diploids are generated. The results demonstrate that gene mutation of leu1-12 to LEU1 and mitotic segregation of heterozygous chromosome-VII markers occur in strong positive nonrandom association, suggesting that the stimulatory DNA lesion is both mutagenic and recombinogenic. In addition, genetic analysis of diploid Leu+ revertants revealed that approximately 3% of mutations of leu1-12 to LEU1 result in LEU1/LEU1 homozygotes. Red-white sectored Leu+ colonies exhibit genotypes that implicate post-replicational chromatid breakage and exchange near the site of leu1-12 reversion, chromosome loss, and subsequent restitution of diploidy, in the sequence of events leading to mutational homozygosis. By analogy, diploid cell populations can yield variants homozygous for novel recessive gene mutations at biologically significant rates. Mutational homozygosis may be relevant to both carcinogenesis and the evolution of asexual diploid organisms.

[Phylogenetic analysis of closely related Leuconostoc citreum species based on partial housekeeping genes].

Science.gov (United States)

Lv, Qiang; Chen, Ming; Xu, Haiyan; Song, Yuqin; Sun, Zhihong; Dan, Tong; Sun, Tiansong

2013-07-04

Using the 16S rRNA, dnaA, murC and pyrG gene sequences, we identified the phylogenetic relationship among closely related Leuconostoc citreum species. Seven Leu. citreum strains originally isolated from sourdough were characterized by PCR methods to amplify the dnaA, murC and pyrG gene sequences, which were determined to assess the suitability as phylogenetic markers. Then, we estimated the genetic distance and constructed the phylogenetic trees including 16S rRNA and above mentioned three housekeeping genes combining with published corresponding sequences. By comparing the phylogenetic trees, the topology of three housekeeping genes trees were consistent with that of 16S rRNA gene. The homology of closely related Leu. citreum species among dnaA, murC, pyrG and 16S rRNA gene sequences were different, ranged from75.5% to 97.2%, 50.2% to 99.7%, 65.0% to 99.8% and 98.5% 100%, respectively. The phylogenetic relationship of three housekeeping genes sequences were highly consistent with the results of 16S rRNA gene sequence, while the genetic distance of these housekeeping genes were extremely high than 16S rRNA gene. Consequently, the dnaA, murC and pyrG gene are suitable for classification and identification closely related Leu. citreum species.

Double heterozygous mutations Gln100Leu and His348Gln of the F7 gene in a patient with factor VII deficiency.

Science.gov (United States)

Li, Min; Zheng, Fangxiu; Jin, Yanhui; Wang, Mingshan; Zhu, Liqing; Yang, Lihong

2013-03-01

A 25-year-old Chinese woman who had a history of easy bruising was admitted to hospital due to uncontrolled epistaxis. She showed factor VII activity level of 2% and factor VII antigen level of 4% of the normal value. We detected a novel missense mutation g.8355 A>T (p.Gln100Leu) in the second epidermal growth factor-like (EGF) domain and a g.11482 T>G (p.His348Gln) in the catalytic domain. Although the Gln100 residue is close to the junction of EGF-2 domain with the serine protease domain, we infer that the substitution of polar negatively charged Gln residue at the position 100 with introduction of nonpolar Leu residue may be likely to perturb proper folding, resulting in decreasing factor VII activity.

Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3.

Science.gov (United States)

Schänzer, A; Rupp, S; Gräf, S; Zengeler, D; Jux, C; Akintürk, H; Gulatz, L; Mazhari, N; Acker, T; Van Coster, R; Garvalov, B K; Hahn, A

2018-03-01

Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age. Detailed morphological analyses of the explanted heart tissue showed intracytoplasmic inclusions, aggregation of BAG3 and desmin, disintegration of myofibers and Z-disk alterations. The presence of undegraded autophagosomes, seen by electron microscopy, as well as increased levels of p62, LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses, indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were not altered. These findings indicate that altered autophagy plays a role in the pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu mutation, which could have implications for future therapeutic strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.

Science.gov (United States)

Zhong, Qian; Shi, Ganggang; Zhang, Yanmei; Lu, Lei; Levy, Daniel; Zhong, Shuping

2015-02-01

Emerging evidence has indicated that alcohol consumption is an established risk factor for breast cancer. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular Pol III gene production, leading to an increase in translational capacity to promote cell transformation and tumor formation. We have reported that alcohol intake increases Pol III gene transcription to promote cell transformation and tumor formation in vitro and in vivo. Studies revealed that tumor suppressors, pRb, p53, PTEN and Maf1 repress the transcription of Pol III genes. BRCA1 is a tumor suppressor and its mutation is tightly related to breast cancer development. However, it is not clear whether BRCA1 expression affects alcohol-induced transcription of Pol III genes. At the present studies, we report that restoring BRCA1 in HCC 1937 cells, which is a BRCA1 deficient cell line, represses Pol III gene transcription. Expressing mutant or truncated BRCA1 in these cells does not affect the ability of repression on Pol III genes. Our analysis has demonstrated that alcohol induces Pol III gene transcription. More importantly, overexpression of BRCA1 in estrogen receptor positive (ER+) breast cancer cells (MCF-7) decreases the induction of tRNA(Leu) and 5S rRNA genes by alcohol, whereas reduction of BRCA1 by its siRNA slightly increases the transcription of the class of genes. This suggests that BRCA1 is associated with alcohol-induced deregulation of Pol III genes. These studies for the first time demonstrate the role of BRCA1 in induction of Pol III genes by alcohol and uncover a novel mechanism of alcohol-associated breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of technology of high density LEU dispersion fuel fabrication

International Nuclear Information System (INIS)

Wiencek, T.; Totev, T.

2007-01-01

Advanced Materials Fabrication Facilities at Argonne National Laboratory have been involved in development of LEU dispersion fuel for research and test reactors from the beginning of RERTR program. This paper presents development of technology of high density LEU dispersion fuel fabrication for full size plate type fuel elements. A brief description of Advanced Materials Fabrication Facilities where development of the technology was carried out is given. A flow diagram of the manufacturing process is presented. U-Mo powder was manufactured by the rotating electrode process. The atomization produced a U-Mo alloy powder with a relatively uniform size distribution and a nearly spherical shape. Test plates were fabricated using tungsten and depleted U-7 wt.% Mo alloy, 4043 Al and Al-2 wt% Si matrices with Al 6061 aluminum alloy for the cladding. During the development of the technology of manufacturing of full size high density LEU dispersion fuel plates special attention was paid to meet the required homogeneity, bonding, dimensions, fuel out of zone and other mechanical characteristics of the plates.

Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.

Science.gov (United States)

Ratbi, Ilham; Jaouad, Imane Cherkaoui; Elorch, Hamza; Al-Sheqaih, Nada; Elalloussi, Mustapha; Lyahyai, Jaber; Berraho, Amina; Newman, William G; Sefiani, Abdelaziz

2016-10-01

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

94-1 R and D program annual operating plan: Fiscal Year 2003

International Nuclear Information System (INIS)

Mason, Richard E.; Dominguez, Pamela D.

2003-01-01

The Laboratory's 94-1 R and D Program is conducted in response to (1) the Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1, 2000-1, and (2) the DNFSB letter to T. J. Glauthier of December 6, 1999, which emphasizes that material stored in a 3013 container must be represented in the Laboratory's Materials Identification and Surveillance (MIS) program. Implementation of the 94-1 R and D Program is the responsibility of the Office of Integration and Disposition. Our program focuses on accelerating the Department of Energy's (DOE's) efforts to reduce health and safety risks to workers, the public, and the environment. Coordinating with the Albuquerque Nuclear Materials Stewardship Office, the Office of Integration of Deposition continues to direct activities under this project that involve the development of stabilization technologies. This program also maintains the viability of the 3013 standard, Section 6, which requires that materials are represented in the MIS inventory. The 94-1 R and D Program focuses on developing the technical basis for stabilizing and safely storing plutonium-bearing materials. To address these issues, we have in place a material identification and stabilization project, a surveillance and monitoring project, and a management team

LEU WWR-M2 fuel assemblies burnable test

International Nuclear Information System (INIS)

Kirsanov, G.A.; Konoplev, K.A.; Pikulik, R.G.; Sajkov, Yu. P.; Tchmshkyan, D.V.; Tedoradze, L.V.; Zakharov, A.S.

2000-01-01

The results of in-pile irradiation tests of LEU WWR-M2 fuel assemblies with reduced enrichment of fuel are submitted in the report. The tests are made according to the Russian Program on Reduced Enrichment for Research and Test Reactors (RERTR). United States Department of Energy and the Ministry of Atomic Energy of Russian Federation jointly fund this Program. The irradiation tests of 5 WWR-M2 experimental assemblies are carried out at WWR-M reactor of the Petersburg Nuclear Physics Institute (PNPI). The information on assembly design and technique of irradiation tests is presented. In the irradiation tests the integrity of fuel assemblies is periodically measured. The report presents the data for the integrity maintained during the burnup of 5 fuel assemblies up to 45%. These results demonstrate the high reliability of the experimental fuel assemblies within the guaranteed burnup limits specified by the manufacturer. The tests are still in progress; it is planned to test and analyze the change in integrity for burnup of up to 70% - 75% or more. LEU WWR-M2 fuel assemblies are to be offered for export by their Novosibirsk manufacturer. Currently, HEU WWR-M2 fuel assemblies are used in Hungary, Ukraine and Vietnam. LEU WWR-M2 fuel assemblies were designed as a possible replacement for the HEU WWR-M2 fuel assemblies in those countries, but their use can be extended to other research reactors. (author)

Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance.

Science.gov (United States)

Mager, Ursula; Kolehmainen, Marjukka; Lindström, Jaana; Eriksson, Johan G; Valle, Timo T; Hämäläinen, Helena; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Tuomilehto, Jaakko O; Pulkkinen, Leena; Uusitupa, Matti I

2006-09-01

Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2+/-4.5 kg/m2, age 55+/-7 years). All six SNPs were screened by the restriction fragment length polymorphism method. Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and Gln90Leu, had the lowest systolic (131+/-11 v 137+/-13 mm Hg, P=.003) and diastolic BP levels (79+/-7 v 83+/-7 mm Hg, P=.004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association. Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance.

What the difference to use LEU and HEU fuel elements separately or together in a research reactor

International Nuclear Information System (INIS)

Kaya, S.; Uestuen, G.

2005-01-01

Concerning of nuclear material safety, most of the research reactors are advised to shift from HEU (high enriched-%93 U-235) to LEU (low enriched-%20 U-235) fuel elements. When LEU and HEU fuel elements are to be used together in a research reactor, some design and safety problems are encountered. According to use of the reactor, some research reactors such as MTR type may not show any considerable difference for HEU or LEU fuel elements, but the efficiency of radioisotope production generated by thermal neutron interaction may decrease about twenty-thirty percent when LEU fuel elements are used. Here, fine mesh-sized 3D neutronic analysis of TR-2 research reactor is presented to indicate the arising problem when LEU end HEU fuel elements are used together in a research reactor. Partial thermohydraulic analysis of the reactor is also given to show the betterness of the LEU fuel element design. However, there might be some points that should be noticed for safer operation of plate type fuelled research reactors. (author)

How LeuT shapes our understanding of the mechanisms of sodium-coupled neurotransmitter transporters.

Science.gov (United States)

Penmatsa, Aravind; Gouaux, Eric

2014-03-01

Neurotransmitter transporters are ion-coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate-free state, inward-open state, and competitive and non-competitive inhibitor-bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.

Preparation results for lifetime test of conversion LEU fuel in plutonium production reactors

International Nuclear Information System (INIS)

Vatulin, A.; Stetskiy, Yu.; Kukharkin, N.; Kalougin, A.; Gavrilov, P.; Ivanov, A.

1999-01-01

The program of converting Russian production reactors for the purpose to stop their plutonium fabrication is currently in progress. The program also provides for operation of these reactors under the conversion mode with using of low-enriched fuel (LEU). LEU fuel elements were developed and activities related to their preparation for reactor tests were carried out. (author)

Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

Energy Technology Data Exchange (ETDEWEB)

Kim, In-Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Lee, Jae-Ha [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, Korea University of Science and Technology (UST), 989-111 Daedeok-daero, Yusong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo-Yoen; Kim, Jeong-Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cho, Eun-Wie [Epigenomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

2014-11-21

Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines

International Nuclear Information System (INIS)

Kim, In-Gyu; Lee, Jae-Ha; Kim, Seo-Yoen; Kim, Jeong-Yul; Cho, Eun-Wie

2014-01-01

Highlights: • FBLN-3 gene was poorly expressed in some pancreatic cancer lines. • FBLN-3 promoter region was highly methylated in some pancreatic cancer cell lines. • FBLN-3 inhibited c-MET activation and expression and reduced cellular level of ALDH1. • FBLN-3/c-Met/ALDH1 axis modulates stemness and EMT in pancreatic cancer cells. - Abstract: Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

Science.gov (United States)

Azeredo, Lucas A de; De Nardi, Tatiana; Levandowski, Mateus L; Tractenberg, Saulo G; Kommers-Molina, Julia; Wieck, Andrea; Irigaray, Tatiana Q; Silva, Irênio G da; Grassi-Oliveira, Rodrigo

2017-01-01

Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

The brain-derived neurotrophic factor (BDNF gene Val66Met polymorphism affects memory performance in older adults

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Lucas A. de Azeredo

Full Text Available Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR, delayed verbal recall (DVR, and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004 and a decline in memory retention (p = 0.017 when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088. Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis pigmentosa

Science.gov (United States)

Pan, Xinyuan; Chen, Xue; Liu, Xiaoxing; Gao, Xiang; Kang, Xiaoli; Xu, Qihua; Chen, Xuejuan; Zhao, Kanxing; Zhang, Xiumei; Chu, Qiaomei; Wang, Xiuying

2014-01-01

Purpose Seven genes involved in precursor mRNA (pre-mRNA) splicing have been implicated in autosomal dominant retinitis pigmentosa (adRP). We sought to detect mutations in all seven genes in Chinese families with RP, to characterize the relevant phenotypes, and to evaluate the prevalence of mutations in splicing genes in patients with adRP. Methods Six unrelated families from our adRP cohort (42 families) and two additional families with RP with uncertain inheritance mode were clinically characterized in the present study. Targeted sequence capture with next-generation massively parallel sequencing (NGS) was performed to screen mutations in 189 genes including all seven pre-mRNA splicing genes associated with adRP. Variants detected with NGS were filtered with bioinformatics analyses, validated with Sanger sequencing, and prioritized with pathogenicity analysis. Results Mutations in pre-mRNA splicing genes were identified in three individual families including one novel frameshift mutation in PRPF31 (p.Leu366fs*1) and two known mutations in SNRNP200 (p.Arg681His and p.Ser1087Leu). The patients carrying SNRNP200 p.R681H showed rapid disease progression, and the family carrying p.S1087L presented earlier onset ages and more severe phenotypes compared to another previously reported family with p.S1087L. In five other families, we identified mutations in other RP-related genes, including RP1 p. Ser781* (novel), RP2 p.Gln65* (novel) and p.Ile137del (novel), IMPDH1 p.Asp311Asn (recurrent), and RHO p.Pro347Leu (recurrent). Conclusions Mutations in splicing genes identified in the present and our previous study account for 9.5% in our adRP cohort, indicating the important role of pre-mRNA splicing deficiency in the etiology of adRP. Mutations in the same splicing gene, or even the same mutation, could correlate with different phenotypic severities, complicating the genotype–phenotype correlation and clinical prognosis. PMID:24940031

The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

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Steven N Steinway

Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

The LEU target development and conversion program for the MAPLE reactors and new processing facility

International Nuclear Information System (INIS)

Malkoske, G.R.

2002-01-01

Historically, the production of molybdenum-99 in the NRU research reactors at Chalk River, Canada has been extracted from reactor targets employing highly enriched uranium (HEU). A reliable supply of HEU metal from the United States used in the manufacture of targets for the NRU research reactor has been a key factor to enable MDS Nordion to develop a secure supply of medical isotopes for the international nuclear medicine community. The molybdenum extraction process from HEU targets provides predictable, consistent yields for our high-volume molybdenum production process. Each link of the isotope supply chain, from isotope production to ultimate use by the physician, has been established using this proven and established method of HEU target irradiation and processing to extract molybdenum-99. To ensure a continued reliable and timely supply of medical isotopes, MDS Nordion is completing the construction of two MAPLE reactors and a New Processing Facility. The design of the MAPLE facilities was based on an established process developed by Atomic Energy of Canada Ltd. (AECL) - extraction of isotopes from HEU target material. However, in concert with the global trend to utilize low enriched uranium (LEU) in research reactors, MDS Nordion has launched a three phase LEU Target Development and Conversion Program for the MAPLE facilities. Phase 1, the Initial Feasibility Study, which identified the technical issues to convert the MAPLE reactor targets from HEU to LEU for large scale commercial production was reported on at the RERTR- 2000 conference. The second phase of the LEU Target Development and Conversion Program was developed with extensive consultation and involvement of experts knowledgeable in target development, process system design, enriched uranium conversion chemistry and commercial scale reactor operations and molybdenum production. This paper will provide an overview of the Phase 2 Conversion Development Program, report on progress to date, and further

Feasibility study for LEU conversion of the WWR-K reactor at the Institute of Nuclear Physics in Kazakhstan using a 5-tube fuel assembly

International Nuclear Information System (INIS)

Hanan, N.A.; Liaw, J.R.; Matos, J.E.

2005-01-01

A feasibility study by the RERTR program for possible LEU conversion of the 6 MW WWR-K reactor concludes that conversion is feasible using an LEU 5-tube Russian fuel assembly design. This 5-tube design is one of several LEU fuel assembly designs being studied (Ref. 1) for possible use in this reactor. The 5-tube assembly contains 200 g 235 U with an enrichment of 19.7% in four cylindrical inner tubes and an outer hexagonal tube with the same external dimensions as the current HEU (36%) 5-tube fuel assembly, which contains 112.5 g 235 U. The fuel meat material, LEU UO 2 -Al dispersion fuel with ∼ 2.5 g U/cm 3 , has been extensively irradiation tested in a number of reactors with uranium enrichments of 36% and 19.7%. Since the 235 U loading of the LEU assemblies is much larger than the HEU assemblies, a smaller LEU core with five rows of fuel assemblies is possible (instead of six rows of fuel assemblies in the HEU core). This smaller LEU core would consume about 60% as many fuel assemblies per year as the current HEU core and provide thermal neutron fluxes in the inner irradiation channels that are ∼ 17% larger than with the present HEU core. The current 21 day cycle length would be maintained and the average discharge burnup would be ∼ 42%. Neutron fluxes in the five outer irradiation channels would be smaller in the LEU core unless these channels can be moved closer to the LEU fuel assemblies. Results show that the smaller LEU core would meet the reactor's shutdown margin requirements and would have an adequate thermal-hydraulic safety margin to onset of nucleate boiling. (author)

Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro).

Science.gov (United States)

Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda; Lodahl, Marianne; Tranebjærg, Lisbeth; Cesur, Yasar; Dogan, Murat; Yilmaz, Cahide; Akgun, Cihangir; Acikgoz, Mehmet

2012-01-01

Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels of protein expression compared to wild-type wolframin, strongly supporting that this mutation is disease-causing. The mutation showed perfect segregation with disease in the family, characterized by early and severe clinical manifestations. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Neutronic analysis for core conversion (HEU–LEU of the low power research reactor using the MCNP4C code

Directory of Open Access Journals (Sweden)

Aldawahra Saadou

2015-06-01

Full Text Available Comparative studies for conversion of the fuel from HEU to LEU in the miniature neutron source reactor (MNSR have been performed using the MCNP4C code. The HEU fuel (UAl4-Al, 90% enriched with Al clad and LEU (UO2 12.6% enriched with zircaloy-4 alloy clad cores have been analyzed in this study. The existing HEU core of MNSR was analyzed to validate the neutronic model of reactor, while the LEU core was studied to prove the possibility of fuel conversion of the existing HEU core. The proposed LEU core contained the same number of fuel pins as the HEU core. All other structure materials and dimensions of HEU and LEU cores were the same except the increase in the radius of control rod material from 0.195 to 0.205 cm and keeping the outer diameter of the control rod unchanged in the LEU core. The effective multiplication factor (keff, excess reactivity (ρex, control rod worth (CRW, shutdown margin (SDM, safety reactivity factor (SRF, delayed neutron fraction (βeff and the neutron fluxes in the irradiation tubes for the existing and the potential LEU fuel were investigated. The results showed that the safety parameters and the neutron fluxes in the irradiation tubes of the LEU fuels were in good agreements with the HEU results. Therefore, the LEU fuel was validated to be a suitable choice for fuel conversion of the MNSR in the future.

Determination of Dancoff correction thermal utilization and thermal disadvantage factors of HEU and LEU cores of an MNSR

International Nuclear Information System (INIS)

Ofori, Y. T.

2013-07-01

Ghana Research Reactor-1 (GHARR-1), an MNSR (Miniature Neutron Source Reactor) is to be converted from HEU (Highly Enriched Uranium) to LEU (Low Enriched Uranium) fuel, along with all current MNSRs in various other countries. The purpose of the conversion is to minimize the use of HEU for non-proliferation of high-grade nuclear fuel. In this research work, a comparative study has been performed for the determination of the Dancoff, thermal utilization and thermal disadvantage factors of highly enriched uranium (HEU) and potential low enriched uranium (LEU) cores of GHARR-1. A one group transport theory and collision probability based methodologies was used to develop mathematical formulations for thermal utilization factor and thermal disadvantage factor assuming isotropic scattering. This methodology was implemented in a FORTRAN 95 based computer program THERMCALC, which uses Bessell and BesselK as subroutines developed to calculate the modified Bessel functions I n and K n respectively using the polynomial approximation method. Furthermore, a Dancoff correction factor of 0.1519 thermal utilization factor of 0.9767 and a thermal disadvantage factor of 1.894 were obtained for the 90.2% highly enriched Uranium core of GHARR-1. The results compare favorably with literature. Thus THERMCALC can be used as a reliable tool for the calculation of Dancoff, thermal utilization and disadvantage factors of MNSR cores. Other potential LEU cores; UO 2 (with different fuel meat densities and enrichments) and U 3 Si 2 have also been analysed. UO 2 with 12.6% of Uranium-235 was chosen as the most potential LEU core for the GHARR-1. (au)

Production of MO-99 from LEU targets - Acid-side processing

International Nuclear Information System (INIS)

Conner, C.; Sedlet, J.; Wiencek, T.C.

2000-01-01

During 2000, additional targets of the new annular design containing low enriched uranium (LEU) foils were irradiated in the Indonesian RSG-GAS reactor. This new design significantly decreases the target fabrication cost. This irradiation allowed us to compare the irradiation performance of several batches of LEU foil. We also processed one of the irradiated foils to recover 99 Mo using a slightly modified Cintichem process. Finally, we measured some important physical properties of uranyl nitrate solutions (i.e., density and solubility), which will be useful in future efforts to further increase the amount of uranium that can be processed by the Cintichem process. (author)

Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Michael Watson

Full Text Available DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG and CHH (H representing A, C or T. Each of these patterns has traditionally been associated with distinct DNA methylation pathways with CHH methylation being controlled by the RNA dependent DNA methylation (RdDM pathway employing small RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2, and maintenance DNA METHYLTRANSFERASE1 (MET1 being responsible for faithful propagation of CG methylation. Here we report an unusual 'dense methylation' pattern under the control of MET1, with methylation in all three sequence contexts. We identified epi-alleles of dense methylation at a non coding RNA locus (At4g15242 in Arabidopsis ecotypes, with distinct dense methylation and expression characteristics, which are stably maintained and transmitted in genetic crosses and which can be heritably altered by depletion of MET1. This suggests that, in addition to its classical CG maintenance function, at certain loci MET1 plays a role in creating transcriptional diversity based on the generation of independent epi-alleles. Database inspection identified several other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes contain distinct epi-alleles of these loci with expression patterns that inversely correlate with methylation density, predominantly within the transcribed region. In Arabidopsis, dense methylation appears to be an exception as it is only found at a small number of loci. Its presence does, however, highlight the potential for MET1 as a contributor to epigenetic diversity, and it will be interesting to investigate the representation of dense methylation in other plant species.

Enkephalins: Raman spectral analysis and comparison as function of pH 1-13

DEFF Research Database (Denmark)

Abdali, Salim; Refstrup, Pia; Nielsen, O.F.

2003-01-01

Raman spectral studies are carried out on Leu- and Met-enkephalin as a function of the pH value in the range of 1-13. The molecules are dissolved in KCI solvent and the pH is controlled at each value. Spectral analyses reveal the dependence of the structural conformation on the pH, and a comparis...

Temporal effects of Notch signaling and potential cooperation with multiple downstream effectors on adenohypophysis cell specification in zebrafish.

Science.gov (United States)

Nakahara, Yoshinari; Muto, Akihiko; Hirabayashi, Ryo; Sakuma, Tetsushi; Yamamoto, Takashi; Kume, Shoen; Kikuchi, Yutaka

2016-05-01

The adenohypophysis (AH) consists of six distinct types of hormone-secreting cells. In zebrafish, although proper differentiation of all AH cell types has been shown to require Notch signaling within a period of 14-16 h postfertilization (hpf), the mechanisms underlying this process remain to be elucidated. Herein, we observed using the Notch inhibitor dibenzazepine (DBZ) that Notch signaling also contributed to AH cell specification beyond 16 hpf. Specification of distinct cell types was perturbed by DBZ treatment for different time frames, suggesting that AH cells are specified by Notch-dependent and cell-type-specific mechanisms. We also found that two hes-family genes, her4.1 and hey1, were expressed in the developing AH under the influence of Notch signaling. her4.1 knockdown reduced expression of proopiomelanocortin a (pomca), growth hormone (gh), and prolactin, whereas hey1 was responsible only for gh expression. Simultaneous loss of both Her4.1 and Hey1 produced milder phenotypes than that of DBZ-treated embryos. Moreover, DBZ treatment from 18 hpf led to a significant down-regulation of both gh and pomca genes only when combined with injection of a subthreshold level of her4.1-morpholino. These observations suggest that multiple downstream effectors, including Her4.1 and Hey1, mediate Notch signaling during AH cell specification. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

The Role of the Catechol-o-methyltransferase (COMT) Gene Val158Met in Aggressive Behavior, A Review of Genetic Studies

Science.gov (United States)

Qayyum, Arqam; Zai, Clement C.; Hirata, Yuko; Tiwari, Arun K.; Cheema, Sheraz; Nowrouzi, Behdin; Beitchman, Joseph H.; Kennedy, James L.

2015-01-01

Aggressive behaviors have become a major public health problem, and early-onset aggression can lead to outcomes such as substance abuse, antisocial personality disorder among other issues. In recent years, there has been an increase in research in the molecular and genetic underpinnings of aggressive behavior, and one of the candidate genes codes for the catechol-O-methyltransferase (COMT). COMT is involved in catabolizing catecholamines such as dopamine. These neurotransmitters appear to be involved in regulating mood which can contribute to aggression. The most common gene variant studied in the COMT gene is the Valine (Val) to Methionine (Met) substitution at codon 158. We will be reviewing the current literature on this gene variant in aggressive behavior. PMID:26630958

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms in dilutional pseudoanemia (sports anemia).

Science.gov (United States)

Miranda-Vilela, Ana L; Akimoto, Arthur K; Alves, Penha C Z; Pereira, Luiz C S; Klautau-Guimarães, Maria N; Grisolia, Cesar K

2010-04-01

Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb.) is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

Ghrelin precursor gene polymorphism and methamphetamine dependence in the Korean population.

Science.gov (United States)

Yoon, Su-Jung; Pae, Chi-Un; Lee, Heejin; Choi, Bomoon; Kim, Tae-Suk; Lyoo, In Kyoon; Kwon, Do-Hoon; Kim, Dai-Jin

2005-12-01

Ghrelin is a recently isolated brain-gut peptide that has growth hormone-releasing and appetite-inducing activities. Several recent studies have suggested that ghrelin plays a major role in the pathophysiology of drug-seeking behavior and anxiety. Therefore, we assessed the effect of the ghrelin precursor polymorphism on methamphetamine dependence in the Korean population. One hundred and eighteen patients with methamphetamine dependence, according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria, and the 144 healthy controls were enrolled in this study. Genotyping for the ghrelin precursor polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism-based technique. The genotypic and allelic distributions of the ghrelin precursor polymorphism in the patients with methamphetamine dependence were not significantly different from those of the control subjects. However, the Met72 carriers were associated with the emotional problems of methamphetamine dependence. The patients with the Met72 allele were more depressed and anxious than the homozygous patients with the wild Leu72 allele. The present study suggests that the ghrelin precursor polymorphism may not confer a susceptibility to the development of methamphetamine dependence in the Korean population. However, the Leu72Met polymorphism could have a potential role in the emotional problems that are associated with this disease.

Gene mapping and functional analysis of the novel leaf color gene SiYGL1 in foxtail millet [Setaria italica (L.) P. Beauv].

Science.gov (United States)

Li, Wen; Tang, Sha; Zhang, Shuo; Shan, Jianguo; Tang, Chanjuan; Chen, Qiannan; Jia, Guanqing; Han, Yuanhuai; Zhi, Hui; Diao, Xianmin

2016-05-01

Setaria italica and its wild ancestor Setaria viridis are emerging as model systems for genetics and functional genomics research. However, few systematic gene mapping or functional analyses have been reported in these promising C4 models. We herein isolated the yellow-green leaf mutant (siygl1) in S. italica using forward genetics approaches. Map-based cloning revealed that SiYGL1, which is a recessive nuclear gene encoding a magnesium-chelatase D subunit (CHLD), is responsible for the mutant phenotype. A single Phe to Leu amino acid change occurring near the ATPase-conserved domain resulted in decreased chlorophyll (Chl) accumulation and modified chloroplast ultrastructure. However, the mutation enhanced the light-use efficiency of the siygl1 mutant, suggesting that the mutated CHLD protein does not completely lose its original activity, but instead, gains novel features. A transcriptional analysis of Chl a oxygenase revealed that there is a strong negative feedback control of Chl b biosynthesis in S. italica. The SiYGL1 mRNA was expressed in all examined tissues, with higher expression observed in the leaves. Comparison of gene expression profiles in wild-type and siygl1 mutant plants indicated that SiYGL1 regulates a subset of genes involved in photosynthesis (rbcL and LHCB1), thylakoid development (DEG2) and chloroplast signaling (SRP54CP). These results provide information regarding the mutant phenotype at the transcriptional level. This study demonstrated that the genetic material of a Setaria species could be ideal for gene discovery investigations using forward genetics approaches and may help to explain the molecular mechanisms associated with leaf color variation. © 2015 Scandinavian Plant Physiology Society.

Patienten met diabetes Mellitus type 1 screenen op coeliakie; Ja of nee

NARCIS (Netherlands)

Greijdanus, T.

2005-01-01

Diabetes mellitus type 1 is een veelvoorkomende ziekte. Deze ziekte blijkt niet op zichzelf te staan maar is onder andere geassocieerd met coeliakie. Coeliakie wordt behandeld middels een glutenvrij dieet. De diabetespatiënten die aan coeliakie lijden blijken zich niet altijd bij de huisarts met

Identification of a novel PSEN1 mutation (Leu232Pro) in a Korean patient with early-onset Alzheimer's disease and a family history of dementia.

Science.gov (United States)

Park, Jiyun; An, Seong Soo A; Giau, Vo Van; Shim, Kyuhwan; Youn, Young Chul; Bagyinszky, Eva; Kim, SangYun

2017-08-01

In the present study, a novel mutation in exon 7 of presenilin 1 (Leu232Pro) was discovered in a Korean patient with early-onset Alzheimer's disease, who represented memory decline at 37 years of age, followed by impairment in spatial activity and concentrations and personality changes. Imaging analyses with magnetic resonance scan showed diffuse atrophy in the frontoparietal regions. Targeted next generation sequencing and Sanger sequencing identified a heterozygous T to C transition at position 695 (c.695T>C) of in presenilin 1 gene (PSEN1), resulting in a novel missense mutation at codon 232 from leucine to proline (L232P). Several family members of the patient developed dementia, suggesting an autosomal dominant inheritance; however, we were unable to perform a segregation analysis to confirm this. Since the proline may play a role as a helix breaker, this mutation could significantly disturb the transmembrane helix domain-V of PSEN1 and perturb its protein functions. This hypothesis was supported by the results from the in silico analyses, predicted a major kink on this helix. Several leucine>proline substitutions in other PSEN1 transmembrane helices revealed aggressive AD phenotypes. Future functional studies would be needed to evaluate the pathogenicity of this mutation in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

MetWAMer: eukaryotic translation initiation site prediction

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Brendel Volker

2008-09-01

Full Text Available Abstract Background Translation initiation site (TIS identification is an important aspect of the gene annotation process, requisite for the accurate delineation of protein sequences from transcript data. We have developed the MetWAMer package for TIS prediction in eukaryotic open reading frames of non-viral origin. MetWAMer can be used as a stand-alone, third-party tool for post-processing gene structure annotations generated by external computational programs and/or pipelines, or directly integrated into gene structure prediction software implementations. Results MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage. Conclusion We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.

The association of ghrelin polymorphisms with coronary artery disease and ischemic chronic heart failure in an elderly Chinese population.

Science.gov (United States)

Zhang, Qin; Huang, Wei-Dong; Lv, Xue-Ying; Yang, Yun-Mei

2011-04-01

To investigate the association of coronary artery disease (CAD) and ischemic heart failure (IHF) with polymorphisms of the ghrelin gene in elderly Chinese patients. Fifty-six patients with ischemic heart failure, sixty patients with coronary artery disease without heart failure, and one hundred healthy control subjects participated in the study. The polymorphisms were evaluated by polymerase chain reaction, sequencing, and fragment length polymorphism analysis. Only one single nucleotide polymorphism (SNP), Leu72Met (408C/A), was observed across all samples. Gene frequencies of CC and allele frequencies of C were significantly greater in the CAD with IHF group than those in the CAD without IHF group (p=0.025, p=0.011). There was no significant association between the Leu72Met SNP with coronary artery disease risk factors. Our results suggest that a C allele at position 408 of the ghrelin gene is associated with genetic susceptibility to ischemic heart failure in Chinese elders. Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A novel missense mutation of the DDHD1 gene associated with juvenile amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

Chujun Wu

2016-12-01

Full Text Available Background: Juvenile amyotrophic lateral sclerosis (jALS is a rare form of ALS with an onset age of less than 25 years and is frequently thought to be genetic in origin. DDHD1 gene mutations have been reported to be associated with the SPG28 subtype of autosomal recessive HSP but have never been reported in jALS patients.Methods: Gene screens for the causative genes of ALS, HSP and CMT using next-generation sequencing (NGS technologies were performed on a jALS patient. Sanger sequencing was used to validate identified variants and perform segregation analysis.Results: We identified a novel c.1483A>G (p.Met495Val homozygous missense mutation of the DDHD1 gene in the jALS patient. All of his parents and young bother were heterozygous for this mutation. The mutation was not found in 800 Chinese control subjects or the data of dbSNP, ExAC and 1000G.Conclusion: The novel c.1483A>G (p.Met495Val missense mutation of the DDHD1 gene could be a causative mutation of autosomal recessive jALS.

Calculation of mixed HEU-LEU cores for the HOR research reactor with the scale code system

International Nuclear Information System (INIS)

Leege, P.F.A. de; Gibcus, H.P.M.; Hoogenboom, J.E.; Vries, J.W. de

1997-01-01

The HOR reactor of Interfaculty Reactor Institute (IRI), Delft, The Netherlands, will be converted to use low enriched fuel (LEU) assemblies. As there are still many usable high enriched (HEU) fuel assemblies present, there will be a considerable reactor operation time with mixed cores with both HEU and LEU fuel assemblies. At IRI a comprehensive reactor physics code system and evaluated nuclear data is implemented for detailed core calculations. One of the backbones of the IRI code system is the well-known SCALE code system package. Full core calculations are performed with the diffusion theory code BOLD VENTURE, the nodal code SILWER, and the Monte Carlo code KENO Va. Results are displayed of a strategy from a HEU core to a mixed HEU-LEU core and eventually a LEU core. (author)

Neutronic feasibility studies for LEU conversion of the HFR Petten reactor

International Nuclear Information System (INIS)

Hanan, N.A.; Deen, J.R.; Matos, J.E.; Hendriks, J.A.; Thijssen, P.J.M.; Wijtsma, F.J.

2000-01-01

Design and safety analyses to determine an optimum LEU fuel assembly design using U 3 Si 2 -Al fuel with up to 4.8 g/cm 3 for conversion of the HFR Petten reactor were performed by the RERTR program in cooperation with the Joint Research Centre and NRG. Credibility of the calculational methods and models were established by comparing calculations with recent measurements by NRG for a core configuration set up for this purpose. This model and methodology were then used to study various LEU fissile loading and burnable poison options that would satisfy specific design criteria. (author)

Neutronics analysis of the proposed 25-MW leu TRIGA Multipurpose Research Reactor

International Nuclear Information System (INIS)

Nurdin, M.; Bretscher, M.M.; Snelgrove, J.L.

1982-01-01

More than two years ago the government of Indonesia announced plans to purchase a research reactor for the Puspiptek Research Center in Serpong Indonesia to be used for isotope production, materials testing, neutron physics measurements, and reactor operator training. Reactors using low-enriched uranium (LEU) plate-type and rod-type fuel elements were considered. This paper deals with the neutronic evaluation of the rod-type 25-MW LEU TRIGA Multipurpose Research Reactor (MPRR) proposed by the General Atomic Company of the United States of America

Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging.

Science.gov (United States)

Su, Weiping; Xing, Rubing; Guha, Abhijit; Gutmann, David H; Sherman, Larry S

2007-05-01

Neurofibromatosis 1 (NF1) is a common genetic disease that predisposes patients to peripheral nerve tumors and central nervous system (CNS) abnormalities including low-grade astrocytomas and cognitive disabilities. Using mice with glial fibrillary acidic protein (GFAP)-targeted Nf1 loss (Nf1(GFAP)CKO mice), we found that Nf1(-/-) astrocytes proliferate faster and are more invasive than wild-type astrocytes. In light of our previous finding that aberrant expression of the MET receptor tyrosine kinase contributes to the invasiveness of human NF1-associated malignant peripheral nerve sheath tumors, we sought to determine whether MET expression is aberrant in the brains of Nf1 mutant mice. We found that Nf1(-/-) astrocytes express slightly more MET than wild-type cells in vitro, but do not express elevated MET in situ. However, fiber tracts containing myelinated axons in the hippocampus, midbrain, cerebral cortex, and cerebellum express higher than normal levels of MET in older (> or =6 months) Nf1(GFAP)CKO mice. Both Nf1(GFAP)CKO and wild-type astrocytes induced MET expression in neurites of wild-type hippocampal neurons in vitro, suggesting that astrocyte-derived signals may induce MET in Nf1 mutant mice. Because the Nf1 gene product functions as a RAS GTPase, we examined MET expression in the brains of mice with GFAP-targeted constitutively active forms of RAS. MET was elevated in axonal fiber tracts in mice with active K-RAS but not H-RAS. Collectively, these data suggest that loss of Nf1 in either astrocytes or GFAP(+) neural progenitor cells results in increased axonal MET expression, which may contribute to the CNS abnormalities in children and adults with NF1. (c) 2007 Wiley-Liss, Inc.

Neutronics Study on LEU Nuclear Thermal Rocket Fuel Options

Energy Technology Data Exchange (ETDEWEB)

Venneri, Paolo; Kim, Yong Hee [KAIST, Daejeon (Korea, Republic of); Howe, Steven [CSNR, Idaho (United States)

2014-10-15

This has resulted in a non-trivial simplification of the tasks needed to develop such an engine and the quick initial development of the concept. There are, however, a series of key core-design choices that are currently under scrutiny in the field that have to be resolved in order for the LEU-NTR to be fully developed. The most important of these is the choice of fuel: carbide composite or tungsten cermet. This study presents a first comparison of the two fuel types specifically in the neutronic application to the LEU-NTR, keeping in mind the unique neutronic environment and the system requirements of the system. The scope of the study itself is limited to a neutronics study of the two fuels and only a cursory overview of the material properties of the fuels themselves... The results of this study have led to two major conclusions. First of all is that the carbide composite fuel is, from a neutronics standpoint, a much better fuel. It has a low absorption cross-section, is inherently a strong moderator, is able to achieve a higher reactivity using smaller amounts of fissile material, and can potentially enable a smaller reactor. Second is that despite its neutronic difficulties (high absorption, inferior moderating abilities, and lower k-infinity values) the tungsten cermet fuel is still able to perform satisfactorily in an LEU-NTR, largely due to its ability to have an extremely high fuel loading.

Analysis of the loss of coolant accident for LEU cores of Pakistan research reactor-1

International Nuclear Information System (INIS)

Khan, L.A.; Bokhari, I.H.; Raza, S.H.

1993-12-01

Response of LEU cores for PARR-1 to a Loss of Coolant Accident (LOCA) has been studied. It has been assumed that pool water drains out to double ended rupture of primary coolant pipe or complete shearing of an experimental beam tube. Results show that for an operating power level of 10 MW, both the first high power and equilibrium cores would enter into melting conditions if the pool drain time is less than 22 h and 11 h respectively. However, an Emergency Core Cooling System (ECCS) capable of spraying the core at flow rate of 8.3 m/sup 3/h, for the above mentioned duration, would keep the peak core temperature much below the critical value. Maximum operating power levels below which melting would not occur have been assessed to 3.4 MW and 4.8 MW, respectively, for the first high power and equilibrium cores. (author) 5 figs

94-1 Research and development project lead laboratory support. Status report, January 1--March 31, 1997

Energy Technology Data Exchange (ETDEWEB)

Rink, N.A. [comp.

1997-08-01

This status report is published for Los Alamos National Laboratory 94-1 Research and Development Project Support. The Department of Energy Office of Environmental Management funds these projects in order to support the storage or disposal of legacy plutonium and plutonium-bearing materials that resulted from weapons production throughout the DOE complex. This report summarizes status and technical progress for Los Alamos 94-1 projects during the second quarter of fiscal year 1997.

94-1 Research and development project lead laboratory support. Status report, January 1--March 31, 1997

International Nuclear Information System (INIS)

Rink, N.A.

1997-08-01

This status report is published for Los Alamos National Laboratory 94-1 Research and Development Project Support. The Department of Energy Office of Environmental Management funds these projects in order to support the storage or disposal of legacy plutonium and plutonium-bearing materials that resulted from weapons production throughout the DOE complex. This report summarizes status and technical progress for Los Alamos 94-1 projects during the second quarter of fiscal year 1997

Documentation Experiences for Jamaican SLOWPOKE-2 Conversion from HEU to LEU

International Nuclear Information System (INIS)

Warner, T.-A.; Dennis, H.; Antoine, J.

2015-01-01

The Jamaican SLOWPOKE–2 (JM–1) is a 20 kW research reactor manufactured by Atomic Energy of Canada Limited and has been operating since March 1984, in the department of the International Centre for Environmental and Nuclear Sciences (ICENS), at the University of the West Indies, Mona Campus in Kingston, Jamaica. The pool type reactor has been primarily used for Neutron Activation Analysis in environmental, agricultural, geochemical, health-related studies and mineral exploration. The University, assisted by the IAEA under the GTRI/RERTR program, is currently in the process of converting from HEU to LEU. Extensive documentation on policies, general requirements, elements of the conversion quality assurance (QA) system and conversion QA administrative procedures is required for the conversion. The core conversion activities are being carried out in accordance with current international standards and regulatory guidelines of the newly established Jamaican Radiation Safety Authority (RSA) with agreement between the RSA and IAEA or DOE related to Nuclear Safety and Control. The documentation structure has taken into consideration nuclear safety and licensing, LEU fuel design and conversion analysis, LEU fuel procurement and fabrication, removal of HEU fuel and reactor maintenance and conversion and commissioning, with the conversion QA manual at the apex of the structure. To a large extent, the documentation format will adhere to that of the IAEA applicable regulatory standards and guidance documents. The major challenge of the conversion activities, it is envisioned, will come from the absence of any previous regulatory framework in Jamaica; however, a timeline for the process, which includes training and equipping of regulators, will guide operation. (author)

Energy expenditure during common sitting and standing tasks: examining the 1.5 MET definition of sedentary behaviour.

Science.gov (United States)

Mansoubi, Maedeh; Pearson, Natalie; Clemes, Stacy A; Biddle, Stuart Jh; Bodicoat, Danielle H; Tolfrey, Keith; Edwardson, Charlotte L; Yates, Thomas

2015-05-29

Sedentary behavior is defined as any waking behavior characterized by an energy expenditure of 1.5 METS or less while in a sitting or reclining posture. This study examines this definition by assessing the energy cost (METs) of common sitting, standing and walking tasks. Fifty one adults spent 10 min during each activity in a variety of sitting tasks (watching TV, Playing on the Wii, Playing on the PlayStation Portable (PSP) and typing) and non-sedentary tasks (standing still, walking at 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, and 1.6 mph). Activities were completed on the same day in a random order following an assessment of resting metabolic rate (RMR). A portable gas analyzer was used to measure oxygen uptake, and data were converted to units of energy expenditure (METs). Average of standardized MET values for screen-based sitting tasks were: 1.33 (SD: 0.24) METS (TV), 1.41 (SD: 0.28) (PSP), and 1.45 (SD: 0.32) (Typing). The more active, yet still seated, games on the Wii yielded an average of 2.06 (SD: 0.5) METS. Standing still yielded an average of 1.59 (SD: 0.37) METs. Walking MET values increased incrementally with speed from 2.17 to 2.99 (SD: 0.5 - 0.69) METs. The suggested 1.5 MET threshold for sedentary behaviors seems reasonable however some sitting based activities may be classified as non-sedentary. The effect of this on the definition of sedentary behavior and associations with metabolic health needs further investigation.

Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T], A Second and Third Case Described in Two Unrelated Dutch Families.

Science.gov (United States)

Pondman, Kirsten M; Brinkman, Jacoline W; van der Straaten, Hanneke M; Stroobants, An K; Harteveld, Cornelis L

2018-01-01

We report two families, members of which are carriers of a hemoglobin (Hb) variant previously described as Hb Nouakchott [α114(GH2)Pro→Leu; HBA1: c.344C>T; p.Pro115Leu]. In the first family of Dutch origin, the proband, a 32-year-old male and his 65-year-old father, were both carriers of Hb Nouakchott. Of the second family we tested, only the proband, a 56-year-old Dutch female was a Hb Nouakchott carrier. Hematological analyses of these cases showed the anomaly behaves as a silent Hb variant without clinical consequences. The Hb variant remained unnoticed using high performance liquid chromatography (HPLC), while an additional peak was detected by capillary electrophoresis (CE). These independent findings of Hb Nouakchott indicate that this Hb variant might not be very rare, but simply remains under diagnosed depending on the Hb separation technique used.

Role of cMET in the Development and Progression of Colorectal Cancer

Directory of Open Access Journals (Sweden)

Ilaria Bossi

2013-09-01

Full Text Available Mesenchymal-epithelial transition (MET is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF. Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC, by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies.

Mutations in intron 1 and intron 22 inversion negative haemophilia A patients from Western India.

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Preethi S Nair

Full Text Available Despite increased awareness and diagnostic facilities, 70-80% of the haemophilia A (HA patients still remain undiagnosed in India. Very little data is available on prevalent mutations in HA from this country. We report fifty mutations in seventy one Indian HA patients, of which twenty were novel. Ten novel missense mutations [p.Leu11Pro (p.Leu-8Pro, p.Tyr155Ser (p.Tyr136Ser, p.Ile405Thr (p.Ile386Thr, p.Gly582Val (p.Gly563Val p.Thr696Ile (p.Thr677Ile, p.Tyr737Cys (p.Tyr718Cys, p.Pro1999Arg (p.Pro1980Arg, p.Ser2082Thr (p.Ser2063Thr, p.Leu2197Trp (p.Leu2178Trp, p.Asp2317Glu (p.Asp2298Glu] two nonsense [p.Lys396* (p.Lys377*, p.Ser2205* (p.Ser2186*], one insertion [p.Glu1268_Asp1269ins (p.Glu1249_Asp1250] and seven deletions [p.Leu882del (p.Leu863del, p.Met701del (p.Met682del, p.Leu1223del (p.Leu1204del, p.Trp1961_Tyr1962del (p.Trp1942_Tyr1943del p.Glu1988del (p.Glu1969del, p.His1841del (p.His1822del, p.Ser2205del (p.Ser2186del] were identified. Double mutations (p.Asp2317Glu; p.Thr696Ile were observed in a moderate HA case. Mutations [p. Arg612Cys (p.Arg593Cys, p.Arg2326Gln (p.Arg2307Gln] known to be predisposing to inhibitors to factor VIII (FVIII were identified in two patients. 4.6% of the cases were found to be cross reacting material positive (CRM+ve. A wide heterogeneity in the nature of mutations was seen in the present study which has been successfully used for carrier detection and antenatal diagnosis in 10 families affected with severe to moderate HA.

MetR and CRP bind to the Vibrio harveyi lux promoters and regulate luminescence.

Science.gov (United States)

Chatterjee, Jaidip; Miyamoto, Carol M; Zouzoulas, Athina; Lang, B Franz; Skouris, Nicolas; Meighen, Edward A

2002-10-01

The induction of luminescence in Vibrio harveyi at the later stages of growth is controlled by a quorum-sensing mechanism in addition to nutritional signals. However, the mechanism of transmission of these signals directly to the lux promoters is unknown and only one regulatory protein, LuxR, has been shown to bind directly to lux promoter DNA. In this report, we have cloned and sequenced two genes, crp and metR, coding for the nutritional regulators, CRP (cAMP receptor protein) and MetR (a LysR homologue), involved in catabolite repression and methionine biosynthesis respectively. The metR gene was cloned based on a general strategy to detect lux DNA-binding proteins expressed from a genomic library, whereas the crp gene was cloned based on its complementation of an Escherichia coli crp mutant. Both CRP and MetR were shown to bind to lux promoter DNA, with CRP being dependent on the presence of cAMP. Expression studies indicated that the two regulators had opposite effects on luminescence: CRP was an activator and MetR a repressor. Disruption of crp decreased luminescence by about 1,000-fold showing that CRP is a major activator of luminescence the same as LuxR, whereas disruption of MetR resulted in activation of luminescence over 10-fold, confirming its function as a repressor. Comparison of the levels of the autoinducers involved in quorum sensing excreted by V. harveyi, and the crp and metR mutants, showed that autoinducer production was not significantly different, thus indicating that the nutritional signals do not affect luminescence by changing the levels of the signals required for quorum sensing. Indeed, the large effects of these nutritional sensors show that luminescence is controlled by multiple signals related to the environment and the cell density which must be integrated at the molecular level to control expression at the lux promoters.

Thermal analysis of LEU modified Cintichem target irradiated in TRIGA reactor

International Nuclear Information System (INIS)

Catana, A; Toma, C.

2009-01-01

Actions conceived during last years at international level for conversion of Molybdenum fabrication process from HEU to LEU targets utilization created opportunities for INR to get access to information and participating to international discussions under IAEA auspices. Concrete steps for developing fission Molybdenum technology were facilitated. Institute of Nuclear Research bringing together a number of conditions like suitable irradiation possibilities, direct communication between reactor and hot cell facility, handling capacity of high radioactive sources, and simultaneously the existence of an expanding internal market, decided to undertake the necessary steps in order to produce fission molybdenum. Over the course of last years of efforts in this direction we developed the steps for fission Molybdenum technology development based on modified Cintichem process in accordance with the Argonne National Laboratory proved methodology. Progress made by INR to heat transfer computations of annular target using is presented. An advanced thermal-hydraulic analysis was performed to estimate the heat removal capability for an enriched uranium (LEU) foil annular target irradiated in TRIGA reactor core. As a result, the present analysis provides an upper limit estimate of the LEU-foil and external target surface temperatures during irradiation in TRIGA 14 MW reactor. (authors)

Mixed core conversion study with HEU and LEU fuels

International Nuclear Information System (INIS)

Matos, J.E.; Freese, K.E.

1984-01-01

The results of a mixed core study are presented for gradual replacement of HEU fuel with LEU fuel using the IAEA generic 10 MW reactor as an example. The key parameters show that the transition can be accomplished safely and economically

A neutronics study of LEU fuel options for the HFR-Petten

International Nuclear Information System (INIS)

Deen, J.R.; Snelgrove, J.L.

1985-01-01

The standard HEU fuel cycle characteristics are compared with those of several different LEU fuel cycles in the new vessel configuration. The primary design goals were to provide similar reactivity performance and neutron flux profiles with a minimal increase in 235 U loading. The fuel cycle advantages of Cd burnable absorbers over 10 B are presented. The LEU fuel cycle requirements were calculated also for an extended 32-day cycle and for a reload batch size reduction from six to five standard elements for the standard 26-day cycle. The effects of typical in-core experiments upon neutron flux profiles and fuel loading requirements are also presented. (author)

The progesterone receptor Val660→Leu polymorphism and breast cancer risk

International Nuclear Information System (INIS)

De Vivo, Immaculata; Hankinson, Susan E; Colditz, Graham A; Hunter, David J

2004-01-01

Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine→leucine, at codon 660), is associated with a decreased risk for breast cancer. Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay. We did not observe any association of breast cancer risk with carrying the G/T (Val660→Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93–1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously. Overall, our study does not support an association between the Val660→Leu PROGINS polymorphism and breast cancer risk

The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism.

Science.gov (United States)

Eagleson, Kathie L; Xie, Zhihui; Levitt, Pat

2017-03-01

People with autism spectrum disorder and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy-the influence of one gene on distinct phenotypes-raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multifunctional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with autism spectrum disorder, reduces transcription and disrupts socially relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways and has a complex protein interactome that is enriched in autism spectrum disorder and other NDD candidates. The interactome is coregulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, affecting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms in dilutional pseudoanemia ("sports anemia"

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Ana L. Miranda-Vilela

2010-01-01

Full Text Available Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb. is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration and RDW (red cell distribution width, the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

The Val{sup 192}Leu mutation in the {alpha}-subunit of {beta}-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease

Energy Technology Data Exchange (ETDEWEB)

Hou, Y.; Vavougios, G.; Hinek, A. [Univ. of Toronto (Canada)] [and others

1996-07-01

Substitution mutations adversely affecting the {alpha}-subunit of {beta}-hexosaminidase A ({alpha}{beta}) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-{alpha} chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an {open_quotes}active-site{close_quotes} residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all {alpha}-specific activity. This biochemical phenotype is referred to as the {open_quotes}B1-variant form{close_quotes} of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and both subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, {alpha}-Val{sup 192}Leu. Chinese hamster ovary cells were permanently cotransfected with an {alpha}-cDNA-construct encoding the substitution and a mutant {beta}-cDNA ({beta}-Arg{sup 211}Lys), encoding a {beta}-subunit that is inactive but normal in all other respects. We were surprised to find that the Val{sup 192}Leu substitution produced a pro-{alpha} chain that did not form {alpha}-{beta} dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val{sup 192}Leu substitution does not specifically affect the {alpha}-active site. 23 refs., 4 figs., 2 tabs.

Performance and economic penalties of some LEU [low enriched uranium] conversion options for the Australian Reactor HIFAR

International Nuclear Information System (INIS)

McCulloch, D.B.; Robinson, G.S.

1987-01-01

Performance calculations for the conversion of HIFAR to low enriched uranium (LEU) fuel have been extended to a wide range of 235 U loadings per fuel element. Using a simple approximate algorithm for the likely costs of LEU compared with highly enriched uranium (HEU) fuel elements, the increases in annual fuelling costs for LEU compared with HEU fuel are examined for a range of conversion options involving different performance penalties. No significant operational/safety problems were found for any of the options canvassed. (Author)

Assessment of the effectiveness of the LEU Reform Rule and its implementation

International Nuclear Information System (INIS)

Moran, B.W.; Nations, J.O.; Hammond, G.A.

1993-11-01

The US Nuclear Regulatory Commission (NRC) amended its material control and accounting (MC ampersand A) requirements in 1985 for licensees possessing and using special nuclear material (SNM) of low strategic significance in quantities larger than one effective kilogram (kg). The goal of the Low-Enriched Uranium (LEU) Reform Rule (i.e., 10CFR 74.31) was to establish MC ampersand A requirements for the LEU licensees at a level consistent with the safeguards risk associated with the relatively low strategic importance of such material. The amended requirements were written in a performance-oriented manner, rather than a prescriptive one, in an effort to allow the licensees the opportunity to choose the most cost-effective means of satisfying the requirements. The LEU Reform Rule was implemented in January 1988 and the fuel cycle facilities have had sufficient experience in implementing the rule to allow a meaningful review of its effectiveness. This document provides technical analysis and recommendations to assist the NRC in making a determination if the rule is achieving its intended purpose, and if not, to make the necessary changes to accomplish this

Structures of LeuT in bicelles define conformation and substrate binding in a membrane-like context

Energy Technology Data Exchange (ETDEWEB)

Wang, Hui; Elferich, Johannes; Gouaux, Eric (Oregon HSU)

2012-02-13

Neurotransmitter sodium symporters (NSSs) catalyze the uptake of neurotransmitters into cells, terminating neurotransmission at chemical synapses. Consistent with the role of NSSs in the central nervous system, they are implicated in multiple diseases and disorders. LeuT, from Aquifex aeolicus, is a prokaryotic ortholog of the NSS family and has contributed to our understanding of the structure, mechanism and pharmacology of NSSs. At present, however, the functional state of LeuT in crystals grown in the presence of n-octyl-{beta}-D-glucopyranoside ({beta}-OG) and the number of substrate binding sites are controversial issues. Here we present crystal structures of LeuT grown in DMPC-CHAPSO bicelles and demonstrate that the conformations of LeuT-substrate complexes in lipid bicelles and in {beta}-OG detergent micelles are nearly identical. Furthermore, using crystals grown in bicelles and the substrate leucine or the substrate analog selenomethionine, we find only a single substrate molecule in the primary binding site.

Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes.

Science.gov (United States)

Kazmier, Kelli; Claxton, Derek P; Mchaourab, Hassane S

2017-08-01

Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na + -coupled amino acid transporter LeuT and the Na + -coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective. Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of Annular Lipids in the Functional Properties of Leucine Transporter LeuT Proteomicelles.

Science.gov (United States)

LeVine, Michael V; Khelashvili, George; Shi, Lei; Quick, Matthias; Javitch, Jonathan A; Weinstein, Harel

2016-02-16

Recent work has shown that the choice of the type and concentration of detergent used for the solubilization of membrane proteins can strongly influence the results of functional experiments. In particular, the amino acid transporter LeuT can bind two substrate molecules in low concentrations of n-dodecyl β-d-maltopyranoside (DDM), whereas high concentrations reduce the molar binding stoichiometry to 1:1. Subsequent molecular dynamics (MD) simulations of LeuT in DDM proteomicelles revealed that DDM can penetrate to the extracellular vestibule and make stable contacts in the functionally important secondary substrate binding site (S2), suggesting a potential competitive mechanism for the reduction in binding stoichiometry. Because annular lipids can be retained during solubilization, we performed MD simulations of LeuT proteomicelles at various stages of the solubilization process. We find that at low DDM concentrations, lipids are retained around the protein and penetration of detergent into the S2 site does not occur, whereas at high concentrations, lipids are displaced and the probability of DDM binding in the S2 site is increased. This behavior is dependent on the type of detergent, however, as we find in the simulations that the detergent lauryl maltose-neopentyl glycol, which is approximately twice the size of DDM and structurally more closely resembles lipids, does not penetrate the protein even at very high concentrations. We present functional studies that confirm the computational findings, emphasizing the need for careful consideration of experimental conditions, and for cautious interpretation of data in gathering mechanistic information about membrane proteins.

Precursor Amino Acids Inhibit Polymyxin E Biosynthesis in Paenibacillus polymyxa, Probably by Affecting the Expression of Polymyxin E Biosynthesis-Associated Genes

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Zhiliang Yu

2015-01-01

Full Text Available Polymyxin E belongs to cationic polypeptide antibiotic bearing four types of direct precursor amino acids including L-2,4-diaminobutyric acid (L-Dab, L-Leu, D-Leu, and L-Thr. The objective of this study is to evaluate the effect of addition of precursor amino acids during fermentation on polymyxin E biosynthesis in Paenibacillus polymyxa. The results showed that, after 35 h fermentation, addition of direct precursor amino acids to certain concentration significantly inhibited polymyxin E production and affected the expression of genes involved in its biosynthesis. L-Dab repressed the expression of polymyxin synthetase genes pmxA and pmxE, as well as 2,4-diaminobutyrate aminotransferase gene ectB; both L-Leu and D-Leu repressed the pmxA expression. In addition, L-Thr affected the expression of not only pmxA, but also regulatory genes spo0A and abrB. As L-Dab precursor, L-Asp repressed the expression of ectB, pmxA, and pmxE. Moreover, it affected the expression of spo0A and abrB. In contrast, L-Phe, a nonprecursor amino acid, had no obvious effect on polymyxin E biosynthesis and those biosynthesis-related genes expression. Taken together, our data demonstrated that addition of precursor amino acids during fermentation will inhibit polymyxin E production probably by affecting the expression of its biosynthesis-related genes.

A neutronic feasibility study for LEU conversion of the IR-8 research reactor